Search Results (198)

In this work, a new approach to high-speed multi-coordinate milling was developed. The new approach is based on a new model of trochoidal machining; this is, in turn, based on the theoretical thickness of a chip and its ratio to the cutting edge’s radius, allowing us to establish the vibroacoustic indicators of cutting efficiency. The new model can be used for the real-time assessment of prevailing cutting mechanisms and chip formation. A set of new indicators and parameters for trochoidal high-speed milling (HSM), which can be used to calculate tool paths during technological preparation of slotting, was determined and verified. The size effect in the multi-coordinate HSM of slots on cast iron was identified based on the dependency of vibroacoustic signals on the cutting tooth’s geometry, HSM’a operational machining modes, theoretical chip thicknesses, the sizes of the cut chips, and the quality/roughness of the surface being machined. Based on the analysis of vibroacoustic signals, a set of the most important indicators for monitoring HSM and determining cutting and crack-formation mechanisms during chip deformation was derived. Based on the new model, recommendations for monitoring HSM and for assigning the tool path relative to the workpiece during production preparation were developed and validated. Full article

Neural stem/progenitor cells (NSPCs) in the subventricular zone (SVZ) of the central nervous system (CNS) are critical for tissue repair following injury or disease. These cells retain the capacity to proliferate, migrate, and differentiate into neurons, astrocytes, and oligodendrocytes, making them a promising therapeutic target for neurodegenerative disorders and traumatic injuries. However, the molecular mechanisms regulating their proliferation remain incompletely understood. This study investigates the role of cAMP responsive element-binding protein 5 (CREB5) in the proliferation of rat SVZ-derived NSPCs and elucidates its regulatory mechanism. Using RNA interference, we demonstrated that CREB5 knockdown significantly reduced cell viability, neurosphere formation capacity, and the number of proliferating cells (BrdU- and Ki-67-positive cells) both in vitro and in vivo. In contrast, CREB5 overexpression played opposing roles in cell proliferation. Additionally, alteration of CREB5 expression did not affect apoptosis, as assessed by TUNEL staining, indicating a specific role in proliferation rather than in cell death. Mechanistically, we identified Nuclear Factor One X (NFIX) as a transcriptional target of CREB5. CREB5 binds to the AP-1 site in the NFIX promoter, enhancing its expression. CREB5 knockdown inhibited NFIX expression, while CREB5 overexpression exerted the opposite function. ChIP and luciferase reporter assays further confirmed that CREB5 directly regulates NFIX promoter activity. More importantly, alteration of NFIX expression could reverse the effect of CREB5 on NSPC proliferation. These findings highlight CREB5 as a key regulator of NSPC proliferation through its interaction with NFIX, providing a potential therapeutic target for stem cell-based treatments of CNS disorders. Full article

Manufacturing in modern industrial sectors involves the machining of components where the undeformed chip thickness inevitably decreases to values comparable to the tool edge radius. Under such conditions, the ploughing effect between the workpiece and the tool becomes dominant, followed by the noticeable formation of a stagnation zone. This paper presents research focused on the analysis of the cutting process for small cross-sections of the removed layers, based on cutting force components. This study investigated the machining of two titanium alloy grades—Ti Grade 5 (Ti-6Al-4V) and Ti Grade 2—with the main focus on process stability. A material separation model was analyzed to demonstrate the mechanism of material flow within the cross-section of the machined layer. It was found that the material has a limited ability to flow sideways at the boundary of the chip thickness, thus determining the probable size of the stagnation zone in front of the cutting edge. Orthogonal cutting experiments enabled the determination of the minimum chip thickness coefficient for constant temperature conditions, independent of the tool edge radius, as $h_{min0}=$0.313. In oblique cutting tests, the sensitivity of thin-layer machining was demonstrated for the determined values of minimum undeformed chip thickness. By applying the 0–1 test for chaos, the measurement time (parameter $T·dt$) was determined for both titanium alloys to determine the range of observable chaotic behavior. The analyses confirmed that Ti Grade 2 enters chaotic dynamics much more rapidly than Ti Grade 5 and displays local cutting instabilities independent of the uncut chip thickness. Full article

Ball-end milling cutters are normally used for complex surface machining. During the milling process, the tool posture and cutting parameters of the ball-end milling cutters have a significant impact on chip formations and morphological changes. Based on the Cutter Workpiece Engagement (CWE) model, this study establishes a chip flow model for ball-end milling cutters with consideration of the tool posture variation. The machining experiments of Ti-6Al-4V with a 15° inclined plane and different feed directions were carried out. The influence mechanism of time-varying tool posture on chip formation was systematically investigated. The results reveal an interaction between the chip flow direction and the cutting velocity direction. The included angle between the chip flow directions at the maximum and minimum contact points in the CWE area affects the degree of chip curling, with a smaller angle leading to weaker curling. This research provides a theoretical foundation for the optimization of posture parameters of ball-end milling cutters and expounds on the influence of the chip flow angle on chip deformation. Full article

During the machining of unidirectional carbon fiber-reinforced polymers (UD-CFRPs), their anisotropic characteristics and the complex cutting conditions often lead to defects such as delamination, burrs, and surface/subsurface damage. This study systematically investigates the effects of different fiber orientation angles (0°, 45°, 90°, and 135°) on cutting force, chip formation, stress distribution, and damage characteristics using a coupled macro–micro finite element model. The model successfully captures key microscopic failure mechanisms, such as fiber breakage, resin cracking, and fiber–matrix interface debonding, by integrating the anisotropic mechanical properties and heterogeneous microstructure of UD-CFRPs, thereby more realistically replicating the actual machining process. The cutting speed is kept constant at 480 mm/s. Experimental validation using T700S/J-133 laminates (with a 70% fiber volume fraction) shows that, on a macro scale, the cutting force varies non-monotonically with the fiber orientation angle, following the order of 0° < 45° < 135° < 90°. The experimental values are 24.8 N/mm < 35.8 N/mm < 36.4 N/mm < 44.1 N/mm, and the simulation values are 22.9 N/mm < 33.2 N/mm < 32.7 N/mm < 42.6 N/mm. The maximum values occur at 90° (44.1 N/mm, 42.6 N/mm), while the minimum values occur at 0° (24.8 N/mm, 22.9 N/mm). The chip morphology significantly changes with fiber orientation: 0° produces strip-shaped chips, 45° forms block-shaped chips, 90° results in particle-shaped chips, and 135° produces fragmented chips. On a micro scale, the microscopic morphology of the chips and the surface damage characteristics also exhibit gradient variations consistent with the experimental results. The developed model demonstrates high accuracy in predicting damage mechanisms and material removal behavior, providing a theoretical basis for optimizing CFRP machining parameters. Full article

During the dry machining of 6061 aluminum alloy, cemented carbide tools often suffer from severe wear and built-up edge (BUE) formation, which significantly shortens tool life. Inspired by the non-smooth surface structure of dung beetles, this study proposes an elliptical dimple–groove composite bionic micro-texture, applied to the rake face of cemented carbide tools to enhance their cutting performance. Four types of tools with different surface textures were designed: non-textured (NT), single-groove texture (PT), circular dimple–groove composite texture (AKGC), and elliptical dimple–groove composite texture (TYGC). The cutting performance of these tools was analyzed through three-dimensional finite element simulations using the Deform-3D (version 11.0, Scientific Forming Technologies Corporation, Columbus, OH, USA) software program. The results showed that, compared to the NT tool, the TYGC tool exhibited the best performance, with a reduction in the main cutting force of approximately 30%, decreased tool wear, and significantly improved chip-breaking behavior. Based on the simulation results, a response surface model was constructed to optimize key texture parameters, and the optimal texture configuration was obtained. In addition, a theoretical model was developed to reveal the mechanism by which the micro-texture reduces interfacial friction and temperature rises by shortening the effective contact length. To verify the accuracy of the simulation and theoretical analysis, cutting experiments were further conducted. The experimental results were consistent with the simulation trends, and the TYGC tool demonstrated superior performance in terms of cutting force reduction, smaller adhesion area, and more stable cutting behavior, validating both the simulation model and the proposed texture design. This study provides a theoretical foundation for the structural optimization of bionic micro-textured cutting tools and offers an in-depth exploration of their friction-reducing and wear-resistant mechanisms, showing promising potential for practical engineering applications. Full article

Rock-breaking cutters are critical components in tunneling, mining, and drilling operations, where efficiency, durability, and energy consumption are paramount. Traditional cutter designs and empirical process optimization methods often fail to address the dynamic interaction between heterogeneous rock masses and tool structures, leading to premature wear, high specific energy, and suboptimal performance. Topology optimization, as an advanced computational design method, offers transformative potential for lightweight, high-strength cutter structures and adaptive cutting process control. This review systematically examines recent advancements in topology-optimized cutter design and its integration with rock-cutting mechanics. The structural innovations in cutter geometry and materials are analyzed, emphasizing solutions for stress distribution, wear/fatigue resistance, and dynamic load adaptation. The numerical methods for modeling rock–tool interactions are introduced, including discrete element method (DEM) simulations, smoothed particle hydrodynamics (SPH) methods, and machine learning (ML)-enhanced predictive models. The cutting process optimization strategies that leverage topology optimization to balance objectives such as energy efficiency, chip formation control, and tool lifespan are evaluated. Full article

Concentration gradient generation plays a pivotal role in advancing applications across drug screening, chemical synthesis, and biomolecular studies, yet conventional methods remain constrained by labor-intensive workflows, limited throughput, and inflexible gradient control. This study presents a novel multilayer microfluidic chip leveraging shear flow-driven partitioning–recombination mechanisms to enable the flexible and high-throughput generation of concentration gradient droplets. The chip integrates interactive upper and lower polydimethylsiloxane (PDMS) layers, where sequential fluid distribution and recombination are achieved through circular and radial channels while shear forces from the oil phase induce droplet formation. Numerical simulations validated the dynamic pressure-driven concentration gradient formation, demonstrating linear gradient profiles across multiple outlets under varied flow conditions. The experimental results revealed that the shear flow mode significantly enhances mixing uniformity and droplet generation efficiency compared to continuous flow operations, attributed to intensified interfacial interactions within contraction–expansion serpentine channels. By modulating hydrodynamic parameters such as aqueous- and oil-phase flow rates, this system achieved tunable gradient slopes and droplet sizes, underscoring the intrinsic relationship between flow dynamics and gradient formation. The proposed device eliminates reliance on complex channel networks, offering a compact and scalable platform for parallelized gradient generation. This work provides a robust framework for optimizing microfluidic-based concentration gradient systems, with broad implications for high-throughput screening, combinatorial chemistry, and precision biomolecular assays. Full article

MSTN has been used as a candidate gene in the genetics, breeding, and improvement of animal breeds. However, the possible mechanism by which the MSTN gene regulates muscle development through PSMA6 is not well understood. Previous methylome and transcriptome sequencing analyses of gluteal muscle tissues from MSTN+/−Luxi cattle and wild-type Luxi cattle identified that the PSMA6 gene exhibited a negative correlation between methylation levels and transcriptional activity. To investigate whether MSTN expression regulates PSMA6 gene expression, we examined the effects of MSTN on DNA methyltransferases (DNMT1, DNMT2, DNMT3A, and DNMT3B) and DNA demethylases (TET1, TET2, and TET3). Additionally, chromatin immunoprecipitation (ChIP) assays were performed to detect the binding interaction between PSMA6 and TET2. In this paper, we first established an MSTN knockdown cellular model to preliminarily validate its regulatory effect on PSMA6 expression. Subsequently, the developmental impact of PSMA6 on bovine skeletal muscle satellite cells was further investigated through both knockdown and overexpression of the PSMA6 gene. Furthermore, we examined changes in the expression of key components of the AKT/mTOR signaling pathway to elucidate the mechanisms underlying the PSMA6-mediated regulation of satellite cell development. The results demonstrate that myostatin (MSTN) inhibition significantly decreased proteasome 20S subunit alpha-6 (PSMA6) gene expression, while increasing demethylase expression, particularly ten-eleven translocation-2 (TET2), which exhibited the most pronounced changes. During the cell proliferation stage, the markers Paired Box 7 (PAX7) and Ki-67 exhibited no significant changes, whereas the PSMA6 gene was either overexpressed or disrupted. Conversely, PSMA6 overexpression altered the myogenic differentiation markers, causing the differential regulation of myosin heavy chain (MyHC) and myogenin (MyoG) expression, with MyHC upregulation and concurrent MyoG downregulation. PSMA6 gene overexpression led to the downregulation of AKT1 and Rac1, as well as the activation of the AKT/mTOR pathway, including key factors such as mTOR, p-mTOR, RPS6, p-RPS6, and RhoA. PSMA6 interference resulted in the downregulation of p-mTOR and the upregulation of p-RPS6. Gene expression profiling in our study revealed that the myostatin (MSTN) knockout model significantly reduced the transcriptional levels of the proteasome α6 subunit (PSMA6) (p < 0.05), with the regulatory intensity showing a significant negative correlation with MSTN expression. This molecular evidence substantiates a negative regulatory axis between MSTN and PSMA6. Functional experiments demonstrated that PSMA6 overexpression specifically enhanced myotube formation rates in bovine skeletal muscle satellite cells, whereas siRNA-mediated PSMA6 knockdown exhibited no significant effects on cellular proliferation, indicating the functional specificity of this gene in myogenic differentiation. Mechanistic investigations further revealed that PSMA6 activates the canonical AKT/mTOR signaling transduction cascade through the phosphorylation of AKT and its downstream effector mTOR, thereby mediating the expression of myogenic regulatory factors MyoD and myogenin. Collectively, these findings demonstrate that MSTN deficiency alleviates the transcriptional repression of PSMA6, remodels skeletal muscle differentiation-associated signaling networks, and ultimately drives the directional differentiation of satellite cells toward myofiber specification. Full article

Owing to potential inaccuracies in the current stress–strain curve used for constructing the Johnson–Cook (JC) constitutive model of amorphous alloys, the parameters of the JC constitutive equation were derived using Oxley’s cutting theory, negative chamfer theoretical mechanics modelling, and the particle swarm optimisation algorithm. A two-dimensional finite element cutting model was subsequently established using AdvantEdge software. The optimised constitutive model was used to simulate the main cutting force (Fz) and the backward force (Fy), which resulted in average errors of 12.461% and 9.161%, respectively. Based on the optimised constitutive model in which the JC constitutive equation parameters were derived using Oxley’s method, the variations in temperature, strain rate, and stress in the deformation zone during the cutting process were analysed. The chip microstructures revealed the transformation of lamellar chips into serrated chips resulting from a combination of plastic deformation, adiabatic shear, and shear slip. Full article

Background and Objectives: Aging-related bone loss still lacks interventions. As bone marrow-derived mesenchymal stem cells (BMSCs) undergo aging, R-loop-induced DNA replication stress impairs the osteogenic ability of BMSCs. High-mobility group A-2 (Hmga2) acts as a DNA-binding protein, and the understanding of its underlying mechanisms is crucial for developing effective preventive and therapeutic strategies. Materials and Methods: Aging mice were used as the experimental model, and mouse BMSCs were isolated from their femurs. Hmga2 was achieved through specific gene delivery methods. R-loop formation was detected using dot blotting, chromatin immunoprecipitation (ChIP), and DNA–RNA immunoprecipitation (DRIP) assays. Osteogenic differentiation was evaluated. Results: R-loops were highly accumulated in aging BMSCs. Notably, the key regulator Hmga2 reversed the accumulation of R-loops in aging BMSCs. Hmga2 overexpression significantly decreased the senescence and improved the osteogenic differentiation of aging mBMSCs. Mechanistically, R-loop-forming sequence (RLFS) regions were confirmed in key osteogenesis-related genes, including runt-related transcription factor 2 (Runx2). Hmga2 bound to the RLFS region of Runx2 and promoted its expression by reducing the R-loop level. More, Hmga2 treatment delivered via the AAV system effectively decreased bone loss in aging mice and increased the serum bone turnover biomarkers and collagen remodeling. Conclusions: Our study demonstrates that Hmga2 acts as an activator of aging BMSCs, significantly promoting their osteogenic ability by eliminating the aging-induced DNA replication stress caused by R-loops. Our findings provide new insights into the mechanisms of aging-related bone loss, suggesting that Hmga2 may be a new strategy for alleviating the bone loss phenotype in aging individuals. Full article

Polyimide (PI) with surface microstructures has broad application prospects in aerospace, integrated circuits, and optical engineering due to its excellent mechanical properties, high thermal stability, and chemical resistance. Ultra-precision fly-cutting (UPFC) is a promising advanced technique for machining PI microstructures. However, few studies on the UPFC of PI materials are reported. In this study, the machining principle of UPFC is analyzed, and a comparative study of different processing strategies is conducted. The experimental results demonstrate that the climb cutting strategy is more suitable for PI microstructure machining, which can significantly reduce burr formation and achieve lower surface roughness. The theoretical models describing tool motion and predicting maximum chip thickness in UPFC are established, and the predicted chip thickness is consistent with the experimental results. Moreover, the influence of process parameters on the surface morphology and dimensional accuracy of microstructures is assessed through a series of experiments. The results indicate that cutting depth and step-over are the dominant factors influencing dimensional accuracy and surface roughness. Furthermore, the cutting force during UPFC is extremely small, only in the range of millinewtons (mN). In addition, the cutting force in the feed direction exhibits a high sensitivity to variations in process parameters compared to other directional components. This study provides theoretical guidance for the establishment of a theoretical model and the selection of UPFC process parameters for fabricating PI microstructures. Full article

In order to study the breaking mechanism of rock of high-speed PDC drill bits, improve the cutting efficiency of cutting teeth, and reduce the wear of cutting teeth, the rock-breaking process of PDC cutting teeth is simulated based on mechanical theory knowledge and experiments in this paper. And the influence of changes in PDC tooth rake angle, cutting depth, and diameter of the cutting tooth was studied by changing the different structural and cutting parameters of the cutting teeth, as well as the changes in cutting force, frictional resistance stress, and contact pressure on PDC teeth during the cutting process. The simulated results show that the total energy of the system increases, and the total energy of the system is the largest when cutting at 45°, which coincides with the maximum contact pressure on the teeth at this time. At the same time, it also shows that the impact resistance of PDC teeth is the strongest when chamfered at 45°. The contact area is also smaller, so the cutting is more conducive to the cutting tooth eating into the formation and prolonging the service life of the cutting tooth when the tooth rake angle is 20°. The experimental results showed that, in the actual design of PDC drill bits, an appropriate smaller side angle is not only beneficial for chip removal, but also helps to prevent lateral vibration and does not have a significant impact on cutting load. Finally, obtaining the relationship curve between structural parameters and rock properties is of great significance for guiding the design of PDC drill bits, understanding the intrinsic mechanism of rock fragmentation, and revealing the macroscopic nonlinear mechanical behavior of rocks. Full article

The growing burden of degenerative, cardiovascular, neurodegenerative, and cancerous diseases necessitates innovative approaches to improve our pathophysiological understanding and ability to modulate biological processes. Organic bioelectronics has emerged as a powerful tool in this pursuit, offering a unique ability to interact with biology due to the mixed ionic–electronic conduction and tissue-mimetic mechanical properties of conducting polymers (CPs). These materials enable seamless integration with biological systems across different levels of complexity, from monolayers to complex 3D models, microfluidic chips, and even clinical applications. CPs can be processed into diverse formats, including thin films, hydrogels, 3D scaffolds, and electrospun fibers, allowing the fabrication of advanced bioelectronic devices such as multi-electrode arrays, transistors (EGOFETs, OECTs), ion pumps, and photoactuators. This review examines the integration of CP-based bioelectronics in vivo and in in vitro microphysiological systems, focusing on their ability to monitor key biological events, including electrical activity, metabolic changes, and biomarker concentrations, as well as their potential for electrical, mechanical, and chemical stimulation. We highlight the versatility and biocompatibility of CPs and their role in advancing personalized medicine and regenerative therapies and discuss future directions for organic bioelectronics to bridge the gap between biological systems and electronic technologies. Full article

In this study, a series of rock cutting tests was conducted using a conical pick to investigate the effect of joints on roadheader performance. Tests were performed on intact rock and jointed rock mass specimens with three different joint spacings. The results indicate that cuttability is enhanced in jointed rock mass compared to intact rock due to the influence of joints on fracture mechanics. When cutting perpendicular to the joint plane, joints shorten the fracture path for rock chip formation, reducing the cutting force (FC). In parallel cutting, the joint plane acts as a barrier to side-crack propagation, leading to a further reduction in FC. The FC and specific energy (SE) were generally lower in parallel cutting than in perpendicular cutting. However, when the cutting depth exceeded 0.2 times the joint spacing and the line spacing surpassed 0.4 times the joint spacing, this trend reversed. This occurred because joints hindered the interaction between adjacent cuts, causing a transition to an unrelieved cutting mode. Additionally, FC and SE increased with joint spacing. When joint spacing reached ten times the cutting depth, their values approached those of intact rock. This suggests that the joint effect becomes negligible. These findings provide a better understanding of the effect of joints on roadheader performance. Full article