Search Results (6,505)

Renal cell carcinoma (RCC) has been described as a metabolic disease as metabolic alterations are common in disparate RCC etiologies. Extracellular vesicles (EVs), the lipid bilayer-enclosed nanoparticles secreted by all living cells, have emerged as crucial mediators of intercellular and inter-organ communication, capable of shuttling functional proteins, lipids, and nucleic acids between cells. This review summarizes the essential events in tumor-associated metabolic reprogramming with a particular focus on renal cancers. We further explore how EVs released by metabolically deranged cells in cancer with altered cargos reprogram the renal cellular landscape, fostering tumor initiation, proliferation, angiogenesis, immune evasion, and therapy resistance. Understanding this EV-mediated axis not only elucidates the pathophysiological link between these conditions but also helps to unveil novel potential therapeutic targets for RCC patients. Full article

Fetal hemoglobin (HbF) plays a central role in mitigating the pathophysiological effects of sickle cell disease (SCD). Understanding the genetic determinants influencing HbF expression is essential for identifying the factors contributing to its modulation. This review provides an updated synthesis of evidence on HbF modulation, focusing on β^s haplotypes and their molecular characterization through Sanger sequencing, polymorphisms consistently associated with HbF levels in genome-wide association studies (GWAS), and recent advances in gene editing targeting HbF expression. An integrative review (2016–2025) was conducted using PubMed/MEDLINE, Scopus, and Web of Science, encompassing original research, experimental studies, systematic reviews, and genomic analyses. Key regulatory loci such as BCL11A, HBS1L-MYB (HMIP), and the HBB cluster explain a significant proportion of HbF variability across populations. Furthermore, additional variants in KLF1, NFIX, BACH2, and ZBTB7A have emerged as potential modulators in specific cohorts. Regarding advances in γ-globin editing, “prime editing”, although still in the experimental phase, has recently emerged as an innovative approach capable of introducing multiple HPFH-like mutations within γ-globin promoters, expanding future therapeutic possibilities in SCD. This review also provides a comparative overview of prime editing and other gene-editing strategies for HbF modulation, such as CRISPR-Cas9 and Base editing. Collectively, this work outlines the current landscape of HbF modulation and provides an informative basis for future research aimed at advancing precision-oriented therapeutic strategies in sickle cell disease. Full article

Small mammals play a central role in northern ecosystems, yet their diversity and habitat associations remain poorly documented in the subarctic mountains of northwestern Canada. I assessed small mammal assemblages across elevational and habitat gradients in Tombstone Territorial Park, located in the Taiga Cordillera Ecozone. My objectives were to document small mammal diversity and habitat associations. In 2005, small mammals were sampled at 27 sites representing seven common habitat types, ranging from lowland boreal forest to subalpine shrublands and alpine tundra. Twelve species of voles, lemmings, mice, and shrews were captured. Species richness and relative abundance were highest in lowland habitats and declined with increasing elevation. Alpine habitats supported fewer, highly specialized species. Several species were restricted to lowland habitats, whereas two species occurred exclusively in alpine tundra. Canonical correspondence analysis revealed a separation of species assemblages based primarily on moisture. These findings demonstrated that moisture, elevation, and habitat type structured small mammal assemblages in this northern mountain landscape. As a first approximation of small mammal assemblages in the Taiga Cordillera Ecozone, I provide a historical baseline for detecting recent and future ecological change. Climate change may facilitate the range expansion of lowland species and alter alpine assemblages, with potential consequences for community composition, trophic interactions, and ecosystem processes, highlighting the importance of small mammal monitoring in a rapidly warming subarctic. Full article

Objective: Given the global trend of ecological protection and sustainable development, Global Geoparks have become an essential platform for resource conservation and regional growth. Changzhi City in Shanxi Province, China, is actively applying for Global Geopark status, relying on its rich geoheritage sites, cultural history, and natural landscapes. This paper presents a systematic evaluation of the city’s geodiversity and relic value, analyzes the feasibility of establishing a Global Geopark in Changzhi City, and provides scientific support for Changzhi City’s Global Geopark application. Methods: Geodiversity data were collected by region using a 1:25,000 grid for sampling. Four methods were adopted for evaluation, namely, the Shannon diversity index, Simpson diversity index, entropy weight method (EWM), and Pielou evenness index. Upon comprehensive comparison of the four approaches, the most suitable approach was selected to produce the final results. For the value evaluation of the geoheritage, a combination of the analytic hierarchy process and the entropy weight method was employed. Results: (1) According to the results of all four methods, the geodiversity of Changzhi City is higher in the eastern and western regions and lower in the central area. (2) The geoheritage sites are mainly distributed in the eastern part of the city and have relatively high relic value. (3) Changzhi City contains abundant natural reserves and cultural resources, meeting the fundamental requirements for Global Geopark construction. Specifically, 38 townships across eight counties were identified as potential geopark areas, encompassing 54 geoheritage sites, 76 provincial-level or higher cultural-relic protection sites, and 15 provincial-level or higher natural protected areas, with a total area of 4458.51 km². Conclusions: Our results suggest that the Shannon diversity index is an effective tool for evaluating geodiversity in Changzhi City. Based on the region’s geological and natural conditions, the delineated geopark area is feasible. In summary, our findings provide essential references for the protection and sustainable development of geoheritage sites, geodiversity, and geoparks and offer strong theoretical and data support for Changzhi City’s Global Geopark application. Full article

B7-H3 (CD276), a member of the B7 family of proteins, is known to play a key role in the progression of a number of cancers. This protein is selectively expressed in both tumor cells and immune cells within the tumor microenvironment. Various investigations, including a number of clinical trials, have reported high levels of expression of this protein in cancerous tissues compared to their healthy counterparts. This difference in expression attracted various research efforts to establish whether such a difference can be linked to the therapeutic potential of this molecule. It is worth noting that B7-H3 is not the only immune checkpoint expressed at different levels in cancerous and healthy cells. Therapeutic strategies, based on different levels of expression, have been tested with other checkpoints. To inhibit the expression of some checkpoints, immune checkpoint inhibitors (ICIs) were developed. The introduction of these inhibitors for the treatment of some forms of advanced-stage tumors has been justly described as an important milestone in the landscape of immune therapy. Years after the launch of these inhibitors, numerous clinical trials revealed that these inhibitors benefit a narrow subset of patients suffering from advanced-stage tumors, while the majority of patients treated with these inhibitors either did not respond positively or simply did not respond at all (refractory patients). Other clinical trials showed that this form of treatment can provoke serious immune-related adverse events (irAEs). It is fair to state that changes in the expression level of a given protein in diseased tissue is an important parameter to take into account in the assessment of such a protein as a therapeutic target. However, the last ten years have demonstrated that taking the level of expression of a given checkpoint within a cancerous tissue is not sufficient to consider such expression a reliable predictive biomarker for the investigated disease. On the other hand, to establish a solid base for a given therapeutic strategy, these varying levels of expression have to be combined with a deep understanding of the biology of the molecule under investigation, as well as the identification and thorough analysis of the relevant signaling pathways, particularly those communicating with both the investigated molecule and the immune system. Recently, a number of pharmaceutical and biotechnology firms have suggested that B7-H3 is a highly promising therapeutic target for the development of immune therapeutics. In this review, we ask why hopes of better therapeutic performance are attached to this immune checkpoint. A partial answer to this question is provided through the careful consideration of the available data generated by various clinical trials. The contribution of mass spectrometry-based proteomics to this area of research is highlighted. Full article

Ice and snow tourism (IST) is a significant global trend, offering Russia opportunities for tourism growth and seasonal diversification. This study investigates the potential of ice and snow art as a distinct subcategory of IST on Lake Baikal. Our research is based on an analysis of academic publications and official policy documents, field surveys conducted in winter 2025, and stakeholder consultations, with the “Olkhon Ice Fest” serving as a case study. The findings indicate a clear shift toward IST, with the number of winter tourists on Olkhon Island increasing by 70% between 2021 and 2024. The festival’s key features—its use of the natural ice landscape, a unique artistic technique, an explicit ecological focus, and strong entrepreneurial initiative—support the development of a conceptual model of IST on Lake Baikal grounded in ecotourism principles. Ensuring the long-term sustainable development of IST in the region requires improved governance, infrastructure, and transport systems, as well as support for green businesses and increased environmental awareness among tourists. This study contributes to the ongoing discourse on sustainable winter tourism by demonstrating the interconnections among environmental sustainability, socioeconomic benefits, and cultural innovation, thereby situating local IST practices within the broader framework of the United Nations Sustainable Development Goals (SDGs). Full article

Tree pollen allergies are influenced by regional atmospheric pollen concentrations and flora distribution. Climate change and urban landscaping have altered airborne pollen profiles in Ukraine, potentially affecting sensitization patterns. We examined 7518 patients (57.63% children) sensitized to at least one of 26 molecular components from 19 tree species using ALEX testing (2020–2022). Atmospheric pollen data from Ukrainian aerobiology stations were integrated with clinical data. Regional sensitization was mapped using the Geographic Information System, and Bayesian network modeling determined hierarchical relationships. Sensitization to Cry j 1 (46.01%), Bet v 1 (41.67%), and Fag s 1 (34.38%) dominated across age groups. High Fagales sensitization correlated with elevated atmospheric Betula, Alnus, and Corylus pollen concentrations, confirming environmental exposure-sensitization relationships. Bayesian modeling identified Bet v 1 as the root allergen (89.43% accuracy) driving cascading sensitization to other Fagales and non-Fagales allergens. Unexpectedly high Cry j 1 sensitization despite minimal atmospheric Cryptomeria presence suggests Thuja and Ambrosia cross-reactivity. Fagales sensitization dominated 10 of 17 regions, correlating with forest geography and urban landscaping. This study validates aerobiological monitoring’s clinical relevance. Diagnostic protocols should prioritize Bet v 1 while interpreting Cry j 1 positivity as potential cross-reactivity. Climate-driven shifts in atmospheric pollen patterns require ongoing coordinated aerobiological and clinical surveillance. Full article

Melanoma was once considered ‘incurable’; however, drug therapy for the condition has dramatically transformed with the advent of immune checkpoint inhibitors and molecular targeted therapies. In this review, we summarize the published literature on melanoma drug therapy, presenting the current landscape of melanoma treatments, and discuss potential future transformations in melanoma therapy. Although the prognosis of advanced-stage melanoma had been extremely poor in the past, new-age immunotherapy has made long-term survival possible. Several immunotherapies and their combinations, as well as personalized vaccines, cell therapies, and intratumoral agents, have been tested with success; however, adverse toxicities have also been detected. Therefore, patient selection and management are critical. Furthermore, new approaches to overcome the limitations of the current treatments are also being developed. To implement these therapies clinically, guideline-recommended treatment algorithms should be followed while optimizing the therapies by considering factors such as presence of BRAF mutations which may lead to treatment resistance, increased disease burden/progression rate, toxicity tolerance, and the presence of brain metastases. In practice, the choice of the initial therapy should depend on the patient, leading to personalized therapy and minimal adverse effects. Full article

Agricultural expansion is a major driver of biodiversity loss in tropical regions, yet human-dominated landscapes also hold potential for biodiversity conservation when managed as multifunctional mosaics that retain patches of native vegetation. We assessed how natural and semi-natural habitats contribute to avian diversity in a tropical livestock farm in northern Costa Rica. Over one year, bird assemblages were sampled across three habitat types (live fences, pastures and riparian forest) at La Balsa farm. Using point counts surveyed every month during the year, we recorded 165 bird species, including 20 migratory and 6 species of global conservation concern, and 4 regionally endemic species. Species richness and overall abundance were lower in the riparian forest compared to live fences and pastures, and bird assemblage composition differed markedly among habitats, with the community in the riparian forest exhibiting a distinct assemblage structure. These results indicate that though the riparian forest hosts fewer species and individuals, it harbors a characteristic bird assemblage, highlighting its irreplaceable ecological role in providing habitat to forest-dependent species. Overall, the findings underscore that structurally diverse agricultural mosaics can sustain remarkably high bird diversity when complemented by habitats including native vegetation. Full article

Wildfires are increasingly frequent and intense due to climate change, resulting in degraded soils with diminished microbial activity, reduced water retention, and low nutrient availability. In many regions, previously restored areas face repeated burning events, which further exhaust soil fertility and limit the potential for natural regeneration. Traditional reforestation approaches such as seed scattering or planting seedlings often fail in these conditions due to extreme aridity, erosion, and lack of biological support. To address this multifaceted problem, this study proposes a living, biodegradable hydrogel that integrates an engineered soil-beneficial microorganism consortium, designed to deliver beneficial compounds and nutrients combined with endemic plant seeds into a single biopolymeric matrix. Acting simultaneously as a biofertilizer, soil conditioner, and reforestation aid, this 3-in-1 system provides a microenvironment that retains moisture, supports microbial diversity restoration, and facilitates plant germination even in nutrient-poor, arid soils. The concept is rooted in circular economy principles, utilizing polysaccharides from food industry by-products for biopolymer formation, thereby ensuring environmental compatibility and minimizing waste. The encapsulated microorganisms, a Bacillus subtilis strain and a Nostoc oryzae strain, are intended to enrich the soil with useful compounds. They are engineered based on synthetic biology principles to incorporate specific genetic modules. The B. subtilis strain is engineered to break down large polyphenolic compounds through laccase overexpression, thus increasing soil bioavailable organic matter. The cyanobacterium strain is modified to enhance its nitrogen-fixing capacity, supplying fixed nitrogen directly to the soil. After fulfilling its function, the matrix naturally decomposes, returning organic matter, while the incorporation of a quorum sensing-based kill-switch system is designed to prevent the environmental escape of the engineered microorganisms. This sustainable approach aims to transform post-wildfire landscapes into self-recovering ecosystems, offering a scalable and eco-friendly alternative to conventional restoration methods while advancing the integration of synthetic biology and environmental engineering for climate resilience. Full article

Mapping forest growth potential across varying environments is challenging, especially when field measurements are limited. In this study, we integrated Airborne Laser Scanning (ALS) terrain derivatives and Sentinel-2 spectral indices to model Site Index (SI), using forest plantations, at 10-m spatial resolution across three ecologically distinct regions in British Columbia (Aleza Lake, Deception, and Eagle Hills). Random Forest regression models were calibrated using field-measured SI and a multistep variable-selection procedure that included Variance Inflation Factor (VIF) screening followed by model-based variable importance assessment. Model performance was evaluated using repeated 10-fold cross-validation. The combined ALS–Sentinel-2 models substantially outperformed single-source models, yielding cross-validated R² values of 0.63, 0.44, and 0.56 for Aleza Lake, Deception, and Eagle Hills, respectively, compared with R² values of 0.40, 0.40, and 0.46 for ALS-only models. Key predictors consistently included terrain metrics, such as the Topographic Position Index (TPI) and the Topographic Wetness Index (TWI), along with satellite-derived chlorophyll-sensitive indices including S2REP (Sentinel-2 red-edge position), MTCI (MERIS terrestrial chlorophyll), and GNDVI (Greenness Normalized Difference Vegetation Index). A general model using predictors common to all regions performed comparably (R² = 0.63, 0.41, 0.52), demonstrating the transferability and operational potential of the approach. These findings demonstrate that integrating ALS-derived terrain metrics with Sentinel-2 spectral indices provides a robust, age-independent framework for capturing spatial variability in forest productivity across landscapes. This multi-sensor fusion approach enhances traditional SI methods and single-sensor models, providing a scalable and operational tool for forest management and long-term planning in changing environmental conditions. Full article

Ocular melanomas, comprising uveal melanoma (UM) and conjunctival melanoma (CoM), represent the most common primary intraocular and ocular surface malignancies in adults. Although rare compared with cutaneous melanoma, they exhibit unique molecular landscapes that provide critical opportunities for biomarker-driven precision medicine. In UM, recurrent mutations in GNAQ and GNA11, together with alterations in BAP1, SF3B1, and EIF1AX, have emerged as key prognostic biomarkers that stratify metastatic risk and guide surveillance strategies. Conversely, in CoM, the mutational spectrum overlaps with cutaneous melanoma, with frequent alterations in BRAF, NRAS, NF1, and KIT, offering actionable targets for personalised treatment. Beyond genomics, epigenetic signatures, microRNAs, and protein-based markers provide further insights into tumour progression, microenvironmental remodelling, and immune evasion. In parallel, liquid biopsy has emerged as a minimally invasive approach for real-time disease monitoring. Analyses of circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and exosome-derived microRNAs demonstrate increasing potential for early detection of minimal residual disease, prognostic assessment, and evaluation of treatment response. However, the clinical integration of these biomarkers remains limited by tumour heterogeneity, technical variability, and the lack of unified translational frameworks. This review synthesises current knowledge of molecular and liquid biopsy biomarkers in ocular melanoma, highlighting their relevance for diagnosis, prognosis, and treatment personalisation. The integration of established tissue-based molecular markers with novel liquid biopsy technologies will enable a unique framework for biomarker-guided precision oncology and risk-adapted surveillance in uveal and conjunctival melanoma, offering insight into strategies for early detection, therapeutic monitoring, and personalised clinical management. Full article

Corticosteroid receptor signaling in primary afferent neurons of the dorsal root ganglion (DRG) has emerged as a potential target to modulate nociception via genomic and nongenomic mechanisms shown in animal pain models. However, the expression landscape of glucocorticoid receptors (GRs) relative to mineralocorticoid receptors (MRs) in human DRG, their association with pain-related markers, and their functional relevance remain incompletely defined. We analyzed human and rat DRG by mRNA profiling and immunofluorescence confocal microscopy to assess GR/MR expression and complemented these studies with a clinical evaluation of neuraxial corticosteroid delivery. Here, GR transcripts in human DRG were the most abundant among corticosteroid receptor-related genes examined (including MR) and were observed alongside transcripts of pain-signaling molecules. Human DRG immunofluorescence analysis revealed substantial colocalization of GR with calcitonin gene-related peptide (CGRP), a marker of nociceptive unmyelinated C-fibers and thinly myelinated Aδ-fibers, as well as with gial fibrillary acidic protein (GFAP), a marker of satellite glial cells (SGCs), but minimal expression in myelinated neurofilament 200 (RT-200) immunoreactive (IR) human DRG neurons. In addition, GR immunoreactivity was primarily distributed to medium-diameter neurons (40–65 µm). Functionally, preclinical experiments showed that GR activation and MR blockade attenuate inflammatory pain via rapid, nongenomic neuronal mechanisms that counter an intrinsic mineralocorticoid receptor-mediated pronociceptive drive. Consistently, clinical analgesia over at least 3 months after transforaminal plus caudal epidural delivery of GR agonists in chronic radicular pain supports a functional role for neuronal GR signaling within spinal cord and DRG circuits. Together, these molecular, functional, and clinical findings identify GR as a key modulator of sensory neuron excitability and pain, highlight MR as a pronociceptive counterpart, and suggest that selectively enhancing GR signaling or inhibiting MR signaling may offer a potential strategy for improving corticosteroid-based analgesic therapies. Full article

Background: The present study set out to identify key miRNAs, TFs and signaling pathways associated with bladder cancer, with a view to elucidating the networks of miRNA-TF-gene interactions that may serve as potential molecular biomarkers for disease diagnosis. Methods: An integrative analysis was conducted using the publicly available microarray dataset GSE130598. Expression profanalyzede analyzed from 42 muscle-invasive bladder cancer (MIBC) tissues and 42 matched adjacent normal bladder tissues. After data preprocessing and normalization, differentially expressed genes (DEGs) were identified. To identify the associated biological processes and signaling pathways, functional enrichment analyses were conducted using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Protein–protein interaction (PPI) network analysis was then employed to identify hub genes and key molecular interaction modules associated with bladder cancer. Results: MYC, TP53, SP1, E2F1, E2F3, NFKB1, and TWIST1 were identified as central transcriptional regulators, indicating their roles in controlling genes involved in cell cycle regulation, DNA damage response, and tumor progression. Several miRNA families, including miR-200, miR-17, miR-29, miR-141, and miR-548, have been identified as key post-transcriptional regulators, suggesting their involvement in oncogenic signaling and cellular differentiation. PPI network analysis revealed MAPK3, AKT1, CHEK1, CDK1, AURKA, and AURKB as hub genes associated with cell proliferation, mitotic control, and intracellular signaling. Conclusions: Fundamental molecular processes underlying bladder cancer pathogenesis include cell cycle control, signal transduction, and genomic stability. These findings provide insight into the molecular regulatory landscape of MIBC and highlight potential targets for diagnostic and prognostic applications. Full article

The red fox (Vulpes vulpes) is a widely distributed and highly adaptive small carnivore known by its generalist diet, which includes small mammals, invertebrates, and fruits. Despite its ecological relevance, how habitat heterogeneity affects its diet across the Mediterranean, a biodiversity hotspot shaped by long-term human disturbance, remains insufficiently synthesized. In this review, we synthesized and analyzed published studies that reported habitat-specific data on the red fox diet in the Mediterranean. Only 12 studies met the selection criteria, and no study directly compared two different habitats. The studied areas covered three dominant habitats: forests, scrublands (garrigue), and agroecosystems, and diet items were grouped in 7 categories: birds, carcasses, fruits, invertebrates, lagomorphs, small mammals, and reptiles. Overall diet composition varied significantly, with invertebrates and fruits being the most frequent diet items. In turn, lagomorphs and reptiles were the least frequent. In turn, diet composition varied little across habitats, indicating that diet variation follows specific local resource abundance regardless of habitat type. Despite the analytical limitations associated with the limited availability of habitat-explicit studies. The results highlight the pronounced dietary plasticity of the red fox and its capacity to integrate resource availability across heterogeneous Mediterranean landscape mosaics. This trophic adaptability and top predator role support various ecosystem functions such as controlling invertebrate and small mammal populations, dispersing seeds, and cycling nutrients, reinforcing the potential of the red fox as functional bioindicator in the Mediterranean. Therefore, sustainable land management, especially in agricultural areas, and restoration efforts for degraded areas should consider the beneficial roles of generalist carnivores like the red fox. Full article