Search Results (4,379)

Marek’s disease (MD), induced by the highly contagious Marek’s disease virus (MDV), remains a significant challenge to global poultry health despite extensive vaccination efforts. This study employed integrated transcriptomic and metabolomic analyses to investigate liver responses in naturally MDV-infected Wenchang chickens during late infection stages. RNA sequencing identified 959 differentially expressed genes (DEGs) between the infected and uninfected groups. Functional enrichment analysis demonstrated that these DEGs were primarily associated with canonical pathways related to metabolism and cellular processes, including lipid, carbohydrate, and amino acid metabolism, as well as the p53 signaling pathway, cell cycle, and apoptosis. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) detected 561 differentially expressed metabolites (DEMs), showing near-significant enrichment (p = 0.069) in phenylalanine metabolism. Integrated analysis of transcriptomics and metabolomics data highlighted that critical gene–metabolite pairs such as SGPL1-palmitaldehyde–sphinganine-1-phosphate and ME1-NADP+–malic acid potentially mediate functional crosstalk between sphingolipid metabolism and cellular redox homeostasis during viral oncogenesis. This comprehensive mapping of regulatory networks provides insights into host–virus interactions during MDV pathogenesis, offering potential applications in immunomodulation approaches, targeted therapeutic strategies, and vaccine adjuvant development. Full article

The intranasal delivery of exogenous mitochondria is a potential therapy for Parkinson’s disease (PD). The regulatory mechanisms and effectiveness in genetic models remains uncertain, as well as the impact of modulating the mitochondrial permeability transition pore (mPTP) in grafts. Utilizing UQCRC1 (p.Tyr314Ser) knock-in mice, and a cellular model, this study validated the transplantation of mitochondria with or without cyclosporin A (CsA) preloading as a method to treat mitochondrial dysfunction and improve disease progression through intranasal delivery. Liver-derived mitochondria were labeled with bromodeoxyuridine (BrdU), incubated with CsA to inhibit mPTP opening, and were administered weekly via the nasal route to 6-month-old mice for six months. Both treatment groups showed significant locomotor improvements in open-field tests. PET imaging showed increased striatal tracer uptake, indicating enhanced dopamine synthesis capacity. The immunohistochemical analysis revealed increased neuron survival in the dentate gyrus, a higher number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN) and striatum (ST), and a thicker granule cell layer. In SN neurons, the function of mitochondrial complex III was reinstated. Additionally, the CsA-accumulated mitochondria reduced more proinflammatory cytokine levels, yet their therapeutic effectiveness was similar to that of unmodified mitochondria. External mitochondria were detected in multiple brain areas through BrdU tracking, showing a 3.6-fold increase in the ST compared to the SN. In the ST, about 47% of TH-positive neurons incorporated exogenous mitochondria compared to 8% in the SN. Notably, GFAP-labeled striatal astrocytes (ASTs) also displayed external mitochondria, while MBP-labeled striatal oligodendrocytes (OLs) did not. On the other hand, fewer ASTs and increased OLs were noted, along with lower S100β levels, indicating reduced reactive gliosis and a more supportive environment for OLs. Intranasally, mitochondrial transplantation showed neuroprotective effects in genetic PD, validating a noninvasive therapeutic approach. This supports mitochondrial recovery and is linked to anti-inflammatory responses and glial modulation. Full article

Camellia azalea is an endemic species within the genus Camellia that exhibits the trait of summer flowering, which is of significant ornamental and research value. Nevertheless, research on the regulatory mechanisms of flower formation in C. azalea is still limited, so in this study, transcriptome sequencing and analysis of endogenous hormone contents were conducted at three distinct growth stages: floral induction, floral organ maturation, and anthesis. Illumina sequencing yielded a total of 20,643 high-quality unigenes. Comparative analyses of representative samples from the three growth stages identified 6681, 1925, and 8400 differentially expressed genes (DEGs), respectively. These DEGs were further analyzed for functional enrichment using the GO and KEGG databases. Additionally, core genes from each flowering pathway underwent expression pattern analysis and network diagram construction. This revealed that the flower development process in C. azalea is linked to the specific expression of the genes involved in the photoperiod, temperature, and autonomous pathways and is subject to comprehensive regulation by multiple pathways. Further analysis of the dynamic trends of five endogenous hormone contents and plant hormone signal transduction genes revealed significant differences in the requirements of endogenous hormones, such as gibberellins and indoleacetic acid, by C. azalea at distinct growth stages. Additionally, the majority of genes on the phytohormone signal transduction pathway demonstrated a high correlation with the changes in the contents of each hormone. The present study integrates physiological and molecular approaches to identify key genes and metabolic pathways that regulate the summer flowering of C. azalea, thereby laying a theoretical foundation for further investigations into its flowering mechanism and related functional genes. Full article

In the decommissioning of nuclear facilities, activated steel often contains radionuclides such as ⁵⁵Fe and ⁶³Ni, which are categorized as hard-to-measure due to their emission of only low-energy beta particles or X-rays. In samples exhibiting very low radioactivity, close to background levels, a large quantity of steel must undergo extensive physical and chemical processing to achieve the Minimum Detectable Activity Concentration (MDC) necessary for clearance, recycling, or reuse. Italian regulations set particularly stringent clearance levels for these radionuclides (1 Bq/g for both ⁵⁵Fe and ⁶³Ni), significantly lower than those specified in the EU Directive 2013/59 (1000 Bq/g for ⁵⁵Fe and 100 Bq/g for ⁶³Ni). Additionally, Italian authorities may enforce even stricter limits depending on specific circumstances. The analytical challenge is compounded by the presence of large amounts of non-radioactive Fe and Ni, which can cause color quenching, further extending analysis times. This study presents a reliable and optimized method for the quantitative determination of ⁵⁵Fe and ⁶³Ni in steel samples with activity levels approaching regulatory thresholds. The methodology was specifically developed and applied to steel from the Frascati Tokamak Upgrade (FTU) facility, under decommissioning by ENEA. The optimization process demonstrated that achieving the required MDCs necessitates acquisition times of approximately 5 days for ⁵⁵Fe and 6 h for ⁶³Ni, ensuring compliance with stringent regulatory requirements and supporting efficient laboratory workflows. Full article

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ⁹-Tetrahydrocannabinol or Δ⁹-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC₅₀ values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article

Artificial intelligence (AI) and machine learning (ML) are increasingly transforming the landscape of cosmetic formulation, enabling the development of safer, more effective, and personalized products. This article explores how AI-driven predictive modeling is applied across various components of cosmetic products, including surfactants, polymers, fragrances, preservatives, antioxidants, and prebiotics. These technologies are employed to forecast critical properties such as texture, stability, and shelf-life, optimizing both product performance and user experience. The integration of computational toxicology and ML algorithms also allows for early prediction of skin sensitization risks, including the likelihood of adverse events such as allergic contact dermatitis. Furthermore, AI models can support efficacy assessment, bridging formulation science with dermatological outcomes. The article also addresses the ethical, regulatory, and safety challenges associated with AI in cosmetic science, underlining the need for transparency, accountability, and harmonized standards. The potential of AI to reshape dermocosmetic innovation is vast, but it must be approached with robust oversight and a commitment to user well-being. Full article

Renewable energy communities (RECs) are increasingly recognized as pivotal instruments in the global energy transition, offering decentralized, participatory, and sustainable solutions for energy management, specifically regarding energy production and consumption. The present review provides a comprehensive examination of the REC concept, tracing its regulatory evolution, particularly within the European Union through the renewable energy directives (RED II and RED III) and by analyzing its practical implementation across various countries. This paper explores the diverse technologies integrated into REC projects, such as photovoltaic systems, wind turbines, biogas, hydroelectric, and storage solutions, while also considering the socioeconomic frameworks, management models, and local engagement strategies that underpin their success. Key case studies from Europe, Asia, Africa, and Australia illustrate the various approaches, challenges, and outcomes of REC initiatives in different geographic and policy contexts. The analysis also highlights barriers to implementing RECs, including regulatory uncertainty and market integration issues, and identifies the best practices and policies that support REC scalability. By synthesizing current trends and lessons learned, this review aims to inform policymakers, researchers, and practitioners about the transformative role of RECs in achieving decarbonization goals and accomplishing resilient energy systems. Full article

Background: Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), are genetically complex and often linked to structural genomic variations such as copy number variants (CNVs). Current diagnostic strategies face challenges in interpreting the clinical significance of such variants. Methods: We developed a customized, gene-oriented chromosomal microarray (CMA) targeting 6026 genes relevant to neurodevelopment, aiming to improve diagnostic yield and candidate gene prioritization. A total of 39 patients with unexplained developmental delay, intellectual disability, and/or ASD were analyzed using this custom platform. Systems biology approaches were employed for downstream interpretation, including protein–protein interaction networks, centrality measures, and tissue-specific functional module analysis. Results: Pathogenic or likely pathogenic CNVs were identified in 31% of cases (9/29). Network analyses revealed candidate genes with key topological properties, including central “hubs” (e.g., NPEPPS, PSMG1, DOCK8) and regulatory “bottlenecks” (e.g., SLC15A4, GLT1D1, TMEM132C). Tissue- and cell-type-specific network modeling demonstrated widespread gene involvement in both prenatal and postnatal developmental modules, with glial and astrocytic networks showing notable enrichment. Several novel CNV regions with high pathogenic potential were identified and linked to neurodevelopmental phenotypes in individual patient cases. Conclusions: Customized CMA offers enhanced detection of clinically relevant CNVs and provides a framework for prioritizing novel candidate genes based on biological network integration. This approach improves diagnostic accuracy in NDDs and identifies new targets for future functional and translational studies, highlighting the importance of glial involvement and immune-related pathways in neurodevelopmental pathology. Full article

Background: Preeclampsia (PE) is a pregnancy-specific disease and hypertensive disorder with a multifactorial pathogenesis involving complex molecular regulatory networks. Recent studies highlight the critical role of non-coding RNAs, particularly miRNAs and lncRNAs, in PE development. This study investigates the molecular interaction between miR-7151-5p and the lncRNA KCNQ1OT1 and their functional contributions to PE pathogenesis. Methods: An integrative approach combining RNAhybrid-based bioinformatics, dual-luciferase reporter assays, qRT-PCR, Transwell migration and invasion assays, and RNA sequencing was employed to characterize the binding between miR-7151-5p and KCNQ1OT1 and assess their influence on trophoblast cell function and gene expression. Results: A bioinformatic analysis predicted a stable binding site between miR-7151-5p and KCNQ1OT1 (minimum free energy: –37.3 kcal/mol). The dual-luciferase reporter assay demonstrated that miR-7151-5p directly targets KCNQ1OT1, leading to suppressed transcriptional activity. In HTR8/SVneo cells, miR-7151-5p overexpression significantly downregulated both KCNQ1OT1 and Notch1 mRNA, whereas its inhibition showed no significant changes, suggesting additional regulatory mechanisms of Notch1 expression. Transwell assays indicated that miR-7151-5p overexpression suppressed trophoblast cell migration and invasion, whereas its inhibition enhanced these cellular behaviors. RNA-seq analysis further revealed that miR-7151-5p overexpression altered key signaling pathways, notably the TGF-β pathway, and significantly modulates PE-associated genes, including PLAC1, ANGPTL6, HIRA, GLA, HSF1, and BAG6. Conclusions: The regulatory effect of miR-7151-5p on KCNQ1OT1, along with its influence on trophoblast cell dynamics via Notch1 and TGF-β signaling pathways, highlights its role in PE pathogenesis and supports its potential as a biomarker in early PE screening. Full article

The construction sector significantly contributes to global environmental degradation through intensive resource extraction, high energy consumption, and substantial waste generation. Addressing this unsustainable trajectory requires integrated approaches that simultaneously improve operational efficiency and material circularity. Lean Construction (LC) and Circular Economy (CE) offer complementary frameworks for enhancing process performance and reducing environmental impacts. However, their combined implementation remains underdeveloped and fragmented. This study conducts a systematic literature review (SLR) of 18 peer-reviewed articles published between 2010 and 2025, selected using PRISMA 2020 guidelines and sourced from Scopus and Web of Science databases. A mixed-method approach combines bibliometric mapping and qualitative content analysis to investigate how LC and CE are jointly operationalized in construction contexts. The findings reveal that LC improves cost, time, and workflow reliability, while CE enables reuse, modularity, and lifecycle extension. Integration is further supported by digital tools—such as Building Information Modelling (BIM), Design for Manufacture and Assembly (DfMA), and digital twins—which enhance traceability and flow optimization. Nonetheless, persistent barriers—including supply chain fragmentation, lack of standards, and regulatory gaps—continue to constrain widespread adoption. This review identifies six strategic enablers for LC-CE integration: crossdisciplinary competencies, collaborative governance, interoperable digital systems, standardized indicators, incentive-based regulation, and pilot demonstrator projects. By consolidating fragmented evidence, the study provides a structured research agenda and practical insights to guide the transition toward more circular, efficient, and sustainable construction practices. Full article

Prenatal and postnatal skeletal muscle development in ruminants is coordinated by interactions between genetic, nutritional, epigenetic, and endocrine factors. This review focuses on the influence of maternal nutrition during gestation on fetal myogenesis, satellite cell dynamics, and myogenic regulatory factors expression, including MYF5, MYOD1, and MYOG. Studies in sheep and cattle indicate that nutrient restriction or overnutrition alters muscle fiber number, the cross-sectional area, and the transcriptional regulation of myogenic genes in offspring. Postnatally, muscle hypertrophy is primarily mediated by satellite cells, which are activated via PAX7, MYOD, and MYF5, and regulated through mechanisms such as CARM1-induced chromatin remodeling and miR-31-mediated mRNA expression. Hormonal signaling via the GH–IGF1 axis and thyroid hormones further modulate satellite cell proliferation and protein accretion. Genetic variants, such as myostatin mutations in Texel sheep and Belgian Blue cattle, enhance muscle mass but may compromise reproductive efficiency. Nutritional interventions, including the plane of nutrition, supplementation strategies, and environmental stressors such as heat and stocking density, significantly influence muscle fiber composition and carcass traits. This review provides a comprehensive overview of skeletal muscle programming in ruminants, tracing the developmental trajectory from progenitor cell differentiation to postnatal growth and maturation. These insights underscore the need for integrated approaches combining maternal diet optimization, molecular breeding, and precision livestock management to enhance muscle growth, meat quality, and production sustainability in ruminant systems. Full article

The implementation of Building Information Modelling (BIM) in public design processes enhances efficiency, transparency, and sustainability. However, public agencies often encounter significant barriers, particularly regarding organisational and managerial readiness. This study develops a BIM implementation framework tailored to the specific needs of an Italian public agency. The research adopts a qualitative approach, combining 15 semi-structured interviews with process mapping Using (Business Process Modeling Notation) BPMN. The current as-is workflows were analysed and validated by internal stakeholders. Based on this analysis, strategic objectives were defined, relevant (Building Information Modelling) BIM uses were selected, and revised to-be processes were proposed, integrating new roles and responsibilities according to the standards. The framework addresses both technical and organisational dimensions of BIM adoption, highlighting the need for training, coordination, and stakeholder engagement. The main outcomes include a structured process model, a priority-based selection of BIM uses, and a role matrix supporting organisational transformation. The added value for researchers lies in the replicable methodology that combines empirical process mapping with implementation planning. For practitioners, especially consultants in sustainable design, the study offers a practical roadmap for aligning BIM adoption with project goals, regulatory compliance, and environmental performance targets in complex public sector contexts. Full article

Energy-intensive industries (EIIs) face mounting pressure to reduce greenhouse gas emissions while maintaining international competitiveness—a balance that is central to achieving the EU’s 2030 and 2050 climate objectives. In this context, energy management (EM) emerges as a strategic instrument to decouple industrial growth from fossil energy consumption. This study proposes a redefinition of EM to support carbon-neutral supply chains within the European Union’s EIIs, addressing critical limitations of conventional EM frameworks under increasingly stringent carbon regulations. Using a modified systematic literature review based on PRISMA methodology, complemented by expert insights from EU Member States, this research identifies structural gaps in current EM practices and highlights opportunities for integrating sustainable innovations across the whole industrial value chain. The proposed EM concept is validated through an analysis of 24 EM definitions, over 170 scientific publications, and over 80 EU legal and strategic documents. The framework incorporates advanced digital technologies—including artificial intelligence (AI), the Internet of Things (IoT), and big data analytics—to enable real-time optimisation, predictive control, and greater system adaptability. Going beyond traditional energy efficiency, the redefined EM encompasses the entire energy lifecycle, including use, transformation, storage, and generation. It also incorporates social dimensions, such as corporate social responsibility (CSR) and stakeholder engagement, to cultivate a culture of environmental stewardship within EIIs. This holistic approach provides a strategic management tool for optimising energy use, reducing emissions, and strengthening resilience to regulatory, environmental, and market pressures, thereby promoting more sustainable, inclusive, and transparent supply chain operations. Full article

In recent years, the rapid development of lightweight Unmanned Aerial Vehicle (UAV) technology under 250 g has begun to challenge the validity of existing mass-based safety classifications. The commonly used 250 g threshold for defining “harmless” UAVs has become a subject requiring more detailed evaluations, especially as new models with increased speed and performance enter the market. This study aims to reassess the adequacy of the current 250 g mass limit by conducting a comprehensive analysis using human-centered injury metrics, including kinetic energy, Blunt Criterion (BC), Viscous Criterion (VC), and the Abbreviated Injury Scale (AIS). Within this scope, an extensive dataset of commercial UAV models under 500 g was compiled, with a particular focus on the sub-250 g segment. For each model, KE, BC, VC, and AIS values were calculated using publicly available technical data and validated physical models. The results were compared against established injury thresholds, such as 14.9 J (AIS-3 serious injury), 25 J (“harmless” threshold), and 33.9 J (AIS-4 severe injury). Furthermore, new recommendations were developed for regulatory authorities, including energy-based classification systems and mission-specific dynamic threshold mechanisms. According to the findings of this study, most UAVs under 250 g continue to remain below the current “harmless” threshold values. However, some next-generation high-speed UAV models are approaching or exceeding critical KE levels, indicating a need to reassess existing regulatory approaches. Additionally, the strong correlation between both BC and VC metrics with AIS outcomes demonstrates that these indicators are complementary and valuable tools for assessing injury risk. In this context, the adoption of an energy-based supplementary classification and dynamic, mission-based regulatory frameworks is recommended. Full article

The pupal stage in necrophagous flies represents the longest and least morphologically distinct phase of development, posing a persistent challenge for accurately estimating postmortem intervals (PMI) in forensic investigations. Here, we present a novel molecular approach to pupal age estimation in Sarcophaga peregrina, a forensically important species, by profiling microRNA (miRNA) expression dynamics. High-throughput sequencing across early, mid, and late pupal stages identified 191 known miRNAs, of which nine exhibited distinct monotonic temporal trends. Six miRNAs (miR-210-3p, miR-285, miR-927-5p, miR-956-3p, miR-92b, and miR-275-5p) were validated by qRT-PCR and demonstrated consistent time-dependent expression patterns. Polynomial regression models revealed a strong correlation between miRNA abundance and developmental age (R² = 0.88–0.99). Functional enrichment analyses of predicted miRNA targets highlighted their roles in key regulatory pathways, including ecdysteroid signaling, hypoxia response, autophagy, and energy metabolism. This study establishes, for the first time, a robust miRNA-based framework for estimating pupal age in forensic entomology, underscoring the potential of miRNAs as temporally precise biomarkers for PMI estimation. Full article