Search Results (3,741)

Foot-worn electromagnetic harvesters are driven by irregular rigid-body motion, while their response is limited by mechanical stroke, coil geometry, mounting direction, and the electrical interface. This paper presents a reproducible numerical design study of a finite-stroke magnetic quasi-zero-stiffness (QZS) moving-magnet harvester. Two public three-axis foot-IMU records are processed with stated gyroscope-bias estimation, six-axis attitude estimation, gravity removal, residual-offset correction, filtering, and angular-acceleration calculation. Three explicit axes are used in the design screen, and the selected candidate is then evaluated over a 62-direction spherical grid. Rigid-body angular-acceleration and centripetal terms are included for specified sensor-to-harvester offsets. Two normalized magnetic force laws are compared. The electrical model uses position-dependent flux linkage, explicit series connection and polarity of coil sections, winding-derived resistance, and a position-dependent electromagnetic reaction force. A fixed-seed random screen evaluates 720 geometry-constrained candidates. The highest-ranked nominal candidate is a 150 mm external foot-worn module with a 40.6 g moving mass, a 30 mm hard half-stroke, 1649 turns in two series sections, and a 25.27 mm coil outer diameter. Across 72 design-screen cases formed from 12 five-second windows, three mounting axes, and two magnetic laws, this candidate remained hard-stroke- and design-stroke-safe. Its conditional ideal load-side power had a 10th percentile of 1.38 mW and a median of 2.03 mW. In the 62-direction check, all 1488 cases remained hard-stroke-safe; two opposite directions each produced one design-stroke exceedance, with a maximum displacement of 24.15 mm. Re-ranking all 30 Stage-2 candidates under coupling and magnetic-stiffness changes retained the long geometry family, although a 30% coupling reduction changed the highest-ranked candidate from 600 to 632. Soft-stop sensitivity, equation-level consistency, and multi-case Runge–Kutta convergence are also reported. The results support finite-stroke design screening, but they do not constitute prototype, finite-element, or delivered-power validation. Full article

Capacitive and resistive electric transfer (TECAR) therapy is increasingly used in equine physiotherapy; however, objective evidence regarding its immediate effects on equine back muscles remains limited. This pilot study aimed to evaluate the effects of TECAR therapy on body surface temperature and muscle tone of the longissimus dorsi muscle in Thoroughbred racehorses. A randomized, single-blinded experimental study was conducted in 20 clinically healthy Thoroughbred racehorses aged 2–3 years. Horses were randomly assigned to either a TECAR treatment group (n = 10) or a sham-treatment control group (n = 10). Thermographic imaging and palpation-based muscle tone assessment were performed before treatment, immediately after treatment, and 10 min post-treatment in the thoracolumbar region (Th15–L6). Differences between groups and changes over time were analyzed using repeated-measures ANOVA for temperature data and Friedman’s test with post hoc Wilcoxon signed-rank tests for palpation scores. TECAR therapy was associated with a significant increase in body surface temperature, with mean values rising from 25.3 ± 1.5 °C before treatment to 28.9 ± 1.3 °C immediately after treatment (p < 0.001) and remaining elevated after 10 min (27.6 ± 1.3 °C; p = 0.002). In contrast, only minor temperature changes were observed in the sham group. Palpation assessment demonstrated a significant reduction in muscle tone following TECAR therapy, with median scores decreasing from 3 [2–3] before treatment to 0 [0–1] immediately afterward (p < 0.001). These findings indicate that TECAR therapy induces an immediate thermal response, which persists for at least 10 min, and is associated with reduced longissimus dorsi muscle tone in racing horses. Further studies are warranted to investigate its clinical applications and long-term effects in equine rehabilitation. Full article

Across societies, judges are entrusted with extraordinary authority to shape legal norms, public policy, and individual rights, with decisions that can influence communities and future generations. This social contract rests on expectations of competence, impartiality, and ethical self-regulation. Popular representations often portray judges as detached, stoic, and immune to typical human emotional reactivity and outside influence. However, judges remain subject to the same biological, psychological, and social realities that affect all humans, including stress physiology, neurocognitive load, emotional strain, and the cumulative effects of allostatic burden. Emerging research suggests that these factors may have important implications for judicial well-being, decision-making, and the effective functioning of justice systems. The recent Nauru Declaration, recognizing that the well-being of judges is essential for a properly functioning judiciary, has led to the 2025 United Nations General Assembly proclamation that the 25th July be recognized as an annual International Day for Judicial Well-being. Drawing on literature identified through scholarly databases, this concept article examines evidence relating to stress, burnout, resilience, and well-being within justice systems, with particular emphasis on judges and judicial well-being. We explore the relevance of lifestyle medicine and whole-person approaches to health in supporting judicial functioning and vitality. Framed through the lens of the judiciary’s societal responsibilities and the broader social contract, we contend that judicial well-being is not merely an individual concern, but one with institutional and societal significance. The article argues that well-being within systems of justice matters to society; it examines evidence relating to judicial stress and self-control fatigue, and concludes with solutions-oriented approaches and future directions for promoting judicial well-being and sustainable justice systems. Full article

Cadmium (Cd) contamination threatens wheat productivity by impairing growth, redox homeostasis, and metal partitioning. Beneficial fungi and phytohormones improve plant stress tolerance, but the combined role of Trichoderma harzianum and the synthetic strigolactone analog GR24 in wheat Cd tolerance remains unclear. This study evaluated whether co-application of T. harzianum and GR24 enhances Cd tolerance by improving growth, photosynthetic activity, and antioxidant defense, and by reducing Cd accumulation. A greenhouse pot experiment was conducted with two Cd levels (Cd₀ and Cd₁), two GR24 treatments (H₀, without GR24; H₁, 100 mg L⁻¹ GR24), and two T. harzianum treatments (TH₀ and TH₁; 2 g kg⁻¹ soil), using five biological replications. Cd stress markedly inhibited wheat growth, photosynthetic performance, and antioxidant defense while increasing oxidative injury and Cd accumulation in plant tissues. Under Cd stress, the combined GR24-T. harzianum treatment increased shoot growth and biomass by 53.04–80.43%, reduced EL, MDA, and H₂O₂ by 18.70–30.36%, enhanced SOD, POD, and CAT activities by 24.01–44.50%, and lowered Cd concentrations in roots, shoots, and leaves by 41.09–56.19%. These responses strengthen the treatment’s practical relevance. Collectively, these findings indicate that T. harzianum-GR24 co-application offers a promising biological approach to improve wheat resilience and reduce Cd accumulation in wheat tissues. Full article

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease of the nasal and paranasal sinus mucosa, associated with significant impairment in quality of life, frequent postoperative recurrence, and repeated need for systemic glucocorticosteroid therapy. Despite the availability of biologics targeting IL-4/IL-13, IL-5, and IgE, a subset of patients shows incomplete or insufficient clinical response. In this context, upstream targeting of epithelial alarmins, particularly thymic stromal lymphopoietin (TSLP), has emerged as a potential therapeutic strategy. To critically review current evidence on the role of TSLP in CRSwNP and to evaluate available data on the mechanism of action, clinical efficacy, and therapeutic potential of tezepelumab in severe and recurrent disease. Materials and Methods: A narrative review was conducted using PubMed, Scopus, and Web of Science. Studies published between 2016 and 2026 were included, comprising experimental research, phase II–III clinical trials, systematic reviews, and international guidelines. Results: TSLP functions as an epithelial alarmin that initiates and amplifies type 2 inflammation via dendritic cell activation, Th2 polarization, and activation of type 2 innate lymphoid cells (ILC2). Data suggests that tezepelumab, a monoclonal antibody targeting TSLP, may reduce inflammation and regulate the immune system. Evidence from asthma populations and relevant CRSwNP subgroups indicates potential improvements in nasal polyp score, congestion, olfactory function and quality of life. It is our understanding that the safety profile appears comparable to placebo, with no new safety concerns having been identified in long-term studies. Conclusions: Tezepelumab is a promising biologic that targets inflammation in CRSwNP. It may benefit severe, recurrent, treatment-resistant disease by modulating immune pathways. However, evidence is indirect and limited, and more trials are needed to define its efficacy, identify biomarkers, and clarify its role in treatment algorithms. Full article

The presence of near-surface cavities poses a significant geohazard due to potential ground subsidence and structural collapse. To mitigate threats to urban stability, this study presents an integrated geophysical framework to locate and characterize abandoned mining galleries and exploitation voids near Linares (Jaén, Spain). The approach combines four complementary techniques: electrical resistivity tomography (ERT), ground-penetrating radar (GPR), frequency-domain electromagnetics (FDEM), and microgravity. The resulting multi-physics responses were cross-referenced with visible surface subsidence features and archival mine plans. Air-filled galleries and shafts generated highly pronounced high-resistivity anomalies. Shallow voids detected at depths of 2–5 m were undocumented in 19th-century mining maps, suggesting older historical origins, whereas deeper ERT profiles and structural disturbance trends (up to 30 m) correlated well with historical records. Within this framework, FDEM provided high-resolution lateral mapping, GPR excelled at resolving ultra-shallow structural boundaries, and ERT characterized deep gallery networks. Crucially, microgravity mitigated inversion non-uniqueness by directly confirming physical mass deficits over the anomalies. This integrated workflow overcomes individual resolution limits, offering a practical tool for land-use planning and early geohazard risk assessment in collapse-susceptible areas. Full article

Orf virus (ORFV) is a major pathogen in goats and sheep, and control currently depends mainly on commercial live vaccines. Although mRNA vaccines have revolutionized human medicine, their use in veterinary settings is largely unexplored. In this study, an mRNA vaccine candidate encoding the ORFV F1L protein (F1L-mRNA-LNP) was developed via in vitro transcription and encapsulated in lipid nanoparticles. BALB/c mice were divided into five groups (n = 14 each): three receiving different doses of F1L-mRNA-LNP (5, 10, or 15 μg), one receiving a commercial live vaccine (CV), and a PBS control group. Mice were immunized intramuscularly and boosted after 14 days; immune responses were assessed 14 days later following ARRIVE 2.0 guidelines. Both the F1L-mRNA-LNP and CV vaccines induced specific antibodies versus PBS (p < 0.01). The 10 μg mRNA group showed Th1 cytokine and CD8⁺ T cell responses comparable to CV (p > 0.05), whereas IL-4 (Th2) was significantly higher in the CV group (p < 0.05). Neutralizing antibody titers did not differ between groups, indicating that the mRNA vaccine induces comparable Th1 cellular immunity but weaker Th2 humoral immunity. Upon ORFV challenge, the 10 μg F1L-mRNA-LNP vaccine protected BALB/c mice, as evidenced by stable body weight, no clinical symptoms, and reduced viral load, with efficacy comparable to CV (p > 0.05). This study provides strong evidence supporting the optimization of ORFV mRNA vaccines and highlights the translational potential of the F1L-mRNA-LNP candidate vaccine for veterinary applications. Full article

Background/Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disorder requiring sustainable therapeutic alternatives. Cannabis sativa L. is a valuable industrial crop rich in bioactive secondary metabolites; its potential as a standardized functional ingredient for promoting skin health has not yet been fully investigated. This study aimed to evaluate the therapeutic effects of a chemically characterized C. sativa inflorescence ethanol extract (CSE) on AD. Methods: To evaluate the efficacy of CSE, phytochemical profiling was performed using UPLC, and its underlying molecular mechanisms were investigated in a DNCB-induced mouse model. Results: UPLC analysis was employed to establish the phytochemical profile, identifying 15 cannabinoids and quantifying 8 major components. CBDA was the most abundant component, with a content of 261.79 mg/g in the extract. In a DNCB-induced mouse model, CSE significantly reduced mast cell infiltration and serum IgE levels while downregulating Th2-associated cytokines. At the molecular level, CSE inhibited the activation of the MAPK, NLRP3 inflammasome, and JAK1/STAT6 signaling pathways. Crucially, CSE treatment substantially increased the expression of skin barrier proteins, such as filaggrin and involucrin, thereby enhancing skin hydration. Conclusions: These findings suggest CSE as a high-value functional ingredient capable of ameliorating AD by modulating multi-target immune responses. This study provides a robust scientific basis for utilizing standardized C. sativa inflorescence as a potent functional ingredient or a nutraceutical agent for the management of chronic skin inflammatory conditions. Full article

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder driven by epidermal barrier defects and dysregulated Th2 cell responses. While therapies primarily address adaptive immunity, the role of Natural Killer (NK) cells remains underappreciated. This review analyzes NK cell dysfunctions in AD pathogenesis, evaluating their contributions to compromised skin immunity, microbial dysbiosis, and secondary infections. Accumulating evidence reveals a systemic deficiency of mature, cytotoxic CD56^dim and NKp80+ NK cell subsets in peripheral blood, correlating with disease severity. Within the cutaneous microenvironment, Staphylococcus aureus subverts defenses by utilizing leukocidins to lyse mature NK cells, while superantigens drive an aberrant, pro-inflammatory CD57⁻NKG2+ phenotype, exacerbating inflammation. Furthermore, localized exhaustion of functional NK cells and failure to produce interferon-gamma directly explains AD patients’ unique susceptibility to severe viral complications like eczema herpeticum. Importantly, treatments such as dupilumab and gut microbiota transplantations demonstrate that these NK cell aberrations are reversible, shifting immunity toward a normalized regulatory state. In conclusion, the NK cell compartment represents a vital regulatory axis bridging innate and adaptive immunity. Targeting this axis, particularly through IL-15 superagonists, offers a promising therapeutic frontier to suppress type 2 inflammation and restore antimicrobial defenses. Full article

Background: Mycosis fungoides (MF) and Sézary syndrome (SS) are the predominant cutaneous T-cell lymphomas. Although malignant T cells in MF/SS overexpress CCR4 and respond to the anti-CCR4 antibody mogamulizumab, skin response rates vary. We hypothesized that immune components within the tumor microenvironment contribute to differential outcomes. Methods: Imaging mass cytometry with a 37-antibody panel was used to characterize immune and structural elements in FFPE tissues from sixteen MF/SS patients (6 MF, 10 SS) treated with Mogamulizumab, including seven skin responders and nine non-responders. Single-cell phenotyping and spatial analyses were performed using the Visiopharm^® Phenoplex™ platform, with supervision. Results: We identified 68,974 cells pre-treatment and 58,852 cells post-treatment. Malignant CD4⁺ T cells showed reduced baseline CD27, CD103, CD25, and ICOS expression compared with non-malignant CD4⁺ cells. Baseline MF lesions were enriched for IL-13⁺ and CD103⁺ malignant T cells, whereas SS lesions contained higher proportions of CD27⁺ and LAG3⁺ cells. IL 13⁺ malignant cells decreased after treatment, most prominently in MF. Myeloid profiles differed by disease and response: MF lesions exhibited baseline enrichment of M1-like macrophages (CD86⁺, HLA-DR⁺), while SS lesions were predominantly M2-polarized macrophages (CD163⁺, CD206⁺). Responders showed increased M1-like macrophages, whereas non-responders displayed reduced M1-features. An increase in DC3-like cells was observed in non-responders following treatment. Conclusions: This single-cell spatial atlas reveals shared and subtype-specific immune features in MF/SS. Th2-skewed malignant T-cell status and myeloid polarization correlate with clinical response, supporting their potential as spatial biomarkers for patient stratification in mogamulizumab therapy. Full article

This study examines the critical relationship between geoenvironmental changes and human occupation patterns in the central Arabian Peninsula, focusing on the Al-Aflaj region. By integrating geospatial modeling with preliminary archeological excavation results that indicated the site is dated to 5th century BCE to 6th century CE, we evaluate how climatic stressors dictated human adaptation and eventual site abandonment. Late Quaternary climatic fluctuations, particularly the Early Holocene pluvial phases, initially created favorable conditions for settlement through sustained freshwater resources. Subsequent aridification triggered significant migration and settlement contraction, demonstrating a high degree of human resilience. The site of Qusayrat Aad serves as a compelling case study of sophisticated adaptation, evidenced by mudbrick architecture and advanced irrigation systems. Integration of geological, topographic, and paleoclimatic factors indicates that the porous sedimentary layers of the Heet and Al Biyadh Formations were essential for groundwater recharge and spring formation. The geospatial analysis reveals that the settlement was strategically localized on a stable surface with a mean slope of 1.51°. Furthermore, the Topographic Wetness Index (TWI) identifies the site as a significant hydrological function, with a mean value of 8.79 (reaching a 90th percentile of 12.37), which is markedly higher than the regional average of 7.96. These quantitative findings establish a causal necessity for the site’s advanced subsurface canal systems as an engineered response to minimize evaporative losses in high-potential moisture zones. Ultimately, the correlation between the archeological record and climatic proxies suggests that the intensification of late Holocene aridification depleted these specific water resources beyond adaptive capacity, serving as the primary driver for the site’s abandonment and the migration of populations toward the eastern and southern parts of the Peninsula. Full article

Background: Host immune responses can be broadly divided into innate and adaptive immunity. Numerous adaptive immune responses have been identified, including TH1, TH2, TH3, TH9, TH17, and TH22 immunity. Within innate immunity, Vγ9-chain γδ T cells are among the most extensively studied immune-cell populations. Knowledge Gap: However, the precise functional classification of these innate and adaptive immunological pathways in responses to different types of pathogens remains incompletely understood. Purpose of the Review: This review proposes an integrated framework for the detailed functional classification of host innate and adaptive immunological pathways. Proposed Framework: Within innate immunity, γδ T cells can be categorized into several functional groups. The clonal anergy and tolerance pathway is associated with Vγ2-chain γδ T cells. The host innate immunological pathway against viruses is associated with Vγ8-chain γδ T cells, whereas the pathway against intracellular microorganisms is associated with Vγ9-chain γδ T cells. The pathway against extracellular microorganisms is associated with Vγ4-chain γδ T cells, the pathway against helminths with Vγ5-chain γδ T cells, and the pathway against insects with Vγ3-chain γδ T cells. Within adaptive immunity, five eradicable immune reactions and four tolerable immune reactions are described. Among the tolerable immune reactions, TH3 is associated with interleukin-35-producing CD4 T cells, whereas TH4 is associated with interleukin-32-producing CD4 T cells. Significance: A more precise functional classification of innate and adaptive immunological pathways may provide a useful conceptual basis for combating infections and hypersensitivity disorders. Full article

Background: Allergic rhinitis (AR) is a chronic condition that affects children’s quality of life. Studies show that adding bacterial lysates (BLs) to treatment can improve outcomes, but their effects on the immune system are still not fully understood. Objectives: This study aimed to evaluate the immunomodulatory impact of sublingually administered polyvalent mechanical BL (PMBL) on the expression of T helper (Th) cell-associated transcription factors and cytokines in children with grass pollen-induced AR. Methods: Immunological analyses were performed on blood samples collected during a previously conducted randomised, double-blind, placebo-controlled clinical trial (NCT04802616). Children aged 5–17 years with grass pollen-induced AR received either sublingual PMBL or placebo in three 10-day treatment cycles, each followed by a 20-day break. Peripheral blood mononuclear cells were collected at baseline before the grass pollen season (V1) and after completion of the study treatment during natural peak pollen exposure (V2) and analysed by flow cytometry to assess the expression of transcription factors and cytokines associated with Th1, Th2, Th10, Th17, and Treg-like immune responses. Results: In the PMBL group, there was a significant increase in the expression of T-bet, E4BP4, FoxP3, IFN-γ, and IL-10, along with a reduction in GATA3 and IL-4 expression (p < 0.001). The placebo group exhibited increased expression of GATA3 (p < 0.001), RORγT (p < 0.001), and IL-4 (p = 0.004) and a reduction in T-bet expression (p = 0.007). Between-group comparisons at V2 revealed significantly higher expression of Th1-, Th10-, and Treg-associated markers, and lower Th2- and Th17-associated markers in the PMBL group compared to placebo. Conclusions: Sublingual PMBL administration modulates the expression of Th cell-associated transcription factors and cytokines in children with grass pollen-induced AR, consistent with enhanced Th1-, Th10-, and Treg-like immune responses and reduced Th2-associated activity. Full article

Operational marine buoys provide essential in situ wind observations, but platform attitude variations induced by wind–wave forcing can affect wind-speed measurement quality. Existing high-frequency motion-correction methods are difficult to apply to routine buoy archives that contain only averaged outputs. This study analyzed 6964 quality-screened half-hourly observations from an operational 10 m buoy in the Changjiang Estuary (7 July–1 December 2025) and developed a Motion Impact Index (MII)-based quality classification framework for buoy wind-speed measurements under attitude and sea-state variations. The composite tilt angle was right-skewed (mean 10.68°, 95th percentile 23.09°) and significantly correlated with significant wave height ($r$ = 0.388, $p$ < 0.001). Theoretical cosine-response analysis indicated a geometric projection effect of −1.7% at the mean tilt and about −8% at the 95th percentile, whereas wind-direction dispersion showed no significant attitude dependence under $U$ ≥ 5 m/s. The MII was defined as $MII={\theta }_{tilt}\times (1+k·{\displaystyle \frac{H_s}{H_{ref}}})$, with $k$ = 1.0 adopted as an engineering default, and four quality classes were established using the 50th, 80th, and 95th percentiles. Time-split testing, parameter-sensitivity analysis, and bootstrap resampling indicated that the thresholds were statistically stable. When stratified by ERA5 wind speed, the buoy–ERA5 bias increased systematically across the four classes, supporting their interpretation as progressively different measurement conditions. The numerical MII thresholds reported here are specific to the platform type and deployment site; when applied to other buoy designs or sea areas, the thresholds should be recalibrated from local data. Full article

Sex- and gender-based immune differences have often been interpreted through a male–female biological binary, overlooking how endocrine signaling dynamically shapes immune function. Gender-affirming hormone therapy (GAHT) offers a unique physiological model to disentangle the effects of sex steroids from chromosomal background and examine immune plasticity in contexts relevant to reproductive health. This hormone-informed framework proposes that estradiol and testosterone regulate immune set-points across innate, adaptive, metabolic, and mucosal compartments. Through genomic and non-genomic signaling via androgen and estrogen receptors (AR, ERα/β), these hormones drive distinct immune outcomes: testosterone dampens type I interferon responses in plasmacytoid dendritic cells and reshapes monocyte inflammatory profiles, while estradiol promotes macrophage polarization and enhances T helper1 (Th1) responses. Hormonal effects are closely coupled to cellular metabolism: androgen signaling acts as a “metabolic brake” on Th17 cells by limiting glutaminolysis, a process reinforced by epigenetic remodeling, and is reflected in shifts in the circulating metabolome, positioning metabolomics as a sensitive tool for monitoring hormone-driven immune adaptation. Regardless, hormones also reshape mucosal barriers and reproductive microbiome composition. GAHT alters vaginal and gut microbial communities and their metabolism, influencing mucosal immunity, local inflammation, and reproductive tract homeostasis, with potential implications for fertility preservation, susceptibility to reproductive tract infections, and long-term genital mucosal health. Collectively, this evidence underscores that human immunity is highly responsive to endocrine context. This review synthesizes evidence linking endocrine trajectories, tissue microenvironments, reproductive biology, and social determinants of health, aiming to advance understanding of immune plasticity and contribute to a more inclusive framework of human immune diversity. Full article