Search Results (80,702)

Subsurface rolling contact fatigue (RCF) failure is one of the primary failure modes in properly installed and lubricated rolling bearings. Its actual service life often exhibits significant scatter, posing a formidable challenge to the reliable life prediction and operational safety of bearings. This study establishes a macro-meso-coupled rolling contact fatigue model that accounts for crystalline anisotropy and grain topological structures. This model utilizes Voronoi tessellations and random Euler angles to construct a polycrystalline mesoscopic model, which is subsequently integrated with a macroscopic Hertzian contact finite element analysis to simulate the roller bearing loading cycles and determine the localized stress responses within the material. The results indicate that variations in macroscopic structural and operating parameters primarily affect the overall stress level of the subsurface RCF failure. The relative fatigue life of the bearing exhibits an exceptionally high sensitivity to changes in macroscopic and operating parameters. Specifically, an increase in radial load leads to an exponential decrease in relative life, with the Weibull slope ranging between 1.001 and 1.129, which is broadly consistent with the classical Lundberg–Palmgren experimental value of 1.125. Conversely, the heterogeneity of the mesoscopic crystalline structure strongly influences the statistical variance of localized extreme stresses. The scatter in bearing fatigue life demonstrates a much more pronounced sensitivity to mesostructural alterations; as the grain size increases from 10 μm to 40 μm, the Weibull slope drops from 1.041 to 0.784. This study provides an analytical basis for the reliable life prediction of rolling bearings. Full article

Zinc oxide promotes poultry growth, but it tends to agglomerate. This necessitates high doses and leads to environmental contamination from unabsorbed, excreted zinc. Undigested zinc is excreted and can enter the food chain, increasing the probability of zinc residues in edible poultry tissues (muscle, liver, and eggs) and raising concerns for consumer safety. MOF-supported single-atom zinc catalysts (SAC) resolve agglomeration by atomic anchoring, enhancing bioavailability. High-temperature/high-pressure fixation of Zn²⁺ surfaces was confirmed by XRD, while FESEM revealed the corresponding surface morphology, collectively verifying SAC formation. SAC exhibited potent antimicrobial efficacy against key pathogens such as Salmonella typhimurium, Escherichia coli, and Staphylococcus aureus (MIC of 3.125 mg/mL, MBC of 25 mg/mL). Co-culture experiments further demonstrated that the antibacterial performance of SAC remained stable over a temperature range of 20–80 °C and a pH range of 2–8, thus exhibiting excellent thermal stability and gastrointestinal tolerance. In 7-day-old chicks, SAC alleviated S. typhimurium-induced inflammation, reduced bacterial adherence, upregulated claudin-1, preserved gut homeostasis, ameliorated tissue lesions, and increased the abundance of Lactobacillus in the cecum, demonstrating promising potential for poultry infection control. Full article

Background: Diabetes mellitus is frequently associated with complications and comorbidities that often require hospitalization and the use of multiple medications for effective management. However, the simultaneous use of these treatments significantly increases the risk of potential drug–drug interactions (pDDIs). Objectives: This study assessed the prevalence, levels, and associated predictors of pDDIs among hospitalized participants with type 2 diabetes mellitus (T2DM) and evaluated their clinical relevance and implications for monitoring and management. Methods: This retrospective cross-sectional study included 430 inpatients with T2DM at Universitas Indonesia Hospital, Indonesia. Lexicomp^® Lexi-Interact™ software Wolters Kluwer was used to analyze and classify pDDIs based on severity, risk rating, and documentation levels. Additionally, logistic regression analysis was conducted to identify the predictors of pDDIs, and the study assessed the clinical relevance of major pDDIs. Results: Of the total participants, 84.7% (n = 364) experienced pDDIs, with 1642 interactions identified. Moderate interactions accounted for 77.5% (n = 1273), whereas major interactions constituted 12.2% (n = 201). The most common risk rating was category C (77.5%, n = 1187), and the predominant evidence support level was ‘fair’ (64.8%, n = 1064). Multivariate logistic regression analysis showed a significant association between pDDIs and of 7–12 medications used (OR = 30.1; p < 0.001), and hospital stays ≥4 days (OR = 9.7; p = 0.001). Major pDDIs were significantly linked to ≥13 medications (OR = 5.5; p = 0.002), ≥4 days hospitalization (OR = 11.3; p < 0.001), and urinary tract infections (OR = 3.5; p = 0.02). Participants with major pDDIs exhibited hypoglycemia, hyperglycemia, electrolyte imbalances, and reduced therapeutic responses. Conclusions: The findings indicate a high prevalence of pDDIs among participants with T2DM, highlighting the impact of polypharmacy, prolonged hospitalization, and comorbidities. Implementing software-based screening, close monitoring, and targeted interventions are essential to reduce adverse clinical outcomes and enhance patient safety. Full article

Background: Anti-MRSA agents are essential for treating severe infections, yet their use is constrained by distinct toxicity profiles. However, comparative real-world data remain scarce. Methods: This nationwide pharmacovigilance study used the Japanese Adverse Drug Event Report (JADER) database (2004–2025). Disproportionality analyses (proportional reporting ratio [PRR]) were performed at the Standardized MedDRA Query and Preferred Term levels, complemented by Weibull-based time-to-onset modeling, to characterize AE patterns associated with vancomycin (VCM), teicoplanin (TEIC), arbekacin (ABK), daptomycin (DAP), linezolid (LZD), and tedizolid (TZD). Results: Distinct agent-specific AE profiles were observed. VCM showed disproportionate reporting of acute renal failure (PRR 6.66) and severe cutaneous reactions. TEIC displayed fewer renal signals but relatively higher reporting of hematologic events (PRR 3.51). ABK demonstrated high disproportionality in acute and chronic renal failure, reflecting aminoglycoside nephrotoxicity. DAP showed a high reporting signal for eosinophilic pneumonia (PRR 23.30), interstitial lung disease, and creatine kinase elevation/rhabdomyolysis, with wear-out hazard patterns suggesting a possible time-dependent reporting tendency. LZD exhibited hematopoietic signals (PRR 6.13) and additional associations with hyponatremia, lactic acidosis, and optic neuropathy, consistent with marrow suppression and mitochondrial toxicity. Weibull analysis indicated cumulative “wear-out” risks for renal, hepatic, and hematologic events, whereas hypersensitivity and many pulmonary events followed random-failure patterns. Conclusions: This large-scale JADER analysis delineated the distinct safety profiles of the six anti-MRSA agents. The key findings included DAP pulmonary and muscle toxicities, LZD hematological events, and VCM nephrotoxicity. Time-to-onset modeling indicates potential cumulative versus random risk patterns, suggesting the need for individualized monitoring and cross-validation. Full article

Background: Ursolic acid (UA) is a natural pentacyclic triterpenoid with notable antitumor activity, yet its poor water solubility and insufficient targeting restrict clinical translation. Methods: Forty novel ursolic acid-phosphine derivatives bearing seven distinct lipophilic cationic moieties were synthesized via C28 modification and structurally characterized by ¹H NMR and ¹³C NMR. Their antitumor activities in PC3-M cells were evaluated via in vitro assays. Mechanistic investigations were performed using transcriptomic analysis and Western blot. Molecular docking was performed to predict the binding profile of Compound 25 with FGFR1. In vivo antitumor efficacy and biosafety were assessed in RM-1 xenograft models in C57BL/6 mice. Results: Compound 25 (bearing a tris(3,5-dimethylphenyl)phosphine group at the C28 position with an alkyl chain length of five methylene units) exhibited the most potent activity against PC3-M cells, dose-dependently inhibiting proliferation, migration, and invasion and inducing apoptosis. It triggered mitochondrial apoptosis via ROS accumulation and disrupted cytoskeletal homeostasis by suppressing the FGFR1/KRAS/RAC1/PIP4K2 axis. Molecular docking results suggested its strong binding affinity and specificity. In vivo studies confirmed its significant antitumor effect and favorable safety. Conclusions: These results highlight the potential of Compound 25 as a promising lead compound and provide valuable insights for further medicinal chemistry optimization and the development of novel anticancer drugs derived from ursolic acid. Full article

Reliable characterization of the wellbore temperature field is essential for ensuring drilling safety and optimizing operational parameters in shale oil horizontal wells. To address the limitations of conventional models that assume constant thermophysical properties and neglect interactions among multiple heat sources, a transient heat transfer model featuring one-dimensional heat transfer in the wellbore and two-dimensional heat transfer in the formation is developed. The model uniquely accounts for variable thermophysical properties along with three internal heat sources: bit–rock interaction heat (BRIH), viscous dissipation heat (VDH), and drillpipe–formation friction heat (DFFH). The governing equations are implemented numerically using a fully implicit finite-difference approach and verified against field measurements from 10 wells in the Shengli Oilfield. The model demonstrates high predictive accuracy, with an average relative error of 1.58%. VDH contributes significantly to wellbore temperature elevation (≈3.33 °C), whereas BRIH and DFFH exert comparatively minor effects (≈0.34 °C). Sensitivity analysis shows that geothermal gradient is the dominant factor controlling BHCT (correlation coefficients: 0.74 for OBDF; 0.65 for WBDF), followed by drilling fluid density, with all parameters exhibiting weak intercorrelations. Furthermore, a PSO-RBF optimization framework is developed, reducing computation time from 48.34 min per evaluation to an average of 9.0 min per well (81.4% efficiency improvement) while maintaining high prediction accuracy. Overall, this study contributes theoretical understanding and practical value to temperature prediction and parameter optimization in shale oil horizontal well drilling. Full article

Background: Percutaneous liver biopsy is a cornerstone in the diagnostic and therapeutic management of pediatric liver diseases. However, data on the optimal needle gauge for coaxial techniques in children remain scarce. Smaller-gauge needles may theoretically enhance safety but could potentially compromise diagnostic yield. Objectives: The primary objective of this study was to evaluate and compare the safety and diagnostic clinical adequacy of ultrasound-guided percutaneous liver biopsies performed with semi-automated 20G versus 18G coaxial needles in pediatric patients. Patients and Methods: This retrospective cohort study included consecutive patients aged ≤19 years who underwent percutaneous non-targeted liver biopsies at a tertiary medical center between 2006 and 2012. Patient demographics, biopsy technique parameters (including needle gauge, number of cores, and tract embolization), and procedure-related complications were analyzed. Procedural success was defined by diagnostic and clinical adequacy, requiring a definitive pathology report and the presence of ≥7 portal tracts (the widely accepted threshold for a reliable histologic diagnosis). Complications were classified according to the Society of Interventional Radiology guidelines. Results: A total of 320 biopsies were performed in 260 patients (44.6% female; mean age 7.4 ± 6.0 years). Common indications included post-liver transplantation surveillance (28.4%) and unexplained liver enzyme elevation (22.5%). Biopsies were performed using 18G (n = 148; 46.3%) or 20G (n = 172; 53.7%) coaxial needles. Diagnostic and clinical adequacy was achieved in 100% of the procedures, with biopsy results directly influencing clinical management in 39.7% of cases. The overall complication rate was 5.3% (3.4% minor, 1.9% major), with no procedure-related mortality. While raw complication rates were numerically higher in the 20G group (likely to reflect an operator-driven selection bias for younger or higher-risk patients), the differences between the 18G and 20G needles were not statistically significant. Notably, the use of the 20G needle was associated with a significantly reduced clinical need for post-biopsy tract embolization. Conclusions: Our findings demonstrate no statistically significant differences in complication rates or diagnostic clinical adequacy between 18G and 20G coaxial needles for pediatric percutaneous liver biopsies. When selected based on appropriate clinical judgment, the 20G needle provides a high diagnostic yield and serves as an effective option, particularly for reducing the need for tract embolization. However, both 18G and 20G needles represent acceptable clinical options within the pediatric interventional armamentarium. Ultimately, the choice of needle gauge should be meticulously tailored to individual patient characteristics, bleeding risk profiles, and specific clinical indications, rather than uniformly recommending a smaller gauge across all pediatric age groups. Full article

Accident reports provide a detailed account of environmental causes, unsafe human behaviors, and subsequent chain reactions. These records serve as essential resources for analyzing accident mechanisms and exploring potential risk patterns within production safety processes. Currently, Graph based Retrieval-Augmented Generation (RAG), which integrates Large Language Models (LLMs) with Knowledge Graphs (KGs), has emerged as a leading approach for complex causal question answering over extensive unstructured accident documentation. However, the application of this technology in the production safety domain still encounters two primary challenges. First, knowledge graph construction using a single granularity fails to capture fine-grained case details and macro-level standard systems. Second, traditional one-step retrieval paradigms lack the capacity to track deep causal chains or interpret the complex logic of multi-factor coupling. To address these limitations, we propose CausalAgent, a hierarchical graph-enhanced multi-agent framework for causal question answering in production safety accident reports. This framework innovatively combines a Hierarchical Causal Graph (HC-Graph) and a Multi-Agent Collaborative Reasoning (MACR) mechanism. Specifically, the HC-Graph employs a two-layer architecture that links a fine-grained instance layer with a national standard causation layer to resolve conflicts in semantic granularity. The MACR mechanism converts complex natural language queries into executable structured queries and logic verification steps through the sequential cooperation of four specialized agents, namely the Graph Parsing Agent, the Problem Analysis Agent, the Query Generation Agent, and the Reasoning Insight Agent. CausalAgent enables in-depth mining of accident causation mechanisms and provides scientific, robust and interpretable intelligent support for data-driven risk assessment and emergency decision-making. Experiments on real-world accident datasets demonstrate that CausalAgent achieves a $100.0\%$ query execution rate and an $87.3\%$ reasoning accuracy, outperforming the SOTA baseline by $45.2\%$ in terms of absolute accuracy. Full article

Introduction. The superficial musculoaponeurotic system (SMAS) is fundamental for facial soft tissue support and surgical rejuvenation. Although its morphology in the midface and neck is well characterized, the structure of its cranial extension to the forehead remains a subject of terminological uncertainty. The aim of this study was to conduct a detailed histological and immunohistochemical examination of the forehead supporting structures to characterize their morphology and propose an expanded, region-specific classification of the SMAS. Material and methods. Full-thickness tissue specimens (n = 30) were obtained from five standardized facial regions (parotid, buccal, temporal, frontal, and cervical) from 12 male and 18 female body donors (aged 25–70 years). Specimens were processed for histological analysis using hematoxylin and eosin, van Gieson staining, and Masson’s trichrome. Immunohistochemical staining for S100 protein was used to identify neural structures. Morphometric analysis was performed on digitized sections to quantify interseptal distances and the depth of superficial nerve trunks. Results. The analysis confirmed the established SMAS types (I–V) in the cheek, parotid gland, and neck, confirming the validity of the method. Two distinct, sequentially arranged structures were identified on the forehead, proposed as new types. Type VI (neurovascular arborization) is a discrete fan-shaped structures with a central collagen core surrounding a neurovascular bundle, showing positive S100 staining. These structures, spaced approximately 2.2 mm apart, function as true retaining ligaments. Type VII (fibroseptal) SMAS patterns is vertically oriented, purely fibrous septa (retinacula cutis) connecting the aponeurosis to the dermis, devoid of neural elements, and spaced approximately 9.2 mm apart. Importantly, the superficial nerve trunks were located at an average depth of only 1.09 mm (range: 0.57–1.97 mm) from the skin surface. Conclusion. This study identified two novel SMAS patterns in the forehead—neurovascular arborization (type VI) and fibroseptal (type VII)—supporting the expanded functional seven-type classification of the SMAS. The extremely superficial location of the forehead nerves (average 1.1 mm) defines a critical “danger zone” for aesthetic procedures. These findings provide a refined anatomical basis for improving the precision and safety of both surgical and minimally invasive facial procedures. Full article

Antibody–drug conjugates (ADCs) are a rapidly evolving class of oncology therapeutics that enable precise delivery of potent cytotoxic agents to tumor cells while minimizing systemic toxicity. While HER2-targeted ADCs such as trastuzumab deruxtecan (T-DXd) in HER2-mutant, Datopotamab deruxtecan (Dato-Dxd) in EGFR-mutant, and telisotumumab vedotin (Teliso-V) in MET IHC 3+ expressing lung cancer have already established a clinical role in non-small cell lung cancer (NSCLC), multiple ADCs targeting alternative antigens, including additional TROP2 ADCs, HER3, MET, CEACAM5, B7-H3, Nectin-4, and others, are now in advanced clinical development. This review synthesizes the current evidence for non-HER2 ADCs in NSCLC, highlighting mechanisms of action, clinical efficacy, safety profiles, biomarker strategies, and emerging resistance mechanisms. Key safety concerns, including interstitial lung disease (ILD), ocular toxicity, and peripheral neuropathy, are emphasized alongside approaches for re-challenge following toxicity. We further discuss next-generation ADC platforms, including bispecific and conditionally activated constructs, as well as combination strategies with immunotherapy. Collectively, ADCs beyond HER2 are poised to reshape treatment paradigms in NSCLC, offering hope for patients with limited therapeutic options. This review identifies current gaps, highlights ongoing research priorities, and proposes practical considerations for integrating these therapies into clinical practice. Full article

Background and Objectives: For patients on anticoagulants, the risk of possible drug–drug interactions (pDDIs) is particularly higher due to complex polypharmacy. Clinical decision-making is largely guided by drug interaction databases (DIDs); however, inconsistencies in programming may compromise therapeutic safety and effectiveness. The current study is designed to assess and contrast the consistency of severity rating, evidence classification, and clinical management of pDDIs across three DIDs. Materials and Methods: The study was conducted using real patient data from the outpatient medicine and cardiology department of a public hospital in the United Arab Emirates. Prescriptions containing anticoagulants were evaluated using three databases for pDDI screening: Micromedex, Lexicomp, and Drugs.com. Consensus was assessed using Fleiss’ kappa, and correlations between variables were evaluated using Spearman’s rank correlation coefficient, using a threshold of p < 0.05 to assess statistical significance. Results: A total of 130 prescriptions were analyzed, and 3237 pDDIs involving 1143 interaction pairs were retrieved. Of these, 107 pDDI pairs were consistently identified across all three databases. Significant inter-database variability was observed in the severity classification and management recommendations of pDDIs across the three databases. Regarding evidence classification, both Micromedex and Lexicomp rated most interactions with fair evidence, while Drugs.com provided no evidence ratings. Although some correlations were observed—particularly between Lexicomp’s and Drugs.com—overall agreement across databases was slight to fair (p < 0.05). Conclusions: Marked inconsistencies across the databases were identified in the classification and categorization of pDDIs and their associated parameters. Category-wise agreement analysis provides more meaningful insights beyond overall agreement by revealing clinically relevant concordance and divergence among databases. Full article

Decarbonizing maritime transport requires hydrogen storage technologies that are efficient, safe, and compatible with fuel cell systems. This study evaluates three hydrogen storage technologies (compressed hydrogen (CH₂), liquid hydrogen (LH₂), and metal hydrides (MH)) based on five key criteria: safety, autonomy, environmental impact, cost, and implementation feasibility. Applying two multi-criteria decision-making (MCDM) methods, Analytic Hierarchy Process (AHP) and Technique for Order Preference by Similarity to Ideal Solution (TOPSIS), the alternatives are systematically ranked to identify the most suitable option. Both methods consistently highlight compressed hydrogen as the most viable storage solution, offering a good balance of safety, infrastructure maturity, and economic performance. Liquid hydrogen, despite its superior autonomy, is limited by high energy and infrastructure costs. Metal hydrides, although safer and more compact in terms of volumetric density, are limited by low gravimetric efficiency at the system level due to the additional weight of the storage material and associated components. Full article

Why should a genome be protected? Because it contains our most private data! A genome contains an organism’s set of genetic material (DNA and, in viruses, RNA), and it contains all genes and non-coding sequences. The structure of DNA was described by Watson and Crick in 1953, but the first studies were conducted a century earlier by Miescher, who described the structure and chemical composition of the nucleus. The first action aimed at securing the results of genetic research was the creation of databases for the results obtained using genetic fingerprinting technology. The discovery of the sequencing method and the introduction of the polymerase chain reaction laid the foundations for understanding the genome’s function. Automated DNA sequencing proved to be hundreds of times faster than traditional methods, thus reducing the cost and time of genome analyses. Thousands of genomic data points are stored in private and governmental databases. The security of patients’ genomic data must be ensured by protecting it from unauthorized use while, at the same time, enabling research for the sake of public health. The falling prices of genome sequencing and the increasing availability of commercial sequencing for the public could result in ethical problems and undermine the safety of personal information. Full article

The development of highly sensitive and reliable strategies for microcystin-LR (MC-LR) monitoring remains critical for environmental safety and public health protection. Herein, we report a metallene-enabled electrochemiluminescence (ECL) biosensing platform based on ultrathin PdMoCu trimetallic metallenes for femtogram-level MC-LR detection. The two-dimensional PdMoCu metallenes provide abundant active sites and accelerated interfacial charge-transfer kinetics through synergistic electronic modulation among Pd, Mo, and Cu atoms, significantly enhancing the Ru(bpy)₃²⁺/TPrA ECL efficiency. By integrating a programmable H1–aptamer duplex interface, electrostatic enrichment of Ru(bpy)₃²⁺ was achieved, enabling target-responsive luminophore release via aptamer-triggered structural switching. This cooperative amplification mechanism, combining catalytic acceleration and DNA-mediated signal modulation, results in a sensitive signal-off detection mode. Under optimized conditions, the biosensor exhibited a wide linear response from 0.1 pg mL⁻¹ to 50 ng mL⁻¹ with a detection limit as low as 37 fg mL⁻¹. The platform demonstrated excellent selectivity against structural analogues, high reproducibility, and satisfactory recovery (99.3–102.0%) in real tap water samples. This work not only highlights the catalytic potential of trimetallic metallenes in ECL systems but also establishes a generalizable interfacial engineering strategy for ultrasensitive detection of trace environmental contaminants. Full article

Background: Post-approval manufacturing changes for biologics require rigorous comparability assessments to ensure uninterrupted quality and clinical performance. CMAB007 (Aomaishu^®), a China-approved (2023) omalizumab biosimilar, underwent process enhancements—including media optimization and anion-exchange chromatography substitution—yielding a 5-fold increase in production without altering the host cell line. Methods: A novel three-arm tiered strategy was adopted to compare post-change CMAB007, pre-change CMAB007, and reference (Xolair^®) products. Critical quality attributes (CQAs) were classified into tiers based on risk impact, with tier-specific acceptance criteria. Comprehensive analytics assessed structure, post-translational modifications, purity/impurities, activity, and Fc-mediated functions. Forced degradation (lyophilized/reconstituted states) and accelerated stability studies were evaluated. Based on the high degree of CMC similarity and to prevent “biological drift”, the pharmacokinetic (PK) and safety comparability of the post-change CMAB007 versus the reference product (Xolair^®) was confirmed in a randomized, double-blind, two-arm study in healthy males (N = 114; single 150 mg subcutaneous administration). The pre-change product was not included in this clinical PK study. Results: Post-change CMAB007 exhibited analytical similarity within tiered acceptance criteria for all CQAs. Stability studies confirmed enhanced robustness under stress conditions. PK equivalence was demonstrated for AUC_0–inf (GMR: 99.82%; 90% CI: 91.46~108.94%), AUC_0–t (99.54%; 91.40~108.41%), and C_max (101.88%; 95.21~109.01%). Immunogenicity (ADA incidence: 10.5% vs. 12.5%, p = 0.742) and safety profiles were comparable. Conclusions: This study pioneers a tiered three-arm comparability strategy for post-approval changes, integrating advanced analytics, risk-based quality assessment, and clinical validation. The approach mitigates “biological drift” risks, ensuring biosimilar quality, efficacy, and safety while enabling sustainable production scalability. Full article