Search Results (153,256)

Nearly all eukaryotic proteins are turned over by the ubiquitin (Ub)-26S proteasome system (UPS). Despite its broad cellular roles, only a handful of UPS members, particularly the Ub E3 ligases that specifically recognize a protein for ubiquitylation, have been characterized in plants to date. The challenge arises from the transient recognition and rapid degradation of ubiquitylation substrates by the UPS. To tackle this challenge, the emerging biotinylation-based proximity labeling (PL) offers an exciting tool for enriching transient interactors of Ub E3 ligases. In this study, we examined the efficacy of TurboID in identifying substrates of Arabidopsis Skp1-cullin1-F-box (SCF) ligases. We demonstrate that the Arabidopsis Skp1 Like (ASK)1-TurboID is not fully functioning in planta, which led us to discover a novel antagonism between biotinylation and ubiquitylation in regulating protein stability in vivo. This discovery lowers the effectiveness of PL in ubiquitylome studies. However, using one long-known SCF substrate, phytochrome A, we succeeded to apply its TurboID fusion for complementing the far-red-light response of the phyA-211 null mutant allele, suggesting an efficacy of PL in characterizing single ubiquitylation pathways. This study highlighted a limitation of PL in ubiquitylome studies, discovered a new antagonistic pathway of biotinylation, and developed a theoretical guidance for future PL-based characterization of ubiquitylation pathways. Full article

Trauma often causes long-lasting functional impairment, but the extent varies across populations. This study investigated disability six months after moderate to severe injury and identified sociodemographic and early injury-related predictors, including estimated rehabilitation complexity. Further, we assessed the implementation of direct transfer from acute care in the trauma centre to specialised inpatient rehabilitation, bypassing local hospitals. In this prospective study 398 adults, treated from January 2020 to January 2021 at two Norwegian trauma centres, were included. Self-reported disability was measured using the 12-item World Health Organization Disability Assessment Schedule 2.0. Ordinal logistic regression was applied to identify predictors of the 6-month disability outcome. At follow-up, 22% reported no disability, 49% mild/moderate and 29% severe. In multivariable analyses, low education, comorbidities, number of injuries and higher estimated rehabilitation complexity at discharge from acute care were significantly associated with greater disability. Only 20% were transferred directly to specialised inpatient rehabilitation, while 17% went via local hospitals. Participants with orthopaedic injuries and women were less likely to be transferred directly. In summary, most participants experienced some disability at 6 months. Indirect pathways to specialised rehabilitation via local hospitals remained common. Understanding predictors of disability and optimising rehabilitation pathways may improve trauma rehabilitation outcomes, highlighting the need for guidelines that identify patients with high rehabilitation needs. Full article

Predictive maintenance (PdM) is a cornerstone of smart manufacturing, enabling the early detection of equipment degradation and reducing unplanned downtimes. This study proposes an advanced machine learning framework that integrates the Extreme Learning Machine (ELM) with a novel hybrid metaheuristic optimization algorithm, the Polar Lights Salp Cooperative Optimizer (PLSCO), to enhance predictive modeling in manufacturing processes. PLSCO combines the strengths of the Polar Light Optimizer (PLO), Competitive Swarm Optimization (CSO), and Salp Swarm Algorithm (SSA), utilizing a cooperative strategy that adaptively balances exploration and exploitation. In this mechanism, particles engage in a competitive division process, where winners intensify search via PLO and losers diversify using SSA, effectively avoiding local optima and premature convergence. The performance of PLSCO was validated on CEC2015 and CEC2020 benchmark functions, demonstrating superior convergence behavior and global search capabilities. When applied to a real-world predictive maintenance dataset, the ELM-PLSCO model achieved a high prediction accuracy of 95.4%, outperforming baseline and other optimization-assisted models. Feature importance analysis revealed that torque and tool wear are dominant indicators of machine failure, offering interpretable insights for condition monitoring. The proposed approach presents a robust, interpretable, and computationally efficient solution for predictive maintenance in intelligent manufacturing environments. Full article

Inverse problems have numerous important applications in science, engineering, medicine, and other disciplines. In this study, we present a numerical solution for a one-dimensional parabolic inverse problem with energy overspecification at a fixed spatial point, using the radial basis function (RBF) method. The collocation matrix arising in RBF-based approaches is typically highly ill-conditioned, and the method’s performance is strongly influenced by the choice of the radial basis function and its shape parameter. Unlike previous studies that focused primarily on Gaussian radial basis functions, this work investigates and compares the performance of three RBF types—Gaussian (GRBF), Multiquadrics (MQRBF), and Inverse Multiquadrics (IMQRBF). By transforming the inverse problem into an equivalent direct problem, we apply the RBF collocation method in both space and time. Numerical experiments on two test problems with known analytical solutions are conducted to evaluate the approximation error, optimal shape parameters, and matrix conditioning. Results indicate that both MQRBF and IMQRBF generally provide better accuracy than GRBF. Furthermore, IMQRBF enhances numerical stability due to its lower condition number, making it a more robust choice for solving ill-posed inverse problems where both stability and accuracy are critical. Full article

Background/Objectives: Soft tissues are essential for maintaining the function and long-term success of dental implants. In many cases, implant placement necessitates soft tissue augmentation procedures such as free gingival grafts (FGGs) or connective tissue grafts (CTGs) to restore lost gingival architecture. Nevertheless, a significant challenge associated with FGG and CTG is postoperative pain, largely due to morbidity at the palatal donor site. To address this issue, various approaches have been proposed to reduce patient discomfort and promote improved wound healing at the donor site. This study aimed to compare the effectiveness of four different methods for protecting the palatal donor site following free gingival graft harvesting. Methods: A total of 76 patients undergoing implant therapy with an indication for free gingival grafting were selected and divided into four groups based on the method used to protect the palatal donor site: an absorbable gelatin sponge secured with sutures (GS); an absorbable gelatin sponge with sutures and cyanoacrylate tissue adhesive (GS+CTA); oxidized regenerated cellulose combined with cyanoacrylate tissue adhesive (ORC+CTA); and an absorbable gelatin sponge covered with a flowable resin composite and stabilized with sutures (GS+FRC). The effectiveness of each method was evaluated in terms of postoperative pain, bleeding, and wound healing. Results: Although the differences in pain intensity among the groups were not statistically significant throughout the observation period (p > 0.05), the GS+FRC group consistently exhibited the lowest mean pain scores. No statistically significant differences were observed between the groups regarding the incidence of secondary bleeding. The highest mean wound healing rate was recorded in the GS+FRC group (75.95 ± 18.75%), whereas the ORC+CTA group demonstrated the lowest rate (43.66 ± 25.74%). Conclusions: The use of an absorbable gelatin sponge covered with a flowable resin composite and secured with sutures, despite the presented limitations, appears to be a promising approach for palatal wound protection. While this group consistently demonstrated the lowest mean pain scores, differences in pain intensity among the groups were not statistically significant. Nonetheless, it achieved the most favorable outcomes in terms of wound epithelialization. Full article

Background: Meniere’s disease (MD) is a rare inner ear disorder characterized by endolymphatic hydrops and symptoms such as vertigo and hearing loss, with no curative treatment currently available. XuanYunNing tablets (XYN) have been clinically used to treat MD, but their molecular mechanisms remain unclear. Objective: This study aimed to systematically evaluate the pharmacological effects of XYN in a guinea pig model of MD and to elucidate the underlying molecular mechanisms of both MD pathogenesis and XYN intervention through integrated multi-omics analyses, including transcriptomics, proteomics, and bioinformatics. Methods: A guinea pig model of endolymphatic hydrops was induced by intraperitoneal injection of desmopressin acetate (dDAVP). Pharmacodynamic efficacy was evaluated via behavioral scoring and histopathological analysis. The differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) modulated by XYN treatment were identified using high-throughput transcriptomic and proteomic sequencing. These data were integrated through multi-omics bioinformatic analysis. Key molecular targets and signaling pathways were further validated using RT-qPCR and Western blotting. Results: Pharmacological evaluations showed that guinea pigs in the model group exhibited a 26% increase in endolymphatic hydrops area, while high-dose XYN treatment reduced this area by 19% and significantly improved functional parameters, including overall physiological condition (e.g., weight and general appearance), auricular reflexes to low-, medium-, and high-frequency sound stimuli, nystagmus, and the righting reflex. High-throughput sequencing combined with integrative omics analysis identified 513 potential molecular targets of XYN. Subsequent network and module analyses pinpointed the JAK-STAT signaling pathway as the central axis. Mendelian randomization (MR) analysis further supported a causal relationship between MD and metabolic, immune, and inflammatory traits, reinforcing the central role of JAK-STAT signaling in both MD progression and XYN-mediated intervention. Mechanistic studies confirmed that XYN downregulated IFNG, IFNGR1, JAK1, p-STAT3/STAT3, and AOX at both mRNA and protein levels, thereby inhibiting aberrant JAK-STAT pathway activation in MD model animals. In addition, a total of 125 chemical constituents were identified in XYN by UHPLC-MS analysis. ZBTB20 and other molecules were identified as potential blood-based biomarkers for MD. Conclusions: This study reveals that XYN alleviates MD symptoms by disrupting a pathological cycle driven by JAK-STAT signaling, inflammation, and metabolic dysfunction. These findings support the clinical potential of XYN in the treatment of Meniere’s disease and may inform the development of novel therapeutic strategies. Full article

Understory-cultivated Panax ginseng possesses high pharmacological and economic value; however, its visual quality grading predominantly relies on subjective manual assessment, constraining industrial scalability. To address challenges including fine-grained morphological variations, boundary ambiguity, and complex natural backgrounds, this study proposes Ginseng-YOLO, a lightweight and deployment-friendly object detection model for automated ginseng grade classification. The model is built on the YOLOv11n (You Only Look Once11n) framework and integrates three complementary components: (1) C2-LWA, a cross-stage local window attention module that enhances discrimination of key visual features, such as primary root contours and fibrous textures; (2) ADown, a non-parametric downsampling mechanism that substitutes convolution operations with parallel pooling, markedly reducing computational complexity; and (3) Slide Loss, a piecewise IoU-weighted loss function designed to emphasize learning from samples with ambiguous or irregular boundaries. Experimental results on a curated multi-grade ginseng dataset indicate that Ginseng-YOLO achieves a Precision of 84.9%, a Recall of 83.9%, and an mAP@50 of 88.7%, outperforming YOLOv11n and other state-of-the-art variants. The model maintains a compact footprint, with 2.0 M parameters, 5.3 GFLOPs, and 4.6 MB model size, supporting real-time deployment on edge devices. Ablation studies further confirm the synergistic contributions of the proposed modules in enhancing feature representation, architectural efficiency, and training robustness. Successful deployment on the NVIDIA Jetson Nano demonstrates practical real-time inference capability under limited computational resources. This work provides a scalable approach for intelligent grading of forest-grown ginseng and offers methodological insights for the design of lightweight models in medicinal plants and agricultural applications. Full article

Objectives: In localized upper-tract urothelial carcinoma (UTUC), radical nephroureterectomy (RNU) represents the surgical gold standard, but kidney-sparing surgery (KSS) offers an alternative. The surgical perspective, including complications, remains understudied in this context. This study aimed to compare KSS and RNU, assess kidney function and survival, and identify the surgical risk factors. Methods: This retrospective analysis included UTUC patients undergoing KSS (n = 46) or RNU (n = 46) at a single center from 2016 to April 2024, matched by propensity scores. The primary endpoint was Clavien–Dindo complications. Other endpoints included Days Alive and Out of the Hospital within 30 days (DAOH30), changes in the eGFR, cancer-specific survival (CSS), and disease-free survival (DFS). A UTUC Surgery Risk Score was developed to identify the surgical risk factors for severe complications. Results: KSS was significantly associated with higher rates of Clavien–Dindo grades ≥ 3 (KSS: 14; RNU: 3). DAOH30 was significantly longer following RNU. The UTUC Surgery Risk Score, based on a non-endoscopic KSS approach, an ASA score ≥ 3, and preoperative creatinine > 0.9 mg/dL, was significantly associated with overall and severe complications and DAOH30 (both p < 0.001). KSS showed significantly better early postoperative eGFR preservation (+0.55 mL/min vs. −4.3 mL/min for RNU, p = 0.015). No significant differences were observed in the median CSS or DFS between the groups. Conclusions: KSS is associated with a higher rate of certain postoperative complications, but offers superior kidney function preservation, with comparable oncological outcomes to RNU. The novel UTUC Surgery Risk Score can aid in patient counseling and personalized decision-making prior to surgery. Full article

Background/Objectives: Fungotherapy has long been recognized as a therapeutic approach for treating and preventing various diseases. As an important representative of the so-called functional mushrooms, Chaga plays a crucial role in this system. Since this species is of limited distribution in Bulgaria, we are interested in studying a related but different species, Inonotus nidus-pici Pilát, with potential benefits for human health. Methods: The phytochemical composition of phenolic compounds in the studied species was analyzed using spectrophotometric methods and high-performance liquid chromatography (HPLC). Additionally, antioxidant activity was assessed using various assays, and the gastroprotective effect was evaluated in experimental rat models with indomethacin-induced gastric damage. Results: The quantities of the main classes of phenolic compounds in the studied object were determined, and an enriched phenolic extract (EPE) was obtained. The amount of phenolic compounds, in decreasing order, is as follows: tannins (1.67 ± 0.02%), phenolic acids (1.50 ± 0.09%), and flavonoids (1.24 ± 0.04%). Quercetin was the most present flavonoid (15.95 ± 0.05 mg/g DWE), followed by (+)-catechin (9.86 ± 0.15 mg/g DWE) and kaempferol (1.67 ± 0.09 mg/g DWE) in the enriched phenolic extract. The quantity of other established compounds was significantly lower. Of all ten phenolic acids identified in the same extract, the highest concentration was found only for rosmarinic acid (6.41 ± 0.08 mg/g DWE) and somewhat for p-coumaric acid (2.13 ± 0.12 mg/g DWE). Among all the applied methods regarding antioxidant activity, the highest potential of the extract for reducing copper ions was the most pronounced (1506.93 μM TE/g DWE), and the ability of the extract to reduce iron ions was almost the same (1354.05 μM TE/g DWE). In the experimental indomethacin-induced gastric ulcer rat model, EPE (25 mg/kg and 10 mg/kg) demonstrated a dose-dependent gastroprotective effect. Conclusions: The results of the experiments confirm the potential of the wood fungus species as a source of valuable biologically active compounds with beneficial and pharmacological effects. However, further studies are needed to fully determine its chemical composition and the biological activities related to it. Full article

Background/Objectives: Oral health plays a crucial role in the physical, emotional, and social well-being of children. Data from 2019 indicate that oral diseases remain a major concern in the Italian paediatric population, affecting not only children’s health but also caregivers’ well-being. This study aimed to assess the importance attributed by Italian families to their children’s oral health and correlate parents’ perceptions with children’s actual oral health status. Methods: A total of 131 children aged 0–12 years, admitted to the IRCCS Giannina Gaslini Children’s Hospital (Genoa, Italy) for reasons other than dental problems, were enroled between January 1 and December 31, 2024. Parents completed validated questionnaires (ECOHIS or PCPQ + FIS) based on their child’s age, along with supplementary questions on socio-demographic background and dental history. Oral examination was performed to assess dmft/DMFT scores, the Index of Orthodontic Treatment Need (IOTN), and the Modified Gingival Index (MGI). Results: In younger children (0–5 years), oral health was generally good, but the presence of caries negatively impacted the family’s quality of life. Older children (6–12 years) showed higher rates of caries and gingival inflammation, affecting their daily functioning and emotional well-being. Poor oral health was more common among children of non-European backgrounds and those with lower parental education. Early dental visits, within the recommended 24 months of age, were rare. Conclusions: Despite clear international recommendations, early dental visits remain uncommon, and many children experience preventable oral health issues. These findings highlight the urgent need to improve caregiver education and public health strategies to promote early preventive dental care. Full article

Background/Objectives: All-inside ACL reconstruction has emerged as a minimally invasive alternative to conventional techniques, with potential advantages in graft configuration and reduced surgical trauma. This study aimed to compare the clinical outcomes of all-inside and full tibial tunnel ACL reconstruction, focusing on graft diameter, postoperative stability, and functional recovery. We hypothesized that the all-inside technique would allow for thicker grafts and yield superior postoperative knee stability and functional outcomes, with postoperative anterior laxity as a major outcome of interest. Methods: This retrospective comparative study reviewed patients who underwent ACL reconstruction between January 2020 and February 2024. From January 2020 to September 2022, a four-strand hamstring autograft with full tibial tunnel technique (FT-4) was used, while from September 2022, a six-strand hamstring autograft with the all-inside technique (AI-6) was adopted to enable thicker grafts and optimize fixation. Among a total of 103 patients, 1:1 propensity score matching (PSM) was performed based on age, sex, BMI, laterality, ALL reconstruction, meniscal lesion, and preoperative anterior laxity (SSD). Graft diameter and clinical outcomes, including knee stability and functional scores, were compared between the matched groups. Results: After PSM, two comparable groups of 29 patients each were established. Graft diameter was significantly larger in the AI-6 group (9.5 ± 0.7 mm) compared to the FT-4 group (7.8 ± 0.8 mm, p < 0.001), while other baseline characteristics remained well balanced between the groups. At the final follow-up, both groups exhibited significant improvements in anterior laxity, functional scores, and pivot shift grades (all p < 0.001). The AI-6 group demonstrated superior outcomes with a significantly higher Lysholm score (82.2 ± 6.7 vs. 75.6 ± 8.9, p = 0.002), lower WOMAC score (8.0 ± 4.3 vs. 12.9 ± 10.5, p = 0.023), and reduced anterior laxity (1.6 ± 1.1 mm vs. 2.5 ± 1.4 mm, p = 0.005) compared to the FT-4 group, whereas no significant differences were observed in the IKDC, Tegner, Korean knee score, or pivot shift test results. A simple linear regression revealed a significant negative correlation between graft diameter and postoperative anterior laxity (B = −0.398, p = 0.048). Conclusions: The present study demonstrated that the use of a six-strand hamstring graft configuration in the AI-6 technique resulted in significantly thicker grafts and was associated with reduced postoperative anterior knee laxity compared to the FT-4 technique. While interpretation of these findings requires caution in light of MCID thresholds, the AI-6 group showed favorable outcomes in anterior laxity and selected functional scores, such as the Lysholm and WOMAC. This technique may offer practical clinical value, particularly in populations prone to smaller graft diameters, as it facilitates adequate graft thickness through multifold preparation, with the all-inside approach accommodating the inherent graft shortening. Full article

Urban lifeline Natech events are coupled systems composed of multiple risks and entities with complex dynamic transmission chains. Predicting risk evolution probabilities is the core task for achieving the safety management of urban lifeline Natech events. First, the risk evolution mechanism is analyzed, where urban lifeline Natech events exhibit spatial evolution characteristics, which involves dissecting the parallel and synergistic effects of risk evolution in spatial dimensions. Next, based on fitting marginal probability distribution functions for natural hazard and urban lifeline risk evolution, a Multi-dimensional Copula (MdC) function for the joint probability distribution of urban lifeline Natech event risk evolution is constructed. Building upon the MdC function, a Markov Chain Monte Carlo (MCMC) model for predicting risk evolution probabilities of urban lifeline Natech events is developed using the Metropolis–Hastings (M-H) algorithm and Gibbs sampling. Finally, taking the 2021 Zhengzhou ‘7·20’ catastrophic rainstorm as a case study, joint probability distribution functions for risk evolution under Rainfall-Wind speed scenarios are fitted for traffic, electric, communication, water supply, and drainage systems (including different risk transmission chains). Numerical simulations of joint probability distributions for risk evolution are conducted, and visualizations of joint probability predictions for risk evolution are generated. Full article

Background: Despite clinical and pathological risk tools, predicting outcomes in non-muscle-invasive bladder cancer (NMIBC), particularly high-grade (HG) cases, remains challenging due to its unpredictable recurrence and progression. There is an urgent need for molecular biomarkers to enhance risk stratification and guide treatment. Methods: We assessed the prognostic potential of eight miRNAs (miR-9, miR-143, miR-182, miR-205, miR-27a, miR-369, let-7c, and let-7g) in a cohort of ninety patients with primary bladder cancer. Expression data were retrieved from our previously published studies. Kaplan–Meier’s and Cox’s regression analyses were used to evaluate the associations with overall survival (OS), metastasis-free survival (MFS), and clinical outcomes. Principal component analysis (PCA) was performed to identify informative miRNA combinations. Target gene prediction, pathway enrichment (DAVID), and drug–gene interaction mapping (DGIdb) were conducted in silico. Results: A high expression of let-7g and miR-9 was significantly associated with better OS in HG NMIBC and MIBC, respectively (p = 0.013 and p = 0.000). MiR-9 downregulation correlated with metastasis in MIBC (p = 0.018). Among all combinations, miR-205 and miR-27a best predicted intermediate-risk NMIBC progression and recurrence (r² = 0.982, p = 0.000). A functional analysis revealed that these miRNAs regulate key cancer-related pathways (MAPK, mTOR, and p53) through genes such as TP53, PTEN, and CDKN1A. Drug interaction mapping identified nine target genes (e.g., DAPK1, ATR, and MTR) associated with eight FDA-approved bladder cancer therapies, including cisplatin and gemcitabine. Conclusion: Let-7g, miR-9, miR-143, miR-182, and miR-205 emerged as promising biomarkers for outcome prediction in NMIBC. Their integration into liquid biopsy platforms could support non-invasive monitoring and personalized treatment strategies. These findings warrant validation in larger, prospective studies and through functional assays. Full article

In this study, glass fiber-reinforced polymer (GFRP) rebars were fabricated using epoxy resin matrix filled with 5 wt.% of hemp and bamboo powder fillers, both untreated and dielectric barrier discharge (DBD) plasma treated. The tensile, flexural, transverse shear, and pull-out bond strengths were evaluated to investigate the effects of filler type and surface modification. The results show that the incorporation of untreated fillers decreased tensile strength from 706.4 MPa for hemp to 682.3 MPa for bamboo. The plasma-treated hemp formulation demonstrated a higher recovery (762.1 MPa), approaching the control value (804.2 MPa). Transverse shear strength increased from 117.0 MPa (untreated hemp) to 128.3 MPa (plasma-treated hemp). The bond strength with concrete remained unaffected across all groups. Scanning electron microscopy (SEM) revealed improved filler dispersion, reduced voids, and enhanced resin wetting in the plasma-treated specimens. Fourier-transform infrared spectroscopy (FTIR) confirmed the introduction of polar functional groups such as hydroxyl and carbonyl groups onto the fiber surfaces following plasma exposure. These modifications contributed to improved interfacial adhesion and mechanical integrity. Overall, the DBD plasma treatment effectively enhanced the performance and interfacial characteristics of natural fiber-filled GFRP rebars, supporting their potential as sustainable reinforcements in structural applications. Full article

Background/Objectives: This study investigates specific neuropsychological functions—visuospatial working memory, attention, planning, and decision-making—among preschool-aged children with Developmental Coordination Disorder (DCD) compared to typically developing (TD) peers. The objective was to assess deficits in selective, sustained, and focused expressive attention, visuospatial and visual/verbal working memory, and decision-making abilities, and to examine their relationship with fundamental motor skills. Methods: A comparative study was conducted with Greek preschool-aged children using the Cognitive Assessment System (CAS) to evaluate cognitive processing (planning, attention, simultaneous processing) and the Movement Assessment Battery for Children—Second Edition (MABC-2) to assess motor skills. Results: Significant performance disparities were identified between DCD and TD children across attentional and planning domains, with notable cognitive–motor correlations. Discriminant function analyses revealed high classification accuracy (e.g., 73.9% for receptive attention, 79.5% for simultaneous processing), reinforcing the diagnostic value of targeted cognitive indices. Notably, approximately one-third of the children with DCD (17 out of 44) exhibited deficits in one or more cognitive domains. Conclusions: These findings highlight the importance of neuropsychological profiling in understanding DCD and suggest that targeted motor interventions may simultaneously enhance executive function. A strength-based, holistic assessment approach is recommended, supported by educator training and evidence-based therapeutic programming. Full article