Search Results (358)

The premetastatic niche (PMN) represents a specialized microenvironment established in distant organs before the arrival of metastatic cells. This concept has fundamentally altered our understanding of cancer progression, shifting it from a random event-driven process to an orchestrated one. This review examines the critical role of extracellular proteases in PMN formation, focusing on matrix metalloproteinases (MMPs), serine proteases, and cysteine cathepsins that collectively orchestrate extracellular matrix remodeling, immune modulation, and vascular permeability changes essential for metastatic colonization. Key findings demonstrate that MMP9 and MMP2 facilitate basement membrane degradation and the recruitment of bone marrow-derived cells. At the same time, tissue inhibitor of metalloproteinase-1 (TIMP-1) promotes organ-specific hepatic PMN recruitment through neutrophil recruitment mechanisms. The plasminogen–plasmin system emerges as a master regulator through its broad-spectrum proteolytic activity and ability to activate downstream proteases, with S100A10-mediated plasmin generation providing mechanistic pathways for remote PMN conditioning. Neutrophil elastase and cathepsin G contribute to the degradation of anti-angiogenic proteins, thereby creating pro-metastatic microenvironments. These protease-mediated mechanisms represent the earliest interventional window in metastatic progression, offering therapeutic potential to prevent niche formation rather than treat established metastases. However, significant methodological challenges remain, including the need for organ-specific biomarkers, improved in vivo methods for measuring protease activity, and a better understanding of temporal PMN dynamics across different target organs. Full article

Habitat fragmentation poses a serious threat to bee communities, which are essential for pollination and biodiversity conservation. This study evaluated how habitat fragmentation in an oak forest in Zapopan, Mexico affected bee diversity, abundance, feeding niches, and bee–plant interaction networks. We compared a protected natural area with a nearby forest fragment that has been isolated from the main forest by urbanization for the past 10 years. Wild bee abundance and species richness in the fragmented area decreased by 74% and 70%, respectively, compared to the natural area, accompanied by a significant reduction in diversity. Community composition shifted mainly due to species loss; furthermore, there was persistence of generalist species such as Apis mellifera, which became more abundant in the forest fragment. Feeding niches in the fragmented area were narrower according to the Levin index, reflecting more restricted diets and increased interspecific competition. Interaction networks were simplified, showing fewer interactions, loss of specialist bees, and decreased equitability, although network specialization remained stable, and an almost-total turnover in interactions indicated a reconfiguration of pollination patterns. These findings suggest that fragmentation negatively affects bee community structures and their interactions with plants, potentially compromising pollination and ecosystem services. Conservation of protected areas and restoration of disturbed sites with native plants are recommended to support the recovery and stability of bee communities and their ecological interactions. Full article

Climate change exacerbates the vulnerability of relict forests. However, plant taxa may buffer extinction risk through range shifts that track suitable habitats or through adjustments in their ecological niches, either via phenotypic plasticity or evolutionary adaptation to prevailing environmental regimes. In addition to these biological responses, the risks associated with climate change can also be mitigated through forest management practices and conservation strategies, including assisted migration. We used presence–absence data from Abies pinsapo Boiss. and environmental variables to describe the past and current natural distribution of the species by using species distribution models (SDMs). Then, we characterized future patterns of habitat suitability and identified potential areas for ecosystem restoration and assisted migration. The models predict a 77% loss of suitable habitat by 2060 and up to 99% by 2100 yet highlight climatically suitable areas outside the species’ current range—particularly in the Sierra Nevada National and Natural Park and Sierras de Cazorla, Segura y Las Villas Natural Park. These results provide spatially explicit guidance for restoration and assisted migration strategies. Our findings demonstrate the need for proactive conservation planning and show that SDMs can help identify climate refugia for long-term species persistence. Full article

This study investigates the changes and driving mechanisms of agritourism landscapes in mountainous regions of Southwest China, providing a scientific basis for sustainable landscape management. We analyzed Hanyuan County (2013–2023) using remote images, POI data, terrain niche index, distribution index, landscape transition matrix, and logistic regression model from a landscape function perspective. These analyses reveal that the landscape pattern maintains overall stability with local fluctuations, with ecologically oriented landscapes being consistently dominant (>76% coverage). The primary conversion direction of development-potential landscapes shifted from ecological to agricultural dominance after 2018. All landscape types have shown more distinct distribution advantages in the fifth-level terrain gradient, with intensified fluctuations in low-gradient areas after 2018. Location factors were the most common driving force, but their effects differ: production-oriented landscapes shifted from location–climate correlation to location–socioeconomic–terrain correlation; living-oriented landscapes remain influenced by slope and location accessibility; ecological-oriented landscapes shifted from a location–climate correlation to location–tourism correlation; development-potential landscapes were positively influenced by multiple factors. This study suggests implementing zoned management based on functions and terrain gradients through policy guidance and technological intervention. The findings of this study can provide a reference for the comprehensive revitalization of rural areas and the sustainable development of landscapes in similar areas. Full article

Background: Recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) after immune checkpoint inhibitor (ICI) progression represents a major clinical challenge. Between 60 and 80% of patients develop resistance, and historical salvage regimens like cytotoxic chemotherapy or chemotherapy plus cetuximab rarely extend median overall survival (mOS) beyond one year. Scope of Review: This review examines systemic therapies evaluated specifically in the post-ICI setting, emphasizing agents advancing to Phase II and III trials. Classes include chemotherapy combinations, ICI-based approaches, small-molecule targeted combinations, bispecific antibodies, antibody-drug conjugates (ADCs), and next-generation vaccines. Results: Promising signals have emerged across multiple therapeutic modalities. Targeted combination strategies have demonstrated encouraging response rates and survival outcomes in difficult-to-treat, PD-1-resistant disease. Antibody-based platforms, including antibody-drug conjugates and bispecific antibodies, continue to show consistent clinical activity across diverse patient populations, offering disease control and prolonged survival. Novel immunotherapies and therapeutic vaccines are also generating durable responses, particularly in biologically defined subgroups, highlighting the potential of immune-based precision treatments in R/M HNSCC. Conclusions: Comparative analysis highlights distinct advantages and limitations: chemotherapy ensures rapid shrinkage but poor durability; biomarker-driven small molecules achieve strong survival gains in narrow niches; ADCs and bispecifics offer balanced efficacy in unselected patients; and vaccine platforms deliver durable benefit in defined subsets. Together, these data signal a paradigm shift toward biomarker-guided, mechanism-driven strategies as the path to closing the post-ICI therapeutic gap in R/M HNSCC. Full article

Candida and other pathogenic yeast species, able to transition from non-invasive commensal organisms to invasive pathogens, are characterized by a high ability to adapt to stress conditions encountered in the human host, such as pH and temperature shifts, CO₂ and oxygen level variations, and nutritional limitations. Although Candida albicans remains the main cause of Candida-related infections, non-albicans Candida (NAC) species, including C. tropicalis, C. parapsilosis, C. krusei, and non-Candida species such as Yarrowia lipolytica, Candidozyma auris, and Nakaseomyces glabratus, are gaining clinical importance. These species exhibit diverse mechanisms of pathogenicity, including morphological transition, modulation of gene expression pathways (cAMP-PKA/MAPK, Hsp, calcineurin, GlcNAc-mediated signaling), cell wall remodeling, post-translational reprogramming, biofilm formation, antifungal resistance, and enzyme secretion. C. albicans exhibits high morphological and metabolic plasticity for survival across body niches. N. glabratus and C. tropicalis show strong azole resistance and biofilm formation, while C. parapsilosis and C. krusei pose risks through surface adhesion and treatment resistance. C. auris stands out for heat tolerance, multidrug resistance, and outbreak potential. Y. lipolytica, though rare, forms persistent filamentous biofilms in critical care settings. Cryptococcus neoformans remains a life-threatening pathogen capable of immune evasion and crossing the blood–brain barrier. This review compares molecular mechanisms of pathogenicity across these fungi, emphasizing environmental adaptation, conserved and species-specific responses, and potentially highlighting targets for therapeutic management. Full article

Ecosystems worldwide are being influenced by climate change in complex ways, leading to profound impacts on biodiversity. While these shifts may constrain the adaptive capacity of some species, they may simultaneously promote the expansion of others, including certain rodents. The Funambulus pennantii (five-striped northern palm squirrel) and Funambulus palmarum (three-striped palm squirrel) demonstrate exceptional adaptability across diverse habitats from rural plantations to densely populated urban areas. Their close association with humans ranges from causing crop damage to becoming urban nuisances, leading to their broad classification as agricultural pests. Hence, this study utilizes ensemble species distribution models to identify the climatic niches of these two species and delineate overlapping suitable habitats within agricultural zones in current and different future climate scenarios. The ensemble model identified 215,748 km² of suitable habitat for F. pennantii and 39,578 km² for F. palmarum under current climatic conditions in India. The future projections indicate habitat increases of about 20.6% for F. pennantii and 48.1% for F. palmarum. The agricultural overlap is also projected to rise by up to 45% and 48%, respectively, compared with present overlaps of 215,595 km² and 39,073 km². The most substantial expansions are projected in the Gangetic Plains, Central Highlands, and parts of the Western and Eastern Ghats and Deccan Plateau. These findings suggest that both species possess high resilience to environmental change and may pose increasing risks to agriculture in a warming climate. The study underscores the need for proactive, ecologically sustainable management strategies to mitigate potential human–squirrel interactions and agricultural losses, offering a foundation for targeted regional interventions. Full article

Background: Stereotactic radiosurgery (SRS) was originally conceived as a noninvasive alternative to functional neurosurgery by the Swedish neurosurgeon Lars Leksell. This review traces the historical development of stereotactic methods from early mechanical frames to advanced image-guided systems and examines the pivotal innovations that enable precise intracranial targeting for SRS. Methods: Using PubMed and Google Scholar, we reviewed the literature on the general history of functional stereotactic neurosurgery and radiosurgery, its indications, and how their treatment methods evolved, focusing mainly on the early period from the end of the 18th century to the 1990s. Results: The origins of stereotaxy as a principle and technique were traced back to the early 20th century with animal studies by Horsley and Clarke, later adapted for human use by Spiegel and Wycis, and then Talairach in the 1940s. This enabled the precise targeting of deep brain structures for lesion-based interventions in movement, pain, and psychiatric disorders. Deep Brain Stimulation (DBS) emerged in the 1980s as a reversible treatment for tremor. Stereotactic radiosurgery was conceived in 1951 as a noninvasive alternative functional approach and saw limited use until the 1990s due to imaging constraints. With MRI-guided planning, its application has expanded mostly to the management of benign and malignant tumors and vascular disorders, as well as for functional approaches, particularly for trigeminal neuralgia, tremor, epilepsy, and OCD. Conclusions: This review underscores how technological progress and shifting clinical priorities have transformed SRS from a niche neurosurgical technique into a cornerstone of modern clinical practice, with functional SRS representing its latest clinical field of expansion. Full article

Trifolium repens L. is a protein-rich, versatile Leguminous lawn plant that is widely distributed across global temperate and subtropical regions. As an invasive species originating in Europe, its distribution in China extends from Xinjiang in the West to Taiwan and the Yangtze River Delta in the East, and is widespread throughout Northeast and Central China. However, in recent years, the distribution pattern of T. repens has become increasingly patchy and irregular. Therefore, unraveling the potential distribution and key environmental drivers of T. repens is critical for understanding its ecological role. This study utilized current species distribution data of T. repens and employed the MaxEnt model to simulate its potentially suitable niches across present and future climate scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5) in China. This study identified Bio2 (mean diurnal temperature range) and Bio14 (precipitation of driest month) as the key drivers shaping the distribution of T. repens. Its current suitable habitats are primarily concentrated in the coastal, central, and Taiwan regions of China. Under future climates, these areas are projected to contract overall and shift toward lower latitudes and higher longitudes, with substantial suitable areas remaining only in the Eastern, Southern, and Taiwan regions. This study quantitatively assessed the ecological niche breadth of T. repens and its future spatial distribution under climate change, thereby laying a theoretical foundation for describing the ecological characteristics of this invasive species, conducting monitoring, and implementing further invasion risk management. Full article

Background: The management of resected stage III colorectal cancer (CRC) has long been reliant on fluoropyrimidine-based adjuvant chemotherapy. However, the 10–15% of patients with mismatch repair-deficient (dMMR) tumors derive limited benefit from this approach. While immunotherapy has revolutionized the treatment of metastatic dMMR CRC, its role in the early-stage setting is rapidly evolving, creating a paradigm shift. Methods: A systematic literature review was conducted to identify pivotal clinical trials evaluating therapeutic strategies for non-metastatic dMMR CRC. Databases including PubMed/MEDLINE and conference proceedings from the American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) were searched up to June 2025. The review focused on phase II and III trials reporting on disease-free survival (DFS), pathological complete response (pCR), and safety. Study selection followed PRISMA guidelines. Results: The systematic review identified 14 key studies that were included for narrative synthesis. The evidence base encompassed three areas: (1) Foundational adjuvant chemotherapy trials (e.g., MOSAIC, IDEA); (2) Pivotal metastatic trials (e.g., KEYNOTE-177) validating immunotherapy efficacy in dMMR CRC; and (3) Modern trials in non-metastatic disease. The phase III ATOMIC trial demonstrated that adding atezolizumab to mFOLFOX significantly improved 3-year DFS versus chemotherapy alone (86.4% vs. 76.6%; Hazard Ratio [HR] 0.50, 95% Confidence Interval [CI] 0.34–0.72; p < 0.001). Concurrently, phase II neoadjuvant immunotherapy trials (e.g., NICHE-2) reported remarkable pCR rates of 68% and a 3-year DFS of 100%, with a more favorable safety profile compared to chemoimmunotherapy. Conclusions: The landscape for non-metastatic dMMR CRC is shifting from a chemotherapy-based model to an immunotherapy paradigm. The ATOMIC trial establishes adjuvant chemoimmunotherapy as a new standard, while robust neoadjuvant data suggest a potential future where short-course, chemotherapy-free immunotherapy could become a preferred strategy. Ongoing trials directly comparing these approaches are awaited. Full article

Understanding the feeding mechanisms and interspecific coexistence of sharks is crucial for effective conservation. This study conducted stable isotope analysis on muscle and liver samples from 449 individuals of eight common bycatch shark species collected via bottom trawling in the northern South China Sea (NSCS). Results revealed significant differences in δ¹³C and δ¹⁵N values among species and tissue types. Scoliodon laticaudus exhibited the highest trophic position (TP_muscle = 4.60 ± 0.33; TP_liver = 4.53 ± 0.29), while Apristurus platyrhynchus had the lowest (TP_muscle = 2.97 ± 0.44; TP_liver = 2.75 ± 0.53). Muscle and liver isotopic signals were consistent, but δ¹³C differences indicated distinct carbon sources, with Carcharhinus sorrah linked to deep-sea organic matter and S. laticaudus to coastal inputs. Significant correlations between δ¹³C/δ¹⁵N and body length in A. platyrhynchus and Cephaloscyllium fasciatum suggest ontogenetic shifts in diet and habitat toward deeper waters. Trophic niche analysis using corrected standard ellipse area (SEAc) showed Halaelurus burgeri with the widest trophic niche (SEAc > 1.7‰²), reflecting a broad diet, while C. fasciatum had the narrowest (SEAc < 0.3‰²), indicating specialized feeding. Additionally, H. burgeri and C. sarawakensis exhibited significant niche differentiation, reducing interspecific competition, whereas C. fasciatum and Squalus megalops showed high niche overlap, suggesting intense resource competition. The narrower liver niche of C. sarawakensis may reflect recent habitat constriction due to bottom trawling. This study elucidates the feeding ecology and habitat resource utilization of NSCS sharks, providing a scientific basis for effective conservation strategies for shark populations in the region. Full article

Radiotherapy (RT) remains a cornerstone of cancer treatment, offering spatially precise cytotoxicity against malignant cells. However, emerging evidence reveals that ionizing radiation (IR) exerts biological effects beyond the targeted tumor volume, manifesting as radiation bystander effects (BEs) and other non-targeted effects (NTEs). These phenomena challenge the traditional paradigm of RT as a localized intervention, highlighting systemic and long-term consequences in non-irradiated tissues. This comprehensive review synthesizes molecular, cellular, and clinical insights about BEs, elucidating the complex intercellular signaling networks gap junctions, cytokines, extracellular vesicles, and oxidative stress that propagate damage, genomic instability, and inflammation. We explore the role of mitochondrial dysfunction, epigenetic reprogramming, immune modulation, and stem cell niche disruption in shaping BEs outcomes. Clinically, BEs contribute to neurocognitive decline, cardiovascular disease, pulmonary fibrosis, gastrointestinal toxicity, and secondary malignancies, particularly in pediatric and long-term cancer survivors. The review also evaluates countermeasures including antioxidants, COX-2 inhibitors, exosome blockers, and FLASH RT, alongside emerging strategies targeting cfCh, inflammasomes, and senescence-associated secretory phenotypes. We discuss the dual nature of BEs: their potential to both harm and heal, underscoring adaptive responses and immune priming in specific contexts. By integrating mechanistic depth with translational relevance, this work posits that radiation BEs are a modifiable axis of RT biology. Recognizing and mitigating BEs is imperative for optimizing therapeutic efficacy, minimizing collateral damage, and enhancing survivorship outcomes. This review advocates for a paradigm shift in RT planning and post-treatment care, emphasizing precision, personalization, and systemic awareness in modern oncology. Full article

The soil microbiome is an essential component of agroecosystems. However, managing it remains a challenge due to our limited knowledge of how various environmental factors interact and shape its spatial distribution. This study presents a hierarchical ecological model to explain the assembly of the microbiome in sloping agricultural landscapes. Through a comprehensive analysis of bacterial and fungal communities, as well as the examination of metabolic and phytopathogenic profiles across a topographic gradient, we have demonstrated that topography acts as the main filter, structuring bacterial communities. Land use, on the other hand, serves as a secondary filter, refining fungal functional guilds. Our results suggest that hydrological conditions in floodplains favor the growth of stress-tolerant bacterial communities with low diversity, dominated by Actinomycetota. Fungal communities, on the other hand, are directly influenced by land use. Long-term fallow periods lead to an enrichment of arbuscular mycorrhiza, while agroecosystems shift towards pathogenic and saprotrophic niches. Furthermore, we identify specific topographic positions that may be hotspots for phytopathogenic pressure. These hotspots are linked to certain taxa, such as Ustilaginaceae and Didymellaceae, which may pose a threat to plant health. The derived hierarchical model provides a scientific foundation for topography-aware precision agriculture. It promotes stratified management, prioritizing erosion control and soil restoration on slopes, customizing nutrient inputs in fertile floodplains, and implementing targeted phytosanitary monitoring in identified risk areas. Our research thus offers a practical framework for harnessing soil spatial variability to improve soil health and proactively manage disease risks in agricultural systems. Full article

Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic immune-mediated disorders characterized by mucosal injury, cycles of inflammation and repair, and tissue damage. Persistent inflammation accelerates epithelial turnover, generates oxidative and replication stress, and remodels the stromal niche, contributing to the risk of colorectal cancer (CRC). Systematic dysplasia surveillance remains essential. Cellular senescence has emerged as a unifying mechanism linking inflammation, impaired epithelial repair, fibrosis, and neoplasia. In UC, p16/p21 upregulation, telomere erosion, and loss of lamin B1 accumulate and adopt a senescence-associated secretory phenotype (SASP) that perpetuates barrier dysfunction. In CD, senescence within stem and stromal compartments limits regeneration, promotes pro-fibrotic remodeling, and sustains cycles of injury and repair via chronic SASP signaling. IBD prevalence continues to rise from environmental factors, dietary changes, antibiotic exposures, and gut microbiota alterations. Pathogenesis integrates genetic factors (e.g., NOD2, IL23R, HLA, and ATG16L1 mutations), environmental modifiers, dysbiosis characterized by loss of short-chain fatty-acid-producing Gram-positive bacteria and expansion of Proteobacteria, and a dysregulated immune system. Therapeutic strategies have shifted toward targeted biologics and small molecules to promote mucosal healing. In this review, we recapitulate the mechanistic axes of inflammation, oxidative stress, and senescence in IBD and then critically evaluate emerging targeted therapies. Topics include anti-TNFα, integrin blockade, IL-12/23 and IL-23 inhibition, JAK inhibitors, S1P receptor modulators, microRNA modulation, senomorphics, mesenchymal cell therapy, and microbiome interventions. We endorse biomarker-guided therapy and propose future directions to break the SASP-driven inflammatory loop and mitigate long-term carcinogenic risk. Full article

This study offers a comprehensive analysis of the performance and systemic dynamics of green finance investments in environmentally sustainable technologies from 2000 to 2025, complemented by scenario-based projections extending to 2050. Empirical results indicate a consistent increase in portfolio returns—from 5.2% in 2000 to 11.8% in 2025—accompanied by a significant reduction in annualized volatility, declining from 8.1% to 3.0%. Concurrently, the portfolio’s sustainability score improved from 0.45 to a full alignment score of 1.00, reflecting a strategic shift towards high-impact green assets. Building on these observed trends, this study introduces the Eco-Financial Resonance Theory (EFRT), an original conceptual framework that interprets sustainable transitions as emergent phenomena arising from resonant interactions among four interdependent domains: financial flows, technological innovation, policy and regulation, and environmental outcomes. Scenario analyses highlight the pivotal roles of policy ambition and innovation pathways in shaping long-term risk-return profiles, with optimistic forecasts projecting returns exceeding 40% by 2050, alongside markedly reduced risks. Regional analysis reveals persistent disparities, underscoring the necessity for context-specific strategies to enhance systemic coherence. Beyond its theoretical contributions, EFRT offers actionable insights for investors and policymakers aiming to align profitability with ecological sustainability. Collectively, these findings position green finance not merely as a niche or ancillary activity but as a transformative mechanism for enabling scalable and resilient sustainability transitions amid accelerating global environmental challenges. Full article