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Keywords = necessary and sufficient mechanism

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26 pages, 5528 KB  
Article
A Deep Learning-Based Method for Mechanical Equipment Unknown Fault Detection in the Industrial Internet of Things
by Xiaokai Liu, Xiangheng Meng, Lina Ning, Fangmin Xu, Qiguang Li and Chenglin Zhao
Sensors 2025, 25(19), 5984; https://doi.org/10.3390/s25195984 (registering DOI) - 27 Sep 2025
Abstract
With the development of the Industrial Internet of Things (IIoT) technology, fault diagnosis has emerged as a critical component of its operational reliability, and machine learning algorithms play a crucial role in fault diagnosis. To achieve better fault diagnosis results, it is necessary [...] Read more.
With the development of the Industrial Internet of Things (IIoT) technology, fault diagnosis has emerged as a critical component of its operational reliability, and machine learning algorithms play a crucial role in fault diagnosis. To achieve better fault diagnosis results, it is necessary to have a sufficient number of fault samples participating in the training of the model. In actual industrial scenarios, it is often difficult to obtain fault samples, and there may even be situations where no fault samples exist. For scenarios without fault samples, accurately identifying the unknown faults of equipment is an issue that requires focused attention. This paper presents a method for the normal-sample-based mechanical equipment unknown fault detection. By leveraging the characteristics of the autoencoder network (AE) in deep learning for feature extraction and sample reconstruction, normal samples are used to train the AE network. Whether the input sample is abnormal is determined via the reconstruction error and a threshold value, achieving the goal of anomaly detection without relying on fault samples. In terms of input data, the frequency domain features of normal samples are used to train the AE network, which improves the training stability of the AE network model, reduces the network parameters, and saves the occupied memory space at the same time. Moreover, this paper further improves the network based on the traditional AE network by incorporating a convolutional neural network (CNN) and a long short-term memory network (LSTM). This enhances the ability of the AE network to extract the spatial and temporal features of the input data, further improving the network’s ability to extract and recognize abnormal features. In the simulation part, through public datasets collected in factories, the advantages and practicality of this method compared with other algorithms in the detection of unknown faults are fully verified. Full article
(This article belongs to the Section Internet of Things)
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16 pages, 958 KB  
Article
Access to Services Within the Entrusted Budgets in Primary Healthcare in Poland from 2022 to 2025
by Magdalena Mrożek-Gąsiorowska
Healthcare 2025, 13(18), 2358; https://doi.org/10.3390/healthcare13182358 - 19 Sep 2025
Viewed by 348
Abstract
Background: Entrusted budgets were introduced as part of the primary healthcare (PHC) system in Poland in July 2022. This initiative aimed to increase the role of PHC and enhance the accessibility of diagnostic services and specialist consultations/advice for patients. Methods: Data [...] Read more.
Background: Entrusted budgets were introduced as part of the primary healthcare (PHC) system in Poland in July 2022. This initiative aimed to increase the role of PHC and enhance the accessibility of diagnostic services and specialist consultations/advice for patients. Methods: Data from the National Health Fund (NHF) databases regarding contracts between the NHF and healthcare providers in the field of PHC from 2022 to 2025 were analyzed. The share of contracts with entrusted budgets in the total number of PHC physician contracts was estimated in individual voivodships, as well as in counties, using the example of the Małopolskie Voivodship. It was assessed whether there were significant differences between voivodships and counties as well as the pace of implementation of the new solution. Results: Only 43.1% of PHC physicians have signed contracts with the NHF for coordinated care services for 2025, with this percentage varying significantly between voivodships, ranging from 24.8% in Opolskie Voivodship to 66.3% in Lubelskie Voivodship (p < 0.0001). For the vast majority of voivodships, no statistically significant increase in the share of service providers was demonstrated in the period from 2022 to 2025. Access to services between counties is also highly varied (from 10.0% to 76.5%), although the differences were not statistically significant (p = 0.217). Conclusions: The results indicate regional and local inequalities in access to services. It is necessary to implement incentive mechanisms within the contracting of health services between the NHF and providers that will ensure equal access to PHC services within entrusted budgets for all patients. The range of available services should be equal regardless of at which PHC facility a patient is registered. The current regulations concerning entrusted budgets, including the voluntary involvement of service providers, are not sufficient. Full article
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28 pages, 2595 KB  
Article
Resilient Leadership and SME Performance in Times of Crisis: The Mediating Roles of Temporal Psychological Capital and Innovative Behavior
by Wen Long, Dechuan Liu and Wei Zhang
Sustainability 2025, 17(17), 7920; https://doi.org/10.3390/su17177920 - 3 Sep 2025
Viewed by 607
Abstract
Small and medium-sized enterprises (SMEs) often face severe resource constraints and operational fragility during crises. However, little is known about how managerial resilience (MR) translates into performance through time-related psychological resources and innovation—two capabilities that are both scarce and critical under such conditions. [...] Read more.
Small and medium-sized enterprises (SMEs) often face severe resource constraints and operational fragility during crises. However, little is known about how managerial resilience (MR) translates into performance through time-related psychological resources and innovation—two capabilities that are both scarce and critical under such conditions. Drawing on Temporal Motivation Theory (TMT), this study develops and tests a dual-mediation model in which employee temporal psychological capital (TPC) and employee innovative behavior (EIB) transmit the effects of MR on performance. As a core methodological innovation, we adopt a multi-method analytical strategy to provide robust and complementary evidence rather than a hierarchy of results: Partial Least Squares Structural Equation Modeling (PLS-SEM) is used to examine sufficiency-based causal pathways and quantify the mediating mechanisms; Support Vector Machine (SVM) classification offers a non-parametric predictive validation of how MR and its mediators distinguish high- and low-performance cases; and Necessary Condition Analysis (NCA) identifies non-compensatory conditions that must be present for high performance to occur. These three methods address different research questions—sufficiency, classification robustness, and necessity—therefore serving as parallel, equally important components of the analysis. A total of 455 SME managers and employees were surveyed, and results show that MR significantly enhances all three dimensions of TPC (temporal control, temporal fit, time pressure resilience) and EIB (idea generation, idea promotion, idea realization), which in turn improve employee performance. SVM classification confirms that high MR, strong TPC, and active innovation align with high performance, while NCA reveals temporal control, idea generation, and idea realization as necessary bottleneck conditions. By integrating sufficiency–necessity logic with predictive classification, our findings suggest that SMEs should prioritize leadership resilience training to strengthen managers’ adaptive capacity, while simultaneously implementing time management interventions—such as temporal control workshops, workload balancing, and innovation pipeline support—to enhance employees’ ability to align tasks with organizational timelines, execute ideas effectively, and sustain performance during crises. Full article
(This article belongs to the Section Economic and Business Aspects of Sustainability)
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28 pages, 2367 KB  
Article
A Polyomavirus-Positive Merkel Cell Carcinoma Mouse Model Supports a Unified Origin for Somatic and Germ Cell Cancers
by Wendy Yang, Sara Contente and Sarah Rahman
Cancers 2025, 17(17), 2800; https://doi.org/10.3390/cancers17172800 - 27 Aug 2025
Viewed by 763
Abstract
Background/Objectives: The Germ Cell Theory of cancer posits that human primordial germ cells (hPGCs) are the cells of origin for malignancies. While this theory is well established for germ cell cancers, a germ cell origin for somatic cancers has been largely overlooked despite [...] Read more.
Background/Objectives: The Germ Cell Theory of cancer posits that human primordial germ cells (hPGCs) are the cells of origin for malignancies. While this theory is well established for germ cell cancers, a germ cell origin for somatic cancers has been largely overlooked despite clinical observations of malignant somatic transformation (MST), wherein germ cell cancers give rise to diverse somatic cancer phenotypes, often without additional mutations. Methods: To test the Germ Cell Theory experimentally in somatic cancer, we established a virus-driven MST model linking hPGC-like cells (hPGCLCs) to Merkel cell polyomavirus (MCPyV)-positive Merkel cell carcinoma (MCC), a highly aggressive somatic cancer with a germ cell cancer-like, low-mutation epigenetic profile. The MCPyV genome was transduced into human induced pluripotent stem cells (hiPSCs) or hPGC-like cells by lentiviral transfection, followed by xenotransplantation. Results: Virus-positive MCC (VP-MCC)-like tumors were consistently induced without additional oncogenic mutations. These tumors recapitulated VP-MCC’s high-grade neuroendocrine carcinoma histology and molecular profiles. DNA methylation analysis revealed near-complete global hypomethylation in VP-MCC-like tumors, matching the unique epigenetic state of late-stage hPGCs. Notably, pluripotent intermediates were neither necessary nor sufficient for MST; transformation required acquisition of a late-hPGC-like epigenetic state. Conclusions: This is the first MST model of a somatic cancer arising through an aberrant germline-to-soma transition. Our findings unify VP-MCC and germ cell cancer biology, challenge mutation- and soma-centric paradigms, and provide a tractable platform to investigate developmental and epigenetic mechanisms of oncogenesis. This MST model supports a unifying germ cell origin for both germ cell and non-germ cell somatic malignancies. Full article
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17 pages, 6566 KB  
Article
Microstructural and Mechanical Property Variations in 316L Stainless Steel Fabricated by Laser Powder Bed Fusion Under High-Density Processing Conditions
by Shun Zhang, Xudong Wu, Zhong Wang, Meiling Jiang, Guoliang Huang, Xiaoqiang Peng, Chen Yang, Junyan Zhu and Ke Huang
Materials 2025, 18(16), 3899; https://doi.org/10.3390/ma18163899 - 20 Aug 2025
Viewed by 753
Abstract
It has become a trend to precisely control the additive manufacturing process parameters within the high-density process window to obtain high-performance metal parts. However, there are few reports on this topic currently, leaving this research without sufficient references. This study took 316L austenitic [...] Read more.
It has become a trend to precisely control the additive manufacturing process parameters within the high-density process window to obtain high-performance metal parts. However, there are few reports on this topic currently, leaving this research without sufficient references. This study took 316L austenitic stainless steel as a case study. In total, 36 groups of specimens were manufactured by Laser powder bed melting (LPBF), and then, two highly dense specimens were selected to study the variation in their microstructure and properties. The densities of the selected specimens, S1 (VED = 81 J/mm3) and S2 (VED = 156.3 J/mm3), are 99.68% and 99.99%, respectively. The results indicated that, compared with the S1 specimen, the S2 specimen significantly decreased in terms of yield strength (YS), ultimate tensile strength (UTS), and elongation (EL), which are 7.28%, 6.34%, and 19.15%, respectively. The differences in mechanical properties were primarily attributed to differences in their microstructures. Further, compared with the S1 specimen, the fitted ellipse aspect ratio and average grain size of the S2 specimen increased by 79.88% and 53.45%, respectively, and the kernel average misorientation (KAM) value and geometric necessary dislocation (GND) density increased by 36.00% and 58.43%, respectively. Furthermore, the S1 specimen exhibited a strong texture in the <101>//Z direction, whereas no obvious texture was observed in the S2 specimen. Obviously, the reason why precise regulation within the dense parameter range can achieve better performance is that the microstructure and mechanical properties of the specimens prepared within the dense range are different. More importantly, this study provides a feasible framework for optimizing alloys with broad and dense parameter ranges, demonstrating the potential to achieve high-performance components through precise parameter control. Furthermore, the results reveal that even within a wide range of high-density forming parameters, significant variations in microstructure and mechanical properties can arise depending on the selected parameter combinations. These findings underscore the critical importance of meticulous process parameter optimization and microstructural regulation in tailoring material properties. Full article
(This article belongs to the Special Issue New Advances in High-Temperature Structural Materials)
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30 pages, 3923 KB  
Article
Exploring the Key Factors Influencing the Plays’ Continuous Intention of Ancient Architectural Cultural Heritage Serious Games: An SEM–ANN–NCA Approach
by Qian Bao, Siqin Wang, Ken Nah and Wei Guo
Buildings 2025, 15(15), 2648; https://doi.org/10.3390/buildings15152648 - 27 Jul 2025
Viewed by 822
Abstract
Serious games (SGs) have been widely employed in the digital preservation and transmission of architectural heritage. However, the key determinants and underlying mechanisms driving users’ continuance intentions toward ancient-architecture cultural heritage serious games (CH-SGs) have not been thoroughly investigated. Accordingly, a conceptual model [...] Read more.
Serious games (SGs) have been widely employed in the digital preservation and transmission of architectural heritage. However, the key determinants and underlying mechanisms driving users’ continuance intentions toward ancient-architecture cultural heritage serious games (CH-SGs) have not been thoroughly investigated. Accordingly, a conceptual model grounded in the stimulus–organism–response (S–O–R) framework was developed to elucidate the affective and behavioral effects experienced by CH-SG users. Partial least squares structural equation modeling (PLS-SEM) and artificial neural networks (ANNs) were employed to capture both the linear and nonlinear relationships among model constructs. By integrating sufficiency logic (PLS-SEM) and necessity logic (necessary condition analysis, NCA), “must-have” and “should-have” factors were identified. Empirical results indicate that cultural authenticity, knowledge acquisition, perceived enjoyment, and design aesthetics each exert a positive influence—of varying magnitude—on perceived value, cultural identification, and perceived pleasure, thereby shaping users’ continuance intentions. Moreover, cultural authenticity and perceived enjoyment were found to be necessary and sufficient conditions, respectively, for enhancing perceived pleasure and perceived value, which in turn indirectly bolster CH-SG users’ sustained use intentions. By creating an immersive, narratively rich, and engaging cognitive experience, CH-SGs set against ancient architectural backdrops not only stimulate users’ willingness to visit and protect heritage sites but also provide designers and developers with critical insights for optimizing future CH-SG design, development, and dissemination. Full article
(This article belongs to the Section Architectural Design, Urban Science, and Real Estate)
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28 pages, 1845 KB  
Article
Numerical Analysis for a Class of Variational Integrators
by Yihan Shen and Yajuan Sun
Mathematics 2025, 13(15), 2326; https://doi.org/10.3390/math13152326 - 22 Jul 2025
Viewed by 439
Abstract
In this paper, we study a geometric framework for second-order differential systems arising in classical and relativistic mechanics. For this class of systems, we derive necessary and sufficient conditions for their Lagrangian description. The main objectives of this work are to construct efficient [...] Read more.
In this paper, we study a geometric framework for second-order differential systems arising in classical and relativistic mechanics. For this class of systems, we derive necessary and sufficient conditions for their Lagrangian description. The main objectives of this work are to construct efficient structure-preserving variational integrators in a variational framework. To achieve this, we develop new variational integrators through Lagrangian splitting and prove their equivalence to composition methods. We display the superiority of the newly derived numerical methods for the Kepler problem and provide rigorous error estimates by analysing the Laplace–Runge–Lenz vector. The framework provides tools applicable to geometric numerical integration of both ordinary and partial differential equations. Full article
(This article belongs to the Special Issue Recent Advances in Numerical Integration of Differential Equations)
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15 pages, 2596 KB  
Article
Startup Process of Pumped Storage Unit for Avoiding S-Shaped Region Based on Geometric Perspective Method
by Xiaohui Yuan, Kunjie Zhao and Yanhe Xu
Water 2025, 17(13), 1999; https://doi.org/10.3390/w17131999 - 3 Jul 2025
Viewed by 356
Abstract
This paper aims to study the mechanism of avoiding the S-shaped region (S-shaped region, SFR) during the startup of pumped storage units (pumped storage units, PSUs). Firstly, the state space model of the PSU in frequency mode is built using the transfer coefficient [...] Read more.
This paper aims to study the mechanism of avoiding the S-shaped region (S-shaped region, SFR) during the startup of pumped storage units (pumped storage units, PSUs). Firstly, the state space model of the PSU in frequency mode is built using the transfer coefficient of the pump turbine. Then, according to the characteristics of the SFR, the accurate range of the SFR is determined in the full characteristic curve. Finally, combined with a specific power station, this paper proposes a novel geometric perspective method to reveal the underlying mechanism for avoiding the SFR during the startup of PSUs. The core innovation lies in establishing, for the first time, the precise spatial relationship (positioning and distance) between the no-load operating point and the upper boundary of the SFR, thereby identifying two critical necessary and sufficient conditions for successful startup avoiding instability. Based on this mechanism, the critical state of PSUs entering the SFR and the influence of operation points on the startup stability that the PSU is putting into PID control are analyzed using the Hopf bifurcation principle. The results show that two conditions need to be met when the PSU starts up to avoid the SFR. One is that the system operation point is in the stable region, and the other is that the speed overshoot is less than the critical speed overshoot. The speed overshoot is the direct cause of the unit entering the SFR, leading to startup failure. When the PSU is started up and put into proportional–integral–derivative (proportional–integral–derivative, PID) control, a certain margin of flow and guide vane opening will help reduce the speed overshoot and prevent the unit from entering the SFR. Full article
(This article belongs to the Section Hydraulics and Hydrodynamics)
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22 pages, 323 KB  
Article
Bridge, Reverse Bridge, and Their Control
by Andrea Baldassarri and Andrea Puglisi
Entropy 2025, 27(7), 718; https://doi.org/10.3390/e27070718 - 2 Jul 2025
Viewed by 441
Abstract
We investigate the bridge problem for stochastic processes, that is, we analyze the statistical properties of trajectories constrained to begin and terminate at a fixed position within a time interval τ. Our primary focus is the time-reversal symmetry of these trajectories: under [...] Read more.
We investigate the bridge problem for stochastic processes, that is, we analyze the statistical properties of trajectories constrained to begin and terminate at a fixed position within a time interval τ. Our primary focus is the time-reversal symmetry of these trajectories: under which conditions do the statistical properties remain invariant under the transformation tτt? To address this question, we compare the stochastic differential equation describing the bridge, derived equivalently via Doob’s transform or stochastic optimal control, with the corresponding equation for the time-reversed bridge. We aim to provide a concise overview of these well-established derivation techniques and subsequently obtain a local condition for the time-reversal asymmetry that is specifically valid for the bridge. We are specifically interested in cases in which detailed balance is not satisfied and aim to eventually quantify the bridge asymmetry and understand how to use it to derive useful information about the underlying out-of-equilibrium dynamics. To this end, we derived a necessary condition for time-reversal symmetry, expressed in terms of the current velocity of the original stochastic process and a quantity linked to detailed balance. As expected, this formulation demonstrates that the bridge is symmetric when detailed balance holds, a sufficient condition that was already known. However, it also suggests that a bridge can exhibit symmetry even when the underlying process violates detailed balance. While we did not identify a specific instance of complete symmetry under broken detailed balance, we present an example of partial symmetry. In this case, some, but not all, components of the bridge display time-reversal symmetry. This example is drawn from a minimal non-equilibrium model, namely Brownian Gyrators, that are linear stochastic processes. We examined non-equilibrium systems driven by a "mechanical” force, specifically those in which the linear drift cannot be expressed as the gradient of a potential. While Gaussian processes like Brownian Gyrators offer valuable insights, it is known that they can be overly simplistic, even in their time-reversal properties. Therefore, we transformed the model into polar coordinates, obtaining a non-Gaussian process representing the squared modulus of the original process. Despite this increased complexity and the violation of detailed balance in the full process, we demonstrate through exact calculations that the bridge of the squared modulus in the isotropic case, constrained to start and end at the origin, exhibits perfect time-reversal symmetry. Full article
(This article belongs to the Special Issue Control of Driven Stochastic Systems: From Shortcuts to Optimality)
17 pages, 2743 KB  
Article
Grinding and Mixing Uniformity in a Feed Preparation Device with Four-Sided Jagged Hammers and Impact-Mixing Mechanisms
by Ruslan Iskakov and Alexandr Gulyarenko
AgriEngineering 2025, 7(6), 183; https://doi.org/10.3390/agriengineering7060183 - 10 Jun 2025
Viewed by 1222
Abstract
This article considers the study of the grinding and homogeneity of a feed mixture in a device that combines the processes of grinding and mixing. It was found that it is important to improve the working elements with the elimination of passive zones. [...] Read more.
This article considers the study of the grinding and homogeneity of a feed mixture in a device that combines the processes of grinding and mixing. It was found that it is important to improve the working elements with the elimination of passive zones. In this regard, the purpose of this study is to improve the working elements of the feed preparation device with an assessment of the quality of the grinding and homogeneity of the feed mixture. For the efficiency of grinding, serrated surfaces have been developed along four planes of the hammer, which maximizes the use of the working surfaces of the hammer and eliminates passive zones. The design parameters of the serrated surfaces are the step between the tops of adjacent serrations (t, mm), the height of the serrations (h, mm), the angle of inclination (α, °) and the sharpness of the serrations (oz, °). It was found that it is necessary to strive to reduce the step between the tops of adjacent serrations t. The results of the experiments with four-sided serrated hammers showed that a significant portion of the crushed grain waste particles was smaller than 1 mm (25.36–34.34%); the particle size was over 1 mm and less than 2 mm (35.09–44.22%); the particle size was over 2 mm and less than 3.55 mm (27.59–28.73%), and an insignificant portion of particles was larger than 3.55 mm (0.99–2.98%). The experiments yielded the following results on the homogeneity of the mixing of grain waste and the control component: 86.6% (after 2 min), 87.2% (after 4 min) and 87.6% (after 6 min). The feed preparation device with the developed four-sided serrated hammers and impact-mixing mechanisms can produce sufficiently crushed and uniformly mixed feed mass. Full article
(This article belongs to the Section Pre and Post-Harvest Engineering in Agriculture)
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21 pages, 3442 KB  
Article
Material Selection for the Development of Orthoses Using Multicriteria Methods (MCDMs) and Simulation
by Rodger Benjamin Salazar Loor, Javier Martínez-Gómez and Josencka Sarmiento Anchundia
Processes 2025, 13(6), 1796; https://doi.org/10.3390/pr13061796 - 5 Jun 2025
Cited by 1 | Viewed by 881
Abstract
Low-energy bone fractures refer to injuries that occur from minimal trauma or impact. These fractures are often a result of activities, such as falls from standing height or minor accidents, where the force exerted on the bone is insufficient to cause a break [...] Read more.
Low-energy bone fractures refer to injuries that occur from minimal trauma or impact. These fractures are often a result of activities, such as falls from standing height or minor accidents, where the force exerted on the bone is insufficient to cause a break under normal conditions. To design an effective orthotic splint, it is critical to select the appropriate material that mimics the mechanical properties of traditional materials like plaster, which has long been used for immobilization purposes. In this case, Ansys CES Edupack 2025 software was utilized to evaluate and identify materials with mechanical characteristics similar to those of plaster. The software provided a list of six materials that met these criteria, but selecting the most suitable material involved more than just mechanical properties. Three different multicriteria decision-making methods were employed to ensure the best choice: TOPSIS, VIKOR, and COPRAS. These methods were applied to consider various factors, such as strength, flexibility, weight, cost, and ease of manufacturing. The results of the analyses revealed a strong consensus across all three methods. Each approach identified PLA (Polylactic Acid) as the most appropriate material for the orthotic design. Following the material selection process, simulations were conducted to assess the structural performance of the orthotic splint. The results determined that the minimum thickness required for the PLA orthosis was 4 mm, ensuring that it met all necessary criteria for acceptable stresses and deformations during the four primary movements exerted by the wrist. This thickness was sufficient to maintain the orthosis’s functionality without compromising comfort or effectiveness. Moreover, a significant improvement in the design was achieved through topological optimization, where the mass of the preliminary design was reduced by 9.58%, demonstrating an efficient use of material while maintaining structural integrity. Full article
(This article belongs to the Special Issue Multi-Criteria Decision Making in Chemical and Process Engineering)
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31 pages, 2546 KB  
Review
Evaluation of Patellar Groove Prostheses in Veterinary Medicine: Review of Technological Advances, Technical Aspects, and Quality Standards
by Mateusz Pawlik, Piotr Trębacz, Anna Barteczko, Aleksandra Kurkowska, Agata Piątek, Zbigniew Paszenda and Marcin Basiaga
Materials 2025, 18(7), 1652; https://doi.org/10.3390/ma18071652 - 3 Apr 2025
Cited by 1 | Viewed by 1660
Abstract
This review explores the technological advancements in, engineering considerations regarding, and quality standards of veterinary patellar groove replacement implants. Veterinary-specific regulations for these implants are currently lacking. Therefore, human knee implant benchmarks are used as references. These benchmarks guide evaluation of the surface [...] Read more.
This review explores the technological advancements in, engineering considerations regarding, and quality standards of veterinary patellar groove replacement implants. Veterinary-specific regulations for these implants are currently lacking. Therefore, human knee implant benchmarks are used as references. These benchmarks guide evaluation of the surface quality, material selection, biocompatibility, and mechanical performance of the implant to ensure reliability and longevity. Patellar luxation is a common orthopedic disorder in small animals which leads to patellofemoral joint instability and cartilage degeneration, and is often caused by angular limb deformities that disrupt patellar alignment. In severe cases, patellar groove replacement is necessary to restore function and alleviate pain. The implant materials must provide durability, mechanical strength, and biocompatibility to withstand joint forces while ensuring minimal wear. High-quality surface finishes reduce the friction experienced by these materials, improving their long-term performance. Advances in 3D printing allow the creation of patient-specific implants. These implants offer an enhanced anatomical fit and enhanced functionality, which is especially beneficial in complex cases. However, challenges remain in achieving consistent manufacturing quality and economic feasibility. While custom implants are invaluable for difficult cases, standardized designs are sufficient for routine applications. Combining human implant standards with new manufacturing technologies improves veterinary orthopedic solutions. This integration expands the treatment options for patellar luxation and enhances the quality and accessibility of implants. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering (Second Edition))
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20 pages, 8747 KB  
Article
Macrophage Proangiogenic VEGF-A Is Required for Inflammatory Arteriogenesis During Vascular Injury
by Sheila Sharma, Julia Pierce, Jade C. Neverson, Rachel Khan, Cadence F. Lee, Saketh Uppuluri, Crystal Parry, Elizabeth Amelotte, Celia A. Butler, Frank W. Sellke, Elizabeth O. Harrington, Gaurav Choudhary, Alan R. Morrison and Chris S. Mantsounga
Biomedicines 2025, 13(4), 828; https://doi.org/10.3390/biomedicines13040828 - 31 Mar 2025
Viewed by 1018
Abstract
Background: Peripheral artery disease is associated with significant morbidity and mortality. Mechanical revascularization strategies are a mainstay of treatment but are often limited by the anatomic complexity of atherosclerotic lesions. Therapeutic angiogenesis has fallen short of being impactful due to fundamental gaps in [...] Read more.
Background: Peripheral artery disease is associated with significant morbidity and mortality. Mechanical revascularization strategies are a mainstay of treatment but are often limited by the anatomic complexity of atherosclerotic lesions. Therapeutic angiogenesis has fallen short of being impactful due to fundamental gaps in our understanding of postdevelopmental angiogenesis. Methods: Using a preclinical model of peripheral artery disease involving acute vascular injury by femoral artery ligation along with cellular and molecular studies of VEGF-A expression, we sought to further understand the early role of macrophages in inflammatory angiogenesis and arteriogenesis. Results: Macrophage depletion studies revealed that the optimal levels of tissue VEGF-A expression, endothelial cell recruitment, and blood flow recovery were dependent on early macrophage recruitment. Proangiogenic VEGF-A expression was highest in macrophages polarized towards an inflammatory phenotype. Myeloid VEGF-A-deletion, while having no impact on the potent inflammatory cytokine, IL-1β, led to reductions in ischemic tissue VEGF-A, endothelial cell recruitment, and blood flow recovery due to impaired angiogenesis and arteriogenesis. Transplant of inflammatory polarized macrophages rescued the myeloid VEGF-A-deletion phenotype, leading to full blood flow recovery. Conclusions: Macrophages are a necessary and sufficient source of tissue VEGF-A during inflammatory-driven angiogenesis and arteriogenesis in response to vascular injury. Although further study is needed, cell-based therapeutic angiogenesis strategies involving the polarization of macrophages toward an inflammatory state, in order to produce high levels of proangiogenic VEGF-A, may be quite effective for improving revascularization in the context of PAD. Full article
(This article belongs to the Special Issue Angiogenesis)
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19 pages, 3362 KB  
Article
The Leucine-Rich Repeat Kinase 2 Variant LRRK2G2019S Up-Regulates L-Type (CaV1.3) Calcium Channel via the CaVβ3 Subunit: Possible Role in the Pathogenesis of Parkinson’s Disease
by Alejandro Sandoval, Alejandra Corzo-López, Paz Duran, Diana Tovar-Soto, Bryan Vargas-Caballero, Valeria Galicia-Saldaña, Ricardo González-Ramírez and Ricardo Felix
Int. J. Mol. Sci. 2025, 26(7), 3229; https://doi.org/10.3390/ijms26073229 - 31 Mar 2025
Viewed by 1043
Abstract
Voltage-gated Ca2+ (CaV) channels are transmembrane proteins comprising the pore-forming subunit CaVα1 and the ancillary proteins CaVα2δ and CaVβ. They are expressed in various tissues, including the nervous system, where they [...] Read more.
Voltage-gated Ca2+ (CaV) channels are transmembrane proteins comprising the pore-forming subunit CaVα1 and the ancillary proteins CaVα2δ and CaVβ. They are expressed in various tissues, including the nervous system, where they regulate Ca2+ entry in response to membrane potential changes. The increase in intracellular Ca2+ allows for regulating cell excitability and releasing neurotransmitters, among other cellular events. Leucine-rich repeat kinase 2 (LRRK2) is a serine–threonine kinase involved in vesicular mobilization. Previously, it has been shown that LRRK2 regulates neurotransmission by phosphorylating the CaVβ auxiliary subunit of the CaV2.1 (P/Q-type) presynaptic channels. However, it is unknown whether the kinase can regulate the activity of other CaV channel subtypes, such as CaV1.3 (L-type), which play a significant role in the excitability of dopaminergic neurons in the substantia nigra pars compacta (SNc) and whose dysregulation contributes to neurodegeneration in Parkinson’s disease (PD). Here, we found potential phosphorylation sites for LRRK2 in CaVβ3 and examined how these molecules interact. We used immunoprecipitation and electrophysiology in HEK-293 cells expressing recombinant CaV1.3 channels, both with and without wild-type LRRK2 or its LRRK2G2019S mutation, which plays a role in familial PD through a possible gain-of-toxic-function mechanism. Our results show that LRRK2G2019S significantly increases current density through CaV1.3 channels, and this effect depends on the presence of CaVβ3. Site-directed mutagenesis revealed that phosphorylation at S152 in the sequence of CaVβ3 is necessary and sufficient to explain the abnormal regulation of the channels mediated by LRRK2G2019S. These data provide new insights into the molecular regulation that mutant LRRK2 may exert on L-type CaV1.3 channels, which determine pacemaker activity in dopaminergic neurons of the SNc and may, therefore, play a relevant role in the molecular pathophysiology of PD. Full article
(This article belongs to the Special Issue Voltage-Gated Ion Channels and Human Diseases)
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14 pages, 9014 KB  
Article
Correction of Significant Urethral Anomalies Using a Tissue-Engineered Human Urethral Substitute: Proof of Concept
by Christophe Caneparo, Elissa Elia, Stéphane Chabaud, François Berthod, Julie Fradette and Stéphane Bolduc
Int. J. Mol. Sci. 2025, 26(5), 1825; https://doi.org/10.3390/ijms26051825 - 20 Feb 2025
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Abstract
Urethral reconstruction remains a challenge. Indeed, the use of oral mucosa, the reference biomaterial for urethroplasty, is associated with two main drawbacks: the limited availability of autologous tissues and potential short- and long-term complications, especially for patients with recurrences or severe anomalies. Therefore, [...] Read more.
Urethral reconstruction remains a challenge. Indeed, the use of oral mucosa, the reference biomaterial for urethroplasty, is associated with two main drawbacks: the limited availability of autologous tissues and potential short- and long-term complications, especially for patients with recurrences or severe anomalies. Therefore, the development of alternative approaches, such as urethral tissue engineering, is necessary. A new type of human urethral substitute devoid of exogenous biomaterials has been reconstructed in vitro. It presented sufficient mechanical strength and had histological and functional properties comparable to native tissues. These reconstructed tissues were implanted in vivo to repair hypospadias induced in tacrolimus-immunosuppressed rabbits via a two-stage urethroplasty. In the first stage, the distal part of the native urethra was removed, and a flat graft was implanted, leaving the urethra open proximally. Twelve weeks later, the graft was tubularized to create a neourethra, reproducing the usual clinical scenario. The results obtained for the experimental group were less effective than for the control group, with a success rate of 50% after excluding the animal affected by unwanted events unrelated to urethroplasty, and it is possible that the animal model or surgical technique used was not suitable and should be modified. Nevertheless, half of the urethral substitutes grafted on rabbits showed successful integration. These self-assembled artificial tissues represent promising substitutes for urethroplasty. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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