Search Results (13,682)

Seasonal fluctuations in the chemical composition of fine particulate matter (PM_2.5) are known to influence its toxicological properties; however, their integrated biological effects remain incompletely understood. In this study, PM_2.5 was continuously collected over two consecutive years at a single urban site in Japan and classified by season. The samples were comprehensively characterized for ionic species, metals, carbonaceous fractions, and polycyclic aromatic hydrocarbons (PAHs), and their pulmonary effects were evaluated in vivo following intratracheal administration in mice. Seasonal PM_2.5 exhibited pronounced compositional differences, with higher levels of secondary inorganic aerosol components in summer and enrichment of PAHs and mineral-associated components in winter. These seasonal differences translated into distinct biological responses. Reactive oxygen species (ROS) production (1.6–2.7-fold increase) and bronchoalveolar lavage (BAL) neutrophil infiltration were strongly associated with PAH-rich PM_2.5, whereas interleukin-1α (IL-1α) showed robust positive correlations with mineral components, including K⁺, Ca²⁺, and Mg²⁺, which were predominantly enriched in winter PM_2.5. In contrast, secondary inorganic aerosol species displayed a limited capacity to induce IL-1α. Compared with summer samples, winter PM_2.5 induced significantly higher levels of ROS production and IL-1α (approximately 1.5–2.6-fold increase). Using TLR2- and TLR4-deficient mice, we further demonstrated that PM_2.5-induced increases in BAL cell counts, ROS, IL-6, and TNF-α were partially attenuated in TLR4 knockout mice, indicating a contributory but not exclusive role for TLR4 signaling in PM_2.5-driven pulmonary inflammation. Collectively, these findings demonstrate that seasonal variations in PM_2.5 composition, not particle mass alone, critically shape oxidative stress and innate immune responses in the lungs. In particular, winter PM_2.5 enriched in mineral-associated components preferentially activates IL-1α-mediated alarmin pathways, underscoring the importance of the particle composition in determining seasonal air pollution toxicity. Full article

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovitis. The prevalence of RA is estimated to be 0.5–1% worldwide. Methods: This work investigated the therapeutic effects and underlying mechanisms of blue mussel (Mytilus galloprovincialis) oil (BMO) on RA in rats, using green-lipped mussel oil (GMO) and Antarctic krill oil (KO) as controls. Results: The results suggested that BMO, GMO, and KO all alleviated paw swelling in rats and reduced serum levels of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, and pro-inflammatory cytokines such as TNF-$\alpha$ and IL-17. Histopathological assessment further revealed that BMO, GMO, and KO prevented synovial fibroplasia, mitigated inflammatory cell infiltration, and improved cartilage damage in ankle joints. Overall, BMO exhibited slightly superior alleviating effects compared with GMO and KO. Plasma lipidomics analysis revealed that the lipid metabolites altered by BMO showed significant correlations with RA-related indicators, particularly pro-inflammatory cytokines. Functional enrichment analysis suggested the involvement of inflammation-related pathways, particularly the NF-$\kappa$B signaling pathway. Further validation demonstrated that BMO effectively suppressed the production of inflammatory cytokines (TNF-$\alpha$, IL-17) and the expression of NF-$\kappa$B p65, JAK2, and STAT3 proteins in synovial tissue. And IL-17 production in footpad tissues is closely associated with CD3-positive T cells. Similar effects were also observed for GMO and KO. Conclusions: Collectively, BMO might ameliorate RA by inhibiting NF-$\kappa$B and JAK2/STAT3 signaling pathways. Full article

SiC/Al matrix composites are prone to forming brittle Al₄C₃ phase via interfacial reactions during fabrication, which severely limits their mechanical properties and engineering applications. Microalloying is an effective method to inhibit this brittle phase, yet the interfacial mechanism of alloying elements at the atomic scale remains unclear. Centered on molecular dynamics simulation combined with experimental verification, this study systematically investigates the laws of Fe and Ni microalloying on the interface regulation and mechanical property optimization of SiC/Al composites. Simulation results show that Fe and Ni atoms tend to segregate at the SiC/Al interface, which can suppress interfacial reactions, promote dislocation nucleation and proliferation, induce new dislocation types, and achieve the synergistic improvement of strength and ductility—with Ni exhibiting a more prominent strengthening effect. Composites prepared by the pressure infiltration-hot extrusion process show no Al₄C₃ phase in phase detection. Mechanical property tests confirm that Fe and Ni microalloying can effectively enhance the comprehensive performance of the materials, among which Ni increases the strength–ductility product by 54%. This study clarifies the interfacial regulation mechanism of Fe and Ni microalloying at the atomic scale, providing theoretical guidance and experimental support for the microalloying design of SiC/Al composites. Full article

Immunotherapy has become a promising treatment for gastric cancer. However, its effectiveness varies significantly across subtypes because of heterogeneous immune microenvironments and genomic alterations. Here, we established Immune&Driver molecular subtypes CS1 and CS2 by systematically integrating multi-omics data for immune-related and driver genes. CS1 was linked to a better prognosis, while CS2 represented a poorer prognostic phenotype. CS1 displayed enhanced genomic instability, marked by higher mutation frequency and chromosomal alterations. In contrast, CS2 exhibited higher immune activity, with a higher density of immune cell infiltration and increased expression of chemokines and immune checkpoint genes. Among FDA-approved anti-cancer agents included in a pan-cancer drug sensitivity prediction framework, CS1 was predicted to be more sensitive to conventional chemotherapeutic agents, whereas CS2 was predicted to be more responsive to immune-related agents. In melanoma datasets, a CS2-like transcriptomic pattern was associated with improved response to anti-PD-1 therapy, with the combination of anti-PD-1 and anti-CTLA-4 showing more favorable response patterns compared to anti-PD-1 monotherapy. Additionally, we developed an immunotherapy response prediction model using PCA-based logistic regression according to the transcriptional expression of CS biomarkers. The model was trained in melanoma immunotherapy cohorts and validated across independent melanoma datasets, and it further achieved a higher AUC in an external gastric cancer cohort treated with anti-PD-1 therapy. Collectively, this study highlights immune and genomic heterogeneity in gastric cancer and provides a hypothesis-generating framework for exploring immunotherapy response. Full article

A nonlinear mathematical model is developed for unsteady groundwater flow in a three-layer heterogeneous aquifer system, comprising a confined aquifer, a covering layer, and a weakly permeable barrier. The model incorporates infiltration and evaporation governed by the M.M. Krylov–S.F. Averyanov law, where evaporation intensity depends on a critical groundwater level. Governing equations are nondimensionalized and solved using the alternating direction implicit (ADI) method with quasi-linearization to treat nonlinearities. Periodic variations in precipitation and evaporation are considered, alongside variable boundary permeabilities. The approach enables realistic simulation of multi-layer aquifer dynamics under diverse climatic and hydrogeological conditions, offering a robust tool for sustainable groundwater management, drought risk assessment, and aquifer protection strategies. Full article

To enhance the climate adaptability and diagnostic precision of university sustainability frameworks, this study presents a critical advancement to the PICSOU (Performance Indicators for Core Sustainability Objectives of Universities) framework’s Indoor Environmental Quality (IEQ) module. The research employs a comparative approach across two distinct climate zones: the campus of Chengdu Jincheng College in a humid subtropical climate (CDJCC; Köppen Cwa) with natural ventilation, and the campus of Tallinn University of Technology in a temperate climate (TalTech; Köppen Dfb) with mechanical ventilation. A key innovation at CDJCC was the deployment of a novel, integrated sensor that combines a Frequency-Modulated Continuous Wave (FMCW) radar module for real-time occupancy detection with standard IEQ sensor suite (CO₂, PM_2.5, temperature, humidity), enabling unprecedented analysis of occupant-IEQ dynamics. At TalTech, comprehensive IEQ monitoring was conducted using standard sensors. Results demonstrated that mechanical ventilation (TalTech) effectively decouples indoor conditions from external fluctuations. In contrast, natural ventilation (CDJCC) exhibits strong seasonal coupling, reflected by a Seasonal Ventilation Efficacy Coefficient (${\lambda }_{\mathit{season}}$), indicating that seasonal differences in effective ventilation are present but vary by indoor space type under occupied conditions. Consistent with this stronger indoor–outdoor linkage, PM_2.5 infiltration was also pronounced in naturally ventilated spaces, as evidenced by a high infiltration factor ($I/O$ ratio) that remained consistently elevated. This work conclusively validates a conditional, climate-resilient workflow for PICSOU’s IEQ category, integrating these empirical coefficients to transform its IEQ assessment into a dynamic and actionable tool for optimizing campus sustainability strategies globally. Full article

Rainfall infiltration is one of the main factors inducing slope instability, while the spatial heterogeneity and uncertainty of soil parameters have profound impacts on slope response characteristics and stability evolution. Traditional deterministic analysis methods struggle to reveal the dynamic risk evolution process of the system under heavy rainfall. Therefore, this paper proposes an uncertainty analysis framework combining Karhunen–Loève Expansion (KLE) random field theory, Polynomial Chaos Kriging (PCK) surrogate modeling, and Monte Carlo simulation to efficiently quantify the probabilistic characteristics and spatial risks of rainfall-induced slope instability. First, for key strength parameters such as cohesion and internal friction angle, a two-dimensional random field with spatial correlation is constructed to realistically depict the regional variability of soil mechanical properties. Second, a PCK surrogate model optimized by the LARS algorithm is developed to achieve high-precision replacement of finite element calculation results. Then, large-scale Monte Carlo simulations are conducted based on the surrogate model to obtain the probability distribution characteristics of slope safety factors and potential instability areas at different times. The research results show that the slope enters the most unstable stage during the middle of rainfall (36–54 h), with severe system response fluctuations and highly concentrated instability risks. Deterministic analysis generally overestimates slope safety and ignores extreme responses in tail samples. The proposed method can effectively identify the multi-source uncertainty effects of slope systems, providing theoretical support and technical pathways for risk early warning, zoning design, and protection optimization of slope engineering during rainfall periods. Full article

Background: Resin infiltration has emerged as a micro-invasive strategy for managing enamel porosities, offering both therapeutic and aesthetic benefits. ICON^® (DMG, Hamburg, Germany) is the most widely used system; however, evidence on its penetration behavior in sound enamel remains limited. Objectives: This in vitro study aimed to evaluate the penetration depth and morphological pattern of ICON resin infiltration in sound human enamel, using quantitative morphometric analysis and scanning electron microscopy (SEM). Methods: Fourteen freshly extracted, caries-free anterior teeth were sectioned longitudinally. ICON^® resin infiltrate was applied to the buccal enamel surfaces according to the manufacturer’s protocol, while the lingual/palatal surfaces served as internal controls. Penetration depth was measured quantitatively on both mesial (surface A) and distal (surface B) halves, and SEM was used to assess resin–enamel interface morphology. Statistical analysis included the Shapiro–Wilk test, paired t-test, Pearson correlation, and percentage difference calculation. Results: The mean difference in penetration depth between surfaces A and B was −21.29 µm (p = 0.525), indicating no statistically significant variation. A strong positive correlation was observed between surfaces (r = 0.783, p = 0.001). The mean percentage difference was −3.57% (SD = 18.61%), suggesting minimal directional bias. SEM images confirmed continuous and homogeneous resin infiltration within enamel prisms. Post-hoc power analysis indicated 15.2% power, reflecting the impact of the limited sample size typical for SEM-based exploratory studies. Conclusions: Within the limitations of this in vitro investigation, ICON resin infiltration demonstrated uniform and consistent penetration in sound enamel, supported by both quantitative and SEM analyses. These findings validate its potential as a reliable preventive and micro-invasive biomaterial in dental practice, particularly for protecting enamel surfaces prior to orthodontic bracket bonding. Further clinical research with larger cohorts is recommended to confirm its long-term stability and prophylactic performance. Full article

Nestmate recognition is the primary defense mechanism maintaining the integrity of eusocial insect colonies. While social parasitism is widespread in Hymenoptera, it is rarely documented in termites, and the behavioral boundaries preventing interspecific infiltration remain poorly understood. Here, we investigated the potential for interspecific integration between two closely related termite species under laboratory conditions. We introduced Reticulitermes labralis workers and reproductives (queens and kings) into orphaned groups of R. aculabialis. We found that host workers exhibited caste-dependent aggression: introduced workers were immediately attacked and eliminated, whereas alien reproductives were partially tolerated. Surviving alien reproductives successfully integrated into host group, receiving allogrooming and trophallactic care from host workers. Crucially, these integrated pairs produced viable eggs and larvae. Molecular analysis confirmed that the brood reared by the host workers were the genetic offspring of the introduced R. labralis pair, demonstrating successful “cuckoo-like” reproduction. These findings reveal that termite colony recognition is sufficiently flexible to permit the acceptance of heterospecific reproductives when native royals are absent. While field evidence remains to be discovered, our results demonstrate that the behavioral and physiological prerequisites for social parasitism exist in termites, supporting the hypothesis that close phylogenetic relatedness (Emery’s rule) facilitates the breach of social barriers. Full article

Resistance training (RT) influences endocrine pathways that control skeletal muscle (SM) growth. This review summarizes 25 years of evidence (January 2000–December 2025) from PubMed, Medline, and ScienceDirect, focusing on three aspects: (1) exercise types such as RT, speed, power, high-intensity interval training, and aerobic training at various intensities; (2) dietary factors, including caloric restriction, total protein, protein sources, amino acids, and carbohydrates; and (3) aging-related physiological factors that may impair the insulin/IGF-1 axis in SM, such as insulin resistance, fat infiltration, physical inactivity, mitochondrial dysfunction, and inflammation. The data from Grade A evidence in systematic reviews and RCTs are prioritized to develop practical recommendations and future research directions for young, middle-aged, older, and very old individuals. Evidence regarding the effects of anabolic amino acids in women, middle-aged, and very old individuals, as well as locally mediated IGF-1 effects of any type of exercise, is limited. Full article

While research on high-incidence tumors such as breast, prostate, and lung cancer has led to significant increases in patient survival in recent years, this has not been the case for low-incidence tumors such as high-grade gliomas, the most common and lethal brain tumors, for which the last significant therapeutic advance dates back to 2005. The high infiltration capacity of these tumors into normal brain tissue essential for both vegetative and relational life, the tumor microenvironment, with poor immunological activity, the multiple resistance mechanisms, and the unattractiveness of research investments due to the limited number of patients have made, and continue to make, the path to achieving significant improvements in the survival of patients with high-grade gliomas long and arduous. The objective of this article is to update the slow but continuous radiotherapeutic progress for adult and pediatric high-grade gliomas to the second half of 2023. We analyzed the progress of preclinical and clinical research on both adult and pediatric high-grade gliomas, with a particular focus on improvements in radiotherapy. Interactions between non-radiant new therapies and radiotherapy were also covered. A literature search was conducted in PubMed using the terms (“glioma* and radio*”) and the time limit of 1 July 2023 to 31 December 2023. The inclusion and exclusion criteria for the review were relevance to advances in radiotherapy for high-grade gliomas in adults and children. Treating patients with advanced disease progression only, using “historical” data as controls, as well as repurposing drugs developed for purposes completely different from their intended use, were the major (but not the only) methods to assess risk of bias in the included studies. The effect measures used in the synthesis or presentation of the results were tabulated and/or displayed in figures. A total of 100 relevant references were reviewed. Advances in preclinical studies and in clinical radiotherapy treatment planning, innovative fractionation, use of radioisotopes/radiopharmaceuticals, radiosensitization procedures, and radiation-induced damage were focused on. While this analysis may be limited by the relatively short publication period, high-grade glioma research remains impacted, especially at the clinical level, by potential issues with trial design, such as treating patients with advanced disease progression, using “historical” data as controls, and repurposing drugs developed for completely different purposes than intended. Addressing these aspects of high-grade glioma research could improve its efficacy, which often remains low despite the associated costs. Full article

Background: Tracheobronchopathia osteochondroplastica (TO) is a rare benign disorder characterized by submucosal cartilaginous and osseous nodules of the tracheobronchial tree, typically sparing the posterior membranous wall. Involvement of the vocal cords is exceedingly rare and may result in critical airway obstruction. The underlying genetic and molecular mechanisms of TO remain largely unexplored. Case presentation: We report a rare case of TO extending from the vocal cords to the bronchi in a 76-year-old man who initially presented with pneumonia and later developed acute respiratory failure due to severe airway narrowing, necessitating emergency tracheostomy. Bronchoscopy and computed tomography revealed diffuse calcified nodules involving the anterior and lateral airway walls, including the subglottic region. Histopathology demonstrated chronic inflammatory cell infiltration with squamous metaplasia. To explore the molecular basis of this condition, whole-genome sequencing (WGS) was performed using peripheral blood samples—the first such application in TO. WGS identified 766 germline mutations (including 27 high-impact variants) and 66 structural variations. Candidate genes were implicated in coagulation and inflammation (KNG1), arachidonic acid metabolism and extracellular matrix remodeling (PLA2G4D), ciliary dysfunction and mineralization (TMEM67), vascular calcification (CDKN2B-AS1), smooth muscle function (MYLK4), abnormal calcification (TRPV2, SPRY2, BAZ1B), fibrotic signaling (AHNAK2), and mucosal barrier integrity (MUC12/MUC19). Notably, despite systemic germline mutations, calcification was restricted to the airway. Conclusions: This case highlights that TO with vocal cord involvement can progress beyond a benign course to cause life-threatening airway obstruction. Integrating clinical, histological, and genomic findings, we propose a novel pathophysiological model in which systemic genetic susceptibility interacts with local immune cell infiltration and fibroblast-driven extracellular matrix remodeling, resulting in airway-restricted dystrophic calcification. This first genomic characterization of TO provides new insights into its pathogenesis and suggests that multi-omics approaches may enable future precision medicine strategies for this rare airway disease. Full article

BST2 has emerged as a multifunctional molecule that bridges antiviral defense, membrane architecture, and tumor immunity. Originally characterized as an interferon-inducible restriction factor that tethers virions to the plasma membrane, BST2 is now recognized as an oncogenic driver and immunoregulatory hub in diverse malignancies. In cancer, BST2 expression is frequently upregulated through promoter hypomethylation and transcriptional activation. Functionally, BST2 promotes proliferation, epithelial–mesenchymal transition, anoikis resistance, and chemoresistance, whereas its loss sensitizes tumor cells to proteotoxic and metabolic stresses. Beyond tumor cells, BST2 modulates the tumor microenvironment by promoting M2 macrophage infiltration, dendritic cell exhaustion, and natural killer (NK)-cell resistance, thereby contributing to immune evasion. Elevated BST2 expression correlates with poor prognosis in glioblastoma, breast, nasopharyngeal, and pancreatic cancers, and it serves as a circulating biomarker within small extracellular vesicles. In conclusion, BST2 is a dual-function molecule that integrates oncogenic signaling and immune regulation, making it an attractive diagnostic and therapeutic target for hematological and solid tumors. Full article

Background: Chronically non-healing thoracic wounds after cardiac and non-cardiac thoracotomy, including cases when coronary artery bypass grafting (CABG) is performed, represent a great clinical challenge. It is often that a conservative treatment of the wounds does not provide effective regeneration of the damaged tissues. It is especially critical in patients with infected wounds, in patients owning a systemic infection, and in elderly people. Methods: The article presents a case report of successful treatment of a 63-year-old man with refractory chronic osteomyelitis of the sternum and mediastinitis four years after CABG, complicated by COVID-19 at the time of reconstructive surgery. Due to the low effectiveness of conservative treatment methods, a two-stage approach was applied: radical surgical wound debridement followed by infiltration of the wound with allogenic mesenchymal stromal cells (MSCs) of Wharton’s jelly (WJ-MSCs). Results: This double-stage therapy successfully modulated the inflammatory environment and stimulated granulation, facilitating final thoracoplasty and osteosynthesis. The patient achieved complete healing of the sternum, demonstrating benefits of WJ-MSCs in treating conservative treatment-resistant infections in the surgical wound. Conclusions: The advantages of using perinatal mesenchymal stem cells, with WJ-MSCs as a type of this class of MSCs, were demonstrated in treating chronically infected sternal surgical wounds. We also compared their regenerative properties to other stem cell types like bone marrow MSCs. Full article

Evaluation of pituitary neuroendocrine tumors remains complex depending on the exact growth pattern, involvement of critical neurovascular structures, pituitary function and endocrinological activity of the tumor. A predominant growth into the sphenoid sinus and clivus poses specific challenges. We reviewed 557 surgeries for pituitary neuroendocrine tumors in an endonasal endoscopic technique performed between 1 January 2015 and 31 August 2025 to identify 13 cases (2.3%). Clinical, radiological and surgical data were selected by chart review. Thirteen cases aged from 31 to 68 years with almost exclusively non-functioning or clinically silent tumors (92%) were identified. Clival infiltration was restricted to the dorsum sellae in 2/13 (15%), spread to the floor of the sphenoid in 6/13 (46%) and extended inferior to the sphenoid in 5/13 (38%) cases with a high rate of cavernous sinus (62%) and sphenoid sinus infiltration (69%). Complete resection was achieved in 31%, and the residual tumor was clival/sphenoidal in 5/13 cases or within the cavernous sinus in 6/13 cases. The diaphragma sellae was reported to be intact in 92% of cases, and postoperative transient arginine vasopressin deficiency did not occur. Pituitary neuroendocrine tumors predominantly growing below the sella and infiltrating the clivus and sphenoid present specific challenges with a high rate of preoperative pituitary insufficiency, frequent cavernous sinus infiltration and postoperative tumor residuals in the cavernous sinus, sphenoid bone and clivus which are sometimes difficult to delineate. The surgical approach must be tailored specifically to treat the clival infiltration zone to reduce the risk of recurrence. Full article