Search Results (244)

This study presents a case-specific joining method for modular, large-scale components manufactured using Selective Laser Sintering (SLS). A T-slot joint reinforced with a pultruded carbon fiber rod was developed to enable the segmental assembly of polymer fan blades that exceed the build volume of common SLS printers. Through an iterative design process, five joint variations were investigated, focusing on the optimization of slot geometry (fillet radii and wall thickness) and the integration of carbon fiber reinforcements to create a high-strength hybrid connection. The experimental findings were validated using a non-linear finite element analysis (FEA) utilizing an iteratively calibrated Young’s modulus of 710 MPa, which accounts for the 50/50 virgin-to-reused PA2200 powder ratio employed in the study. The numerical model identified that the primary sites for crack initiation were the fillet radii of the female slot, where localized equivalent plastic strains reached critical levels of up to 84% in tension and 78% in bending. The final design achieved an average tensile strength of 27.6 MPa, exceeding the design threshold of 21.9 MPa with a safety factor of 2.5. While unreinforced joints showed a 73.4% reduction in bending strength compared to solid specimens, the addition of an 8 mm carbon rod increased performance by 238.7%, restoring over 90% of the monolithic material’s strength. Numerical results confirmed that the reinforcement assumed the primary load-bearing role, effectively mitigating stresses in the polymer matrix below the ultimate tensile strength. Failure analysis clarified that the observed audible failure originated from internal fiber breakage within the rod at stresses between 900–1050 MPa. This work demonstrates that a segmental, reinforcement-based joining method can effectively overcome size constraints in polymer additive manufacturing, providing a robust and repeatable solution for rotating components subject to complex loading conditions. Full article

This study focuses on the machinability optimization of bio-waste corn husk fiber–reinforced epoxy composites during drilling, with the objective of minimizing delamination and improving hole quality required for mechanical fastening applications. While natural fiber composites have been widely investigated, systematic statistical optimization of drilling parameters for corn husk fiber composites remains limited. The novelty of this work lies in identifying the dominant drilling parameter and establishing a clear damage-control strategy using a Taguchi L16 design coupled with ANOVA. Drilling experiments were conducted by varying spindle speed (1000, 1500, 2000, and 2500 rpm), drill diameter (6, 8, 10, and 12 mm), feed rate (00.05, 0.10, 0.15, and 0.20 mm/rev), and point angle (90°, 100°, 110°, and 120°). The results show that the drill diameter is the governing factor affecting delamination, contributing 73.52% of the total variation, followed by spindle speed (22.68%), whereas feed rate (3.14%) and point angle (0.38%) have minimal influence. The optimal condition (2500 rpm, 6 mm drill diameter, and 0.05 mm/rev feed rate) produced the lowest delamination and improved surface integrity. Microscopic observations confirmed reduced fiber pull-out and matrix cracking under these conditions. The main advantage of the proposed approach is the clear identification of parameter priority, enabling the industry to control drilling damage by primarily selecting appropriate drill diameter and spindle speed. The findings provide practical machining guidelines for the use of corn husk fiber composites in lightweight panels, automotive interior parts, and secondary structural components where reliable bolted joints are required. Full article

Retinol-binding protein 4 (RBP4), an adipokine secreted by adipose tissues, has been implicated in metabolic inflammation and insulin resistance. Type 2 diabetes (T2D) is a recognized risk factor for osteoarthritis, with both conditions characterized by chronic low-grade inflammation, suggesting potential links between metabolic disorder and joint degeneration. This study aimed to investigate whether inflammatory and metabolic stresses regulate RBP4 expression and function in joint-related cells. Murine immature chondrocyte cells (iMACs) and the mouse AT805 teratocarcinoma cell line, clone 5, that differentiates into chondrogenic cells (ATDC5), were used as in vitro models for chondrocyte cells. Rbp4 mRNA expression increased during differentiation of iMACs, with 3.6- and 2.2-fold elevations observed on days 7 and 14, respectively (p < 0.01 vs. undifferentiated controls). Inflammatory stimulation with interleukin-6 (IL-6) significantly increased Rbp4 mRNA expression in ATDC5 cells (p < 0.05 vs. vehicle), along with elevated expression of catabolic and inflammatory mediators, including monocyte chemoattractant protein-1 (Mcp1), cyclooxygenase-2 (Cox2), and matrix metalloproteinase-3 (Mmp3) (p < 0.05 vs. vehicle). Pharmacological inhibition of RBP4 using fenretinide (FEN) attenuated chondrogenic differentiation marker expression, reduced glycosaminoglycan synthesis during chondrogenic differentiation, and mitigated high-glucose-induced catabolic responses, as indicated by reduced Mcp2 (p = 0.04) and Mmp13 (p = 0.01) expression in ATDC5 cells treated with FEN compared with cells treated with the vehicle under high-glucose conditions. Furthermore, in RAW 264.7 cells, a murine macrophage cell line commonly used as an in vitro model for osteoclastogenesis, FEN significantly reduced the expression of osteoclast differentiation markers, dendritic cell-specific transmembrane protein (DC-Stamp), nuclear factor of activated T-cells, cytoplasmic 1 (Nf-atc1), cathepsin k (Cath.k), and tartrate-resistant acid phosphatase (Trap) under osteoclastogenic conditions (p < 0.01 vs. vehicle). Collectively, these findings suggest that RBP4 functions as a metabolic–inflammatory mediator influencing both cartilage and bone-remodeling processes. This study reveals a previously unrecognized role of RBP4 in regulating osteoclast-associated pathways. Targeting RBP4 may, therefore, represent a promising therapeutic strategy for delaying or preventing osteoarthritis progression, particularly in metabolically compromised conditions. Full article

Traffic flow prediction is a pivotal task in intelligent transportation systems. The primary challenge lies in accurately modeling the dynamically evolving and directional spatio-temporal dependencies inherent in road networks. Existing graph neural network-based methods suffer from three main limitations: (1) symmetric adjacency matrices fail to capture the causal propagation of traffic flow from upstream to downstream; (2) the serial combination of graph and temporal convolutions lacks an explicit modeling of joint spatio-temporal state transition probabilities; (3) the inherent low-pass filtering property of temporal convolutional networks tends to smooth high-frequency abrupt signals, thereby weakening responsiveness to sudden events. To address these issues, this paper proposes a causal-enhanced spatio-temporal Markov graph convolutional network (CSHGCN). At the spatial modeling level, we construct an asymmetric causal adjacency matrix by decoupling source and target node embeddings to learn directional traffic flow influences. At the spatio-temporal joint modeling level, we design a spatio-temporal Markov transition module (STMTM) based on spatio-temporal Markov chain theory, which explicitly learns conditional transition patterns through temporal dependency encoders, spatial dependency encoders, and a joint transition network. At the temporal modeling level, we introduce differential feature enhancement and high-frequency residual compensation mechanisms to preserve key abrupt change information through frequency-domain complementarity. Experiments on four datasets—PEMS03, PEMS04, PEMS07, and PEMS08—demonstrate that CSHGCN outperforms existing baselines in terms of MAE, RMSE, and MAPE, with ablation studies validating the effectiveness of each module. Full article

Objective: The oral cavity is the beginning of the digestive tract and the composition of saliva could indicate immune events in the gut and joints. The objective of this research was to evaluate the diagnostic accuracy of salivary interleukin (IL)-17A for temporomandibular joint (TMJ) internal derangements (IDs) in patients with spondyloarthritis (SpA). Methods: SpA disease activity was assessed using the Bath Ankylosing Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS) and Disease Activity Index for Psoriatic Arthritis (DAPSA). Salivary cytokines were analyzed using enzyme-linked immunosorbent assay. TMJ conditions were evaluated using The Diagnostic Criteria for Temporomandibular Disorder (DC/TMD) protocol. A symptomatic TMJ-ID group with intracapsular arthralgia (n = 64) and asymptomatic TMJ-ID group without intracapsular arthralgia (n = 50), regardless of joint sounds, were compared with controls (healthy TMJs, n = 86). Results: Women were more prevalent and salivary IL-17A concentration was higher in both ID groups than in controls. Salivary IL-17A levels positively correlated with erythrocyte sedimentation rate, anti-streptolysin-O titer, salivary IL-12/23 p40 and matrix metalloproteinase-3 levels, sore and swollen joint counts, BASDAI, chronic TMJ pain and anxiety. IL-17A demonstrated diagnostic accuracy for currently symptomatic (cutoff, 11 pg/mL) and asymptomatic (cutoff, 11.6 pg/mL) TMJ-ID vs. controls. Patients with IL-17A levels above these cutoffs more frequently exhibited disc displacement with reduction and degenerative TMJ disease, higher self-reported spinal pain and higher SpA activity, as assessed by ASDAS, than patients with IL-17A levels ≤ cutoffs. TMJ-related headache and somatization contributed to greater TMJ pain in those with IL-17A > cutoffs, when compared with dichotomous controls. Conclusions: Salivary IL-17A concentration provides an accurate laboratory marker of SpA activity and enables the diagnosis of both currently symptomatic and asymptomatic TMJ-IDs in patients with SpA. Full article

One of the most critical damage modes affecting the structural performance of traditional composite materials, and therefore their durability, is the occurrence of interlaminar cracks (delamination), which are prone to grow under different loading conditions. In this study, the feasibility of repairing carbon fiber reinforced polymer (CFRP) laminates using structural adhesives was experimentally investigated by evaluating the Mode I interlaminar fracture toughness. Two unidirectional AS4 CFRP systems were analyzed, manufactured with epoxy 8552 and epoxy 3501-6 matrix resins. Mode I delamination behavior was characterized using Double Cantilever Beam (DCB) specimens. Three commercial structural adhesives were used in the repair process: two epoxy-based systems, (Loctite^® EA 9460™, manufactured by Henkel adhesives (Düsseldorf, Germany), and Araldite^® 2015 manufactured by Huntsman Advanced Materials (The Woodlands, TX, USA) and one low-odor acrylic adhesive, 3M Scotch-Weld^® DP8810NS manufactured by 3M Company (St. Paul, MN, USA). Adhesive joints were applied to previously fractured specimens, and the results were compared with those obtained from baseline composite specimens. The results indicate that repaired joints based on the 8552 matrix exhibited higher strain energy release rate (G_Ic) values, approaching those of the original material. The 3501-6 system showed increased fiber bridging, contributing to higher apparent fracture toughness. Among the adhesives evaluated, the acrylic-based adhesive provided the highest delamination resistance for both composite systems. Full article

Knee osteoarthritis (KOA) is one of the most prevalent chronic joint disorders, with its incidence rising over the past decade due to an increase in risk factors, including age, obesity, metabolic conditions, sedentary behavior, and mechanical stress on the knee joints. We conducted a cross-sectional, two-group comparison including 70 knee-pain patients aged ≥ 44 years: 50 patients meeting clinical and radiological criteria for TKA and 20 patients undergoing knee arthroscopy as controls. All patients underwent clinical assessments, WOMAC scoring, radiography, and 3T knee MRI. Serum interleukin-6 (IL-6), cartilage oligomeric matrix protein (COMP), vitamin D3, calcium, and phosphorus were measured at admission. TKA patients were older and had higher WOMAC scores. WOMAC discriminated groups perfectly (AUC = 1.000), but age discriminated well (AUC = 0.911). IL-6 (AUC = 0.819) and COMP (AUC = 0.838) were significant discriminators, with IL-6 threshold ≥ 4.585 pg/mL achieving 66% sensitivity and 85% specificity and COMP cutoff ≥ 11.52 ng/mL achieving 84% sensitivity and 75% specificity. TKA group vitamin D3 levels were considerably lower but had limited discriminatory performance (AUC = 0.683). Although all patients had adequate mineral metabolism, TKA patients had lower serum calcium and higher serum phosphorus levels than controls. Full article

Friction stir welding (FSW) of high-strength aluminum alloys, including EN AW 7020-T651, encounters significant challenges under weld line gap conditions, leading to compromised joint integrity. This study develops a predictive, data-driven framework to assess and optimize the gap bridgeability performance of FSW joints with weld line gaps ranging from 0 to 4 mm in 2 mm thick plates. A structured experimental matrix was implemented, systematically varying rotational speed, welding speed, axial force, and tool shoulder diameter. To promote stable material flow and consistent weld quality under varying gap conditions, a multi-pin tool was employed throughout the welding trials. This configuration supported defect-free weld formation across a broad process window and contributed to improved weld soundness under gap conditions. Weld quality was evaluated using a comprehensive, multi-criteria approach that required (i) defect-free joints verified by visual and cross-sectional (metallographic) inspection, (ii) an ultimate tensile strength of at least 230 MPa, and (iii) a novel metric termed weak area percentage (WAP). Derived from micro-hardness mapping, WAP quantified the proportion of the heat-affected zone (HAZ) exhibiting hardness below 96 HV, providing a more robust and spatially sensitive measure of mechanical integrity than conventional average hardness values. Two machine learning models, Logistic Regression and Random Forest, were trained to classify weld acceptability. The Random Forest model demonstrated superior performance, achieving 92.5% classification accuracy and an F1-score of 0.90. Feature importance analysis identified the interaction terms “welding speed × gap size” and “rotational speed × gap size” as the most influential predictors of weld quality. Full article

Temporomandibular joint (TMJ) disorders represent chronic degenerative musculoskeletal conditions with a high prevalence in the general population and limited regenerative treatment options. Owing to the insufficient efficacy of current conservative and surgical therapies, there is a growing clinical need for biologically based regenerative approaches. Tissue engineering (TE), particularly scaffold-based strategies, has emerged as a promising avenue for TMJ regeneration. This systematic review analyzed preclinical in vivo studies investigating scaffold-based interventions for TMJ disc and osteochondral repair. A structured literature search of PubMed and Scopus databases identified 39 eligible studies. Extracted data included scaffold composition, use of cellular and bioactive components, animal models, and reported histological, radiological, and functional outcomes. Natural scaffolds, such as decellularized extracellular matrix and collagen-based hydrogels, demonstrated favorable biocompatibility and support for fibrocartilaginous regeneration, whereas synthetic materials including polycaprolactone, poly (lactic-co-glycolic acid), and polyvinyl alcohol provided superior mechanical stability and structural tunability. Cells were used in 17/39 studies (43%); quantitative improvements were variably reported across these studies. Bioactive molecule delivery, including transforming growth factor-β, histatin-1, and platelet-rich plasma, further enhanced tissue regeneration, while emerging drug- and gene-delivery approaches showed potential for modulating local inflammation. Despite encouraging results, the reviewed studies exhibited substantial heterogeneity in experimental design, outcome measures, and animal models, limiting direct comparison and translational interpretation. Scaffold-based approaches show preclinical promise but heterogeneity in design and incomplete quantitative reporting limit definitive conclusions. Future research should emphasize standardized methodologies, long-term functional evaluation, and the use of clinically relevant large-animal models to facilitate translation toward clinical application. However, functional and biomechanical outcomes were inconsistently reported and rarely standardized, preventing robust conclusions regarding the relationship between structural regeneration and restoration of TMJ function. Full article

Quaternion-valued neural networks (QVNNs) that have multiple types of delays (leakage, time-varying, distributed, and neutral) and defined on time scales are discussed in this paper. Quaternions form a 4D normed division algebra and allow for a better representation of 3D and 4D data. QVNNs have been proposed and applications have appeared lately. Time-scale calculus was developed to allow the joint treatment of systems, or any hybrid mixing of them, and was also applied with success to the analysis of dynamic properties for neural networks (NNs). Because of its generality, encompassing the common properties of discrete-time (DT) and continuous-time (CT) NNs, time-scale NNs dynamics research does not benefit from a fully-developed Lyapunov theory. So, Halanay-type inequalities have to be used instead. To this end, we provide a novel generalization of inequalities of Halanay-type on time scales specifically suited for neutral systems, i.e., systems with neutral delays. Then, this new lemma is employed to obtain sufficient conditions presented both as linear matrix inequalities (LMIs) and as algebraic inequalities for the exponential stability and exponential synchronization of QVNNs on time scales with the mentioned delay types. The model put forward in this paper has a generality which is appealing for practical applications, in which both DT and CT dynamics are interesting, and all the discussed types of delays appear. For both the DT and CT scenarios, four numerical applications are used to illustrate the four theorems put forward in this research. Full article

Background/Objectives: Autologous conditioned serum (ACS) is an intra-articular orthobiologic for osteoarthritis (OA) intended to shift the joint cytokine milieu toward an anti-inflammatory, pro-regenerative profile. In the present study, we compared the molecular composition of ACS (specifically IMPACT^® ACS) from OA patients with that of healthy controls and assessed demographic and lifestyle influences on mediator levels. Methods: ACS was prepared from the whole blood of 50 OA patients and 20 healthy controls using the IMPACT^® centrifugation system (Plasmaconcept, Cologne, Germany) with glass-bead incubation and standardized handling. Cytokines, growth factors, and matrix metalloproteinases (MMPs) were quantified using multiplex immunoassays and ELISA. To account for demographic imbalances across cohorts, the primary findings were verified using age- and sex-adjusted multiple linear regression models. Results: Pro-inflammatory mediators were minimal in both cohorts, with IL-1β undetectable and IL-6 and TNF-α at very low levels. IL-1 receptor antagonist (IL-1RA) was consistently present. Notably, OA-derived ACS exhibited a catabolic shift compared to controls, characterized by significantly higher MMP-2 and MMP-3 levels. Growth factor profiling showed lower TGF-β1 and TGF-β3 in OA-derived ACS, with TGF-β2 showing no significant difference after adjustment. Exploratory stratified analyses indicated potential differences across sex, BMI, smoking status, and diet for select mediators, though subgroup sizes were limited. Conclusions: ACS prepared with a standardized IMPACT^® protocol displays a broad anti-inflammatory profile. However, increased MMPs and isoform-specific differences in TGF-β reflect a disease-associated molecular imprint. Consequently, patient-related heterogeneity supports the need for standardized reporting and motivates further research into stratified ACS therapy. Full article

Joint acidosis is increasingly recognized as an important determinant of cellular behavior in osteoarthritis (OA). Declines in extracellular pH (pHe) occur across cartilage, meniscus, synovium, and subchondral bone, where they influence inflammation, matrix turnover, and pain. Among proton-sensing G protein-coupled receptors, GPR68 responds to the acidic pH range characteristic of human OA joints. The receptor is activated between pH 6.8 and 7.0, couples to Gq/PLC-MAPK, cAMP-CREB, G12/13-RhoA-ROCK signaling pathways, and is expressed most prominently in articular cartilage, with additional expression reported in synovium, bone, vasculature, and some neuronal populations. These pathways regulate transcriptional programs relevant to cartilage stress responses, inflammation, and matrix turnover. GPR68 expression is increased in human OA cartilage and aligns with regions of active matrix turnover. We previously reported that pharmacologic activation of GPR68 suppresses IL1β-induced MMP13 expression in human chondrocytes under acidic conditions, indicating that increased GPR68 expression may represent a microenvironment-responsive, potentially adaptive signaling response rather than a driver of cartilage degeneration. Evidence from intestinal, stromal, and vascular models demonstrates that GPR68 integrates pH changes with inflammatory and mechanical cues, providing mechanistic context, although these effects have not been directly established in most joint tissues. Small-molecule modulators, including the positive allosteric agonist Ogerin and the inhibitor Ogremorphin, illustrate the tractability of GPR68 as a drug target, although no GPR68-directed therapies have yet been evaluated in preclinical models of OA. Collectively, current data support GPR68 as a functionally relevant proton sensor within the acidic OA joint microenvironment. Full article

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage loss, extracellular matrix degradation, chondrocyte apoptosis, and elevated inflammatory mediators. Chondrocytes respond to IL-1β and other inflammatory signals by secreting cytokines and activating transcriptional pathways that perpetuate inflammation. Because current therapies do not prevent OA progression, bioactive compounds with cytoprotective and immunomodulatory activity are of considerable interest. Lonomia obliqua bristle extract (LOCBE) and its recombinant proteins rLOPAP and rLOSAC exhibit cytoprotective, proliferative, and antioxidant effects in mammalian cells, as well as the ability to influence cytoskeletal dynamics. Given the importance of Rac-1, RhoA, Rab9, and β-catenin in chondrocyte function and cartilage homeostasis, we evaluated LOCBE, rLOPAP, and rLOSAC in human chondrocytes stimulated or not with IL-1β. LOCBE and rLOPAP induced IL-6 and IL-8 secretion, although at lower levels than IL-1β. LOCBE exerts a cytoprotective effect in IL-1β-treated chondrocytes and reduces β-catenin, RhoA, and Rab9 expression without affecting NF-κB p65 translocation. rLOPAP increased mitochondrial activity, cytokine secretion, Rab9 expression, and membrane-associated β-catenin, and under inflammatory conditions, enhanced Rac-1 levels. In contrast, rLOSAC did not induce inflammatory cytokines and decreased RhoA and Rac-1 expression while increasing membrane-associated β-catenin. These findings suggest that L. obliqua extract and its derived-proteins rLOPAP and rLOSAC modulate cytoskeletal regulatory pathways and inflammatory responses in chondrocytes, supporting their potential as therapeutic leads for targeting mechanisms relevant to OA progression. Full article

Mechanical control systems structure, derived from Euler–Lagrange dynamics, is directly tied to physically meaningful coordinates such as joint angles, positions, and velocities. This work investigates when a mechanical control system can be transformed, without changing its physical coordinates, into an equivalent form whose Christoffel symbols vanish, thereby eliminating the configuration-dependent coupling terms in the inertia matrix. We establish a necessary and sufficient condition under which a mechanical control system can, via pure mechanical feedback, be transformed into an equivalent system with zero Christoffel symbols. For three representative examples of mechanical systems, we extensively discuss the global stabilization problem. These case studies demonstrate, respectively, global linearization; local linearization with singularities that can be globalized through an appropriate switching control strategy; and partial linearization, where eliminating the Christoffel symbols enables the design of a globally stabilizing nonlinear controller for a system that is not fully feedback linearizable. These findings demonstrate that achieving vanishing Christoffel symbols, while preserving physically meaningful coordinates, provides a powerful and broadly applicable tool for addressing complex control problems. Full article

Osteoarthritis (OA) is a multifactorial degenerative joint disease in which aberrant mechanical cues act in concert with metabolic dysregulation and chronic low-grade inflammation, with chondrocyte hypertrophy representing a key pathological event driving cartilage degeneration. Alterations in extracellular matrix (ECM) properties—including mechanical loading, stiffness and viscoelasticity, topological organization, and surface chemistry—regulate hypertrophic differentiation and matrix degradation in a zone-, stage-, and scale-dependent manner. Microscale measurements often reveal localized stiffening in superficial zones during early OA, whereas bulk tissue testing can show softening or heterogeneous changes in deeper zones or advanced stages, highlighting the context-dependent nature of ECM mechanics. These biophysical signals are sensed by integrin-based adhesion complexes, primary cilia, mechanosensitive ion channels (TRP/Piezo), and the actin cytoskeleton–nucleus continuum, and are transduced into intracellular pathways with zone- and stage-specific effects, governing chondrocyte fate under physiological and osteoarthritic conditions. Mechanism-based anti-hypertrophic strategies include biomimetic scaffold design for focal defects, dynamic mechanical stimulation targeting early OA, and multimodal approaches integrating mechanical cues with biochemical factors, gene modulation, drug delivery, or cell-based therapies. Collectively, this review provides an integrated mechanobiological framework for understanding cartilage degeneration and highlights emerging opportunities for disease-modifying interventions targeting chondrocyte hypertrophy. Full article