Search Results (554)

Fracture healing failure affects millions globally, yet early molecular mechanisms remain poorly understood. This study aimed to characterize initial fracture response through analyzing peripheral blood hematology, multiplex cytokine profiles, and microRNA (miRNA) expression in fracture hematoma within the first 5 days post-injury. In a prospective cohort of 64 patients with acute clavicle fractures, we assessed hematological parameters, cytokine levels via multiplex immunoassays, and miRNA expression through RNA sequencing, and quantitative PCR (qPCR) validation. Fracture severity and time elapsed post-injury were key drivers of molecular response variability. Severe fractures (type C) were associated with older patient age and impaired hematological parameters, including reduced hemoglobin, erythrocyte counts, and hematocrit. Leukocyte counts declined over time, reflecting evolving systemic inflammation. Severity-dependent cytokines included eotaxin, interferon alpha-2 (IFNα2), interleukin-1 alpha (IL-1α), macrophage inflammatory protein-1 (MIP-1α), whereas interferon gamma-induced protein 10 (IP-10) and MIP-1α distinguished temporal healing phases. MiRNA profiling revealed 55 miRNAs with significant time-dependent expression changes (27 downregulated, 28 upregulated). Five key miRNAs (miR-140-5p, miR-181a-5p, miR-214-3p, miR-23a-3p, miR-98-5p) showed robust temporal patterns and enrichment in cytokine signaling pathways critical for bone repair. This work presents the first detailed molecular portrait of early human fracture healing, highlighting hematological, immune cytokine, and miRNA networks orchestrating repair. These insights provide a foundation for biomarkers development to predict healing outcomes and support precision-targeted interventions in fracture management. Full article

Background/Objectives: Composite resins are widely used in restorative dentistry due to their aesthetic properties and ease of handling. Preheating prior to light polymerization has been proposed to improve flowability, degree of conversion, and mechanical properties. This in vitro study aimed to evaluate the effect of preheating on the microhardness of three nanoparticulate composite resins—IPS Empress Direct (Ivoclar), Filtek Z350 XT (3M-ESPE), and Forma (Ultradent)—when cured with a high-power LED light. Methods: Sixty disc-shaped samples (n = 20 per material) were fabricated and divided into preheated and non-preheated groups. After polishing and 24 h storage in distilled water at 37 °C, samples were subjected to Knoop microhardness testing under a 300 g load for 15 s. Statistical analysis was conducted using R software. Results: Preheating produced a significant increase in surface microhardness for IPS Empress Direct (32.8%) and Filtek Z350 XT (5.8%) (p < 0.05 for both), whereas Forma showed no significant change. Conclusions: Under the conditions of this in vitro study, preheating can enhance the mechanical performance of specific composite resins by increasing microhardness; however, the effect is material-dependent. Full article

Counting and density estimation of cone cells using adaptive optics (AO) imaging plays an important role in the clinical management of retinal diseases. A novel deep learning approach for the cone counting task with minimal manual labeling of cone cells in AO images is described in this paper. We propose a hybrid multi-task semi-supervised learning (MTSSL) framework that simultaneously trains on unlabeled and labeled data. On the unlabeled images, the model learns structural and relational features by employing two self-supervised pretext tasks—image inpainting (IP) and learning-to-rank (L2R). At the same time, it leverages a small set of labeled examples to supervise a density estimation head for cone counting. By jointly minimizing the image reconstruction loss, the ranking loss, and the supervised density-map loss, our approach harnesses the rich information in unlabeled data to learn feature representations and directly incorporates ground-truth annotations to guide accurate density prediction and counts. Experiments were conducted on a dataset of AO images of 120 subjects captured using a device with a retinal camera (rtx1) with a wide field-of-view. MTSSL gains strengths from hybrid self-supervised pretext tasks of generative and predictive pretraining that aid in learning global and local context required for counting cones. The results show that the proposed MTSSL approach significantly outperforms the individual self-supervised pipelines with an RMSE score improved by a factor of 2 for cone counting. Full article

Mitochondria-associated membranes (MAMs) are essential for cellular homeostasis. MAMs are specialized contact sites located between the endoplasmic reticulum (ER) and mitochondria and control apoptotic pathways, lipid metabolism, autophagy initiation, and calcium signaling, processes critical to the survival and function of neurons. Although this area of membrane biology remains understudied, increasing evidence links MAM dysfunction to the etiology of major neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). MAMs consist of a network of protein complexes that mediate molecular exchange and ER–mitochondria tethering. MAMs regulate lipid flow in the brain, including phosphatidylserine and cholesterol; disruption of this process causes membrane instability and impaired synaptic function. Inositol 1,4,5-trisphosphate receptor—voltage-dependent anion channel 1 (IP3R-VDAC1) interactions at MAMs maintain calcium homeostasis, which is required for mitochondria to produce ATP; dysregulation promotes oxidative stress and neuronal death. An effective therapeutic approach for altering neurodegenerative processes is to restore the functional integrity of MAMs. Improving cell-to-cell interactions and modulating MAM-associated proteins may contribute to the restoration of calcium homeostasis and lipid metabolism, both of which are key for neuronal protection. MAMs significantly contribute to the progression of neurodegenerative diseases, making them promising targets for future therapeutic research. This review emphasizes the increasing importance of MAMs in the study of neurodegeneration and their potential as novel targets for membrane-based therapeutic interventions. Full article

This study investigates global innovation trends in machine learning (ML) and deep learning (DL) technologies within the automotive sector through a patent analysis of 5314 applications filed between 2005 and 2022 across the five major patent offices (IP5). Using Cooperative Patent Classification (CPC) codes and keyword analysis, we identify seven sub-technology domains and examine both geographical and corporate patenting strategies. Our findings show that the United States dominates in overall filings, while Japan demonstrates a notably high share of triadic patents, which reflects a strong global-reach strategy. Patent activity is heavily concentrated in vehicle control and infrastructure traffic control, with emerging growth observed in battery management and occupant analytics. In contrast, security-related technologies remain underrepresented, indicating a potential blind spot in current innovation efforts. Corporate strategies diverge markedly; for example, some firms, such as Toyota and Bosch, pursue balanced tri-regional protection, whereas others, including Ford and GM, focus on dual-market coverage in the United States and China. These patterns illustrate how market priorities, regulatory environments, and technological objectives influence patenting behavior. By mapping the technological and strategic landscape of ML/DL innovation in the automotive industry, this study provides actionable insights for industry practitioners seeking to optimize intellectual property portfolios and for policymakers aiming to address gaps such as automotive cybersecurity in future R&D agendas. Full article

MicroRNA319 (miR319) and its targets TEOSINTE-BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors are well-characterized regulators of leaf and flower development, yet their role in root development remains elusive. Here, we demonstrated that overexpression of miR319a led to a decrease in the number and density of lateral roots in poplar, while repressing miR319a by short tandem target mimics (STTM) promoted lateral root (LR) development. The auxin signaling repressors IAA3.1 and IAA3.2 were upregulated in miR319a-OE plants but downregulated in miR319a-STTM plants. After exogenous applications of naphthaleneacetic acid (NAA), which exhibited the characteristics and physiological functions of the endogenous auxin indole-3-acetic acid, the number and density of LR in WT increased by 30% and 44%, respectively. In miR319a-OE plants, the LR number increased by 23% and 48%, and the LR density increased by 10% and 26%. NAA treatment can partially compensate for the phenotype of inhibited LR development caused by the overexpression of miR319a. After N-1-naphthylphthalamic acid (NPA) treatment, which is a key inhibitor of the directional (polar) transport of the auxin hormone in plants, the LR number in WT decreased by 70%. In the overexpression plants, the number of lateral roots decreased by 85–87%, and in the STTM plants, the number of lateral roots decreased by about 83%. It was proved that NPA treatment could reverse the phenotype of increased LR number in miR319a-STTM plants. Expression analysis revealed that miR319a significantly inhibited the expression of the key auxin-regulated genes IAA3.1 and IAA3.2, suggesting that auxin signaling might mediate its effects on lateral root formation. Additionally, we compared the fluorescence signal in the reporter line with GFP expression driven by the auxin-responsive DR5 promoter within the genetic backgrounds of WT, miR319a-OE, and miR319a-STTM plants, which revealed that auxin signaling was stronger in the epidermal cells and elongation zone cells in the LR of miR319a-OE plants, whereas in LR of WT and miR319a-STTM plants, auxin signaling was more pronounced in the root tip meristematic cells. Furthermore, transactivation assays and expression analysis indicated that IAA3.2 was a downstream target of TCP19. Chromatin immunoprecipitation coupled with quantitative PCR (ChIP-qPCR) confirmed that TCP19 directly bound to the promoter region of IAA3.2. These findings establish that miR319a targeted and cleaved TCP19, and TCP19 further directly and negatively regulates the expression of IAA3.2, thereby controlling LR development in Populus tomentosa (P. tomentosa). The formation of LR can expand the plant root system, which is of great significance for the vegetative propagation of plants and the in-vitro regeneration of explants. Moreover, the formation of LR is an important strategy for plants to cope with environmental stresses. This study provides a theoretical basis for breeding poplars more suitable for vegetative propagation. Full article

This study investigated the relationships between inspiratory performance (IP) and glenohumeral rotation in Division 1 Collegiate baseball players (D1CBP). Thirty D1CBP were recruited. The Test of Incremental Respiratory Endurance (TIRE) provides maximal inspiratory pressure (MIP), sustained maximal inspiratory pressure (SMIP), and inspiratory duration (ID). Right and left glenohumeral internal and external rotation (RGHIR, RGHER, LGHIR, and LGHER, respectively) were measured with the shoulder in 90 degrees(d) of abduction. Significant differences between position groups were observed. IP of the entire group was significantly correlated to height, weight, and negatively correlated to right total rotational motion (RTRM) (r = −0.41; p < 0.05). The IP of all pitchers was significantly negatively correlated to both RTRM and LTRM (r = −0.56 to −0.61; p < 0.05). IP of right-handed pitchers was significantly correlated negatively to RGHER (r = −0.83 to −0.93; p < 0.05). IP of left-handed pitchers was significantly correlated negatively to LGHER (r = −0.82; p = 0.04). GH motions are significantly related to the IP of D1CBP. This association may be explained by the involvement of overstretched internal rotators, which act as accessory inspiratory muscles. Full article

Synthetic dyes are highly recalcitrant and are discharged in large volumes in industrial wastewater, which represents a serious environmental pollution problem. Biological methods for dye degradation are a potentially effective option for these synthetic products. In this study, a strain of Pleurotus ostreatus was used to evaluate the decolorization of the Remazol Brilliant Blue R (RBBR) dye added to the culture medium in the exponential growth phase of the fungus. The dye removal capacity of live and inactivated pellets by biosorption, as well as the enzymatic degradation of the dye using a cell-free culture broth considered an extracellular extract (EE), were also evaluated. The activity of laccase and dye-decolorizing peroxidase was determined in both the EE and the intrapellet extract (IPE); their values increased in the presence of dye in the culture medium. A decolorization of 98.5% and 98.0% was obtained in the culture broth and by the EE, respectively; biosorption of the dye by the inactivated pellets was 17 mg/g. The results suggest that the decolorization of the dye is primarily enzymatic, although there are also bioadsorption and bioaccumulation of the dye, which is then enzymatically degraded, and could be used as a carbon source. Full article

Reproductive efficiency is largely impacted during heifer development, which generally requires nutrient supplementation for proper maturation. Nutritional status can also influence inflammation within the reproductive tract. Therefore, we hypothesized that cytokine concentrations in uterine luminal fluid (ULF) will be impacted by protein supplementation following exposure to semen via artificial insemination (AI). Commercial heifers (n = 60) were utilized to determine the effects of protein supplementation and AI on cytokine concentrations in ULF. Heifers were randomly assigned to one of three crude protein (CP) treatments (11%, 15%, and 19% overall CP) via supplementation: (1) CON (10% CP), (2) P20 (20% CP), and (3) P40 (40% CP). All heifers underwent estrus synchronization and ULF was collected 14 d after insemination. Cytokine profiles were constructed in MetaboAnalyst 5.0, and R Studio was used for individual cytokine analyses. Control heifers had increased (p = 0.05) MIP-1β concentrations (148.7 ± 123.9 pg) over P20 heifers (42.3 ± 123.9 pg), and P40 heifers (75.5 ± 123.9 pg) had intermediate concentrations. Semen exposure (1877 ± 550 pg) showed a trend (p = 0.06) to increase concentrations of IP-10 compared with heifers who were not inseminated (1556 ± 550 pg). In conclusion, although protein supplementation and semen exposure had minimal effects on overall cytokine profiles, MIP-1β, IP-10, and MIP-1α were identified as potential key regulators of uterine inflammation during early gestation. Full article

The venom of Bothrops jararaca (BjV) induces intense and prolonged pain, which is not alleviated by antivenom, along with hemorrhage and inflammation. In this study, we investigated the effects of the specialized pro-resolving lipid mediator (SPM) maresin 2 (MaR2) in a murine model of BjV-evoked pain and inflammation. Mice received a single intraperitoneal (i.p.) injection of MaR2 30 min before the intraplantar BjV injection. MaR2 treatment significantly attenuated mechanical (electronic aesthesiometer) and thermal (hot plate) hyperalgesia in a dose-dependent manner. Additionally, MaR2 restored the balance for the hind-paw static weight distribution. When BjV (0.01, 0.1, and 1 μg) stimulus was administered intraperitoneally, pre-treatment with MaR2 (0.3, 1, or 3 ng) ameliorated mechanical and thermal hyperalgesia in a dose-dependent manner. Moreover, MaR2 (3 ng) effectively reduced the levels of myeloperoxidase activity and cytokines (TNF-α, IL-1β, and IL-6) and superoxide anion (O₂^•−) production induced by intraplantar injection of BjV while enhancing total antioxidant levels (ABTS scavenging). For the peritonitis model induced by BjV, MaR2 pretreatment decreased leukocyte recruitment, hemorrhage, nitric oxide (NO), and O₂^•− generation and gp91phox and inducible nitric oxide synthase (iNOS) mRNA expression. In conclusion, this study presents the first evidence that MaR2 effectively mitigated BjV-induced pain, hemorrhage, and inflammation. Full article

This study explores the mechanical behavior of polymer and composite specimens fabricated using fused deposition modeling (FDM), focusing on three material configurations: acrylonitrile butadiene styrene (ABS), carbon fiber-reinforced polyphthalamide (PPA/Cf), and a sandwich-structured composite. A systematic experimental plan was developed using the Box–Behnken design (BBD) to investigate the effects of material type (MT), infill pattern (IP), and printing direction (PD) on tensile and flexural strength. Experimental results showed that the PPA/Cf material with a “Cross” IP printed “Flat” yielded the highest mechanical performance, achieving a tensile strength of 75.8 MPa and a flexural strength of 102.3 MPa. In contrast, the lowest values were observed in ABS parts with a “Grid” pattern and “Upright” orientation, recording 37.8 MPa tensile and 49.5 MPa flexural strength. Analysis of variance (ANOVA) results confirmed that all three factors significantly influenced both outputs (p < 0.001), with MT being the most dominant factor. Machine learning (ML) algorithms, Bayesian linear regression (BLR), and Gaussian process regression (GPR) were employed to predict mechanical performance. GPR achieved the best overall accuracy with R² = 0.9935 and MAPE = 11.14% for tensile strength and R² = 0.9925 and MAPE = 12.96% for flexural strength. Comparatively, the traditional BBD yielded slightly lower performance with MAPE = 13.02% and R² = 0.9895 for tensile strength. Validation tests conducted on three unseen configurations clearly demonstrated the generalization capability of the models. Based on actual vs. predicted values, the GPR yielded the lowest average prediction errors, with MAPE values of 0.54% for tensile and 0.45% for flexural strength. In comparison, BLR achieved 0.79% and 0.60%, while BBD showed significantly higher errors at 1.76% and 1.32%, respectively. Full article

Material wear significantly impacts the clinical success and longevity of dental ceramic restorations. This in vivo study aimed to assess the wear behavior of IPS Empress^® glass-ceramic inlays and onlays over 14 years, considering the influence of different antagonist materials. Fifty-four indirect restorations of 21 patients were available for comprehensive wear analysis, with complete follow-up data for up to 14 years. Three-dimensional measurements relied on digitized epoxy resin models produced immediately post-insertion (baseline) and subsequently at 2, 4, and 14 years. The occlusal region on the baseline model was delineated for comparative analysis. Three-dimensional superimpositions with models from subsequent time points were executed to assess wear in terms of average linear wear and volumetric loss. Statistical analyses were conducted in R (version 4.4.1), employing Mann–Whitney U tests (material comparisons) and Wilcoxon signed rank tests (time point comparisons), with a significance threshold of p ≤ 0.05. During the entire study period, an increase in wear was observed at each assessment interval, gradually stabilizing over time. Significant differences in substance loss were found between the follow-up time points, both for mean (−0.536 ± 0.249 mm after 14a) and integrated distance (−18,935 ± 11,711 mm³ after 14a). In addition, significantly higher wear was observed after 14 years with gold as antagonist compared to other materials (p ≤ 0.03). The wear behavior of IPS Empress^® ceramics demonstrates clinically acceptable long-term outcomes, with abrasion characteristics exhibiting stabilization over time. Full article

Accumulating studies have shown that astrocytes are essential for regulating neurons at both synaptic and circuit levels. The main mechanism of brain astrocytic intracellular Ca²⁺ activity is through the release of Ca²⁺ via the inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) from the endoplasmic reticulum (ER). Studies using IP3R2 knockout mouse models (Itpr2^−/−) have shown that eliminating IP3R2 leads to a significant reduction in astrocytic Ca²⁺ activity However, there is ongoing controversy regarding the effect of this IP3R2-dependent reduction in astrocytic Ca²⁺ transients on neuronal activity. In our study, we employed dual-color two-photon Ca²⁺ imaging to study astrocytes and neurons simultaneously in vibrissa somatosensory cortex (vS1) in awake-behaving wild-type and Itpr2^−/− mice. We systematically characterized and compared both recorded astrocytic and neuronal Ca²⁺ activities in wild-type and Itpr2^−/− mice during various animal behaviors, particularly during the transition period from stillness to locomotion. We report that vS1 astrocytic Ca²⁺ elevation in both wild-type and Itpr2^−/− mice was significantly modulated by free whisking and locomotion. However, vS1 neurons were only significantly modulated by locomotion in wild-type mice, but not in Itpr2^−/− mice. Our study suggests a non-synaptic modulatory mechanism on functions of astrocytic IP3R2-dependent Ca²⁺ transients to local neurons. Full article

Background: Reliable and non-invasive methods for assessing welfare in poultry are essential for improving evidence-based welfare monitoring and advancing management practices in commercial production systems. The iris-to-pupil (IP) ratio, previously validated by our group in primates and cattle, reflects autonomic nervous system balance and may serve as a physiological indicator of stress in laying hens. This study evaluated the utility of the IP ratio under field conditions across diverse commercial layer housing systems. Materials and Methods: In total, 296 laying hens (Lohmann Brown, n = 269; White Leghorn, n = 27) were studied across four locations in Canada housed under different systems: Guelph (indoor; pen), Spring Island (outdoor and scratch; organic), Ottawa (outdoor, indoor and scratch; free-range), and Toronto (outdoor and hobby; free-range). High-resolution photographs of the eye were taken under ambient lighting. Light intensity was measured using the light meter app. The IP ratio was calculated using NIH ImageJ software (Version 1.54p). Statistical analysis included one-way ANOVA and linear regression using GraphPad Prism (Version 5). Results: Birds housed outdoors had the highest IP ratios, followed by those in scratch systems, while indoor and pen-housed birds had the lowest IP ratios (p < 0.001). Subgroup analyses of birds in Ottawa and Spring Island farms confirmed significantly higher IP ratios in outdoor environments compared to indoor and scratch systems (p < 0.001). The IP ratio correlated weakly with ambient light intensity (r² = 0.25) and age (r² = 0.05), indicating minimal influence of these variables. Although White Leghorn hens showed lower IP ratios than Lohmann Browns, this difference was confounded by housing type; all White Leghorns were housed in pens. Thus, housing system but not breed was the primary driver of IP variation. Conclusions: The IP ratio is a robust, non-invasive physiological marker of welfare assessment in laying hens, sensitive to housing environment but minimally influenced by light or age. Its potential for integration with digital imaging technologies supports its use in scalable welfare assessment protocols. Full article

Nicotine-induced oxidative stress contributes significantly to vascular endothelial dysfunction. While negative air ions (NAIs) demonstrate potential blood-pressure-regulating and antioxidant properties, their mechanistic role remains unclear. This study examined the effects of NAIs against nicotine-induced oxidative damage and vascular endothelial injury in spontaneously hypertensive rats (SHRs). Western blotting was used to detect the expression levels of the α7nAChR/MAPK/AP1 pathway. Transcriptomic sequencing was performed to identify the differentially expressed genes after treatment with nicotine or NAIs. Furthermore, reactive oxygen species (ROS), endothelin-1 (ET-1), and [Ca²⁺]_i levels were detected in human aortic endothelial cells (HAECs) treated with nicotine, and the relationship between transcription factor activator protein 1 (AP1) and the target genes was further elucidated through ChIP–qPCR. Nicotine exposure in SHRs elevated blood pressure and induced oxidative damage through α7nAChR/MAPK/AP1 pathway activation, causing endothelial structural disruption. These effects manifested as decreased NO/eNOS and increased ET-1/ET_ab expression, while these changes were reversed by NAIs. In HAECs, nicotine impaired proliferation while increasing oxidative stress and [Ca²⁺]_i levels. This endothelial damage was markedly attenuated by either NAIs or fibronectin 1 (Fn1)/secreted phosphoprotein 1 (Spp1) knockdown. Mechanistically, we identified AP1 as the transcriptional regulator of FN1 and SPP1. NAIs attenuate nicotine-induced endothelial dysfunction in hypertension by inhibiting AP1-mediated FN1 and SPP1 activation, providing novel insights for smoking-associated cardiovascular risk. Full article