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关键词： 3D assembly model   feature assembly relation network   feature change   change propagation impact assessment   propagation dynamics  

摘要： 3D CAD assembly model is appropriately changed to meet diverse functions and performance requirements of the product, which will cause a series of change propagations within the 3D assembly model. To predict and assess in advance the scope of change propagation impact for 3D assembly model reuse, an approach for feature-oriented change propagation impact assessment for complex mechanical 3D CAD assembly based on a complex network is proposed. The feature and part relation network for describing 3D CAD parts and assembly models are constructed respectively from the feature granularity and part granularity perspectives. Through analysing the mapping relationship among features, part and assemblies, the feature assembly relation network for the 3D CAD assembly model is constructed. The complex network centrality and entropy are employed to evaluate the importance of assembly topological structure of assembled parts, for assessing change propagation impact in the 3D assembly model at the part level. Subsequently, the feature change propagation impact on the 3D assembly model is comprehensively evaluated considering the feature change propagation path, feature change propagation index and feature change propagation evolution law at the feature level. The 3D CAD assembly model of the worm gear reducer is taken as an example, and the feasibility and effectiveness of the proposed approach are verified. .It is helpful for feature change scheme optimisation and control of change propagation in 3D CAD assembly model.

关键词： 3D bioprinting   CAM plants   chemotype   GC-MS metabolomics   molecular docking   oxidative stress  

摘要： Crassulacean Acid Metabolism (CAM) plants possess unique stress-adaptive physiologies, yet their chemotype-bioactivity relationships remain poorly understood. We established an integrated workflow combining GC-MS metabolomics, 2D/3D functional validation, and in silico profiling to evaluate hydrothermal extracts from four CAM species (BDAE [Bulbophyllum drymoglossum CRSAE [Crassula rupestris ECAE [Echeveria and STAE [Hylotelephium telephium]). PCA and marker analysis resolved three distinct chemotypes: acid-rich, sugar-rich, and lipid/sterol-enriched. Using standardized noncytotoxic concentrations, we demonstrated that acid-rich extracts (BDAE/CRSAE) most consistently attenuated H2O2-induced oxidative stress in NIH/3T3 fibroblasts. These cytoprotective effects included significant ROS reduction and preservation of mitochondrial membrane potential. Importantly, these antioxidant properties were robustly retained in a 3D bioprinted tissue-mimetic model with high biocompatibility, as confirmed by live/dead imaging. Furthermore, in silico docking justifies prioritizing phaselic acid as a bioactive marker, showing reproducible interactions with Keap1, COX-2, and MMP-1. While acknowledging the specific analytical scope of GC-MS and the predictive nature of computational modeling, this study successfully connects chemical composition, biological activity, and mechanistic hypotheses within a robust chemotype-resolved framework. Our findings offer a strategic scientific rationale for the selective application of CAM-derived metabolites in antioxidant strategies.

关键词： 3D printing   CAD-CAM denture   fracture load   monolithic dentures   tooth debonding  

摘要： Purpose To assess the fracture load at the tooth-denture base interface in dentures fabricated using three different production methods: compression mold, computer-aided design and computer-aided manufacturing (CAD-CAM) milled (monolithic and bonded and 3D- printed dentures (monolithic and bonded). Materials and Methods Seven groups (n = 10/group) were fabricated using a standardized segmented digital denture design that included tooth #8. Fabrication techniques included conventional compression molding, single, two-disc milling or with bonded tooth designs, and 3D printing monolithic or with bonded tooth designs, utilizing either prefabricated, milled, or 3D-printed teeth. Specimens were embedded in cylindrical molds exposing 2 mm of the denture base and subjected to fracture load testing. Failure modes were analyzed via scanning electron microscopy and classified as adhesive, cohesive, or mixed. One-way analysis of variance with Fisher's LSD was used to compare fracture loads among groups. Results Statistical analysis revealed significant differences in fracture load among the seven denture fabrication methods (p < 0.001). The monolithic milled group demonstrated the highest fracture load (504.7 +/- 76 N) and reliability, as confirmed by Weibull analysis. Both 3D-printed denture bases with bonded teeth groups also showed high fracture load values (361.2 +/- 0.4 and 348.7 +/- 0.8 N, respectively outperforming the conventional group (p < 0.001, p = 0.002). Milled base with bonded milled tooth and monolithic print exhibited moderate fracture load. In contrast, compression-molded and milled base with bonded prefabricated tooth exhibited the lowest fracture load (251.7 +/- 69.6 and 232.8 +/- 47.7 N, respectively). Fracture modes varied, with cohesive failures more evident in stronger groups and adhesive or mixed failures in weaker ones. Conclusion Denture fabrication method had a significant effect on tooth-base fracture load. Monolithic CAD-CAM-milled denture outperfo

关键词： anticoagulant   atrial fibrillation   coronary artery disease   hemorrhage   ischemia  

摘要： Background Oral anticoagulation is essential for stroke prevention in atrial fibrillation, whereas antiplatelet therapy remains standard for coronary artery disease (CAD raising concerns about bleeding when both are combined. The effect of these regimens on recurrent events, reflecting cumulative disease burden, has not been fully evaluated. Methods This post hoc analysis of the EPIC-CAD (Edoxaban Versus Edoxaban With Antiplatelet Agent in Patients With Atrial Fibrillation and Chronic Stable Coronary Artery Disease) trial included 1040 patients with atrial fibrillation and stable CAD randomized to edoxaban monotherapy or edoxaban plus a single antiplatelet agent. The primary end point was the total number of net adverse clinical events at 12 months. Results Over a median follow-up of 12.1 months, 155 total events occurred (123 first, 32 subsequent). Event rates were lower with edoxaban monotherapy than with dual therapy (9.4 versus 19.8 per 100 person-years;incidence rate ratio, 0.47 [95% CI, 0.34-0.67]). Monotherapy reduced first events (incidence rate ratio, 0.46 [95% CI, 0.32-0.68 and showed a lower cumulative hazard of total events (hazard ratio, 0.48 [95% CI, 0.32-0.71];P<0.001). Bleeding was the predominant event type in both groups but occurred more often with dual therapy (85.7% versus 55.3%;P<0.001). Rates of ischemic events and death were similar between groups. Conclusions Edoxaban monotherapy significantly reduced the overall burden of clinical events compared with dual antithrombotic therapy in patients with atrial fibrillation and stable CAD. Bleeding complications were more frequent than ischemic events, emphasizing the need to minimize bleeding risk in this population.

关键词： HCHO capture   ionic liquids   metal-organic frameworks   nanodots   synergistic effect  

摘要： Formaldehyde (HCHO) poses a serious threat to human health due to its irritability and carcinogenicity. However, developing HCHO capture materials with ultra-high HCHO capacity under humid conditions remains an enormous challenge. Herein, a novel strategy for polymerization-based anchorage of HCHO is first reported. The ionic liquids (ILs, Carbamide sulfate CAM][SO4 can exhibit a visual perceptual capture effect, representing a new type of adsorption interaction. [SO4]2- of [CAM][SO4] nanodots dissolve the generated H2O while ensuring the anchorage of HCHO in [CAM]2+, thereby promoting the reaction and increasing the HCHO capacity. Specifically CAM][SO4]@MIL-101(Cr)-20%, based on [CAM][SO4] and metal-organic frameworks (MOFs, MIL-101(Cr has exhibited recorded HCHO capture (19.38 mmol/g which is 4.73 times as high as that of the parent MIL-101(Cr). Not only that, the breakthrough experiment proves that the superior separation factor (SF) of HCHO/H2O can reach 10.0 while the HCHO concentration can be reduced by 5 orders of magnitude (from 800 ppm to less than 1 ppb within 1210 min/g). Furthermore, mechanism analysis elucidates that the superior performance is attributed to the synergistic effect of the tripartite functional structure in [CAM][SO4]@MIL-101(Cr). Our findings provide new molecular-level insights into HCHO capture, expanding our understanding of the principles for the rational design of future adsorbents.

关键词： CAD   prostate cancer   PSMA  

摘要： Background Prostate cancer (PCa) patients frequently experience biochemical recurrence (BCR) following definitive primary treatment. Although fluorine-18-labeled prostate-specific membrane antigen positron emission tomography/computed tomography (18F-PSMA PET/CT) is an imaging modality that is highly sensitive for BCR, false-positive findings owing to benign nonspecific uptake complicate diagnosis. Existing artificial intelligence (AI) tools have attempted to address this challenge but are often limited by their reliance on ground-truth labels derived from expert visual interpretation;thus, these tools reproduce expert opinion rather than confirming disease status.Purpose The purpose of this study was to develop a computer-aided diagnosis (CAD) system for classifying benign and malignant findings on 18F-PSMA PET/CT imaging in patients with PCa and BCR. Post-therapy imaging follow-up was used as an objective reference standard for malignancy.Methods A dataset of 69 patients with PCa and BCR who underwent 18F-PSMA PET/CT imaging was used to develop a CAD. The system was evaluated under two classification schemes based on different ground truths: Task 1 used post-therapy imaging follow-up as the objective reference standard for malignant findings (in a subset of 45 patients whereas task 2 relied on expert visual interpretation at baseline. In total, after data augmentation and filtering, 334 findings were analyzed for task 1, and 467 findings were analyzed for task 2. Suspicious findings were manually segmented using LifeX software (version 25.06.1). One-dimensional intensity profiles were extracted along the x-, y-, and z-axes at the maximum intensity voxel of each finding, from which profile-based and Gaussian-fit features were derived. The intensity profiles were used directly as inputs to a multilayer perceptron (MLP) classifier and were also used to extract profile- and Gaussian-fit-based features to train a random forest (RF) classifier using feature-importance a

关键词： aberrant splicing   deep intronic variant   human urine-derived cells   L1CAM   minigene assay  

摘要： Background: Pathogenic variants in L1CAM, located at Xq28, cause a spectrum of neurodevelopmental disorders of varying severity, including congenital hydrocephalus, MASA syndrome, agenesis of the corpus callosum, and intellectual disability. Material and Methods: Exome sequencing (ES) and RNA studies using urine-derived cells were performed in the younger sibling with agenesis of the corpus callosum, ventriculomegaly, and hearing impairment. A minigene assay was performed to quantitively evaluate the splicing impact of the L1CAM variant. Results: We identified a deep intronic L1CAM variant (NM_001278116.2:c.1124-24T>G) in Intron 10, for which SpliceAI predicts creation of a cryptic acceptor site (score 0.99) via introduction of an AG dinucleotide. The same L1CAM variant was also detected in the older affected brother. RNA studies using of urine-derived cells UDCs demonstrated retention of a 23-bp intronic segment in the transcripts, consistent with nonsense-mediated decay (NMD). Specifically, TA-cloning of reverse transcription PCR products detected the mutant allele in 2% of colonies, and RNA-seq recovered the aberrant junction in only 5 of 18 reads. A minigene assay corroborated the mechanism, yielding a variant-specific larger product corresponding to the 23-bp retained sequence. Conclusion: This report broadens the molecular spectrum of intronic L1CAM variants and underscores the practical value of non-invasive, UDC-based RNA testing in combination with complementary minigene assays for interpreting deep intronic variants.

关键词： CAD-CAM   implant-supported dental prosthesis   polymethylmethacrylate   provisional restoration   quality of life   3D printing  

摘要： Purpose Clinical evidence regarding 3D-printed complete arch interim prostheses remains limited. This randomized crossover trial was designed to compare mechanical complications between milled polymethylmethacrylate (PMMA) and a hybrid ceramic 3D-printed interim restoration and assess mechanical complications, passive fit, optical behavior, and oral health-related quality of life. Materials and Methods Twenty edentulous patients received two complete arch interim prostheses, one milled PMMA and one hybrid ceramic resin 3D-printed restoration, each used for 3 months in a randomized crossover sequence. Mechanical complications, passive fit, optical parameters (L*, a*, b*, Delta E00 and oral health-related quality of life were assessed. Paired nonparametric tests, including the Wilcoxon signed-rank test and McNemar test, were applied (alpha = 0.05 and risk differences with 95% confidence intervals were calculated. Results Milled PMMA exhibited fewer mechanical complications than 3D-printed (10% vs. 45%;p = 0.016;risk difference +35.0 percentage points;95% CI: 9.5-60.5). Passive fit showed no statistically significant differences between materials (p = 0.500). Mean Delta E00 did not differ significantly (PMMA 4.68 +/- 6.57;3D-printed 4.73 +/- 4.75;p = 0.243). The 3D-printed material presented higher L* values at both evaluations (p < 0.001) and a significant increase in a* over time (p = 0.008). Both materials improved Oral Health Impact Profile-14 scores;at 3 months, 3D-printed prostheses showed slightly lower scores than PMMA (p = 0.045). Conclusions Milled PMMA showed more favorable mechanical performance. Both materials demonstrated passive fit, stable optical behavior, and improvements in patient-reported outcomes during the 3-month period.

关键词： condition monitoring   multi-body dynamics   ball bearing dynamics   gear dynamics   signal processing  

摘要： Reliable fault diagnosis in rotating machinery demands accurate prediction of their condition before failure occurs. Model-based diagnosis of faults in rotating machinery is an effective method to overcome the high cost of experimental investigation. This work develops and validates experimentally two complementary dynamic models of a coupled bearing-gear pair transmission system: a 15-degrees-of-freedom physics-based model formulated in MATLAB/Simulink, which captures nonlinear bearing contact and time-varying gear mesh stiffness, and a high-fidelity CAD-based multi-body model built in MSC ADAMS to closely replicate the physical configuration. Defects are intentionally introduced into the bearing subsystem in both simulations and a machine-fault simulator. Responses of the systems acquired in the load zone are processed using short-time synchronous averaging (related to fault characteristics time) to suppress non-synchronous disturbances (not related to faulty conditions followed by envelope analysis to extract bearing characteristic frequencies. A comparative evaluation (qualitative and quantitative) across different faulty conditions of the system's bearing demonstrates strong agreement between the simulated and experimental fault signatures. The study confirms that both models serve as effective virtual platforms, significantly reducing reliance on time-consuming, costly experimental campaigns and enabling the scalable development of condition-monitoring strategies for rotating machinery.

关键词： anxiety   compositions   depression   fluoxetine   tandospirone  

摘要： Background and Objective: To address the high mortality, slow onset, and suboptimal efficacy of current treatments for comorbid anxiety and depression (CAD this study developed and systematically evaluated a novel combination formulation. Methods: The anxiolytic tandospirone (TDS) was combined with fluoxetine (FLU escitalopram, or milnacipran for cell-based screening. The optimal combination was selected for pharmacokinetic studies in rats, followed by a 49-day pharmacodynamic evaluation and mechanistic investigation in a CAD mouse model. Results: Two optimal TDS-FLU combinations, TF-1 (TDS:FLU = 1.2:1,w/w) and TF-2 (TDS:FLU = 2.4:1,w/w were obtained, both exhibiting good neuroprotective effects. Pharmacokinetic results showed that TF-1 and TF-2 significantly increased drug exposure and prolonged half-life compared with monotherapies of TDS and FLU. Pharmacodynamically, TF-1 and TF-2 exhibited superior anxiolytic-antidepressant efficacy compared with monotherapies after 28-day and 49-day interventions. At day 28, both formulations significantly increased open-field central-zone activity and sucrose preference, and reduced immobility time (all P < 0.05). Their therapeutic benefits were further augmented at day 49, with sustained and improved behavioral improvements upon long-term treatment. Mechanistic studies showed that both combinations elevated plasma and hippocampal 5-HT and BDNF levels, upregulated hippocampal 5-HT1AR and TrKB expression, and enhanced neuronal plasticity. Conclusion: TF-1 and TF-2 were superior to single agents in pharmacokinetics and long-term CAD efficacy, acting via 5-HT modulation and BDNF-TrKB activation, supporting their development as CAD combination therapies.