Search Results (6,550)

Background: Bone marrow mesenchymal stem cells (BM-MSCs) are significant in chemo- and radiotherapy resistance. Previous research has focused on BM-MSCs, demonstrating their functional involvement in cancer progression as mediators in the tumor microenvironment. They play multiple roles in tumorigenesis, angiogenesis, and metastasis. BM-MSC-derived exosomes (BM-MSCs-exo) are small vesicles, typically 50–300 nm in diameter, isolated from BM-MSCs. Some studies have demonstrated the tumor-suppressive effects of BM-MSCs-exo. Objective: This study aimed to investigate their role in modulating the impact of chemoradiotherapy (CRT) in different types of cervical cancer spheroid cells. Methods: The spheroids after treatment were subject to size measurement, cell viability, and caspase activity. Then, the molecular mechanism was elucidated by Western blot analysis. Results: We observed a reduction in spheroid size and an increase in cell death in HeLa spheroids, while no significant changes in size or cell viability were found in SiHa spheroids. At the molecular level, CRT treatment combined with BM-MSCs-exo in HeLa spheroids induced apoptosis through the activation of the NF-κB pathway, specifically via the NF-κB1 (P50) transcription factor, leading to the upregulation of apoptosis-related molecules. In contrast, CRT combined with BM-MSCs-exo in SiHa spheroids exhibited an opposing effect: although cellular viability decreased, caspase activity also decreased, which correlated with increased HSP27 expression and the subsequent downregulation of apoptotic molecules. Conclusion: Our study provides deeper insight into the potential of BM-MSCs-exo in cervical cancer treatment, supporting the development of more effective and safer therapeutic strategies for clinical application. Full article

Background/Objectives: Given the multifaceted role of estrogen hormones in skeletal muscle pathophysiology and their well-established immunomodulatory properties, this study aimed to characterize the expression of the G-protein-coupled estrogen receptor (GPER) in patients with inflammatory myopathies (IM). Methods: Immunohistochemical analysis was performed on muscle biopsies from 13 patients with IM, 11 with non-inflammatory myopathies (N.IM), and 5control subjects. Intergroup differences in GPER score were statistically evaluated. We performed an analysis based on the Visual Analog Scale (VAS). The scoring system evaluates overall pathology (VAS score) based on four distinct components: inflammation, vascular involvement, myopathic changes, and connective tissue alterations. Results: Immunolocalization analysis demonstrated that GPER is constitutively expressed in human skeletal muscle and is upregulated in IM. Enhanced expression included both sarcolemmal and intracellular membrane localization. Notably, GPER upregulation showed a positive correlation with the severity of tissue inflammation. The IM group had significantly higher VAS scores compared to both the N.IM and control groups. Conclusions: We provide the first histopathological characterization of GPER expression in human skeletal muscle. In IM, GPER upregulation may play a protective role by negatively modulating the release of inflammatory mediators, as suggested by experimental evidence from other models of inflammation. The emerging therapeutic development of GPER agonists may represent a promising avenue for the treatment of inflammatory myopathies. Full article

Background: Dendritic cells (DCs) play an important role as a bridge between innate and adaptive immunity, and changes in gene expression of DCs during the immune response to Mycobacterium tuberculosis (M.tb) may affect the development of tuberculosis. Methods: Using systems biology methods, mRNA and miRNA expression profile data of DCs infected with M.tb were obtained. A total of 1398 differentially expressed mRNAs and 79 differentially expressed miRNAs were identified, and a corresponding miRNA–mRNA regulatory network was constructed using Cytoscape 3.9.1 software. The functional annotations and pathway classifications of the miRNA–mRNA network were identified using the DAVID tool. Then, the key pathway modules in the miRNA–mRNA network were screened and subjected to PPI network analysis to identify hub nodes. Subsequently the miRNA/mRNA axis was determined, validated by qRT-PCR, and evaluated through ROC curve analysis. Results: The TNF signaling pathway and the Tuberculosis pathway were key pathway modules, with miR-34a-3p/TNF and miR-190a-3p/IL1B being the greatest correlations with the two pathway modules. qRT-PCR results showed that IL1B and miR-190a-3p exhibited significant differences in both the H37Ra and BCG infection groups. The AUC of two factors (IL1B and miR-190a-3p) was 0.9561 and 0.9625, respectively, showing high sensitivity and specificity. Conclusions: Consequently, miR-190a-3p/IL1B might be a good candidate marker to characterize the immune response of DCs to M.tb and a transition signal from innate to adaptive immunity. Full article

Background and objectives: Duloxetine is widely used for the treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), and various types of neuropathic pain. While its efficacy is well documented in clinical trials, less is known about how it is perceived and utilized in routine psychiatric practice. To address this knowledge gap, we conducted a cross-sectional observational study involving 80 psychiatrists from Spain to assess real-world clinical attitudes toward duloxetine. Methods: Participants completed a 20-item multiple-choice questionnaire that examined familiarity, perceived efficacy in multiple conditions (MDD, GAD, neuropathic pain, somatization, and quality of life), and perspectives on tolerability, safety, adherence, and overall satisfaction. Results: Survey results indicated that a large majority of psychiatrists frequently prescribe duloxetine, particularly for patients with MDD and comorbid chronic pain. Notably, 94% rated it as either “more effective” or “much more effective” for diabetic peripheral neuropathic pain. Psychiatrists reported a high perceived efficacy of duloxetine: 94% rated it as “more effective” or “much more effective” for diabetic peripheral neuropathy, and 93% gave similarly positive ratings for general neuropathic pain. For somatization, 70% found it “effective” or “very effective”, and 83% observed improvements in quality of life for many of their patients. Psychiatrists generally reported favorable perceptions of duloxetine’s tolerability profile: 97.5% rated it as the antidepressant associated with the least weight gain, and 82.5% perceived fewer sexual side effects compared to other options. Sedation and gastrointestinal side effects were generally considered mild or less severe. In terms of treatment adherence, 69% rated it as “better” or “much better” than other antidepressants, and 80% found its combination with other antidepressants to be “favorable” or “very favorable”. Overall satisfaction was high, with 99% of psychiatrists reporting being either “satisfied” or “very satisfied” with its use. The side effect profile was generally viewed as manageable, with low perceived rates of weight gain, sedation, and sexual dysfunction. Furthermore, 96% of respondents expressed a willingness to recommend duloxetine to their colleagues. Conclusions: Psychiatrists reported highly favorable attitudes toward duloxetine, viewing it as a flexible treatment option in routine care. However, these findings reflect clinicians’ subjective perceptions rather than objective clinical outcomes and should be interpreted accordingly. Full article

Arugula leaves (Diplotaxis tenuifolia L. and Eruca sativa L.) are a must-have ingredient in ready-to-eat salads, as they are prized for their appearance, taste, and flavor. The nutraceutical properties of this leafy vegetable are attributed to the presence of valuable secondary metabolites, such as phenolic acids and glucosinolates. Using UHPLC-Q-Orbitrap HRMS analysis and ion chromatography, we characterized the content of phenolic acids, glucosinolates, nitrates, and organic acids in organic arugula [Diplotaxis tenuifolia (L.) DC] and evaluated how the foliar application of three different non-microbial biostimulants (a seaweed extract, a vegetable protein hydrolysate, and a tropical plant extract) modulated the expression of these. Although the application of vegetable protein hydrolysate increased, compared to control plants, the nitrate content, the application of the same biostimulant increased the total content of glucosinolates and phenolic acid derivatives by 5.2 and 17.2%. Specifically, the foliar application of the plant-based biostimulant hydrolyzed protein significantly increased the content of glucoerucin (+22.9%), glucocheirolin (+76.8%), and ferulic acid (+94.1%). The highest values of flavonoid derivatives (173.03 μg g⁻¹ dw) were recorded from plants subjected to the exogenous application of seaweed extract. The results obtained underscore how biostimulants, depending on their origin and composition, can be exploited not only to improve agronomic performance but also to enhance the nutraceutical content of vegetables, guaranteeing end consumers a product with premium quality characteristics. Full article

Descola describes western culture, influenced by the Christian worldview, as “naturalist”. However, semiotic and ethnographic research shows that different perspectives about the relationship between humans and animals coexist with mainstream naturalism. In particular, the introduction of animals in churches is not rare in Italy today, even though it fuels an ongoing debate. The relationship with animals is central in Saint Anthony’s figure and feast, which includes the blessing of animals. This article first focuses on the figure of Saint Anthony, finding in its first sources the seeds of a worldview based on love for creation that fully flourishes centuries later with Saint Francis, then it contextualizes the blessing of animals in the context of a changing sensitivity towards animals, which are often considered from an affective perspective and as part of an ecological standpoint that is also expressed in the institutional discourse of the Catholic Church. Then, the patronal feast of Saint Anthony and the blessing of animals in two different urban communities of Turin (Italy) are the subject of an ethnosemiotic analysis highlighting the animals’ position (inside or at the border of the sacred space), the rite’s structure and the relation between the verbal discourse and the performance of celebrants and worshipers. The position of the animals is thus considered as the expression plane of semantic values about their status in relation to the family. Full article

This study identifies the novel effects of soluble factors derived from murine erythroblasts on lymphoid cell phenotypes. These effects were observed following the treatment of splenic mononuclear cells with erythroblast-conditioned media received from both healthy mice and mice subjected to hematopoiesis-activating conditions (hypoxia, blood loss, and hemolytic anemia), suggesting a common mechanism of action. Using flow cytometry, we elucidated that erythroblast-derived soluble products modulate T cell differentiation by promoting Treg development and increasing PD-1 surface expression on B cells. The immunoregulatory potential of erythroblasts is subpopulation-dependent: CD45+ erythroblasts respond to hemolytic stress by upregulating the surface expression of immunosuppressive molecules PDL1 and Galectin-9, while CD45- erythroblasts primarily increase TGFb production. These findings highlight the regulatory role of erythroblasts in modulating immune responses. Full article

The ultimate goal of research on seismic mitigation technologies is engineering application. However, current studies primarily focus on the application of dampers in planar structures, while actual engineering structures are three-dimensional (3D) in nature. A type of damper, making up tuned mass dampers (TMDs) and inerters, has excellent vibration mitigation performance and needs brackets to connect to structures. In this work, a coupled dynamic model of an energy dissipation system (EDS) comprising a TMD, an inerter, a bracket, and a 3D building structure is presented, along with analytical solutions for stochastic seismic responses. The main work is as follows. Firstly, based on D’Alembert’s dynamics principle, the seismic dynamic equations of an EDS considering a realistic damper and a 3D structure are formulated. The general dynamic equations governing the bidirectional horizontal motion of the EDS are further derived using the dynamic finite element technique. Secondly, analytical expressions for spectral moments and variances of seismic responses are obtained. Finally, four numerical examples are presented to investigate the following: (1) verification of the proposed response solutions, showing that the calculation time of the proposed method is approximately 1/500 of that of the traditional method; (2) examination of spatial effects in 3D structures under unidirectional excitation, revealing that structural seismic responses in the direction along the earthquake ground motion is approximately 10⁴ times that in the direction perpendicular to the ground motion; (3) investigation of the spatial dynamic characteristics of a 3D structure subjected to unidirectional seismic excitation, showing that the bracket parameters significantly affect the damping effects on an EDS; and (4) application of the optimization method for the damper’s parameters that considers system dynamic reliability and different weights of the damper’s parameters as constraints, indicating that the most economical damping parameters can achieve a reduction in displacement spectral moments by 30–50%. The proposed response solutions and parameter optimization technique provide an effective approach for evaluating stochastic seismic responses and optimizing damper parameters in large-scale and complex structures. Full article

Inclusive music education refers to the use of musical experiences and practices as tools for promoting participation, equity, and meaningful engagement among all learners, including those with Special Educational Needs (SEN). Music education has long been recognized not only for its value in emotional expression and cultural transmission but also for its cognitive and relational benefits. This entry examines the inclusive and transformative potential of music, highlighting how it can foster equitable, accessible, and culturally relevant learning environments. Drawing from pedagogy, neuroscience, and educational technology, the entry explores how music contributes to cognitive, emotional, and social development, with a focus on learners with SEN. It emphasizes the importance of early exposure to music, the strong connections between music and language acquisition, and the need to challenge persistent misconceptions about innate musical talent. The findings demonstrate that when supported by digital tools and educational games, music education becomes a powerful driver of inclusion, enhancing participation, relational dynamics, and cognitive engagement. The entry concludes by advocating for a reimagining of music not as a secondary subject, but as a foundational component of holistic and inclusive education, capable of building more empathetic, connected, and equitable societies. Full article

Structural analysis of motoneuron somas and their associated proteins via immunohistochemistry (IHC) remains tedious and subjective, requiring costly software or adapted 2D manual methods that lack reproducibility and analytical rigor. Yet, neurodegenerative disease and aging research demands precise structural comparisons to elucidate mechanisms driving neuronal degeneration. To address this need, we developed a novel algorithm that automates repetitive and subjective IHC analysis tasks, enabling thorough, objective, blinded, order-agnostic, and reproducible 3D batch analysis. With no manual tracing, the algorithm produces 3D Cartesian reconstructions of motoneuron somas from 60× IHC images of mouse lumbar spinal tissue. From these reconstructions, it measures 3D soma volume and efficiently quantitates net somatic protein expression and macro-cluster size. In this validation study, we applied the algorithm to assess soma size and C-bouton expression in various healthy control mice, comparing its measurements against manual measurements and across multiple algorithm users to confirm its accuracy and reproducibility. This novel, customizable tool enables efficient and high-fidelity 3D motoneuron analysis, replacing tedious, qualitative, cell-by-cell manual tuning with automatic threshold adaptation and quantified batch settings. For the first time, we attain reproducible results with quantifiable accuracy, exhaustive sampling, and a high degree of objectivity. Full article

Cardiovascular disease and hypertension are major global health challenges, and increasing dietary salt intake is a known contributor. Emerging evidence suggests that excessive salt exposure during pregnancy may impact fetal development, yet its effects on early embryogenesis remain poorly understood. In this study, we used zebrafish (Danio rerio) embryos as a model to investigate the developmental and molecular consequences of high-salt exposure during early vertebrate development. Embryos subjected to elevated salt levels exhibited delayed hatching, reduced heart rates, and significant alterations in gene expression profiles. Transcriptomic analysis revealed over 4000 differentially expressed genes, with key disruptions identified in calcium signaling, MAPK signaling, cardiac muscle development, and vascular smooth muscle contraction pathways. These findings indicate that early salt exposure can perturb crucial developmental processes and signaling networks, offering insights into how prenatal environmental factors may contribute to long-term cardiovascular risk. Full article

The structural modal parameter identification method can be classified into time-domain and frequency-domain methods. Practically, two types of methods are characterized by different advantages, and the estimated modal parameters are always subjected to statistical uncertainties due to measurement noise. In this work, an uncertainty-based fusion method for structural mode identification is proposed to merge the advantages of different methods. The extensively applied time-domain AutoRegressive (AR) and frequency-domain Left-Matrix Fraction (LMF) models are expressed in a unified parametric model. With this unified model, a generalized framework is developed to identify the modal parameters of structures and compute variances associated with modal parameter estimates. The final modal parameter estimates are computed as the inverse-variance weighted sum of the results identified from different methods. A numerical and an experimental example demonstrate that the proposed method can obtain reliable modal parameter estimates, substantially mitigating the occurrence of extremely large estimation errors. Furthermore, the fusion method demonstrates enhanced identification capabilities, effectively reducing the likelihood of missing structural modes. Full article

It is of great importance to explore how plants respond to excess accumulation of Cu and Ni in soil, yet the mechanisms by which Euphorbia marginata, a common ornamental plant in China, responds to heavy metal stress remain unclear. In this study, E. marginata seedlings were subjected to CK, Ni 500 mg/kg, and Cu 900 mg/kg, with Ni-Cu combined stress, and their growth, physiological indexes, heavy metal accumulation, and their corresponding gene expression were evaluated after 45 d. The results showed that the two heavy metals mainly accumulated in plant roots and severely inhibited root growth, while the combined stress promoted the accumulation of heavy metals to a small extent. Either Cu or Ni stresses inhibit photosynthetic pigment synthesis as well as activate antioxidant and osmoregulatory systems, but there are differences in their effects. Combined stress has a synergistic stress effect, severely damaging the cell membrane structure and leading to dysregulation of antioxidant and osmoregulatory systems. The expression of CDPK, CaMCML, MEKK3/6 signaling factors, UFGT, and COMT was severely suppressed under the combined stresses of Cu and Ni compared to the single stress of both. These results provide evidence of a specific defense response to heavy metal stress in E. marginata, which could help guide new research efforts and support the development of strategies for phytoremediation using E. marginata. Full article

Expressive imitation in the performing arts is typically trained through animal behavior imitation, aiming not only to reproduce action trajectories but also to recreate rhythm, style and emotional states. However, evaluation of such animal imitation behaviors relies heavily on teachers’ subjective judgments, lacking structured criteria, exhibiting low inter-rater consistency and being difficult to quantify. To enhance the objectivity and interpretability of the scoring process, this study develops a machine learning and structured pose data-based auxiliary evaluation framework for imitation quality. The proposed framework innovatively constructs three types of feature sets, namely baseline, ablation, and enhanced, and integrates recursive feature elimination with feature importance ranking to identify a stable and interpretable set of core structural features. This enables the training of machine learning models with strong capabilities in structured modeling and sensitivity to informative features. The analysis of the modeling results indicates that temporal–rhythm features play a significant role in score prediction and that only a small number of key feature values are required to model teachers’ ratings with high precision. The proposed framework not only lays a methodological foundation for standardized and AI-assisted evaluation in performing arts education but also expands the application boundaries of computer vision and machine learning in this field. Full article

Atopic dermatitis (AD) is a chronic, multifactorial inflammatory skin disease characterized by persistent pruritus, immune system dysregulation, and an increased expression of cyclooxygenase-2 (COX-2), an enzyme that plays a central role in the production of prostaglandins and the promotion of inflammatory responses. In this study, we employed a comprehensive computational pipeline to identify phytocompounds capable of inhibiting COX-2 activity, offering an alternative to traditional non-steroidal anti-inflammatory drugs. The African and Traditional Chinese Medicine natural product databases were subjected to molecular screening, which identified six top compounds, namely, Tophit1 (−16.528 kcal/mol), Tophit2 (−10.879 kcal/mol), Tophit3 (−9.760 kcal/mol), Tophit4 (−9.752 kcal/mol), Tophit5 (−8.742 kcal/mol), and Tophit6 (−8.098 kcal/mol), with stronger binding affinities to COX-2 than the control drug rofecoxib (−7.305 kcal/mol). Molecular dynamics simulations over 200 ns, combined with MM/GBSA binding free energy calculations, consistently identified Tophit1 and Tophit2 as the most stable complexes, exhibiting exceptional structural integrity and a strong binding affinity to the target protein. ADMET profiling via SwissADME and pkCSM validated the drug-likeness, oral bioavailability, and safety of the lead compounds, with no Lipinski rule violations and favorable pharmacokinetic and toxicity profiles. These findings underscore the therapeutic potential of the selected phytocompounds as novel COX-2 inhibitors for the management of atopic-prone skin and warrant further experimental validation. Full article