Search Results (8,859)

Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) possesses dual enzymatic functions, i.e., kinase and E3 ubiquitin ligase activities, orchestrating proliferation, survival, apoptosis, DNA damage response, and immune modulation. Recent genomic and mechanistic studies have revealed MAP3K1’s paradoxical, context-dependent roles as both an oncogene and a tumor suppressor. We discuss MAP3K1’s multidomain architecture, featuring an N-terminal RING and PHD domain (E3 ligase activity), a TOG domain (microtubule dynamics), and a C-terminal kinase domain, enabling the integration of c-jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), and nuclear factor kappa B (NF-κB) signaling pathways. MAP3K1 functions as a molecular switch balancing survival and apoptosis, with caspase-3 cleavage at Asp878 activating pro-apoptotic JNK/p38 signaling. Genomic analyses across >35 cancer types reveal MAP3K1 alterations at frequencies of <1–14%, highest in breast and endometrial cancers. These alterations show tissue specificity: loss-of-function mutations predominate in hormone receptor-positive breast cancer with a favorable prognosis, whereas gain-of-function mutations in melanoma activate oncogenic ERK signaling. MAP3K1 mutations predict response to mitogen-activated protein kinase kinase (MEK) and phosphoinositide 3-kinase (PI3K) inhibitors, with mutant cancers showing higher MEK inhibitor response than wild-type tumors. Despite substantial progress, critical gaps remain regarding MAP3K1’s E3 ligase substrates, context-dependent activity determinants, and therapeutic strategies. Addressing these through inhibitor development, biomarker validation, and mechanistic studies will accelerate potential clinical translation of MAP3K1 biology. Full article

This study presents a calibrated analytical micromechanical framework for predicting the linear elastic behavior of unidirectional glass fiber/epoxy and carbon fiber/epoxy composites over a wide range of fiber volume fractions. The approach combines the classical rule of mixtures for the longitudinal Young’s modulus with the semi empirical Halpin–Tsai equations to estimate the transverse Young’s modulus and the in-plane shear modulus. The framework is specifically formulated to support durability-oriented composite design through rapid and physically consistent estimation of elastic properties governing load transfer and stress distribution. Material parameters, including fiber and matrix Young’s moduli (Ef, Em), shear moduli (Gf, Gm), Poisson’s ratios (νf, νm), and fiber volume fraction (Vf up to 0.80), are taken from established material property databases and implemented within a literature-informed modeling scheme. To preserve physical realism at high fiber contents, a shear correction factor is introduced for Vf > 0.50 to account for microstructural interaction and fiber clustering effects. The predicted effective elastic constants (E₁, E₂, G₁₂, ν₁₂) exhibit consistent and physically meaningful trends across the full fiber volume fraction range. The model predictions were evaluated against trends widely reported in the composite micromechanics literature, and the results showed overall agreement in the nonlinear reduction in stiffness gains at elevated fiber volume fractions. Comparative results indicate that carbon fiber/epoxy composites achieve up to approximately 30% higher stiffness than glass fiber/epoxy systems at equivalent fiber contents, reflecting the influence of stiffness contrast on composite response. The analysis further indicates that stiffness saturation begins approximately in the Vf = 0.60–0.70 range, where the incremental gains in E2 and G12 become noticeably smaller for both composite systems. This behavior provides design-relevant guidance by showing that, beyond this range, further increases in fiber content may offer limited stiffness improvement relative to the associated manufacturing complexity. Overall, the calibrated Halpin–Tsai methodology offers a practical and computationally efficient tool for preliminary evaluation and design-stage optimization of the elastic performance of high-performance composite structures. Full article

Biotissues represent a new technology in tissue regeneration in otolaryngology. Various biomaterials functioning in different combinations are used as bioinks for 3D bioprinting of tissues/tissue fragments. The scaffolds can be populated with several cell categories, each offering distinct advantages and disadvantages, depending on the targeted pathology. Results from in vitro and in vivo studies on animal models are promising, with superior therapeutic potential. The combination of these elements provides promising results, enabling their potential application in personalized medicine. Based on these findings, their application in ENT (ear, nose, and throat) pathology is starting to gain traction. Despite being an emerging field, 3D/4D bioprinting in otolaryngology is rapidly evolving, increasingly replacing conventional inert materials with more sophisticated, bio-integrated alternatives. These alternatives are based on novel bioink formulation involving cells capable of proliferating and integrating the new neo-fragment organ into the host’s endogenous tissues. In this context, this review outlines novel applications that could enhance traditional procedures in ENT reconstructive medicine. Furthermore, biomimetic scaffolds for otolaryngology can be tailored to address factors influencing implant fate during the procedure and in the early and late postoperative periods. Full article

Background: Genetic causes of growth failure should be suspected in patients born small for gestational age (SGA) who fail to show postnatal catch-up growth, present with severe short stature (SS), and exhibit a poor or absent response to growth hormone (rhGH) therapy. Mutations in the insulin-like growth factor 1 receptor (IGF1R) gene are associated with impaired growth, intrauterine growth restriction (IUGR), low birth weight and/or length, and postnatal SS. Case Description: A 9-year-old boy, born SGA for birth length, was evaluated for severe SS. Common causes of SS were excluded. At 9 years and 7 months of age, his height was 112.6 cm (−3.99 SDS), weight 18 kg (−3.79 SDS), and BMI 14.2 kg/m² (−1.8 SDS); pubertal development was Tanner stage 1. The target height was 158 cm (−2.62 SDS). Bone age was delayed by approximately one year compared with chronological age. Serum IGF-1 levels were within the upper-normal range for age. GH therapy (0.035 mg/kg/day) was initiated due to the lack of catch-up growth in an SGA subject. After three years of treatment, the height gain was only 0.5 SDS. IGF-1 levels showed a transient treatment-related increase, followed by persistent normalization during ongoing therapy. Next-generation sequencing (NGS) analysis identified novel heterozygous paternal nonsense variant in the IGF1R gene: c.3498C>G (p.Tyr1166Ter). At 12 years of age, impaired fasting glucose and reduced glucose tolerance were detected; consequently, it was decided to discontinue rhGH therapy, also in light of the IGF1R mutation and the lack of height recovery. Conclusions: This case underlines the critical role of genetic testing in the evaluation of patients born SGA. The coexistence of SGA status and an IGF1R gene mutation may provide a clear explanation for both the poor response to rhGH therapy and the increased risk of alterations in glucose metabolism. An extensive narrative review of the literature on growth outcomes and glucose metabolism abnormalities during GH treatment in SGA patients carrying IGF1R variants was also performed. Full article

Public project performance is shaped by both organisational capability and governance controls, yet the interaction between these factors remains underexamined in decentralised public administration contexts. This study examines the direct effects of team capability and ethical compliance on project performance, and tests whether ethical compliance conditions the capability–performance relationship. A quantitative explanatory survey design was adopted. Structured questionnaires were administered to 320 senior officers involved in project evaluation, procurement, budgeting and technical oversight, and the data were analysed using PLS-SEM to estimate the hypothesised direct and moderating relationships. Team capability and ethical compliance each have a significant positive effect on project performance, and team capability is positively associated with ethical compliance. The moderating effect of ethical compliance is significant but small in magnitude, indicating that higher levels of compliance modestly attenuate the marginal performance gains associated with greater team capability. These findings suggest that while compliance mechanisms strengthen accountability and directly support performance, they may simultaneously constrain the discretionary flexibility through which capable teams generate incremental improvements. The study contributes to public management research by empirically demonstrating a conditional capability–governance relationship in a local government project context. Given the moderate explanatory power of the model, future research should incorporate additional institutional and political variables to further clarify performance drivers in public-sector project systems. Full article

Phage-encoded Shiga toxin (Stx) released by Shiga toxin-producing E. coli (STEC) can kill multiple eukaryotic bacterial predators, including Acanthamoeba castellanii, Tetrahymena thermophila and Caenorhabditis elegans. However, the impact of Stx type, Stx amount, and the serogroup of the E. coli on the effectiveness of this exotoxin are poorly understood. These factors impact the severity of Stx-mediated disease in humans and therefore, by studying their role in modulating predator–prey interactions, we may gain insight into how these virulence factors evolved to contribute to human pathogenicity. Herein, we investigated the effects of these factors on predator killing by measuring the efficiency with which five different hemolytic uremic syndrome (HUS)-causing STEC strains consume and/or kill A. castellanii and C. elegans. These strains express various combinations of Stx types and amounts and O-antigens. We found that variations in Stx types and amounts significantly affect the ability of a given bacterial strain to kill predator A. castellanii and C. elegans, with higher Stx1 titers (HUSEC 31 vs. 19) and the presence of Stx2 alone (HUSEC 20) correlating with significantly greater predator killing. These attributes also affect STEC pathogenicity in humans, suggesting that ecological selective pressures for anti-predator defense inadvertently drive the evolution of strains with higher virulence potential in humans. Full article

This study integrates phase change material (PCM) with semi-transparent photovoltaic (PV) glazing to develop a composite window providing thermal buffering and PV temperature regulation in summer. A PCM-PV double glazing window (PCM-PV-DGW) using paraffin PCM and CdTe semi-transparent PV glass was fabricated and evaluated through outdoor hot-box experiments and transient modeling in Qingdao, China. Four window types—DGW, PCM-DGW, PV-DGW, and PCM-PV-DGW—were tested under identical boundary conditions. The coupled system showed improved photothermal performance, achieving a daily average Solar Heat Gain Coefficient (SHGC) of 0.105, compared with 0.180 for PV-DGW without PCM filling, together with a temperature attenuation factor of 0.904 and a 35 min peak temperature delay. A two-dimensional transient heat transfer model incorporating radiative transfer through semi-transparent layers and an enthalpy-based phase change method was established and validated against measured inner-surface temperatures, showing good agreement (RMSE 1.54–1.80 °C). Parametric and sensitivity analyses indicate that PCM phase transition temperature is the dominant parameter (suggested 28–32 °C), while ~12 mm PCM thickness and 50% PV coverage offer a practical balance for the Qingdao summer scenario. The results provide preliminary guidance for PCM–PV window design under the investigated summer conditions. Full article

The upscaling of turbines in the offshore wind industry has been unprecedented, as compared to 5–6 MW rated turbines 10 years ago. A typical 20–26 MW rated turbine in modern commercial applications (MingYang MySE 18.X-20 MW installed in 2025 and 26 MW prototype by Dongfang Electric tested in 2025) has been demonstrated. This scaling has been made possible by increasing rotor diameters (>250 m) and hub heights (>150–180 m) to achieve capacity factors of up to 55–65%, annual energy generation of more than 80 GWh/turbine, and significant decreases in levelised cost of energy (LCOE) to current values of up to 63–65 USD 2023/MWh globally averaged in 2023 (with minor variability in 2024 due to market changes and new regional areas). The paper analyses turbine upscaling over three levels of hierarchy, including turbine scale—rated capacity and physical aspect, project scale—multi-gigawatts of farms, and market scale—the global pipeline > 1500 GW level, and combines techno-economic evaluation, structural evaluation of loads, and infrastructure needs assessment. The upscaling has the advantage of reducing the number of turbines dramatically (e.g., 500 to 67 turbines in a 1 GW farm, as turbine size is increased to 15 MW) and balancing-of-plant (BoP) CAPEX (turbine-to-turbine foundations and cables) by some 20 to 30 percent per unit of capacity, and serial production learning rates of between 15 and 18% per doubling of capacity. But the problems that come with the increase in ultra-large designs are nonlinear increments in mass and load (i.e., blade-root and tower-bending moments), logistical constraints (blades > 120 m, nacelle up to 800–1000 tonnes demanding special vessels and ports), supply-chain issues (rare-earth materials, vessel shortages increase day rates by 30–50%), and technology limitations (aeroelastic compounded by numerical differences between reference 5 MW, 10 MW, and 15 MW models), it becomes evident that there is a significant increase in deflections of the tower and blades and platform surge/pitch responses with continued increases in power levels, but without a correspondingly mature infrastructure. The regional differences (mature ports of Europe vs. U.S. Jones Act restrictions vs. scale-up of vessels/manufacturing in China) lead to the necessity of optimisation depending on the context. The analysis concludes that, to the extent of mature markets with adapted logistics, continuous upscaling is an effective business strategy and can result in 5 to 12 percent further reductions in LCOE, but beyond that point, gains become marginal or even negative, as risks and costs increase. The competitiveness of the future depends on multi-scale/multi-market-based approaches—modular-based families of turbines, programmatic standardisation, vibration control innovations, and industry coordination towards supply-chain alignment and standards. Its major strength is that it transcends mere size–cost relationships and shows how nonlinear structural processes, aero-hydro-servo-elastic interactions, and bottlenecks in logistical systems are becoming more determinant of the efficiency of ultra-large turbines. The study demonstrates that upscaling turbines has LCOE benefits through the support of associated improvements in installation facility, supply-chain preparedness, and structural vibration control potential, based on the comparisons of quantitative loads, techno-economic scaling trends, and regional market differentiation. Full article

Curcumin, a polyphenolic compound obtained from the rhizome of Curcuma longa, is the main bioactive component of turmeric and exhibits a wide range of biological properties. This naturally occurring polyphenolic compound is widely known for its protective properties on the vascular endothelium and its anti-inflammatory effects. Curcumin has been recognized as a factor in improving antioxidant defenses and lipid metabolism and as a neuroprotective agent. Thanks to its broad spectrum of activity, curcumin is gaining popularity as an ingredient in dietary supplements and as part of a healthy diet that supports overall health. In this article, we will take a closer look at curcumin—based on a review of the current literature, we will learn what curcumin is and what health benefits it can provide. Full article

Conservation easements (CEs) represent a complex policy instrument designed to mediate the feedback loops within coupled human and natural systems in protected areas. However, their efficacy is often constrained by a lack of systemic understanding of the localized drivers of community support. Building upon the successful implementation of Forest Land Easements (FLEs) within China’s Qianjiangyuan National Park Pilot, this study investigates the potential to expand this policy model to other land types. This study investigates the multilevel factors influencing residents’ willingness to adopt three types of CEs, including forest land (FLE), agricultural land (ALE) and homestead land (HLE) easements in China’s Qianjiangyuan National Park Pilot, the country’s primary CE reform site. We conceptualize a hierarchical support model wherein community participation (CP) and human well-being (HW) interact with support for park management (SM), forming a subsystem that drives decisions within the broader land-use. Utilizing structural equation modelling (SEM) and stepwise regression analysis on survey data from 336 households, we tested this model. The results reveal that SM acts as a critical direct mediator and positive driver of CE acceptance, while CP and HW exert significant indirect effects through SM, demonstrating a key feedback pathway. Regression analyses further elucidate that support for different CE types is driven by distinct configurations of factors, highlighting the heterogeneous nature of subsystems. Notably, livelihood benefits and prior participation experiences emerged as consistent, cross-cutting systemic leverages. It demonstrates that leveraging the implementation experience and community support gained from existing forest land easements is crucial. This study concludes that effective CE design must move beyond one-size-fits-all approaches. It necessitates differentiated, adaptive policies that are coherently aligned with local livelihood subsystems and strategically strengthen participatory feedback mechanisms initiated by successful FLEs. Our findings provide an evidence-based framework for designing resilient, socially sustainable conservation policies in complex protected area systems, grounded in proven practice. Full article

This study examines retailers’ information sharing aimed at enhancing product greenness within green supply chains, with consumer participation as a pivotal factor and the overarching goal of advancing the sustainable development of the whole supply chain ecosystem. Each supply chain comprises a green product supplier and a retailer with uncertain demand information. A tripartite evolutionary game model involving manufacturers, retailers, and consumers is constructed to analyze the factors influencing information sharing behavior, which serves as a critical pathway to achieve environmental and economic sustainability in green supply chain operations. The findings highlight two key insights: First, strong consumer willingness to purchase green products may inhibit retailers’ inclination towards information sharing, a counterintuitive outcome that needs to be addressed to align individual stakeholder behaviors with long-term sustainable development goals. Second, lower information sharing costs can motivate retailers to share information with manufacturers; otherwise, manufacturers must adopt technological measures to assist retailers in reducing information sharing-related costs, thereby achieving win–win outcomes across the supply chain and fostering a sustainable and collaborative green supply chain system that balances ecological benefits, economic gains, and social value co-creation. Full article

The research conducted in this paper is a practical example of the Design of Experiments methodology. In accordance with the assumptions of the experimental design, the authors drew attention to the problem: how should the spark plasma sintering process be planned to obtain the maximum amount of information needed to optimise the consolidation of the WC-6Co composite at the lowest possible cost? The DOE methodology—a powerful technique for investigating new processes and gaining knowledge about existing ones in order to optimise them for high performance—was employed in the study. The aim of the research was to optimise the consolidation of the spark-plasma sintering process of the WC-6Co composite using the DoE (Design of Experiments) methodology. Four sintering factors were selected for the study: sintering temperature (factor A, 1300–1400 °C); heating rate (factor B, 100–300 °C/min); sintering time (factor C, 150–600 s); and pressure (factor D, 40–50 MPa). Each consolidation factor was designed to cover three levels. The L9 orthogonal array was used. It was found that sintering temperature and heating rate had the greatest impact on apparent density. To validate the statistical model, sintering tests were performed at a temperature of 1380 °C, a heating rate of 100 °C/min, a sintering time of 150 s and a pressing pressure of 45 MPa. Validation analysis of the statistical model demonstrated consistency with the experimental results. The WC-6Co composite achieved an apparent density of 14.85 g/cm³, corresponding to 97.42% of the theoretical density, with a hardness of 1809 HV30 and total porosity of 2.583%. X-ray diffraction studies revealed the presence of tungsten carbide and cobalt in the structure. Full article

Education occupies an important place among the 17 Sustainable Development Goals. It plays a role in the process of spreading awareness of the concept—its directions, meaning, and goals. According to the idea of the SDG, it is to be universally available to the world’s communities, with the aim of bridging social inequalities, as well as increasing the capacity for responsible functioning and development. The authors of this study believe that knowledge about sustainable development is crucial for shaping social attitudes that determine the uninterrupted development of the world’s economies towards sustainability. In their opinion, it is essential to pay particular attention to ensuring sustainable competences in the education process, which is aimed at preparing staff to perform professional roles in the socio-economic sphere and to be competent in the field of sustainable development. Hence, the aim of this study is to examine the level of awareness of students from selected higher education schools in Poland in this area. The study was conducted on the basis of a diagnostic survey, and the analysis of the results was carried out using qualitative methods, as well as quantitative methods in an in-depth study (logistic regression, supported by PQStat software version 1.8.4.164. The research results indicated that the surveyed students’ knowledge of sustainable development is good, as confirmed by 91% of responses. A key factor in strengthening this knowledge is the educational process implemented as part of their studies (64% of responses). Events supporting the teaching process, such as conferences or meetings with experts, are particularly important for shaping this knowledge. This indicates a high level of student motivation to explore this knowledge and apply it to a model of social behavior, which is rated as responsible by 94% of respondents. In-depth research confirms the above. The odds ratio of 12.994 with a confidence interval of −95% CI: 1.894–+95% CI: 3.238 for the factor of scientific events in the process of supporting green education demonstrates the significance of the findings. Strengthening green education with thematic scientific events is, therefore, an attractive and anticipated form of gaining knowledge on the SDGs by students, and undertaking these events is a recommendation resulting from the presented research. These results are important for modeling sustainable education in terms of the development potential of human resources. Full article

Menopause is a natural biological transition marked by the cessation of regular menstrual cycles and is associated with significant endocrine, hormonal, and metabolic changes. Sleep disturbances are among the most common and distressing symptoms during this period, affecting approximately 40–60% of women in the menopausal transition and postmenopause. Vasomotor symptoms, including hot flushes and night sweats, often occur alongside fatigue, anxiety, and mood disturbances. These symptoms frequently coexist with sleep disorders such as insomnia, early morning awakenings, fragmented sleep, obstructive sleep apnea, restless legs syndrome, and circadian rhythm disruptions. Evidence from animal models, translational research, and clinical studies highlights the complex interaction between hormonal fluctuations, neuroendocrine dysregulation, metabolic changes, and circadian rhythm disruption. These factors contribute to altered sleep regulation, appetite control, and weight gain during the menopausal transition. This review summarizes current evidence on the mechanisms of underlying sleep disturbances in menopause, their clinical manifestations, diagnostic approaches, and available therapeutic strategies. Improving the management of sleep disorders during this stage may substantially enhance overall health and quality of life in menopausal women. We discuss presentation of different sleep disorders in menopause, their current management and future direction of research for development of precision-based algorithm of treatment considering the endocrine and hormonal profile of the women. Full article

Upstream binding transcription factor (UBTF) is a nuclear transcription factor implicated in ribosome biogenesis, yet its pancancer relevance and immunological associations remain incompletely understood. We integrated datasets from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA), Cancer Cell Line Encyclopedia (CCLE), and cBioPortal databases to characterize UBTF expression, genomic alterations, and prognostic value across 33 cancer types. Immune microenvironment analyses were performed using ESTIMATE and multiple deconvolution algorithms. CRISPR-Cas9–mediated UBTF depletion was conducted in breast invasive carcinoma (BRCA) cell lines to evaluate functional roles. UBTF was broadly upregulated in multiple tumors with recurrent copy number gains. Survival analyses revealed cancer type–dependent prognostic associations. UBTF expression correlated with immune/stromal contexture, checkpoint features, and predicted immunotherapy response. In BRCA, UBTF depletion reduced proliferation and migration while increasing apoptosis. A UBTF-related prognostic signature effectively stratified patient outcomes and was associated with immune infiltration and predicted immunotherapy response. UBTF represents a pancancer biomarker linked to tumor immunity, with validated functional significance in BRCA and potential utility for risk stratification. Full article