Search Results (15,761)

Background/Objectives: The diminished efficacy of azoles in treating fungal infections is attributed to the emergence of resistance among pathogenic fungi. Employing a synergistic approach with other compounds to enhance the antifungal activity of azoles has shown promise, yet the availability of clinically valuable adjuvants for azoles and allylamines remains limited. Studies have demonstrated that the human host environment provides multiple carbon sources, which can influence the susceptibility of C. albicans to antifungal agents. Therefore, a comprehensive investigation into the mechanisms by which carbon sources modulate the susceptibility of C. albicans to azoles may uncover a novel pathway for enhancing the antifungal efficacy of azoles. Methods: This study explored the impact of various carbon sources on the antifungal efficacy of azoles through methodologies including minimum inhibitory concentration (MIC) assessments, super-MIC growth (SMG) assays, disk diffusion tests, and spot assays. Additionally, the mechanism by which galactose augments the antifungal activity of azoles was investigated using a range of experimental approaches, such as gene knockout and overexpression techniques, quantitative real-time PCR (qRT-PCR), Western blot analysis, and cycloheximide (CHX) chase experiments. Results: This study observed that galactose enhances the efficacy of azoles against C. albicans by inhibiting the translation of Erg1. This results in the suppression of Erg1 protein levels and subsequent inhibition of ergosterol biosynthesis in C. albicans. Conclusions: In C. albicans, the translation of Erg1 is inhibited when galactose is utilized as a carbon source instead of glucose. This novel discovery of galactose’s inhibitory effect on Erg1 translation is expected to enhance the antifungal efficacy of azoles. Full article

Background/Objectives: Non-coding microRNA-34a (miR-34a) regulates the expression of key factors involved in several cellular processes, such as differentiation, apoptosis, proliferation, cell cycle, and senescence. Deregulation of the expression of these factors is implicated in the onset and progression of several human diseases, including cancer, neurodegenerative disorders, and pathologies associated with viral infections and inflammation. Despite numerous studies, the molecular mechanisms regulated by miR-34a remain to be fully understood. The present study aimed to generate miR-34a knockout cell lines to identify novel genes potentially regulated by its expression. Methods: We employed the CRISPR-Cas9 gene editing system to knock out the hsa-miR-34a gene in HeLa and 293T cell lines, two widely used models for studying molecular and cellular mechanisms. We compared proliferation rates and gene expression profiles via RNA-seq and qPCR analyses between the wild-type and miR-34a KO cell lines. Results: Knockout of miR-34a resulted in a decreased proliferation rate in both cell lines. Noteworthy, the ablation of miR-34a resulted in increased expression of the long non-coding RNA MALAT1. Additionally, miR-34a-5p silencing in the A375 melanoma cell line led to MALAT1 overexpression. Conclusions: Our findings support the role of the miR-34a/MALAT1 axis in regulating proliferation processes. Full article

Sexual health constitutes a fundamental aspect of overall well-being, with direct implications for individual development and the broader social and economic progress of communities. Promoting environments that ensure sexual experiences free from coercion, discrimination, and violence is a key public health priority. Sexuality, in this regard, should be understood as an inherent dimension of human experience, shaped by biological, cultural, cognitive, and ideological factors. Accordingly, sexual health education requires a holistic and multidimensional approach that integrates sociocultural, biographical, and professional perspectives. This study aims to examine the level of knowledge and training in sexual health among nursing students and healthcare professionals, as well as to assess the extent to which sexual health content is incorporated into nursing curricula at Spanish universities. A scoping review was conducted using the Dialectical Structural Model of Care (DSMC) as the theoretical framework. The findings indicate a significant lack of knowledge regarding sexual health among both nursing students and healthcare professionals, largely due to educational and structural limitations. Furthermore, sexual health education remains underrepresented in nursing curricula and is frequently addressed from a narrow, fragmented biomedical perspective. These results highlight the urgent need for the comprehensive integration of sexual health content into nursing education. Strengthening curricular inclusion is essential to ensure the preparation of competent professionals capable of delivering holistic, inclusive, and empowering care in this critical area of health. Full article

The Caco-2 in vitro model of the intestinal barrier is a well-established system for the investigation of the intestinal fate of orally ingested chemicals and drugs, and it has been used for over ten years by pharmaceutical industries as a model for absorption in preclinical studies. The Caco-2 model shows a fair correlation with in vivo drug absorption, though some inherent biases remain unresolved. Its main limitation lies in the lack of structural complexity, as it does not replicate the diverse cell types and mucus layer present in the human intestinal epithelium. Consequently, the development of advanced in vitro models of the intestinal barrier, that more structurally resemble the human intestinal epithelium physiology, has increased the potential applications of these models. Recently, Caco-2-based advanced intestinal models have proven effective in predicting nanomaterial uptake and transport across the intestinal barrier. The aim of this review is to provide a state-of-the-art of human in vitro intestinal barrier models for the study of translocation/uptake of nanoparticles relevant for oral exposure, including inorganic nanomaterials, micro/nano plastic, and fiber nanomaterials. The main effects of the above-mentioned nanomaterials on the intestinal barrier are also reported. Full article

Since 2014, the Paleoanthropology Group of the National Museum of Natural Sciences (CSIC), in collaboration with Equatoguinean researchers, has been conducting archeo-paleontological fieldwork in Equatorial Guinea, continuing a longstanding Spanish naturalist tradition in this region of West Central Africa. These multidisciplinary investigations, framed within an archeo-paleo-anthropological approach, aim primarily to identify early human occupation in the Central African rainforests. To date, robust evidence of Pleistocene human presence has been documented, particularly through lithic assemblages. Although the scarcity and fragmentation of well-dated sites in Central Africa complicate chronological placement, technological traits observed in the lithic industries recorded in Equatorial Guinea show clear affinities with the African Middle Stone Age (MSA). Complementary taphonomic analyses of faunal remains have been undertaken to better understand bone preservation and fossilization processes under tropical rainforest conditions, thereby contributing to the interpretation of archeological contexts. In parallel, ongoing primatological research within the project—focused on extant primates in their natural habitats—seeks to provide ethological models relevant to the study of hominin locomotor evolution. Notably, the project has led to the ecogeographic characterization of the Engong chimpanzee group in Monte Alén National Park, one of the country’s most pristine protected areas. Full article

Magnetic parameters of river sediments are commonly used as end-members for source tracing in the coasts and shelves. The eastern continental shelf area of China, with multiple sources of input, is a key region for discussing sediment sources. However, magnetic parameters are influenced by grain size, and the nature of this influence remains unclear. In this study, the Jiulong River was selected as a case to analyze the magnetic parameters and mineral characteristics for both the coarse (>63 μm) and fine-grained (<63 μm) fractions. Results show that the magnetic minerals mainly contain detrital-sourced magnetite and hematite. In the North River, a tributary of the Jiulong River, the content of coarse-grained magnetic minerals increases from upstream to downstream, contrary to fine-grained magnetic minerals, suggesting the influence of hydrodynamic forces. Some samples with abnormally high magnetic susceptibility may result from the combined influence of the parent rock and human activities. In the scatter diagrams of magnetic parameters for provenance tracing, samples of the <63 μm fractions have a more concentrated distribution than that of the >63 μm fractions. Hence, magnetic parameters for the <63 μm fraction are more useful in provenance identification. Full article

With the global aging population on the rise, identifying environmental factors that modulate immunosenescence is critical for health interventions. While urban green spaces are known to confer health benefits, the long-term effects of forest exposure on immunosenescence remain unclear. This study investigated the differential impacts of urban forest versus urban environments on immunosenescence using a D-galactose-induced murine model. Mice were assigned to urban or forest environments for 8 weeks, with serum cytokines (IL-2, IL-6, TNF-α, IFN-γ), T-cell subsets, and organ indices analyzed. Forest environments exhibited significantly higher humidity and negative air ion concentrations alongside lower noise levels compared to urban settings. Aged forest-exposed mice showed attenuated immunosenescence markers, including significantly lower IL-6 levels (p < 0.01) and improved thymic indices, suggesting urban forest environments may mitigate immune decline. These findings highlight the potential of urban forests in promoting healthy aging, advocating for their integration into urban planning. Further human studies are warranted to translate these findings into public health strategies. Full article

We studied Galápagos barn owls on Santa Cruz Island in the Galápagos Archipelago. We collected and analyzed pellets to determine diet composition. Barn-owl diet consisted—in terms of biomass—of ~89% rodents and ~10% insects. Bird remains occurred in 1% of the pellets. Foraging was studied with data loggers, a method not previously applied to the study of Galápagos barn owls. Owls rested during the day in natural and human-built roosts such as lava holes, trees, or huts. Night-time foraging was characterized by periods during which the bird moved and periods during which the bird stayed within one place, with the latter amounting to ~56% of the time away from the day roost. Birds began foraging shortly after sunset and returned to their day roost before sunrise. The duration of foraging was approximately 11 h per night. Foraging areas were small (median value: 0.28 km²). Although our data demonstrate a continued presence of the subspecies, we regard the situation for this subspecies as labile, as multiple threats, such as road kills, poisoning, and intentional killing by farmers, have increased recently, and suggest the development of a management plan to improve its conservation. Full article

Soil salinization in oasis areas of arid regions is recognized as a dynamic and multifaceted environmental threat influenced by both natural processes and human activities. In this study, 13 spatiotemporal predictors derived from field surveys and remote sensing are utilized to construct a spatial probabilistic model of salinization. A Bayesian Belief Network is integrated with spline interpolation in ArcGIS to map the likelihood of salinization, while Partial Least Squares Structural Equation Modeling (PLS-SEM) is applied to analyze the interactions among multiple drivers. The test results of this model indicate that its average sensitivity exceeds 80%, confirming its robustness. Salinization risk is categorized into degradation (35–79% probability), stability (0–58%), and improvement (0–48%) classes. Notably, 58.27% of the 1836.28 km² Keriya Oasis is found to have a 50–79% chance of degradation, whereas only 1.41% (25.91 km²) exceeds a 50% probability of remaining stable, and improvement probabilities are never observed to surpass 50%. Slope gradient and soil organic matter are identified by PLS-SEM as the strongest positive drivers of degradation, while higher population density and coarser soil textures are found to counteract this process. Spatially explicit probability maps are generated to provide critical spatiotemporal insights for sustainable oasis management, revealing the complex controls and limited recovery potential of soil salinization. Full article

If God cares and is present, can God use pain and suffering in my life? Absolutely. Does this mean that God planned, ordained, or designed the pain (or cancer) to be instrumental in my life for some sort of higher spiritual purpose? If so, why? Why does God allow cancer to invade and interrupt one’s life? There are no theologically sound or definitive answers to these questions. Although asking such questions is basic to our humanity, as we will observe in various passages of Scripture, the answers will always remain elusive. Instead of seeking to answer the question “why?”, I will suggest two areas for theological and pastoral reflection with respect to those facing cancer: humility and hope. Enduring cancer, from diagnosis through treatment, requires humility in mind and body before our Creator and before our caregivers. Cancer also provides an opportunity for Christians to embed themselves in the hope of resurrection and new creation. Resurrection hope is also not reduced to hope beyond death but hope that is manifested now through embodied resurrection “signs” and actions of human sacrificial love, both received and practiced by the patient undergoing illness and by the patient’s caregivers, family, and friends. Full article

Pet ownership and wildlife tourism are two prominent ways people interact with non-human animals in contemporary contexts. Despite this, there is a need for further exploration of the interconnections between pets, wildlife, and visitors. Utilizing an ecological-phenomenological framework, this study examines how these multispecies interactions contribute to experiences that extend beyond the human domain. This research is based on a quantitative survey of 1422 participants at the Panda Center that were analyzed using inferential statistical methods to assess differences in visitor experiences. The statistical results reveal that pet ownership and wildlife encounters mediate the environmental affordances and constraints encountered by visitors, creating a dynamic and intricate nexus among pets, wildlife, and tourists. Specifically, pet ownership is shown to enhance both the richness and frequency of wildlife encounters. Nonetheless, the study highlights that human dominance over non-human animals remains a central environmental constraint in multispecies interactions despite the adoption of a more humane approach to animal management through tourism activities. Full article

Microbes perform diverse and vital functions in animals, plants, and humans, and among them, plant-associated microbiomes, especially endophytes, have attracted growing scientific interest in recent years. Numerous plant species thriving in diverse environments have been shown to host endophytic microbes. While endophytic bacteria commonly colonize plant tissues such as stems, roots, and leaves, seed-associated endophytes generally exhibit lower diversity compared to those in other plant compartments. Nevertheless, seed-borne microbes are of particular importance, as they represent the initial microbial inoculum that influences a plant’s critical early developmental stages. The seed endophytic microbiome is of particular interest due to its potential for vertical transmission and its capacity to produce a broad array of phytohormones, enzymes, antimicrobial compounds, and other secondary metabolites. Collectively, these functions contribute to enhanced plant biomass and yield, especially under abiotic and biotic stress conditions. Despite their multifaceted roles, seed microbiomes remain underexplored in plant ecology, and their potential benefits are not yet fully understood. This review highlights recent advances in our understanding of the diversity, community composition, mechanisms of action, and agricultural significance of seed endophytic microbes. Furthermore, it synthesizes current insights into how seed endophytes promote plant health and productivity and proposes future research directions to fully harness their potential in sustainable agriculture. 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

Collagen implants in neurosurgery are widely used due to their biocompatibility, biodegradability, and ability to support tissue regeneration, but their mechanical properties, such as low tensile strength and susceptibility to enzymatic degradation, remain challenging. Current technologies are improving these implants through cross-linking, synthetic reinforcements, and advanced manufacturing techniques such as 3D bioprinting to improve durability and predictability. Industry 4.0 is contributing to this by automating production, using data analytics and machine learning to optimize implant properties and ensure quality control. In Industry 5.0, the focus is shifting to personalization, enabling the creation of patient-specific implants through human–machine collaboration and advanced biofabrication. eHealth integrates digital monitoring systems, enabling real-time tracking of implant healing and performance to inform personalized care. Despite progress, challenges such as cost, material property variability, and scalability for mass production remain. The future lies in smart biomaterials, AI-driven design, and precision biofabrication, which could mean the possibility of creating more effective, accessible, and patient-specific collagen implants. The aim of this article is to examine the current state and determine the prospects for the development of mechanical properties of collagen implant used in neurosurgery towards Industry 4.0/5.0, including ML model. Full article

Human cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is a complex parasitic disease marked by dynamic host–parasite interactions and immunomodulation. Extracellular vesicles (EV) derived from immune cells have emerged as key mediators of intercellular communication and potential biomarkers in infectious diseases. In this study, we combined a modified lymphocyte proliferation assay with nano-flow cytometry to quantify and phenotype EV released by CD4⁺, CD8⁺, and CD14⁺ cells in PBMC cultures from CL patients at different clinical stages: before treatment (PBT), during treatment (PDT), and post-treatment (PET) with antimonial. Healthy individuals (HI) were included as physiological controls. Upon stimulation with L. (V.) braziliensis antigens, we observed a distinct modulation of EV subsets. In the PBT group, CD4⁺ and CD14⁺ EV were significantly reduced, while CD8⁺ EV remained elevated. During PDT and PET, EV concentrations were restored across all subsets. These findings suggest that L. (V.) braziliensis selectively modulates the release of immune cell–derived EV, possibly as an immune evasion mechanism. The restoration of EV release following antimonial therapy highlights their potential as sensitive biomarkers for disease activity and treatment monitoring. This study offers novel insights into the immunoregulatory roles of EV in CL and underscores their relevance in host–parasite interactions. Full article