Search Results (6,573)

Urban rail transit networks’ rapid expansions have led to increasing intersections between existing and new lines, particularly in dense urban areas where new stations must underpass existing infrastructure at zero distance. Deformation controls during construction are critical for maintaining the operational safety of existing stations, especially in soft soil conditions where construction-induced settlement poses significant risks to structural integrity. This study systematically investigates the influence mechanisms of different construction schemes on base plate deformation when an open-top UBIT (underground bundle composite pipe integrated by transverse pre-stressing) underpasses existing stations. Through precise numerical simulation using PLAXIS 3D, the research comparatively analyzed the effects of 12 pipe jacking sequences, 3 pre-stress levels (1116 MPa, 1395 MPa, 1674 MPa), and 3 soil chamber excavation schemes, revealing the mechanisms between the deformation evolution and soil unloading effects. The continuous jacking strategy of adjacent pipes forms an efficient support structure, limiting maximum settlement to 5.2 mm. Medium pre-stress level (1395 MPa) produces a balanced deformation pattern that optimizes structural performance, while excavating side chambers before the central chamber effectively utilizes soil unloading effects, achieving controlled settlement distribution with maximum values of −7.2 mm. The optimal construction combination demonstrates effective deformation control, ensuring the operational safety of existing station structures. These findings enable safer and more efficient urban underpassing construction. Full article

The carbon dioxide spillover effects and influencing factors of the “Belt and Road Initiative” (BRI) in African countries must be assessed to evaluate the effectiveness, promote low-carbon transmissions in African countries, and provide recommendations for achieving the 2030 Sustainable Development Goals. This novel study employs carbon dioxide emission intensity (CEI) and per capita carbon dioxide emissions (PCE) as dual indicators to evaluate the spatial spillover effects of 54 BRI African countries on their neighboring countries’ carbon emissions from 2007 to 2023. It identifies the key factors and mechanisms affecting these spillover effects using the spatial differences-in-differences (SDID) model. Results indicate that since the launch of the BRI, the CEI and PCE of BRI African countries have significantly increased, largely due to trade patterns and industrialization structures. Greater trade openness has further boosted local economic development, thereby increasing carbon dioxide’s spatial spillover. Government management and corruption control levels show some heterogeneity in the spillover effects, which may be attributed to long-standing issues of weak institutional enforcement in Africa. Overall, this study reveals the complex relationship between BRI African economic development and environmental outcomes, highlighting the importance of developing sustainable development strategies and establishing strong differentiated regulatory regimes to effectively address environmental challenges. Full article

This study investigates the seasonal effectiveness of high-efficiency particulate air (HEPA) purifiers and window-opening behaviors in three London nurseries, using continuous indoor and outdoor PM_2.5 monitoring, window state and air purifier use, and occupant questionnaire data collected from March 2021 to February 2022. Of the approximately 40–50 nurseries contacted, only three agreed to participate. Results show that HEPA purifiers substantially reduced indoor particulate matter (PM_2.5), with the greatest effect observed during the heating season when windows remained closed for longer periods. Seasonal and behavioral analysis indicated more frequent and longer window opening in the non-heating season (windows were open 41.5% of the time on average, compared to 34.2% during the heating season) driven by both ventilation needs and heightened COVID-19 concerns. Predictive modeling identified indoor temperature as the main driver of window opening, while carbon dioxide (CO₂) had a limited effect. In addition, window opening often increased indoor PM_2.5 under prevailing outdoor air quality conditions, with mean concentrations rising from 2.73 µg/m³ (closed) to 3.45 µg/m³ (open), thus reducing the apparent benefit of air purifiers. These findings underscore the complex interplay between mechanical purification and occupant-controlled ventilation, highlighting the need to adapt indoor air quality (IAQ) strategies to both seasonal and behavioral factors in educational settings. Full article

Phage therapy, long overshadowed by antibiotics in Western medicine, has a well-established history in some Eastern European countries and is now being revitalized as a promising strategy against antimicrobial resistance (AMR). This resurgence of phage therapy is driven by the urgent need for innovative countermeasures to AMR, which will cause an estimated 10 million deaths annually by 2050. However, the emergence of phage-resistant variants presents challenges similar to AMR, thus necessitating a deeper understanding of phage resistance mechanisms and control strategies. The highest priority must be to prevent the emergence of phage resistance. Although phage cocktails targeting multiple receptors have demonstrated a certain level of phage resistance suppression, they cannot completely suppress resistance in clinical settings. This highlights the need for strategies beyond simple resistance suppression. Notably, recent studies examining fitness trade-offs associated with phage resistance have opened new avenues in phage therapy that offer the potential of restoring antibiotic susceptibility and attenuating pathogen virulence despite phage resistance. Thus, controlling phage resistance may rely on both its suppression and strategic redirection. This review summarizes key concepts in the control of phage resistance and explores evolutionary engineering as a means of optimizing phage therapy, with a particular focus on Pseudomonas infections. Harnessing evolutionary dynamics by intentionally breaking the spontaneous evolutionary trajectories of target bacterial pathogens could potentially reshape bacterial adaptation by acquisition of phage resistance, unlocking potential in the application of phage therapy. Full article

Cancer is a major global health issue, with rising incidence rates highlighting the urgent need for more effective treatments. Despite advances in cancer therapy, challenges such as adverse effects and limitations of existing treatments remain. Immunotherapy, which harnesses the body’s immune system to target cancer cells, offers promising solutions. Gamma delta (γδ) T cells are noteworthy due to their potent ability to kill various cancer cells without needing conventional antigen presentation. Recent studies have focused on the role of γδ T cells in α-galactosylceramide (α-GalCer)-mediated immunity, opening new possibilities for cancer immunotherapy. We engineered humanized T cell receptor (HuTCR)-T1 γδ mice by replacing mouse sequences with human counterparts. This study investigates the cytotoxic activity of humanized γδ T cells against several human cancer cell lines (A431, HT-29, K562, and Daudi) in vitro, aiming to elucidate mechanisms underlying their anticancer efficacy. Human cancer cells were co-cultured with humanized γδ T cells, with and without α-GalCer, for 24 h. The humanized γδ T cells showed enhanced cytotoxicity across all tested cancer cell lines compared to wild-type γδ T cells. Additionally, γδ T cells from HuTCR-T1 mice exhibited higher levels of anticancer cytokines (IFN-γ, TNF-α, and IL-17) and Granzyme B, indicating their potential as potent mediators of anticancer immune responses. Blocking γδ T cells’ cytotoxicity confirmed their γδ-mediated function. These findings represent a significant step in preclinical development of γδ T cell-based cancer immunotherapies, providing insights into their mechanisms of action, optimization of therapeutic strategies, and identification of predictive biomarkers for clinical application. Full article

Background: The aim of this review is to summarize and evaluate the properties of antibacterial polysaccharides for application in dental implantology to identify knowledge gaps and provide new research ideas. Methods: The electronic databases PubMed, Medline, ProQuest, and Google Scholar were used to search for peer-reviewed scientific publications published between 2018 and 2025 that provide insights to answer research questions on the role of antibacterial polysaccharides in combating pathogens in dental implantology without triggering immune reactions and inflammation. Further research questions relate to the efficacy against various dental pathogens and the understanding of the antibacterial mechanism, which may enable the development of functionalized polysaccharides with long-term antibacterial activity. Results: Biomedical implants have revolutionized medicine but also increased the risk of infections. Implant infections are a major problem in implantology and lead to implant failure and replacement. An antibacterial coating could be an excellent strategy to extend the lifespan of implants and improve the quality of the patient’s life. Bacterial resistance to antibiotics poses significant challenges for researchers, forcing them to search for new ways to prevent bacterial infections in implantology. Antibacterial natural polymers have recently received considerable research attention due to their long-term antibacterial activity. Polysaccharides from marine sources, such as chitosan and alginate, or pectin, xanthan, etc., from various plants, appear to be promising biopolymers for such applications in implantology due to their antibacterial activity, biocompatibility, and osteogenic properties. The antibacterial activity of these natural biopolymers depends on their chemical and physical properties. Nanopolysaccharides exhibit higher antibacterial activity than conventional polysaccharides, but their toxicity to human cells must be considered. Their antibacterial activity is based on the disruption of bacterial DNA or RNA synthesis, increased cell wall permeability, membrane disruption, and cytoplasmic leakage. Conclusions: Polysaccharides are a class of natural polymers with a broad spectrum of biological activities. They exhibit antioxidant, immunomodulatory, anticoagulant, anticancer, anti-inflammatory, antibacterial, and antiviral activity. Furthermore, polysaccharides are non-cytotoxic and exhibit good biocompatibility with osteogenic cells. Bactericidal polysaccharides are attractive new antibacterial materials against implant infections and open up new perspectives in implantology. Full article

The search for the biomarkers of Alzheimer’s disease (AD) may prove essential in the diagnosis and prognosis of the pathology, and the differential expression of key proteins may assist in identifying new therapeutic targets. In this proof-of-concept (POC) study, a new approach of data mining and matching combined with the biochemical analysis of proteins was applied to AD investigation. Three influential online open databases (UniProt, AlzGene, and Allen Human Brain Atlas) were explored to identify the genes and encoded proteins involved in AD linked to mitochondrial and iron dysmetabolism. The databases were searched using specific keywords to collect information about protein composition, and function, and meta-analysis data about their correlation with AD. The extracted datasets were matched to yield a list of relevant proteins in AD. The biochemical analysis of their amino acid content suggested a defective synthesis of these proteins in poorly oxygenated brain tissue, supporting their relevance in AD progression. The result of our POC study revealed several potential new markers of AD that deserve further molecular and clinical investigation. This novel database search approach can be a valuable strategy for biomarker search that can be exploited in many diseases. Full article

This literature-based review draws on studies of thirty-four fish species; most are from northern temperate regions. Fish have flexible and indeterminate growth, and often they do not reach their growth and size potential. They may become stunted with impaired growth and early maturity, chiefly as a phenotypically plastic reaction. The main causes of stunted growth are negatively density-dependent food availability and keen intraspecific competition leading to environmental stress. Typically, their growth levels off early in life as energy consumptions approach energy costs of maintenance. Females typically attain maturity soon after the energy surplus from feeding starts to decrease. Males are often more variable in size at maturity owing to alternative mating strategies, and their size at maturity depends on both species-specific mating behaviours and environmental opportunities. In polyphenic/polymorphic populations, one phenotype may be stunted and the other phenotype non-stunted; stunted individuals do not perform the required ontogenetic niche shift needed to grow larger. The adult morphology of stunted fish is typically like the morphology of juveniles. Their secondary sexual characters are less pronounced, and they phenotypically retain adaptation to their early feeding niche, which is different from that of large-growing individuals. There are open questions regarding to what extent genetics and epigenetics regulate the life histories of stunted phenotypes. Full article

Enhancing the yield and qualitative traits of horticultural crops without further hampering the environment constitutes an urgent challenge that could be addressed by implementing innovative agronomic tools, such as plant biostimulants. This study investigated the effects of three commercial biostimulants—BIO1 (fulvic/humic acids), BIO2 (leonardite-humic acids), and BIO3 (plant-based extracts)—on leaf ecophysiology, yield, and fruit quality in two raspberry cultivars, ‘Autumn Bliss’ (AB) and ‘Zeva’ (Z), grown in an open-field context, to assess their effectiveness in raspberry cultivation. Experimental activities involved two Research Years (RYs), namely, year 2023 (RY 1) and 2024 (RY 2). Leaf parameters such as chlorophyll, flavonols, anthocyanins, and the Nitrogen Balance Index (NBI) were predominantly influenced by the interaction between Treatment, Year and Cultivar factors, indicating context-dependent responses rather than direct biostimulant effects. BIO2 showed a tendency to increase yield (g plant⁻¹) and berry number plant⁻¹, particularly in RY 2 (417.50 g plant⁻¹, +33.93% vs. control). Fruit quality responses were cultivar and time-specific: BIO3 improved soluble solid content in AB (12.8 °Brix, RY 2, Intermediate Harvest) and Z (11.43 °Brix, +13.91% vs. BIO2). BIO2 reduced titratable acidity in AB (3.12 g L⁻¹) and increased pH in Z (3.02, RY 2) but also decreased °Brix in Z. These findings highlight the potential of biostimulants to modulate raspberry physiology and productivity but underscore the critical role of cultivar, environmental conditions, and specific biostimulant composition in determining the outcomes, which were found to critically depend on tailored application strategies. Full article

Potato (Solanum tuberosum L.) is one of the most important food crops in the world, ranking fourth after rice, maize, and wheat. Potatoes are exposed to biotic and abiotic environmental factors, which lead to economic losses and increase the possibility of food security threats in many countries. Traditional potato breeding faces several challenges, primarily due to its genetic complexity and the time-consuming nature of the process. Therefore, gene editing—CRISPR-Cas technology—allows for more precise and rapid changes to the potato genome, which can speed up the breeding process and lead to more effective varieties. In this review, we consider CRISPR-Cas technology as a potential tool for plant breeding strategies to ensure global food security. This review summarizes in detail current and potential technological breakthroughs that open new opportunities for the use of CRISPR-Cas technology for potato breeding, as well as for increasing resistance to abiotic and biotic stresses, and improving potato tuber quality. In addition, the review discusses the challenges and future perspectives of the CRISPR-Cas system in the prospects of the development of potato production and the regulation of gene-edited crops in different countries around the world. Full article

Plaque erosion (PE) is now recognized as a common and clinically significant cause of acute coronary syndromes (ACSs), accounting for up to 40% of cases. Unlike plaque rupture (PR), PE involves superficial endothelial loss over an intact fibrous cap and occurs in a low-inflammatory setting, typically affecting younger patients, women, and smokers with fewer traditional risk factors. The growing recognition of PE has been driven by high-resolution intracoronary imaging, particularly optical coherence tomography (OCT), which enables in vivo differentiation from PR. Identifying PE with OCT has opened the door to personalized treatment strategies, as explored in recent trials evaluating the safety of deferring stent implantation in selected cases in favor of intensive medical therapy. Given its unexpectedly high prevalence, PE is now recognized as a common pathophysiological mechanism in ACS, rather than a rare exception. This growing awareness underscores the importance of its accurate identification through OCT in clinical practice. Early recognition and a deeper understanding of PE are essential steps toward the implementation of precision medicine, allowing clinicians to move beyond “one-size-fits-all” models toward “mechanism-based” therapeutic strategies. This narrative review aims to offer an integrated overview of PE, tracing its epidemiology, elucidating the molecular and pathophysiological mechanisms involved, outlining its clinical presentations, and placing particular emphasis on diagnostic strategies with OCT, while also discussing emerging therapeutic approaches and future directions for personalized cardiovascular care. Full article

Recent advancements in large language models (LLMs) have significantly enhanced the effectiveness of Retrieval-Augmented Generation (RAG) systems. This study focuses on the development and evaluation of a domain-specific AI chatbot designed to support international student admissions by leveraging LLM-based RAG pipelines. We implement and compare multiple pipeline configurations, combining retrieval methods (e.g., Dense, MMR, Hybrid), chunking strategies (e.g., Semantic, Recursive), and both open-source and commercial LLMs. Dual evaluation datasets of LLM-generated and human-tagged QA sets are used to measure answer relevancy, faithfulness, context precision, and recall, alongside heuristic NLP metrics. Furthermore, latency analysis across different RAG stages is conducted to assess deployment feasibility in real-world educational environments. Results show that well-optimized open-source RAG pipelines can offer comparable performance to GPT-4o while maintaining scalability and cost-efficiency. These findings suggest that the proposed chatbot system can provide a practical and technically sound solution for international student services in resource-constrained academic institutions. Full article

Lactic acid bacteria (LAB) are central to food, feed, and health biotechnology, yet their genomes have long resisted rapid, precise manipulation. This review charts the evolution of LAB genome-editing strategies from labor-intensive RecA-dependent double-crossovers to state-of-the-art CRISPR and CRISPR-associated transposase systems. Native homologous recombination, transposon mutagenesis, and phage-derived recombineering opened the door to targeted gene disruption, but low efficiencies and marker footprints limited throughput. Recent phage RecT/RecE-mediated recombineering and CRISPR/Cas counter-selection now enable scar-less point edits, seamless deletions, and multi-kilobase insertions at efficiencies approaching model organisms. Endogenous Cas9 systems, dCas-based CRISPR interference, and CRISPR-guided transposases further extend the toolbox, allowing multiplex knockouts, precise single-base mutations, conditional knockdowns, and payloads up to 10 kb. The remaining hurdles include strain-specific barriers, reliance on selection markers for large edits, and the limited host-range of recombinases. Nevertheless, convergence of phage enzymes, CRISPR counter-selection and high-throughput oligo recombineering is rapidly transforming LAB into versatile chassis for cell-factory and therapeutic applications. Full article

Floating solar technology has gained significant attention as part of the global expansion of renewable energy due to its potential for installation in underutilized water bodies. Several countries, including the Netherlands, have initiated efforts to extend this technology from inland freshwater applications to open offshore environments, particularly within offshore wind farm areas. This development is motivated by the synergistic benefits of increasing site energy density and leveraging the existing offshore grid infrastructure. The deployment of offshore floating photovoltaic (OFPV) systems involves assembling multiple modular units in a marine environment, introducing operational risks that may give rise to safety concerns. To mitigate these risks, weather windows must be considered prior to the task execution to ensure continuity between weather-sensitive activities, which can also lead to additional time delays and increased costs. Consequently, optimizing marine logistics becomes crucial to achieving the cost reductions necessary for making OFPV technology economically viable. This study employs a simulation-based approach to estimate the installation duration of a 5 MWp OFPV plant at a Dutch offshore wind farm site, started in different months and under three distinct risk management scenarios. Based on 20 years of hindcast wave data, the results reveal the impacts of campaign start months and risk management policies on installation duration. Across all the scenarios, the installation duration during the autumn and winter period is 160% longer than the one in the spring and summer period. The average installation durations, based on results from 12 campaign start months, are 70, 80, and 130 days for the three risk management policies analyzed. The result variation highlights the additional time required to mitigate operational risks arising from potential discontinuity between highly interdependent tasks (e.g., offshore platform assembly and mooring). Additionally, it is found that the weather-induced delays are mainly associated with the campaigns of pre-laying anchors and platform and mooring line installation compared with the other campaigns. In conclusion, this study presents a logistics modeling methodology for OFPV systems, demonstrated through a representative case study based on a state-of-the-art truss-type design. The primary contribution lies in providing a framework to quantify the performance of OFPV installation strategies at an early design stage. The findings of this case study further highlight that marine installation logistics are highly sensitive to local marine conditions and the chosen installation strategy, and should be integrated early in the OFPV design process to help reduce the levelized cost of electricity. Full article

Endometriosis is a disease characterized by the presence of endometrial glands and stroma outside of the uterine corpus, often clinically presenting with pain and/or infertility. Ectopic lesions exhibit features characteristic of epithelial-to-mesenchymal transition (EMT), a process in which epithelial cells lose polarity and acquire mesenchymal traits, including migratory and invasive capabilities. During the process of EMT, epithelial traits are downregulated, while mesenchymal traits are acquired, with cells developing migratory ability, increasing proliferation, and resistance to apoptosis. EMT is promoted by exposure to hypoxia and stimulation by transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), and estradiol. Signaling pathways that promote EMT are activated in most ectopic lesions and involve transcription factors such as Snail, Slug, ZEB-1/2, and TWIST-1/2. EMT-specific molecules present in the serum of women with endometriosis appear to have diagnostic potential. Strategies targeting EMT in animal models of endometriosis have demonstrated regression of ectopic lesions, opening the door for novel therapeutic approaches. This review summarizes the current understanding of the role of EMT in endometriosis and highlights potential targets for EMT-related diagnosis and therapeutic interventions. Full article