Search Results (6,457)

Background/Objective: Larazotide acetate (LA) is a synthetic octapeptide under development as a therapeutic candidate for celiac disease, acting to reduce intestinal permeability and regulate tight junctions (TJs). Although several studies have shown barrier-protective effects, the cellular mechanisms underlying LA’s actions in the intestinal epithelium remain unclear. This study aimed to elucidate the mechanistic roles of LA in maintaining intestinal epithelial integrity during cellular injury. Methods: C2BBe1 and leaky IPEC-J2 cell monolayers were pretreated with 10 mM LA and subjected to anoxia/reoxygenation (A/R) injury. Transepithelial electrical resistance (TEER), TJ protein localization, and phosphorylation of myosin light chain-2 (MLC-2) were analyzed. In addition, RNA sequencing was conducted to identify differentially expressed genes and signaling pathways affected by LA treatment. Results: LA pretreatment significantly increased TEER and preserved TJ protein organization during A/R injury. Transcriptomic analysis revealed enrichment of genes related to barrier regulation, small GTPase signaling, protein phosphorylation, proliferation, and migration. LA pretreatment markedly reduced MLC-2 phosphorylation, likely through modulation of the ROCK pathway, consistent with RNA-seq findings. Moreover, LA enhanced cellular proliferation, validating transcriptomic predictions. Conclusions: LA exerts a protective effect on intestinal epithelial integrity by stabilizing tight junctions, reducing MLC-2 phosphorylation, and promoting epithelial proliferation. These findings highlight a novel mechanism for LA and support its therapeutic potential in treating gastrointestinal disorders associated with “leaky gut” and mucosal injury. Full article

Category management (CM) is crucial for optimising retailer–supplier partnerships via technological integration and data sharing. However, the role of CM in Saudi Arabia’s unique fast-moving consumer goods sector (FMCG) remains underexplored. This study aimed to answer the following research question: How do cloud-based inventory platforms and real-time data sharing improve forecasting accuracy and inventory turnover for retailer–supplier CM partnerships in Saudi Arabia’s FMCG sector? A systematic review of 87 studies from the Web of Science and Scopus databases was conducted, followed by thematic analysis. The findings indicate that CM improves demand forecasting, inventory optimisation, and collaborative decision-making. Key implementation barriers include cultural resistance to data sharing, high technology costs for small and medium-sized enterprises, and infrastructural limitations. Success relies on phased technology adoption, relational data governance, and trust building that aligns with Saudi cultural norms. The study concludes that CM is essential for leveraging technology and data capabilities, and it offers a contextualised framework to overcome local barriers and support the achievement of Vision 2030 objectives. This study provides practical strategies for sector stakeholders to adopt high-impact, low-cost technology and a basis for future comparative studies in Gulf Cooperation Council markets. Full article

Ginsenosides, the primary bioactive components of Panax ginseng, have demonstrated significant immunomodulatory potential. While major ginsenosides have been extensively studied, rare ginsenosides produced through deglycosylation, heating, and steaming show enhanced biological activities with improved bioavailability. This review aimed to comprehensively analyze the immunomodulatory mechanisms, structure-activity relationships (SARs), therapeutic applications, and clinical translation strategies of five emerging rare ginsenosides: F1, Rg5, Rk1, Rh1, and Rg2. We conducted a comprehensive literature review examining the production methods, immunological effects, molecular mechanisms, pharmacokinetics, safety profiles, and clinical applications of these five compounds. Analysis focused on chemical structures, immune cell modulation, signaling pathways, disease model efficacy, and bioavailability enhancement strategies. Ginsenoside F1 uniquely demonstrated immunostimulatory effects, enhancing natural killer (NK) cell cytotoxicity and macrophage phagocytosis through mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) activation. Conversely, Rg5, Rk1, Rh1, and Rg2 exhibited anti-inflammatory properties via distinct mechanisms: Rg5 through Toll-like receptor 4 (TLR4)/NF-κB inhibition, Rk1 via triple pathway modulation (NF-κB, p38 MAPK, signal transducer and activator of transcription (STAT)), Rh1 by selective p38 MAPK and STAT1 inhibition, and Rg2 through modulation of both central nervous system (neuroinflammation) and peripheral organ systems. Structure-activity analysis revealed that sugar moiety positions critically determine immunological outcomes. Crucially, advanced delivery systems including nanostructured lipid carriers, self-microemulsifying systems, and specialized liposomes have overcome the major translational barrier of poor bioavailability, achieving up to 2.6-fold improvements and enabling clinical development. Safety assessments demonstrated favorable tolerability profiles across preclinical and clinical studies. These five rare ginsenosides represent promising immunomodulatory agents with distinct therapeutic applications. F1’s unique immunostimulatory properties position it for cancer immunotherapy, while the complementary anti-inflammatory mechanisms of Rg5, Rk1, Rh1, and Rg2 offer opportunities for precision medicine in inflammatory diseases. Advanced formulation technologies and optimized production methods now enable their significant clinical translation potential, providing promising therapeutic options for immune-related disorders pending further development. Full article

The aviation industry is responsible for approximately 2–3% of worldwide CO₂ emissions and is increasingly subjected to demands for the attainment of net-zero emissions targets by the year 2050. Traditional fossil jet fuels, which exhibit lifecycle emissions of approximately 89 kg CO₂-eq/GJ, play a substantial role in exacerbating climate change, contributing to local air pollution, and fostering energy insecurity. In contrast, Sustainable Aviation Fuels (SAFs) derived from renewable feedstocks, including biomass, municipal solid waste, algae, or through CO₂- and H₂-based power-to-liquid (PtL) represent a pivotal solution for the immediate future. SAFs generally accomplish lifecycle greenhouse gas (GHG) reductions of 50–80% (≈20–30 kg CO₂-eq/GJ), possess reduced sulfur and aromatic content, and markedly diminish particulate emissions, thus alleviating both climatic and health-related repercussions. In addition to their environmental advantages, SAFs promote energy diversification, lessen reliance on unstable fossil fuel markets, and invigorate regional economies, with projections indicating the creation of up to one million green jobs by 2030. This comprehensive review synthesizes current knowledge on SAF sustainability advantages compared to conventional aviation fuels, identifying critical barriers to large-scale deployment and proposing integrated solutions that combine technological innovation, supportive policy frameworks, and international collaboration to accelerate the aviation industry’s sustainable transformation. Full article

Background: Preliminary evidence supports high-intensity functional training (HIFT) for improving various health outcomes in non-disabled adults with overweight/obesity. It remains unknown whether HIFT produces similar benefits in individuals who are overweight/obese and also have a mobility disability (e.g., spinal cord injury, multiple sclerosis)—a population disproportionately affected by obesity-related health conditions and systemic barriers to exercise. This pilot study aimed to evaluate the feasibility and preliminary effects of a 24-week HIFT intervention, delivered at community sites by certified trainers, for adults with mobility disabilities (MDs) who were overweight/obese. Methods: Twenty adults with MD and overweight/obesity (self-reported BMI 25–46 kg/m²) enrolled in a 24-week HIFT intervention (3 days/wk, 60 min sessions) delivered at four community-based facilities by certified trainers. Feasibility indicators included recruitment, retention, and attendance; adverse events were tracked. Effect sizes (Cohen’s d) were calculated for changes in obesity-related measures, physical function, work capacity, and psychological measures from baseline to post-intervention. Results: Feasibility targets were met, with a recruitment rate of 72.2%, 76.9% retention, and 80.7% attendance. Thirteen adverse events occurred. Effects on obesity-related measures ranged from negligible to moderate, with stable weight/BMI, reduced waist circumference (45% ≥ 3 cm decrease), decreased body fat, and increased lean mass. Functional outcome effects ranged from small to large and included grip strength, balance, and walking speed. Large improvements were observed for the endurance, speed, work capacity, and self-reported physical function. Conclusions: A community-based HIFT program is feasible and may improve health outcomes in adults with MD and overweight/obesity. Full article

Life cycle cost (LCC) analysis has become a key tool for evaluating the long-term economic and environmental performance of built assets, yet its application in marinas and marine infrastructure remains underdeveloped. This review provides the first structured attempt to apply LCC to marina infrastructure, addressing the lack of sector-specific models for pontoons, mooring systems, and marina operations. It also synthesizes research on LCC methodologies, challenges, and emerging trends relevant to coastal facilities, with a particular focus on pontoons, mooring systems, and marina management practices. Studies reveal persistent barriers to effective implementation, including fragmented data systems, inconsistent regulations, and limited sector-specific tools. Existing models, largely adapted from other construction contexts, often overlook the unique technical, environmental, and operational demands of marine assets. The review critically examines international standards, procurement frameworks, and methodological approaches, highlighting opportunities to integrate sustainability considerations and address gaps in cost forecasting. It also identifies the need for standardized data collection practices and risk-based maintenance strategies tailored to harsh marine environments. By mapping current knowledge and methodological limitations, this work provides a foundation for developing more accurate, sector-specific LCC models and guidance. This literature review contributes to the advancement of sustainable coastal infrastructure planning by consolidating scattered research, emphasizing knowledge gaps, and outlining priorities for future studies, supporting policymakers, practitioners, and researchers seeking to optimize investment decisions in marinas and related facilities. Full article

The hydrogen economy stands at the forefront of the global energy transition, and additive manufacturing (AM) is increasingly recognized as a critical enabler of this transformation. AM offers unique capabilities for improving the performance and durability of hydrogen energy components through rapid prototyping, topology optimization, functional integration of cooling channels, and the fabrication of intricate, hierarchical, structured pores with precisely controlled connectivity. These features facilitate efficient heat and mass transfer, thereby improving hydrogen production, storage, and utilization efficiency. Furthermore, AM’s multi-material and functionally graded printing capability holds promise for producing components with tailored properties to mitigate hydrogen embrittlement, significantly extending operational lifespan. Collectively, these advances suggest that AM could lower manufacturing costs for hydrogen-related systems while improving performance and reliability. However, the current literature provides limited evidence on the integrated techno-economic advantages of AM in hydrogen applications, posing a significant barrier to large-scale industrial adoption. At present, the technological readiness level (TRL) of AM-based hydrogen components is estimated to be 4–5, reflecting laboratory-scale progress but underscoring the need for further development, validation and industrial-scale demonstration before commercialization can be realized. Full article

Background: Inclusion of under-represented rare-disease communities in research remains limited, threatening representativeness and equity. Methods: To assess equality, equity, diversity, and inclusion in research and identify barriers to participation faced by the rare disease community, utilising a mixed-methods online survey of a convenience sample of community advocates using Likert scales and free response options. Results: The findings from seventeen stakeholders in the rare disease community showed unanimous agreement that anxiety, fear, safety concerns, and lack of trust hinder participation in research. A total of 82% agreed or strongly agreed that additional financial resources are needed, and 76% agreed or strongly agreed that research grant applications often lack sufficient funds. The free-text responses demonstrate that the rare disease communities are keen to be involved in research but faces barriers to inclusion. Rare disease communities are willing to participate in research, but those responsible for research need to address the challenges related to language, misconceptions and fear. Conclusions: Key legislation in the United Kingdom, specifically the Proposed Patient and Public Involvement Strategy 2020–2025, emphasises the importance of involving patients and the public in health and social care. This survey marks the first step toward gaining valuable insights into the challenges faced by this community in participating in healthcare research, which is crucial for developing a solid evidence base for their treatment and care. Involving stakeholders is essential in health and social care policy and practice, rooted in advocacy and social justice. Full article

Aim: As the global population ages, the number of bilingual individuals living with dementia is increasing, yet their communication needs remain underrepresented in both clinical practice and research. This evidence review examines the intersection of language regression, communication challenges, and cultural–linguistic identity in bilingual dementia, with a particular focus on the role of speech–language pathologists (SLPs). Methods: Twelve peer-reviewed studies were critically reviewed and thematically analysed across four domains: (1) language regression and retention in bilingual dementia, (2) communication challenges in bilingual dementia care, (3) the marginal role of speech–language pathology, and (4) cultural–linguistic identity and health equity. The included studies span clinical case reports, experimental research, qualitative caregiver studies, and systematic reviews, with bilingual populations across Asia, Europe, North America, and the Middle East. Results: Findings reveal that language deterioration in bilingual dementia is dynamic and highly individualised, often influenced by language history, emotional context, and usage patterns. Caregivers and clinicians face persistent communication breakdowns, particularly in linguistically mismatched settings. Despite their specialised expertise in communication, SLPs remain largely peripheral in dementia care, constrained by systemic, educational, and methodological barriers. Moreover, linguistic and cultural identity play a critical role in how dementia is experienced and managed, yet are rarely integrated into care frameworks. Conclusions: This review highlights a significant knowledge–practice gap in bilingual dementia care and underscores the need to embed culturally and linguistically responsive communication practices, especially through speech–language therapy, at the centre of bilingual dementia care and support. It outlines key research and practice directions to advance equity, accuracy, and relational care in this growing population. Full article

The cement industry accounts for approximately 7–8% of global CO₂ emissions, primarily due to energy-intensive clinker production and limestone calcination. With cement demand continuing to rise, particularly in emerging economies, decarbonization has become an urgent global challenge. The objective of this study is to systematically map and synthesize existing evidence on technological pathways, policy measures, and economic barriers to four core decarbonization strategies: clinker substitution, energy efficiency, alternative fuels, as well as carbon capture, utilization, and storage (CCUS) in the cement sector, with the goal of identifying practical strategies that can align industry practice with long-term climate goals. A scoping review methodology was adopted, drawing on peer-reviewed journal articles, technical reports, and policy documents to ensure a comprehensive perspective. The results demonstrate that each mitigation pathway is technically feasible but faces substantial real-world constraints. Clinker substitution delivers immediate reduction but is limited by SCM availability/quality, durability qualification, and conservative codes; LC₃ is promising where clay logistics allow. Energy-efficiency measures like waste-heat recovery and advanced controls reduce fuel use but face high capital expenditure, downtime, and diminishing returns in modern plants. Alternative fuels can reduce combustion-related emissions but face challenges of supply chains, technical integration challenges, quality, weak waste-management systems, and regulatory acceptance. CCUS, the most considerable long-term potential, addresses process CO₂ and enables deep reductions, but remains commercially unviable due to current economics, high costs, limited policy support, lack of large-scale deployment, and access to transport and storage. Cross-cutting economic challenges, regulatory gaps, skill shortages, and social resistance including NIMBYism further slow adoption, particularly in low-income regions. This study concludes that a single pathway is insufficient. An integrated portfolio supported by modernized standards, targeted policy incentives, expanded access to SCMs and waste fuels, scaled CCUS investment, and international collaboration is essential to bridge the gap between climate ambition and industrial implementation. Key recommendations include modernizing cement standards to support higher clinker replacement, providing incentives for energy-efficient upgrades, scaling CCUS through joint investment and carbon pricing and expanding access to biomass and waste-derived fuels. Full article

Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke, disproportionately affecting older adults and is associated with high rates of mortality, functional dependence, and long-term cognitive decline. Aging profoundly alters the structure and function of the cerebral vasculature, predisposing the brain to both covert hemorrhage and the development of cerebral microbleeds (CMBs), small, often subclinical lesions that share common pathophysiological mechanisms with ICH. These mechanisms include endothelial dysfunction, impaired cerebral autoregulation, blood–brain barrier breakdown, vascular senescence, and chronic inflammation. Systemic factors such as age-related insulin-like growth factor 1 (IGF-1) deficiency further exacerbate microvascular vulnerability. CMBs and ICH represent distinct yet interconnected manifestations along a continuum of hemorrhagic small vessel disease, with growing recognition of their contribution to vascular cognitive impairment and dementia (VCID). Despite their increasing burden, older adults remain underrepresented in clinical trials, and few therapeutic approaches specifically target aging-related mechanisms. This review synthesizes current knowledge on the cellular, molecular, and systemic drivers of ICH and CMBs in aging, highlights diagnostic and therapeutic challenges, and outlines opportunities for age-sensitive prevention and individualized care strategies. Full article

Quantitative magnetic resonance imaging (qMRI) denotes MRI methods that estimate physical tissue parameters in units, rather than relative signal. Typical readouts include T1/T2 relaxation (ms; or R1/R2 in s⁻¹), proton density (%), diffusion metrics (e.g., ADC in mm²/s, FA), magnetic susceptibility (χ, ppm), perfusion (e.g., CBF in mL/100 g/min; rCBV; K^trans), and regional brain volumes (cm³; cortical thickness). This review synthesizes brain qMRI across T1/T2 relaxometry, myelin/MT (MWF, MTR/MTsat/qMT), diffusion (DWI/DTI/DKI/IVIM), susceptibility imaging (SWI/QSM), perfusion (DSC/DCE/ASL), and volumetry using a unified framework: physics and signal model, acquisition and key parameters, outputs and units, validation/repeatability, clinical applications, limitations, and future directions. Our scope is the adult brain in neurodegenerative, neuro-inflammatory, neuro-oncologic, and cerebrovascular disease. Representative utilities include tracking demyelination and repair (T1, MWF/MTsat), grading and therapy monitoring in gliomas (rCBV, K^trans), penumbra and tissue-at-risk assessment (DWI/DKI/ASL), iron-related pathology (QSM), and early dementia diagnosis with normative volumetry. Persistent barriers to routine adoption are protocol standardization, vendor-neutral post-processing/QA, phantom-based and multicenter repeatability, and clinically validated cut-offs. We highlight consensus efforts and AI-assisted pipelines, and outline opportunities for multiparametric integration of complementary qMRI biomarkers. As methodological convergence and clinical validation mature, qMRI is poised to complement conventional MRI as a cornerstone of precision neuroimaging. Full article

Childhood, adolescent, and young adult cancer (CAYAC) survivors often face challenges entering the workforce due to long-term physical, cognitive, and psychological late effects, defined as chronic health conditions resulting from cancer and its treatments. This study evaluated a vocational integration programme that addresses these barriers and promotes psychosocial well-being. The multidisciplinary intervention combined career guidance, soft-skills training, and a paid internship. Using a mixed-method design with questionnaires and semi-structured interviews, we assessed feasibility, satisfaction, and psychosocial outcomes. Thirteen participants (mean-age-at-diagnosis: 12.9 years, SD 5.2; mean-age-at-interview: 27.2 years, SD 5.3) reported over 40 late effects, mostly of moderate severity. Health-Related Quality of Life (HRQoL), measured by the SF-12, showed a Physical Component Score mean of 45.2 (SD 9.1) and a Mental Component Score mean of 43.5 (SD 11.2), indicating greater psychological impact. The programme received high satisfaction ratings (mean 8.3/10) and was described as motivating and valuable, enhancing self-confidence and career prospects. Social support emerged as a key facilitator, while participants noted the need for flexibility and individualised pacing. Despite a limited sample size and potential recruitment bias, this study provides preliminary insights into the feasibility and perceived value of tailored vocational programmes, emphasising the importance of adaptable, socially supportive interventions for CAYAC survivors. Full article

Glioblastoma multiforme (GBM) is an aggressive brain cancer characterized by highly invasive growth driven by glial-mesenchymal transition (GMT). Given the urgent need for effective therapies targeting this process, we aimed to discover potential GMT inhibitors using transcriptomic-based repurposing applied to both approved and experimental drugs. Deep bioinformatic analysis of transcriptomic data from GBM patient tumors and GBM cell lines with mesenchymal phenotype using gene set variation analysis (GSVA), weighted gene co-expression network analysis (WGCNA), reconstruction of GMT-related gene association networks, gene set enrichment analysis (GSEA), and the search for correlation with transcriptomic profiles of known GMT markers, revealed a novel 31-gene GMT signature applicable as relevant input data for the connectivity map-based drug repurposing study. Using this gene signature, a number of small-molecule compounds were predicted as potent anti-GMT agents. Further ranking according to their blood–brain barrier permeability, as well as structural and transcriptomic similarities to known anti-GBM drugs, revealed SP600125, vemurafenib, FG-7142, dibenzoylmethane, and phensuximide as the most promising for GMT inhibition. In vitro validation showed that SP600125, which is most closely associated with GMT-related hub genes, effectively inhibited TGF-β1- and chemical hypoxia-induced GMT in U87 GBM cells by reducing morphological changes, migration, vasculogenic mimicry, and mesenchymal marker expression. These results clearly demonstrate the applicability of connectivity mapping as a powerful tool to accelerate the discovery of effective GMT-targeting therapies for GBM and significantly expand our understanding of the antitumor potential of SP600125. Full article

This review synthesizes recent research on alternative fuels for piston-engine aircraft and related propulsion technologies. Biofuels show substantial promise but face technological, economic, and regulatory barriers to widespread adoption. Among liquid options, biodiesel offers a high cetane number and strong lubricity yet suffers from poor low-temperature flow and reduced combustion efficiency. Alcohol fuels (bioethanol, biomethanol) provide high octane numbers suited to high-compression engines but are limited by hygroscopicity and phase-separation risks. Higher-alcohols (biobutanol, biopropanol) combine favorable heating values with stable combustion and emerge as particularly promising candidates. Biokerosene closely matches conventional aviation kerosene and can function as a drop-in fuel with minimal engine modifications. Emissions outcomes are mixed across studies: certain biofuels reduce NO_x or CO, while others elevate CO₂ and HC, underscoring the need to optimize combustion and advance second- to fourth-generation biofuel production pathways. Beyond biofuels, hydrogen engines and hybrid-electric systems offer compelling routes to lower emissions and improved efficiency, though they require new infrastructure, certification frameworks, and cost reductions. Demonstrated test flights with biofuels, synthetic fuels, and hydrogen confirm technical feasibility. Overall, no single option fully replaces aviation gasoline today; instead, a combined trajectory—biofuels alongside hydrogen and hybrid-electric propulsion—defines a pragmatic medium- to long-term pathway for decarbonizing general aviation. Full article