Search Results (993)

This research presents a novel methodology to classify copper tailings according to their potential as alkali-activated materials (AAMs) for construction applications. The methodology includes geochemical and mineralogical characterization via QEMSCAN and X-ray fluorescence, with mechanical performance evaluation through compressive strength test (UCS). A three-phase diagram based on Al₂O₃, Fe₂O₃, and CaO-MgO-K₂O is proposed for a fast screening of copper tailing potential to be used as a construction material. In this paper, three copper tailings were chosen to test the methodology, and a set of five samples for each tailing have been geopolymerized for testing. Copper tailing samples were mixed with 0, 2.5, 5, 7.5 and 10% by mass of Ordinary Portland Cement (OPC) to evaluate the effect on performance when a chemical co-activator is used to improve material reactivity. Compressive strength testing was applied on 2 cm³ cubes after 28 days of curing at 60 °C, yielding values from 6 to 26.1 MPa. The best performing sample featured a Si/Al ≅ 3 ratio and a mineralogy with significant presence of reactive species such as plagioclase and K-feldspar (≅42%). In contrast, high levels of Fe₂O₃ (≥12%), clay (≥7%), and pyrite (≥4%) were associated with reduced mechanical performance. Full article

Spinal health depends on the dynamic interplay between mechanical forces, biochemical signaling, and cellular behavior. This review explores how key molecular pathways, including integrin, yeas-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), Piezo, and Wingless/Integrated (Wnt) with β-catenin, actively shape the structural and functional integrity of spinal tissues. These signaling mechanisms respond to physical cues and interact with inflammatory mediators such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α), driving changes that lead to disc degeneration, vertebral fractures, spinal cord injury, and ligament failure. New research is emerging that shows scaffold designs that can directly harness these pathways. Further, new stem cell-based therapies have been shown to promote disc regeneration through targeted differentiation and paracrine signaling. Interestingly, many novel bone and ligament scaffolds are modulating anti-inflammatory signals to enhance tissue repair and integration, as well as prevent scaffold degradation. Neural scaffolds are also arising. These mimic spinal biomechanics and activate Piezo signaling to guide axonal growth and restore motor function. Scientists have begun combining these biological platforms with brain–computer interface technology to restore movement and sensory feedback in patients with severe spinal damage. Although this technology is not fully clinically ready, this field is advancing rapidly. As implantable technology can now mimic physiological processes, molecular signaling, biomechanical design, and neurotechnology opens new possibilities for restoring spinal function and improving the quality of life for individuals with spinal disorders. Full article

Type 2 diabetes (T2D), a growing global health concern, is closely linked to obesity and sedentary behavior. Central to its development are insulin resistance and impaired glucose metabolism in peripheral tissues, particularly skeletal muscle, which plays a key role in energy expenditure, glucose uptake, and insulin sensitivity. Notably, increased accumulation of lipid metabolites in skeletal muscle is observed both in endurance exercise—associated with improved insulin sensitivity—and in high-fat diets that induce insulin resistance. The review examines the contrasting metabolic adaptations of skeletal muscle to these opposing conditions and highlights the key signaling molecules involved. The focus then shifts to the role of the stress kinase p38α mitogen-activated protein kinase (MAPK) in skeletal muscle adaptation to overnutrition and endurance exercise. p38α enhances mitochondrial oxidative capacity and regulates nutrient utilization, both critical for maintaining metabolic homeostasis. During exercise, it cooperates with AMP-activated protein kinase (AMPK) to boost glucose uptake and fatty acid oxidation, key mechanisms for improving insulin sensitivity. The co-activation of p38α and AMPK in skeletal muscle emerges as a promising therapeutic avenue to combat insulin resistance and T2D. The review explores strategies for selectively enhancing p38α activity in skeletal muscle. In conclusion, it advocates a comprehensive approach to T2D prevention and treatment, combining established caloric intake-reducing therapies, such as GLP-1 receptor agonists, with interventions aimed at increasing energy expenditure via activation of p38α and AMPK signaling pathways. Full article

Background/Objectives: Sarcopenic obesity, defined by the coexistence of excessive fat accumulation and progressive muscle loss, is associated with an increased risk of metabolic dysfunction and physical disability. While 5,7-dimethoxyflavone (DMF), a bioactive flavone derived from Kaempferia parviflora, has demonstrated anti-obesity and muscle-preserving properties, its effects on sarcopenic obesity remain unclear. Methods: Four-week-old male C57BL/6J mice were fed a high-fat diet (HFD) for 6 weeks to induce sarcopenic obesity, followed by 8 weeks of continued HFD with the oral administration of DMF. Muscle function was assessed through grip strength and treadmill running tests, while muscle and fat volumes were measured using micro-CT. Mechanistic analyses were performed using gene expression and Western blot analysis. Results: DMF significantly reduced body weight, fat mass, and adipocyte size while enhancing grip strength, endurance, skeletal muscle mass, and the muscle fiber cross-sectional area. In the gastrocnemius muscle, DMF increased the gene expression of peroxisome proliferator-activated receptor gamma coactivator-1α (Ppargc1a) and its isoform Ppargc1a4, thereby promoting mitochondrial biogenesis. It also improved protein turnover by modulating protein synthesis and degradation via the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin signaling pathway. In subcutaneous and brown adipose tissues, DMF increased mitochondrial DNA content and the expression of thermogenic and beige adipocyte-related genes. These findings suggest that DMF alleviates sarcopenic obesity by improving mitochondrial function and regulating energy metabolism in both skeletal muscle and adipose tissues via PGC-1α-mediated pathways. Thus, DMF represents a promising therapeutic candidate for the integrated management of sarcopenic obesity. Full article

Nociceptin/orphanin FQ (N/OFQ) is a neuropeptide that activates the nociceptin opioid peptide (NOP) receptor, a G protein-coupled receptor structurally similar to classical opioid receptors but with distinct pharmacological properties. Unlike μ-opioid receptor (MOR) agonists, NOP receptor agonists provide analgesia with a reduced risk of respiratory depression, tolerance, and dependence. This review synthesizes current evidence from molecular studies, animal models, and clinical trials to evaluate the therapeutic potential of the N/OFQ–NOP system in pain management and anesthesia. A literature review was conducted through a PubMed search of English language articles published between 2015 and 2025 using keywords such as “nociceptin,” “NOP receptor,” “bifunctional NOP/MOR agonists,” and “analgesia.” Primary research articles, clinical trials, and relevant reviews were selected based on their relevance to NOP pharmacology and therapeutic application. Additional references were included through citation tracking of seminal papers. Comparisons with classical opioid systems were made to highlight key pharmacological differences, and therapeutic developments involving NOP-selective and bifunctional NOP/MOR agonists were examined. In preclinical models of chronic inflammatory and neuropathic pain, NOP receptor ago-nists reduced hyperalgesia by 30–70%, while producing minimal effects in acute pain as-says. In healthy human volunteers, bifunctional NOP/MOR agonists such as cebrano-padol provided significant pain relief, achieving ≥30% reduction in pain intensity in up to 70% of subjects, with lower incidence of respiratory depression compared with morphine. Sunobinop, another NOP/MOR agent, demonstrated reduced next-day residual effects and a favorable cognitive safety profile. Clinical data also suggest that co-activation of NOP and MOR may attenuate opioid-induced hyperalgesia and tolerance. However, challenges remain, including variability in receptor signaling and limited human trial data. The N/OFQ–NOP receptor system represents a promising and potentially safer target for analgesia and perioperative care. Future efforts should focus on developing optimized NOP ligands, incorporating personalized approaches based on receptor variability, and advancing clinical trials to integrate these agents into multimodal pain management and enhanced recovery protocols. Full article

Background: DEAD/H box 5 (DDX5) serves as a transcriptional coactivator for several transcription factors including E2F1, the primary target of the tumor suppressor pRB. E2F1 physiologically activated by growth stimulation activates growth-related genes and promotes cell proliferation. In contrast, upon loss of pRB function due to oncogenic changes, E2F1 is activated out of restraint by pRB (deregulated E2F1) and stimulates tumor suppressor genes such as ARF, which activates the tumor suppressor p53, to suppress tumorigenesis. We have recently reported that DDX5 augments deregulated E2F1 activity to induce tumor suppressor gene expression and apoptosis. During the analyses, we noted that over-expression of E2F1 increased DDX5 expression, suggesting a feed forward loop in E2F1 activation through DDX5. Objective: We thus examined whether the DDX5 gene is a target of deregulated E2F1. Method: For this purpose, we performed promoter analysis and ChIP assay. Result: The DDX5 promoter did not possess typical E2F binding consensus but contained several GC repeats observed in deregulated E2F1 targets. Insertion of point mutations in these GC repeats decreased responsiveness to deregulated E2F1 induced by over-expression of E2F1, but scarcely affected responsiveness to growth stimulation. ChIP assays showed that deregulated E2F1 induced by over-expression of E2F1 or expression of E1a, which binds pRB and releases E2F1, bound to the DDX5 gene, while physiological E2F1 induced by growth stimulation did not. Conclusions: These results suggest that the DDX5 gene is a target of deregulated E2F1, generating a feed forward loop mediating tumor suppressive E2F1 activity. Full article

Background/Objectives: Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) function as effectors in the Hippo pathway and have attracted attention due to their association with tumor formation. Glucose transporter (GLUT) proteins also contribute to the proliferation of cancer cells. In this study, we investigated the effect of YAP/TAZ on GLUT1 expression in endometrial carcinoma, as well as the clinical relevance and prognostic value of YAP/TAZ. Methods: The effects of YAP and TAZ knockdown and YAP overexpression on GLUT1 expression in human endometrial carcinoma-derived HHUA and Ishikawa cells were evaluated using RT-qPCR. In addition, we performed immunohistochemical expression of 100 tissue samples of diagnosed endometrial carcinoma. Based on staining intensity and the percentage of positively stained tumor cells, the immunoreactivity score was calculated, which ranged from 0 to 12. Results: YAP/TAZ were identified as important factors in the regulation of GLUT1 expression in HHUA and Ishikawa cells. In addition, a significant correlation (progression-free survival p < 0.05) was observed between TAZ and GLUT1 expression in tissues from endometrial carcinoma patients, and nuclear expression of TAZ was associated with poor prognosis (p < 0.05). Conclusions: YAP/TAZ promote tumor growth via GLUT1. Therapeutic targeting of YAP/TAZ could therefore be useful in the development of future treatments. Full article

Background/Objectives: HIF-1α and ERRα are both implicated in breast cancer progression, yet their functional interplay remains poorly understood. This study investigates their molecular crosstalk in the context of hypoxia-induced drug resistance. Methods: MCF-7 (estrogen receptor, ER-positive) spheroids and CoCl₂-treated SK-BR-3 (ER-negative) cells were used to model tumor hypoxia. Protein expression, coimmunoprecipitation, chromatin immunoprecipitation (ChIP), pharmacological inhibition, and siRNA-mediated gene silencing were employed to assess physical and functional interactions. Immunohistochemistry (IHC) on a tissue microarray (TMA) of 168 invasive breast carcinomas was performed to evaluate clinical relevance. Results: ERRα levels remained unchanged under hypoxia, while its coactivator, Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 α (PGC-1α), was upregulated. ERRα physically interacted with HIF-1α and was required for HIF-1 transcriptional activity under hypoxic conditions. ChIP assays showed that ERRα-driven overexpression of Permeability glycoprotein 1 (P-gp) and Vascular Endothelial Growth Factor (VEGF) was mediated by HIF-1α binding to the MDR1 and VEGF promoters. Inhibition or silencing of ERRα reversed P-gp overexpression and restored intracellular doxorubicin. TMA analysis confirmed the clinical correlation between ERRα, HIF-1α, and P-gp expression, highlighting the role of ERRα in hypoxia-induced drug resistance. ERRα expression was independent of ER status, suggesting an estrogen-independent function. Conclusions: This study identifies a novel physical and functional interaction between ERRα and HIF-1α that promotes chemoresistance in hypoxic breast tumors. Targeting ERRα may represent a promising therapeutic strategy to overcome drug resistance in aggressive, ER-independent breast cancer subtypes. Full article

In this perspective, we highlight the relevance of the FA-Hippo signaling pathway and its regulation of the Yes-associated protein (YAP) and the transcriptional coactivator with a PDZ-binding domain (TAZ) as main players in the process of implants integration. The modulation and responses of YAP/TAZ triggered by substrate and ECM stiffness are of particular interest in the construction of materials used for medical implants. YAP/TAZ nuclear localization and activity respond to the substrate stiffness by several mechanisms that involve the canonical and non-canonical Hippo signaling and independently of the Hippo cascade. YAP/TAZ regulate the expression of genes involved in several mechanisms of relevance for implant integration such as the proliferation and differentiation of cell precursors and the immune response to the implant. The influence of substrate stiffness on the regulation of the immune response is not completely understood and the progress in this field can contribute to the designing of an adequate implant design. Though the use of nano-biomaterials has been proved to contribute to implant success, the relationship between grain size and stiffness of the material has not been explored in the biomedical field; filling these gaps in the knowledge of biomaterials will highly contribute to the design of biomaterials that could take advantage of the cells sensing and response to the stiffness at the implant interface. Full article

Background/Objectives: Although public health organizations encourage family walking, no studies have examined children’s physical activity and enjoyment during outdoor parent–child walks. This study addresses those gaps by examining children’s moderate-to-vigorous physical activity (MVPA) and enjoyment during outdoor walks with their parents, along with parental barriers and their relationship with parent’s self-efficacy and co-activity minutes. Methods: Fifty parent–child dyads (children aged 6–12 years) completed 10 min, self-paced outdoor walks while wearing waist-worn ActiGraph monitors. Parents reported perceived barriers to walking outdoors with their child and self-efficacy for supporting their child’s daily physical activity. Results: Children reported high enjoyment (mean = 5.1 on a six-point scale) and attained high physical activity intensity (71.3% of time in MVPA, 22.0% in vigorous activity, mean step count = 1200). Parents reported an average of 2.6 barriers (SD = 1.0) to walking outdoors with their child, with poor weather (70%) and lack of time (70%) reported most frequently. Each additional barrier was associated with a 1.3-point reduction in parents’ self-efficacy (p = 0.007). Two barriers (‘diverse interests between parent and child’ and ‘other parent-suggested barriers’) were significantly associated with fewer co-activity minutes per week (p < 0.001). Conclusions: Our study highlights the benefits of parent–child outdoor walking for promoting MVPA and enjoyment in children. Because perceived barriers may lower parents’ self-efficacy in supporting their child’s physical activity, addressing these barriers may be essential for the success of family-based interventions that encourage walking together outdoors. Full article

Rosacea is a chronic inflammatory skin condition characterized by persistent erythema and abnormal vascular response. Although current treatments focus on symptomatic relief, they often provide only temporary improvement and may be associated with side effects or recurrence. Cannabigerol (CBG), a non-psychoactive cannabinoid, has recently garnered attention for its pharmacological activities, including anti-inflammatory, antioxidant, neuroprotective, and skin barrier–supportive effects. However, its role in modulating pathological responses in rosacea remains unclear. In this study, we investigated the therapeutic potential of topically applied CBG in an LL-37-induced rosacea-like mouse model. Clinical and histological assessments revealed that CBG markedly reduced erythema, epidermal hyperplasia, and mast cell infiltration. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed downregulation of Il1b, Il4, Il6, Il13, Il22, Il31, Tlr2, Vegfa, and Mmp9. Immunohistochemistry and Western blot analyses further demonstrated suppression of CD31, vascular endothelial growth factor (VEGF), and Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), along with reduced activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, including decreased levels of JAK1, STAT3, and phosphorylated STAT3. These findings suggest that topical CBG alleviates rosacea-like skin inflammation by targeting inflammatory and vascular pathways, including JAK/STAT and YAP/TAZ signaling. Full article

Humans are inherently social beings, and the quality of their interactions is essential for maintaining physical and mental health. Effective social interaction involves understanding not just people’s visible behavior but also the underlying factors like thoughts and emotions. This review investigates the convergence and divergence of meta-analytic brain activation for mentalizing, empathy, and social interaction engagement. To achieve this, we re-analyzed data from our prior meta-analysis on mentalizing and empathy using the same methodology as an existing meta-analysis on social interaction engagement. The comparison of brain activation maps focused on the question of whether the co-activation of cognitive and affective brain systems is an overarching characteristic of intermediate mentalizing/empathy tasks and social interaction engagement. Our findings support the general assumption that social interaction engagement co-recruits cognitive and affective brain systems also implicated in mentalizing and empathy. However, we found little direct overlap of brain activation for intermediate mentalizing/empathy tasks and social interaction engagement. Finally, applying a network neuroscience perspective, we suggest that social interaction engagement, affective/empathy, and intermediate mentalizing/empathy tasks are collectively characterized by co-recruitment of the default mode network and control networks. Full article

Background and Objective: This study aimed to examine the possibility of using surface electromyography (sEMG) to aid in assessing the correctness of overhead deep squat performance. Electromyography signals were recorded for 20 athletes from the lower (rectus femoris (RF), vastus medialis (VM), biceps femoris (BF), and gluteus (GM)) and upper (deltoid (D), latissimus dorsi (L)) muscles. The sEMG signals were categorized into three groups based on physiotherapists’ evaluations of deep squat correctness. Methods: The raw sEMG signals were filtering at 10–250 Hz, and then the mean frequency, median frequency, and kurtosis were calculated. Next, the maximum excitation of the muscles expressed in percentage of maximum voluntary contraction (%MVC) and co-activation index (CAI) were estimated. To determine the muscle excitation level, the pulse interference filter and variance analysis of the sEMG signal derivative were applied. Next, analysis of variance (ANOVA) tests, that is, nonparametric Kruskal–Wallis and post hoc tests, were performed. Results: The parameter that most clearly differentiated the groups considered turned out to be %MVC. The statistically significant difference with a large effect size in the excitation of RF & GM (p = 0.0011) and VM & GM (p = 0.0002) in group 3, where the correctness of deep squat execution was the highest and ranged from 85% to 92%, was pointed out. With the decrease in the correctness of deep squat performance, an additional statistically significant difference appeared in the excitation of RF & BF and VM & BF for both groups 2 and 1, which was not present in group 3. However, in group 2, with the correctness of the deep squat execution at 62–77%, the statistically significant differences in muscle excitation found in group 3 were preserved, in contrast to group 1, with the lowest 23–54% correctness of the deep squat execution, where the statistical significance of these differences was not confirmed. Conclusions: The results indicate that sEMG can differentiate muscle activity and provide additional information for physiotherapists when assessing the correctness of deep squat performance. The proposed analysis can be used to evaluate the correctness of physical exercises when physiotherapist access is limited. Full article

Defective placentation is a recognized etiology for several gestational complications that include early pregnancy loss, preeclampsia, and intrauterine growth restriction. Sustained viability, migration, and invasion are essential cellular properties for embryonic extravillous trophoblasts to execute their roles in placental development and function, while derailment of these cellular processes is linked to placental disorders. Although the cellular functions of extravillous trophoblasts are well recognized, our understanding of the pivotal molecular determinants of these functions is incomplete. Using the HTR-8/SVneo immortalized human extravillous trophoblast cell line, we report that steroid receptor coactivator-2 (SRC-2), a coregulator of transcription factor-mediated gene expression, is essential for extravillous trophoblast cell viability, motility, and invasion. Genome-scale transcriptomics identified an SRC-2-dependent transcriptome in HTR-8/SVneo cells that encodes a diverse spectrum of proteins involved in placental tissue development and function. Underscoring the utility of this transcriptomic dataset, we demonstrate that WNT family member 9A (WNT 9A) is not only regulated by SRC-2 but is also crucial for maintaining many of the above SRC-2-dependent cellular functions of human extravillous trophoblasts. Full article

Humor is widely recognized for its positive effects on well-being, including stress reduction, mood enhancement, and cognitive benefits. Yet, the lack of reliable tools to objectively quantify amusement—particularly its temporal dynamics—has limited progress in this area. Existing measures often rely on self-report or coarse summary ratings, providing little insight into how amusement unfolds over time. To address this gap, we developed a Random Forest model to predict the intensity of amusement evoked by humorous video clips, based on participants’ facial expressions—particularly the co-activation of Facial Action Units 6 and 12 (“% Smile”)—and video features such as motion, saliency, and topic. Our results show that exposure to humorous content significantly increases “% Smile”, with amusement peaking toward the end of videos. Importantly, we observed emotional carry-over effects, suggesting that consecutive humorous stimuli can sustain or amplify positive emotional responses. Even when trained solely on humorous content, the model reliably predicted amusement intensity, underscoring the robustness of our approach. Overall, this study provides a novel, objective method to track amusement on a fine temporal scale, advancing the measurement of nonverbal emotional expression. These findings may inform the design of emotion-aware applications and humor-based therapeutic interventions to promote well-being and emotional health. Full article