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31 pages, 34013 KiB  
Article
Vision-Based 6D Pose Analytics Solution for High-Precision Industrial Robot Pick-and-Place Applications
by Balamurugan Balasubramanian and Kamil Cetin
Sensors 2025, 25(15), 4824; https://doi.org/10.3390/s25154824 - 6 Aug 2025
Abstract
High-precision 6D pose estimation for pick-and-place operations remains a critical problem for industrial robot arms in manufacturing. This study introduces an analytics-based solution for 6D pose estimation designed for a real-world industrial application: it enables the Staubli TX2-60L (manufactured by Stäubli International AG, [...] Read more.
High-precision 6D pose estimation for pick-and-place operations remains a critical problem for industrial robot arms in manufacturing. This study introduces an analytics-based solution for 6D pose estimation designed for a real-world industrial application: it enables the Staubli TX2-60L (manufactured by Stäubli International AG, Horgen, Switzerland) robot arm to pick up metal plates from various locations and place them into a precisely defined slot on a brake pad production line. The system uses a fixed eye-to-hand Intel RealSense D435 RGB-D camera (manufactured by Intel Corporation, Santa Clara, California, USA) to capture color and depth data. A robust software infrastructure developed in LabVIEW (ver.2019) integrated with the NI Vision (ver.2019) library processes the images through a series of steps, including particle filtering, equalization, and pattern matching, to determine the X-Y positions and Z-axis rotation of the object. The Z-position of the object is calculated from the camera’s intensity data, while the remaining X-Y rotation angles are determined using the angle-of-inclination analytics method. It is experimentally verified that the proposed analytical solution outperforms the hybrid-based method (YOLO-v8 combined with PnP/RANSAC algorithms). Experimental results across four distinct picking scenarios demonstrate the proposed solution’s superior accuracy, with position errors under 2 mm, orientation errors below 1°, and a perfect success rate in pick-and-place tasks. Full article
(This article belongs to the Section Sensors and Robotics)
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27 pages, 11710 KiB  
Article
Assessing ResNeXt and RegNet Models for Diabetic Retinopathy Classification: A Comprehensive Comparative Study
by Samara Acosta-Jiménez, Valeria Maeda-Gutiérrez, Carlos E. Galván-Tejada, Miguel M. Mendoza-Mendoza, Luis C. Reveles-Gómez, José M. Celaya-Padilla, Jorge I. Galván-Tejada and Antonio García-Domínguez
Diagnostics 2025, 15(15), 1966; https://doi.org/10.3390/diagnostics15151966 - 5 Aug 2025
Abstract
Background/Objectives: Diabetic retinopathy is a leading cause of vision impairment worldwide, and the development of reliable automated classification systems is crucial for early diagnosis and clinical decision-making. This study presents a comprehensive comparative evaluation of two state-of-the-art deep learning families for the task [...] Read more.
Background/Objectives: Diabetic retinopathy is a leading cause of vision impairment worldwide, and the development of reliable automated classification systems is crucial for early diagnosis and clinical decision-making. This study presents a comprehensive comparative evaluation of two state-of-the-art deep learning families for the task of classifying diabetic retinopathy using retinal fundus images. Methods: The models were trained and tested in both binary and multi-class settings. The experimental design involved partitioning the data into training (70%), validation (20%), and testing (10%) sets. Model performance was assessed using standard metrics, including precision, sensitivity, specificity, F1-score, and the area under the receiver operating characteristic curve. Results: In binary classification, the ResNeXt101-64x4d model and RegNetY32GT model demonstrated outstanding performance, each achieving high sensitivity and precision. For multi-class classification, ResNeXt101-32x8d exhibited strong performance in early stages, while RegNetY16GT showed better balance across all stages, particularly in advanced diabetic retinopathy cases. To enhance transparency, SHapley Additive exPlanations were employed to visualize the pixel-level contributions for each model’s predictions. Conclusions: The findings suggest that while ResNeXt models are effective in detecting early signs, RegNet models offer more consistent performance in distinguishing between multiple stages of diabetic retinopathy severity. This dual approach combining quantitative evaluation and model interpretability supports the development of more robust and clinically trustworthy decision support systems for diabetic retinopathy screening. Full article
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25 pages, 9834 KiB  
Article
Vegetation Succession Dynamics in the Deglaciated Area of the Zepu Glacier, Southeastern Tibet
by Dan Yang, Naiang Wang, Xiao Liu, Xiaoyang Zhao, Rongzhu Lu, Hao Ye, Xiaojun Liu and Jinqiao Liu
Forests 2025, 16(8), 1277; https://doi.org/10.3390/f16081277 - 4 Aug 2025
Abstract
Bare land exposed by glacier retreat provides new opportunities for ecosystem development. Investigating primary vegetation succession in deglaciated regions can provide significant insights for ecological restoration, particularly for future climate change scenarios. Nonetheless, research on this topic in the Qinghai–Tibet Plateau has been [...] Read more.
Bare land exposed by glacier retreat provides new opportunities for ecosystem development. Investigating primary vegetation succession in deglaciated regions can provide significant insights for ecological restoration, particularly for future climate change scenarios. Nonetheless, research on this topic in the Qinghai–Tibet Plateau has been exceedingly limited. This study aimed to investigate vegetation succession in the deglaciated area of the Zepu glacier during the Little Ice Age in southeastern Tibet. Quadrat surveys were performed on arboreal communities, and trends in vegetation change were assessed utilizing multi-year (1986–2024) remote sensing data. The findings indicate that vegetation succession in the Zepu glacier deglaciated area typically adheres to a sequence of bare land–shrub–tree, divided into four stages: (1) shrub (species include Larix griffithii Mast., Hippophae rhamnoides subsp. yunnanensis Rousi, Betula utilis D. Don, and Populus pseudoglauca C. Wang & P. Y. Fu); (2) broadleaf forest primarily dominated by Hippophae rhamnoides subsp. yunnanensis Rousi; (3) mixed coniferous–broadleaf forest with Hippophae rhamnoides subsp. yunnanensis Rousi and Populus pseudoglauca C. Wang & P. Y. Fu as the dominant species; and (4) mixed coniferous–broadleaf forest dominated by Picea likiangensis (Franch.) E. Pritz. Soil depth and NDVI both increase with succession. Species diversity is significantly higher in the third stage compared to other successional stages. In addition, soil moisture content is significantly greater in the broadleaf-dominated communities than in the conifer-dominated communities. An analysis of NDVI from 1986 to 2024 reveals an overall positive trend in vegetation recovery in the area, with 93% of the area showing significant vegetation increase. Temperature is the primary controlling factor for this recovery, showing a positive correlation with vegetation cover. The results indicate that Key ecological indicators—including species composition, diversity, NDVI, soil depth, and soil moisture content—exhibit stage-specific patterns, reflecting distinct phases of primary succession. These findings enhance our comprehension of vegetation succession in deglaciated areas and their influencing factors in deglaciated areas, providing theoretical support for vegetation restoration in climate change. Full article
(This article belongs to the Section Forest Inventory, Modeling and Remote Sensing)
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16 pages, 19147 KiB  
Article
Surface Assessment of a Novel Acid-Etching Solution on CAD/CAM Dental Ceramics
by Fabio Andretti, Carlos A. Jurado, Mark Antal, Alfredo I. Hernandez, Silvia Rojas-Rueda, Franklin Garcia-Godoy, Brian R. Morrow and Hamid Nurrohman
Biomimetics 2025, 10(8), 508; https://doi.org/10.3390/biomimetics10080508 - 4 Aug 2025
Viewed by 47
Abstract
Background: This study investigated a new multi-acid-etching formulation for zirconia ceramics, containing hydrochloric, hydrofluoric, nitric, orthophosphoric, and sulfuric acids. The solution was tested on polycrystalline (5Y-TZP zirconia), lithium disilicate, hybrid ceramic, and feldspathic porcelain to assess compatibility, etching selectivity, and surface conditioning. Methods: [...] Read more.
Background: This study investigated a new multi-acid-etching formulation for zirconia ceramics, containing hydrochloric, hydrofluoric, nitric, orthophosphoric, and sulfuric acids. The solution was tested on polycrystalline (5Y-TZP zirconia), lithium disilicate, hybrid ceramic, and feldspathic porcelain to assess compatibility, etching selectivity, and surface conditioning. Methods: Two-hundred-and-forty CAD/CAM specimens were etched for 20 s, 60 s, 30 min, or 1 h, and their surface roughness and etching patterns ware evaluated using 3D optical profilometry and scanning electron microscopy (SEM). Results: A positive correlation was observed between etching time and surface roughness (Ra values). The most pronounced changes were observed in lithium disilicate and feldspathic porcelain, with Ra values increasing from 0.733 ± 0.082 µm (Group 5) to 1.295 ± 0.123 µm (Group 8), and from 0.902 ± 0.102 µm (Group 13) to 1.480 ± 0.096 µm (Group 16), respectively. Zirconia increased from 0.181 ± 0.043 µm (Group 1) to 0.371 ± 0.074 µm (Group 4), and the hybrid ceramic from 0.053 ± 0.008 µm (Group 9) to 0.099 ± 0.016 µm (Group 12). Two-way ANOVA revealed significant effects of material and etching time, as well as a significant interaction between the two factors (p < 0.001). SEM observation revealed non-selective etching pattern for the lithium disilicate groups, indicating a risk of over-etching. Conclusions: The tested etching solution increased surface roughness, especially for the lithium disilicate and feldspathic porcelain specimens. In zirconia, one-hour etching improved surface characteristics with minimal observable damage. However, additional studies are necessary to validate the mechanical stability and bond effectives of this approach. Full article
(This article belongs to the Special Issue Biomimetic Bonded Restorations for Dental Applications)
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24 pages, 5644 KiB  
Article
Design and Optimization of Target Detection and 3D Localization Models for Intelligent Muskmelon Pollination Robots
by Huamin Zhao, Shengpeng Xu, Weiqi Yan, Defang Xu, Yongzhuo Zhang, Linjun Jiang, Yabo Zheng, Erkang Zeng and Rui Ren
Horticulturae 2025, 11(8), 905; https://doi.org/10.3390/horticulturae11080905 (registering DOI) - 4 Aug 2025
Viewed by 67
Abstract
With the expansion of muskmelon cultivation, manual pollination is increasingly inadequate for sustaining industry development. Therefore, the development of automatic pollination robots holds significant importance in improving pollination efficiency and reducing labor dependency. Accurate flower detection and localization is a key technology for [...] Read more.
With the expansion of muskmelon cultivation, manual pollination is increasingly inadequate for sustaining industry development. Therefore, the development of automatic pollination robots holds significant importance in improving pollination efficiency and reducing labor dependency. Accurate flower detection and localization is a key technology for enabling automated pollination robots. In this study, the YOLO-MDL model was developed as an enhancement of YOLOv7 to achieve real-time detection and localization of muskmelon flowers. This approach adds a Coordinate Attention (CA) module to focus on relevant channel information and a Contextual Transformer (CoT) module to leverage contextual relationships among input tokens, enhancing the model’s visual representation. The pollination robot converts the 2D coordinates into 3D coordinates using a depth camera and conducts experiments on real-time detection and localization of muskmelon flowers in a greenhouse. The YOLO-MDL model was deployed in ROS to control a robotic arm for automatic pollination, verifying the accuracy of flower detection and measurement localization errors. The results indicate that the YOLO-MDL model enhances AP and F1 scores by 3.3% and 1.8%, respectively, compared to the original model. It achieves AP and F1 scores of 91.2% and 85.1%, demonstrating a clear advantage in accuracy over other models. In the localization experiments, smaller errors were revealed in all three directions. The RMSE values were 0.36 mm for the X-axis, 1.26 mm for the Y-axis, and 3.87 mm for the Z-axis. The YOLO-MDL model proposed in this study demonstrates strong performance in detecting and localizing muskmelon flowers. Based on this model, the robot can execute more precise automatic pollination and provide technical support for the future deployment of automatic pollination robots in muskmelon cultivation. Full article
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17 pages, 1097 KiB  
Article
Mapping Perfusion and Predicting Success: Infrared Thermography-Guided Perforator Flaps for Lower Limb Defects
by Abdalah Abu-Baker, Andrada-Elena Ţigăran, Teodora Timofan, Daniela-Elena Ion, Daniela-Elena Gheoca-Mutu, Adelaida Avino, Cristina-Nicoleta Marina, Adrian Daniel Tulin, Laura Raducu and Radu-Cristian Jecan
Medicina 2025, 61(8), 1410; https://doi.org/10.3390/medicina61081410 - 3 Aug 2025
Viewed by 125
Abstract
Background and Objectives: Lower limb defects often present significant reconstructive challenges due to limited soft tissue availability and exposure of critical structures. Perforator-based flaps offer reliable solutions, with minimal donor site morbidity. This study aimed to evaluate the efficacy of infrared thermography [...] Read more.
Background and Objectives: Lower limb defects often present significant reconstructive challenges due to limited soft tissue availability and exposure of critical structures. Perforator-based flaps offer reliable solutions, with minimal donor site morbidity. This study aimed to evaluate the efficacy of infrared thermography (IRT) in preoperative planning and postoperative monitoring of perforator-based flaps, assessing its accuracy in identifying perforators, predicting complications, and optimizing outcomes. Materials and Methods: A prospective observational study was conducted on 76 patients undergoing lower limb reconstruction with fascio-cutaneous perforator flaps between 2022 and 2024. Perforator mapping was performed concurrently with IRT and Doppler ultrasonography (D-US), with intraoperative confirmation. Flap design variables and systemic parameters were recorded. Postoperative monitoring employed thermal imaging on days 1 and 7. Outcomes were correlated with thermal, anatomical, and systemic factors using statistical analyses, including t-tests and Pearson correlation. Results: IRT showed high sensitivity (97.4%) and positive predictive value (96.8%) for perforator detection. A total of nine minor complications occurred, predominantly in patients with diabetes mellitus and/or elevated glycemia (p = 0.05). Larger flap-to-defect ratios (A/C and B/C) correlated with increased complications in propeller flaps, while smaller ratios posed risks for V-Y and Keystone flaps. Thermal analysis indicated significantly lower flap temperatures and greater temperature gradients in flaps with complications by postoperative day 7 (p < 0.05). CRP levels correlated with glycemia and white blood cell counts, highlighting systemic inflammation’s impact on outcomes. Conclusions: IRT proves to be a reliable, non-invasive method for perforator localization and flap monitoring, enhancing surgical planning and early complication detection. Combined with D-US, it improves perforator selection and perfusion assessment. Thermographic parameters, systemic factors, and flap design metrics collectively predict flap viability. Integration of IRT into surgical workflows offers a cost-effective tool for optimizing reconstructive outcomes in lower limb surgery. Full article
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18 pages, 4468 KiB  
Article
Proteomic and Functional Analysis Reveals Temperature-Driven Immune Evasion Strategies of Streptococcus iniae in Yellowfin Seabream (Acanthopagrus latus)
by Yanjian Yang, Guanrong Zhang, Ruilong Xu, Yiyang Deng, Zequan Mo, Yanwei Li and Xueming Dan
Biology 2025, 14(8), 986; https://doi.org/10.3390/biology14080986 (registering DOI) - 2 Aug 2025
Viewed by 263
Abstract
Streptococcus iniae (S. iniae) is a globally significant aquatic pathogen responsible for severe economic losses in aquaculture. While the S. iniae infection often exhibits distinct seasonal patterns strongly correlated with water temperature, there is limited knowledge regarding the temperature-dependent immune evasion [...] Read more.
Streptococcus iniae (S. iniae) is a globally significant aquatic pathogen responsible for severe economic losses in aquaculture. While the S. iniae infection often exhibits distinct seasonal patterns strongly correlated with water temperature, there is limited knowledge regarding the temperature-dependent immune evasion strategies of S. iniae. Our results demonstrated a striking temperature-dependent virulence phenotype, with significantly higher A. latus mortality rates observed at high temperature (HT, 33 °C) compared to low temperature (LT, 23 °C). Proteomic analysis revealed temperature-dependent upregulation of key virulence factors, including streptolysin S-related proteins (SagG, SagH), antioxidant-related proteins (SodA), and multiple capsular polysaccharide (cps) synthesis proteins (cpsD, cpsH, cpsL, cpsY). Flow cytometry analysis showed that HT infection significantly reduced the percentage of lymphocyte and myeloid cell populations in the head kidney leukocytes of A. latus, which was associated with elevated caspase-3/7 expression and increased apoptosis. In addition, HT infection significantly inhibited the release of reactive oxygen species (ROS) but not nitric oxide (NO) production. Using S. iniae cps-deficient mutant, Δcps, we demonstrated that the cps is essential for temperature-dependent phagocytosis resistance in S. iniae, as phagocytic activity against Δcps remained unchanged across temperatures, while NS-1 showed significantly reduced uptake at HT. These findings provide new insights into the immune evasion of S. iniae under thermal regulation, deepening our understanding of the thermal adaptation of aquatic bacterial pathogens. Full article
(This article belongs to the Special Issue Aquatic Economic Animal Breeding and Healthy Farming)
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30 pages, 4011 KiB  
Article
Multitarget Design of Steroidal Inhibitors Against Hormone-Dependent Breast Cancer: An Integrated In Silico Approach
by Juan Rodríguez-Macías, Oscar Saurith-Coronell, Carlos Vargas-Echeverria, Daniel Insuasty Delgado, Edgar A. Márquez Brazón, Ricardo Gutiérrez De Aguas, José R. Mora, José L. Paz and Yovanni Marrero-Ponce
Int. J. Mol. Sci. 2025, 26(15), 7477; https://doi.org/10.3390/ijms26157477 - 2 Aug 2025
Viewed by 226
Abstract
Hormone-dependent breast cancer, particularly in its treatment-resistant forms, remains a significant therapeutic challenge. In this study, we applied a fully computational strategy to design steroid-based compounds capable of simultaneously targeting three key receptors involved in disease progression: progesterone receptor (PR), estrogen receptor alpha [...] Read more.
Hormone-dependent breast cancer, particularly in its treatment-resistant forms, remains a significant therapeutic challenge. In this study, we applied a fully computational strategy to design steroid-based compounds capable of simultaneously targeting three key receptors involved in disease progression: progesterone receptor (PR), estrogen receptor alpha (ER-α), and HER2. Using a robust 3D-QSAR model (R2 = 0.86; Q2_LOO = 0.86) built from 52 steroidal structures, we identified molecular features associated with high anticancer potential, specifically increased polarizability and reduced electronegativity. From a virtual library of 271 DFT-optimized analogs, 31 compounds were selected based on predicted potency (pIC50 > 7.0) and screened via molecular docking against PR (PDB 2W8Y), HER2 (PDB 7JXH), and ER-α (PDB 6VJD). Seven candidates showed strong binding affinities (ΔG ≤ −9 kcal/mol for at least two targets), with Estero-255 emerging as the most promising. This compound demonstrated excellent conformational stability, a robust hydrogen-bonding network, and consistent multitarget engagement. Molecular dynamics simulations over 100 nanoseconds confirmed the structural integrity of the top ligands, with low RMSD values, compact radii of gyration, and stable binding energy profiles. Key interactions included hydrophobic contacts, π–π stacking, halogen–π interactions, and classical hydrogen bonds with conserved residues across all three targets. These findings highlight Estero-255, alongside Estero-261 and Estero-264, as strong multitarget candidates for further development. By potentially disrupting the PI3K/AKT/mTOR signaling pathway, these compounds offer a promising strategy for overcoming resistance in hormone-driven breast cancer. Experimental validation, including cytotoxicity assays and ADME/Tox profiling, is recommended to confirm their therapeutic potential. Full article
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15 pages, 2307 KiB  
Article
Two B-Box Proteins, GhBBX21 and GhBBX24, Antagonistically Modulate Anthocyanin Biosynthesis in R1 Cotton
by Shuyan Li, Kunpeng Zhang, Chenxi Fu, Chaofeng Wu, Dongyun Zuo, Hailiang Cheng, Limin Lv, Haiyan Zhao, Jianshe Wang, Cuicui Wu, Xiaoyu Guo and Guoli Song
Plants 2025, 14(15), 2367; https://doi.org/10.3390/plants14152367 - 1 Aug 2025
Viewed by 169
Abstract
The red plant phenotype of R1 cotton is a genetic marker produced by light-induced anthocyanin accumulation. GhPAP1D controls this trait. There are two 228 bp tandem repeats upstream of GhPAP1D in R1 cotton. In this study, GUS staining assays in transgenic Arabidopsis thaliana [...] Read more.
The red plant phenotype of R1 cotton is a genetic marker produced by light-induced anthocyanin accumulation. GhPAP1D controls this trait. There are two 228 bp tandem repeats upstream of GhPAP1D in R1 cotton. In this study, GUS staining assays in transgenic Arabidopsis thaliana (L.) Heynh. demonstrated that tandem repeats in the GhPAP1D promoter-enhanced transcriptional activity. GhPAP1D is a homolog of A. thaliana AtPAP1. AtPAP1’s expression is regulated by photomorphogenesis-related transcription factors such as AtHY5 and AtBBXs. We identified the homologs of A. thaliana AtHY5, AtBBX21, and AtBBX24 in R1 cotton, designated as GhHY5, GhBBX21, and GhBBX24, respectively. Y1H assays confirmed that GhHY5, GhBBX21, and GhBBX24 each bound to the GhPAP1D promoter. Dual-luciferase reporter assays revealed that GhHY5 weakly activated the promoter activity of GhPAP1D. Heterologous expression assays in A. thaliana indicated that GhBBX21 promoted anthocyanin accumulation, whereas GhBBX24 had the opposite effect. Dual-luciferase assays showed GhBBX21 activated GhPAP1D transcription, while GhBBX24 repressed it. Further study indicated that GhHY5 did not enhance GhBBX21-mediated transcriptional activation of GhPAP1D but alleviates GhBBX24-induced repression. Together, our results demonstrate that GhBBX21 and GhBBX24 antagonistically regulate anthocyanin accumulation in R1 cotton under GhHY5 mediation, providing insights into light-responsive anthocyanin biosynthesis in cotton. Full article
(This article belongs to the Section Plant Molecular Biology)
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16 pages, 3616 KiB  
Article
A Multiband Dual Linear-to-Circular Polarization Conversion Reflective Metasurface Design Based on Liquid Crystal for X-Band Applications
by Xinju Wang, Lihan Tong, Peng Chen, Lu Liu, Yutong Yin and Haowei Zhang
Appl. Sci. 2025, 15(15), 8499; https://doi.org/10.3390/app15158499 (registering DOI) - 31 Jul 2025
Viewed by 119
Abstract
A novel reflective metasurface (RMS) is proposed in this paper. The MS measures 128 × 128 × 2.794 mm3 and consists of a six-layer vertically stacked structure, with a liquid crystal (LC) cavity in the middle layer. A dual fan-shaped direct current [...] Read more.
A novel reflective metasurface (RMS) is proposed in this paper. The MS measures 128 × 128 × 2.794 mm3 and consists of a six-layer vertically stacked structure, with a liquid crystal (LC) cavity in the middle layer. A dual fan-shaped direct current (DC) bias circuit is designed to minimize the interaction between the radio frequency (RF) signal and the DC source, allowing control of the LC dielectric constant via bias voltage. This enables multi-band operation to improve communication capacity and quality for x-band devices. The polarization conversion (PC) structure employs an orthogonal anisotropic design, utilizing logarithmic functions to create two pairs of bowtie microstrip patches for linear-to-circular polarization conversion (LCPC). Simulation results show that for x-polarized incident waves, with an LC dielectric constant of εr = 2.8, left- and right-handed circularly polarized (LHCP and RHCP) waves are achieved in the frequency ranges of 8.15–8.46 GHz and 9.84–12.52 GHz, respectively. For εr = 3.9, LHCP and RHCP are achieved in 9–9.11 GHz and 9.86–11.81 GHz, respectively, and for εr = 4.6, they are in 8.96–9.11 GHz and 9.95–11.51 GHz. In the case of y-polarized incident waves, the MS reflects the reverse CP waves within the same frequency ranges. Measured results show that at εr = 2.8, the axial ratio (AR) is below 3 dB in the frequency ranges 8.16–8.46 GHz and 9.86–12.48 GHz, with 3 dB AR relative bandwidth (ARBW) of 3.61% and 23.46%, respectively. For εr = 4.6, the AR < 3 dB in the frequency range of 9.78–11.34 GHz, with a 3 dB ARBW of 14.77%. Finally, the measured and simulated results are compared to validate the proposed design, which can be applied to various applications within the corresponding operating frequency band. Full article
(This article belongs to the Section Applied Physics General)
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22 pages, 2239 KiB  
Article
10-Year Fracture Risk Assessment with Novel Adjustment (FRAXplus): Type 2 Diabetic Sample-Focused Analysis
by Oana-Claudia Sima, Ana Valea, Nina Ionovici, Mihai Costachescu, Alexandru-Florin Florescu, Mihai-Lucian Ciobica and Mara Carsote
Diagnostics 2025, 15(15), 1899; https://doi.org/10.3390/diagnostics15151899 - 29 Jul 2025
Viewed by 302
Abstract
Background: Type 2 diabetes (T2D) has been placed among the risk factors for fragility (osteoporotic) fractures, particularly in menopausal women amid modern clinical practice. Objective: We aimed to analyze the bone status in terms of mineral metabolism assays, blood bone turnover [...] Read more.
Background: Type 2 diabetes (T2D) has been placed among the risk factors for fragility (osteoporotic) fractures, particularly in menopausal women amid modern clinical practice. Objective: We aimed to analyze the bone status in terms of mineral metabolism assays, blood bone turnover markers (BTM), and bone mineral density (DXA-BMD), respectively, to assess the 10-year fracture probability of major osteoporotic fractures (MOF) and hip fracture (HF) upon using conventional FRAX without/with femoral neck BMD (MOF-FN/HF-FN and MOF+FN/HF+FN) and the novel model (FRAXplus) with adjustments for T2D (MOF+T2D/HF+T2D) and lumbar spine BMD (MOF+LS/HF+LS). Methods: This retrospective, cross-sectional, pilot study, from January 2023 until January 2024, in menopausal women (aged: 50–80 years) with/without T2D (group DM/nonDM). Inclusion criteria (group DM): prior T2D under diet ± oral medication or novel T2D (OGTT diagnostic). Exclusion criteria: previous anti-osteoporotic medication, prediabetes, insulin therapy, non-T2D. Results: The cohort (N = 136; mean age: 61.36 ± 8.2y) included T2D (22.06%). Groups DM vs. non-DM were age- and years since menopause (YSM)-matched; they had a similar osteoporosis rate (16.67% vs. 23.58%) and fracture prevalence (6.66% vs. 9.43%). In T2D, body mass index (BMI) was higher (31.80 ± 5.31 vs. 26.54 ± 4.87 kg/m2; p < 0.001), while osteocalcin and CrossLaps were lower (18.09 ± 8.35 vs. 25.62 ± 12.78 ng/mL, p = 0.002; 0.39 ± 0.18 vs. 0.48 ± 0.22 ng/mL, p = 0.048), as well as 25-hydroxyvitamin D (16.96 ± 6.76 vs. 21.29 ± 9.84, p = 0.013). FN-BMD and TH-BMD were increased in T2D (p = 0.007, p = 0.002). MOF+LS/HF+LS were statistically significant lower than MOF-FN/HF-FN, respectively, MOF+FN/HF+FN (N = 136). In T2D: MOF+T2D was higher (p < 0.05) than MOF-FN, respectively, MOF+FN [median(IQR) of 3.7(2.5, 5.6) vs. 3.4(2.1, 5.8), respectively, 3.1(2.3, 4.39)], but MOF+LS was lower [2.75(1.9, 3.25)]. HF+T2D was higher (p < 0.05) than HF-FN, respectively, HF+FN [0.8(0.2, 2.4) vs. 0.5(0.2, 1.5), respectively, 0.35(0.13, 0.8)] but HF+LS was lower [0.2(0.1, 0.45)]. Conclusion: Type 2 diabetic menopausal women when compared to age- and YSM-match controls had a lower 25OHD and BTM (osteocalcin, CrossLaps), increased TH-BMD and FN-BMD (with loss of significance upon BMI adjustment). When applying novel FRAX model, LS-BMD adjustment showed lower MOF and HF as estimated by the conventional FRAX (in either subgroup or entire cohort) or as found by T2D adjustment using FRAXplus (in diabetic subgroup). To date, all four types of 10-year fracture probabilities displayed a strong correlation, but taking into consideration the presence of T2D, statistically significant higher risks than calculated by the traditional FRAX were found, hence, the current model might underestimate the condition-related fracture risk. Addressing the practical aspects of fracture risk assessment in diabetic menopausal women might improve the bone health and further offers a prompt tailored strategy to reduce the fracture risk, thus, reducing the overall disease burden. Full article
(This article belongs to the Special Issue Diagnosis and Management of Metabolic Bone Diseases: 2nd Edition)
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12 pages, 5171 KiB  
Article
Investigation and Application of Key Alignment Parameters for Overlay Accuracy in 3D Structures
by Miao Jiang, Mingyi Yao, Ganlin Song, Yuxing Zhou, Jiani Su, Yuejing Qi and Jiangliu Shi
Micromachines 2025, 16(8), 876; https://doi.org/10.3390/mi16080876 - 29 Jul 2025
Viewed by 206
Abstract
With the growing adoption of 3D stacked memory structures, precise alignment and overlay control have become critical for multi-layer overlay accuracy. The metrology accuracy and stability of alignment marks are crucial to ensuring optimal alignment and overlay performance. This study systematically investigates the [...] Read more.
With the growing adoption of 3D stacked memory structures, precise alignment and overlay control have become critical for multi-layer overlay accuracy. The metrology accuracy and stability of alignment marks are crucial to ensuring optimal alignment and overlay performance. This study systematically investigates the contributions of two key alignment parameters—Wafer Quality (WQ) and Alignment Position Deviation (APD)—to the alignment model residue in 3D structures. Through experimental and simulation approaches, we analyze the interplay between WQ, APD and overlay performance. Results reveal that APD exhibits a stronger correlation with uncorrectable model residue, particularly under global process variations such as etch non-uniformity. Furthermore, APD sensitivity varies directionally (X/Y direction marks) and spatially (wafer edge versus center), highlighting the need for targeted mark designs in process-sensitive zones. These findings provide actionable insights for optimizing alignment strategies, mark designs and process monitoring throughout R&D, technology development and high-volume manufacturing phases. Full article
(This article belongs to the Special Issue Recent Advances in Lithography)
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24 pages, 4103 KiB  
Article
SARS-CoV-2 Remdesivir Exposure Leads to Different Evolutionary Pathways That Converge in Moderate Levels of Drug Resistance
by Carlota Fernandez-Antunez, Line A. Ryberg, Kuan Wang, Long V. Pham, Lotte S. Mikkelsen, Ulrik Fahnøe, Katrine T. Hartmann, Henrik E. Jensen, Kenn Holmbeck, Jens Bukh and Santseharay Ramirez
Viruses 2025, 17(8), 1055; https://doi.org/10.3390/v17081055 - 29 Jul 2025
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Abstract
Various SARS-CoV-2 remdesivir resistance-associated substitutions (RAS) have been reported, but a comprehensive comparison of their resistance levels is lacking. We identified novel RAS and performed head-to-head comparisons with known RAS in Vero E6 cells. A remdesivir escape polyclonal virus exhibited a 3.6-fold increase [...] Read more.
Various SARS-CoV-2 remdesivir resistance-associated substitutions (RAS) have been reported, but a comprehensive comparison of their resistance levels is lacking. We identified novel RAS and performed head-to-head comparisons with known RAS in Vero E6 cells. A remdesivir escape polyclonal virus exhibited a 3.6-fold increase in remdesivir EC50 and mutations throughout the genome, including substitutions in nsp12 (E796D) and nsp14 (A255S). However, in reverse-genetics infectious assays, viruses harboring both these substitutions exhibited only a slight decrease in remdesivir susceptibility (1.3-fold increase in EC50). The nsp12-E796D substitution did not impair viral fitness (Vero E6 cells or Syrian hamsters) and was reported in a remdesivir-treated COVID-19 patient. In replication assays, a subgenomic replicon containing nsp12-E796D+nsp14-A255S led to a 16.1-fold increase in replication under remdesivir treatment. A comparison with known RAS showed that S759A, located in the active site of nsp12, conferred the highest remdesivir resistance (106.1-fold increase in replication). Nsp12-RAS V166A/L, V792I, E796D or C799F, all adjacent to the active site, caused intermediate resistance (2.0- to 11.5-fold), whereas N198S, D484Y, or E802D, located farther from the active site, showed no resistance (≤2.0-fold). In conclusion, our classification system, correlating replication under remdesivir treatment with RAS location in nsp12, shows that most nsp12-RAS cause moderate resistance. Full article
(This article belongs to the Special Issue Viral Resistance)
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20 pages, 4727 KiB  
Article
Developing a Novel Fermented Milk with Anti-Aging and Anti-Oxidative Properties Using Lactobacillus kefiranofaciens HL1 and Lactococcus lactis APL015
by Sheng-Yao Wang, Wei-Chen Yen, Yen-Po Chen, Jia-Shian Shiu and Ming-Ju Chen
Nutrients 2025, 17(15), 2447; https://doi.org/10.3390/nu17152447 - 27 Jul 2025
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Abstract
Background/Objectives: Lactobacillus kefiranofaciens HL1, isolated from kefir, exhibits antioxidant and anti-aging activities, defined here as improved cognitive function and reductions in oxidative stress and inflammatory markers. However, its poor milk viability limits application. This study developed a novel fermented milk by co-culturing [...] Read more.
Background/Objectives: Lactobacillus kefiranofaciens HL1, isolated from kefir, exhibits antioxidant and anti-aging activities, defined here as improved cognitive function and reductions in oxidative stress and inflammatory markers. However, its poor milk viability limits application. This study developed a novel fermented milk by co-culturing HL1 with Lactococcus lactis subsp. cremoris APL015 (APL15) to enhance fermentation and health benefits. Methods: HL1 and APL15 were co-cultured to produce fermented milk (FM), and fermentation performance, microbial viability, texture, and syneresis were evaluated. A D-galactose-induced aging BALB/c mouse model was used to assess cognitive function, oxidative stress, inflammation, antioxidant enzyme activity, and gut microbiota after 8 weeks of oral administration. Results: FM reached pH 4.6 within 16 h, with high viable counts (~109 CFU/mL) for both strains. HL1 viability and texture were maintained, with smooth consistency and low syneresis. In vivo, FM improved cognitive behavior (Y-maze, Morris water maze), reduced oxidative damage (MDA), lowered IL-1β and TNF-α, and enhanced brain SOD levels. FM-fed mice exhibited increased short-chain fatty acid producers, higher cecal butyrate, and reduced Clostridium perfringens. Conclusions: The co-cultured fermented milk effectively delivers HL1 and provides antioxidant, anti-inflammatory, and anti-aging effects in vivo, likely via gut–brain axis modulation. It shows promise as a functional food for healthy aging. Full article
(This article belongs to the Section Prebiotics and Probiotics)
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18 pages, 2593 KiB  
Article
Accuracy of Drill Sleeve Housing in 3D-Printed and Milled Implant Surgical Guides: A 3D Analysis Considering Machine Type, Layer Thickness, Sleeve Position, and Steam Sterilization
by Anna Seidel, Kai Zerrahn, Manfred Wichmann and Ragai Edward Matta
Bioengineering 2025, 12(8), 799; https://doi.org/10.3390/bioengineering12080799 - 25 Jul 2025
Viewed by 257
Abstract
Successful dental implant therapy relies on accurate planning and placement, e.g., through static, computer-aided implant surgery using CAD/CAM-fabricated surgical guides. This study examined production methods’ influence on surgical guide sleeve housing geometry. A model with two edentulous spaces was digitized using intraoral scanning [...] Read more.
Successful dental implant therapy relies on accurate planning and placement, e.g., through static, computer-aided implant surgery using CAD/CAM-fabricated surgical guides. This study examined production methods’ influence on surgical guide sleeve housing geometry. A model with two edentulous spaces was digitized using intraoral scanning and CBCT, and two virtually positioned implants were planned. Ten guides per group were produced using milling (MCX5), DLP printing (ASIGA and SHERA), and SLA printing (FORM), printing with 50 µm and 100 µm layers each. Each guide (n = 70) was then digitized using an industrial scanner before and after sterilization. Superimposition of the actual guide data with the reference data allowed for evaluation of deviations at the drill sleeve housing along the x-, y-, z-, and dxyz-axes. Descriptive and statistical evaluation was performed (significance level: p ≤ 0.0125). Significant differences existed among the production methods: Milling and SLA showed higher deviations than the DLP group (p < 0.001). Milled guides post-sterilization showed the highest deviations (0.352 ± 0.08 mm), while one DLP printer at 50 μm layer thickness showed lowest deviations (0.091 ± 0.04 mm). The layer thickness was insignificant, whereas sterilization increased deviation (p < 0.001). DLP produced the most precise implant surgical guides. All 3D printers were suitable for fabricating clinically acceptable surgical guides. Full article
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