Search Results (88)

GPS-derived floating car data (FCD) provide spatially continuous urban traffic observations without fixed-sensor infrastructure. This study develops a spatiotemporal baseline framework jointly modelling day type and precipitation for 1189 junction-level nodes in Budapest. A six-phase pipeline—GPS preprocessing, coordinate reprojection, FME (Feature Manipulation Engine, Safe Software Inc., Surrey, BC, Canada)-based map-matching, junction-level aggregation, Voronoi meteorological allocation, and dataset assembly—was applied to 44.1 million 10 s records from approximately 1100 probe vehicles (November 2024–December 2025). Public holidays form a structurally distinct traffic flow pattern compared to Sundays (r = 0.71) and to regular workdays (r = 0.42); morning peak shifts to 09:00–11:00 and pooling holidays with Sundays introduces reference errors of 15–25%. Precipitation raises morning peak volumes by 6–17% across all zones while afternoon peaks remain statistically unchanged, consistent with commuter inertia; Saturday volumes fall by 7–15%. Rainy Wednesdays reach 109–112% of the Monday dry reference in inner zones, attributed to hybrid workers advancing their office day. Pairwise junction correlations show a non-monotonic distance-decay pattern, and time-lagged cross-correlation identifies 23 anticipative junction pairs with 60–90 min lead times. The results could potentially help decision making when developing city-wide infrastructure and tuning traffic signals so that traffic can be optimised and adapt to both real-time natural and social effects. The resulting baselines map onto DATEX II (Data Exchange standard, CEN EN 16157) ElaboratedDataPublication fields, supporting metadata publication on the Hungarian National Access Point under EU Regulation 2022/670/EU. Full article

Background:/ Over the past decade, increasing evidence has shifted attention from the brain to the gut microbiota (MB) as a source and site of systemic dissemination of amyloid-β (Aβ), an APP derivative responsible for plaque formation in the brains of Alzheimer’s disease (AD) patients. Furthermore, AD patients and APP/PS1 mice, a transgenic model of AD, exhibit dysbiosis. Objectives: Using APP/PS1 mice treated from 2 to 8 months of age, we studied ileal and colonic epithelial integrity, intestinal barrier (IB) integrity assessed through tight junction (TJ) protein expression, local immune system, the presence/increase in Aβ expression in enterocytes, and the protective effects of synbiotic treatment. Methods: The tissue was stained with Periodic Acid-Schiff and Alcian Blue to evaluate epithelial morphology and mucus production, and immunohistochemistry was performed to assess TJs, immune markers, and Aβ expression. Results: Our results demonstrate that colonic and ileal epithelium of 8-month-old APP/PS1 mice displays IB impairment in term of alterations of goblet cells staining and TJ protein expression and signs of immune involvement. The ileum was more severely affected, showing a reduced epithelial surface area, decreased lysozyme production, and fewer tuft cells. Long-term synbiotic treatment largely prevented APP/PS1 mouse changes and caused a significant increase in Aβ expression in all treated mice. Conclusions: These findings support the belief in early intestinal involvement in AD and highlight the potential of the microbiota as a target for early intervention aimed at modifying the progression to neurodegeneration. Increased epithelial Aβ labeling after treatment raises the possibility of intestinal management of Aβ, which requires further validation. Full article

The demand for naturally derived ingredients in cosmetics is constantly growing, with marine algae emerging as promising candidates due to their rich antioxidant and protective metabolites. Skin aging, driven by oxidative stress, impaired hydration, and weakening of the dermal–epidermal junction (DEJ), manifests as dryness, loss of elasticity, and reduced density. Conventional synthetic antioxidants raise safety concerns, highlighting the need for effective natural alternatives. Ecklonia cava, an edible brown seaweed abundant in phlorotannins, has been reported to possess strong antioxidant and anti-inflammatory properties, yet its effects on key molecular markers of hydration and DEJ integrity remain underexplored. In this study, we standardized an E. cava extract (ECE) and evaluated its antioxidant activity, gene regulatory effects, and clinical efficacy. ECE was standardized by measuring total polyphenols and flavonoids, evaluated by DPPH scavenging assay, and shown to upregulate DEJ-related genes, reinforcing dermal–epidermal cohesion. A randomized clinical trial further confirmed that topical application of ECE improved hydration, elasticity, and density compared with placebo, with benefits evident within weeks. Collectively, these findings establish ECE as a multifunctional cosmetic ingredient capable of protecting the skin while enhancing structural and functional aspects of skin health, supporting its potential application in anti-aging skincare. Full article

Background and Clinical Significance: Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a CD30-positive T-cell lymphoproliferative disorder that can clinically resemble various non-melanoma skin cancers, making diagnosis challenging. Although histopathology remains the diagnostic gold standard, non-invasive imaging modalities such as dermoscopy and reflectance confocal microscopy (RCM) are increasingly used as complementary tools to support the differential diagnosis. To date, no data on RCM features of C-ALCL have been described. Case Presentation: We report the case of an 80-year-old man presenting with a rapidly enlarging nodule on the lateral aspect of his right eyelid, providing a detailed account of dermoscopic and RCM findings integrated with clinicopathological correlation. Dermoscopy revealed a red-orange homogeneous background with white streaks, and polymorphic vascular structures, while subsequent RCM (Vivascope 3000 probe) demonstrated marked architectural disarray of the epidermis and dermoepidemal junction, with prominent epidermal involvement characterized by aggregates of highly reflective cells. In the absence of alternative diagnostic patterns, these features raised suspicion for a cutaneous lymphoproliferative disorder, which was later confirmed by histopathological and immunohistochemical analyses. Conclusions: Our findings support the value of RCM as a practical tool in guiding differential diagnosis and biopsy, particularly for rapidly growing lesions located in anatomically sensitive areas. Full article

How do ryanodine receptors (RyRs) open simultaneously to trigger the contraction of whole myofibrils within a large skeletal muscle cell? One possible answer is the uniformity of mechanosensitive RyRs, which is mechanically forced by the neighboring environment, including proteins. Here, we review papers addressing this proposed “mechanical sarcoplasmic reticulum (SR) paradigm”. Crystals of the molecular complexes comprising RyR and L-type voltage-gated Ca²⁺ channels were observed at the T-tubule/SR junction in situ using cryo-electron tomography. Observations of the SR vesicles isolated from rabbit and scallop cross-striated muscles using negative staining and transmission electron microscope raised a hypothesis of dynamic rearrangement of the Ca²⁺-ATPase (ATPase) molecules in response to cytoplasmic calcium concentration, as follows: (i) At a low calcium concentration where the ratio of operating ATPase molecules to the total molecules is at a submaximal level, the ATPase molecules form, at least in part, their cylindrical crystals in the SR membrane with the help of ATP; this results in the elongation of the SR vesicles. (ii) High concentrations of calcium, at which the ratio of operating ATPase molecules is maximal, reversibly collapse the ATPase crystals to transform the elongated vesicles into round forms comprising tightly attached crystal patches. These data further lead to the idea that the reversible growth of cylindrical ATPase crystals provides a dynamic crystalline network, which acts as an “SR membrane-endoskeletal motor” to manipulate the SR movement. The possibility of interactions between ATPase crystals and neighboring RyR crystals is also discussed. Full article

Cryptorchidism is one of the major reproductive diseases affecting testicular function in yaks. However, the mechanisms underlying its impact on testicular spermatogenesis remain unclear. In this study, high-throughput transcriptomics (RNA-seq) and proteomics technologies were employed to analyze the key signaling pathways involved in cryptorchidism-induced spermatogenic dysfunction in yak, and a mouse model was established for validation. The results indicate that differentially expressed genes (DEGs) in the testes of yak with cryptorchidism are primarily enriched in the hypoxia-inducible factor (HIF) signaling pathway and the PI3K-AKT signaling pathway. Experimental results from the hypoxic mouse model indicate that the hypoxic environment remarkably raised HIF-1α content in the blood of mice while activating the PI3K-AKT signaling pathway, accompanied by decreased testicular expression of the cell adhesion molecules (CAMs) claudin 2, claudin 3, E-cadherin, and N-cadherin. Cell culture experiments showed that cell adhesion molecule expression was significantly downregulated when HIF-1α and PI3K expression were inhibited among mouse Sertoli cells, indicating that the HIF-1α/PI3K-AKT signaling pathway regulated cell adhesion molecule expression among mouse testes. Decreased CAMs directly affect tight junctions and the adhesion of spermatogenic and Sertoli cells, thus affecting sperm production and potentially also testis development. This study provides data to support research on the regulatory mechanisms involved in reproductive function and hypoxia adaptation in male animals in a low-oxygen environment. Full article

Diabetic retinopathy (DR) is a common cause of vision loss in diabetes, and it often progresses without early symptoms. DR reflects injury of the retinal neurovascular unit (NVU), which includes neurons, Müller glia, astrocytes, endothelial cells, pericytes, and immune cells. Chronic hyperglycemia drives oxidative stress, advanced glycation end products–receptor for advanced glycation end products (AGE–RAGE) signaling, mitochondrial injury, and low-grade inflammation. These changes disrupt endothelial junctions, promote leukostasis, weaken pericyte support, increase basement membrane thickening, and lead to capillary dropout and hypoxia. Hypoxia-related signaling increases anti-vascular endothelial growth factor (VEGF) activity, which raises vascular leakage and supports neovascular disease. Glial stress and microglial activation add cytokines and reactive oxygen species, and neural dysfunction can appear early and can weaken neurovascular coupling. Modern diabetes care changes the short-term risk landscape because potent therapies can lower HbA1c quickly. Large and rapid HbA1c reductions can trigger early worsening of diabetic retinopathy (EWDR), mainly in patients with high baseline HbA1c and moderate-to-severe baseline DR. Semaglutide’s retinopathy complication signal in SUSTAIN-6 fits an EWDR-like pattern that tracks with rapid glycemic improvement in vulnerable eyes. In parallel, surgery adds acute stress, inflammation, glucose swings, hemodynamic shifts, and medication interruptions. These factors can worsen microvascular instability during recovery. Current perioperative guidelines and regulatory recommendations describe glucose targets and medication safety considerations, including preoperative interruption of SGLT2 inhibitors to reduce euglycemic ketoacidosis risk; however, the retina-specific implications of these measures remain indirect. This review summarizes current evidence linking NVU biology, EWDR risk, and perioperative diabetes-related factors. It discusses how these factors may interact in patients with diabetes and how they may influence retinal outcomes. The review is intended to synthesize current evidence and mechanistic interpretations rather than to provide formal clinical practice recommendations. Full article

Background: The extensive use of insecticides in modern agriculture has raised concerns about potential chronic effects on human health beyond acute toxicity. Limited evidence exists regarding their impact on immune regulation and intestinal barrier integrity, two key components of host-environment interactions. Methods: Human in-vitro models were used to investigate the immunomodulatory and intestinal effects of several commonly used agricultural insecticides. Primary human macrophages derived from peripheral blood mononuclear cells were exposed to insecticides to assess cell viability and polarization status. Intestinal barrier function was evaluated using Caco-2 cell monolayers by measuring oxidative stress, epithelial integrity, paracellular permeability, and tight junction organization. Results: The tested insecticides induced a pro-inflammatory macrophage phenotype, characterized by increased expression of M1 markers and reduced M2 markers, without affecting cell viability. In Caco-2 cells, insecticide exposure compromised epithelial barrier integrity and disrupted tight junction organization. In this context, neither Spinetoram nor Spirotetramat induced notable oxidative stress under pro-oxidant conditions. However, Spirotetramat caused a significant increase in paracellular permeability. Conclusions: These findings indicate that commonly used insecticides can modulate immune responses and impair intestinal barrier function, suggesting potential mechanisms by which chronic low-level exposure may contribute to immune dysregulation and epithelial dysfunction in humans. Full article

Background/Objectives: Ulcerative colitis (UC) involves inflammatory response, oxidative stress, changes in metabolites, and the gut microbiota. Jingangteng capsule (JGTC) has been utilized clinically for the treatment of inflammatory diseases for many years. However, the efficacy of JGTC in ameliorating UC remains unclear, and the underlying mechanisms have not yet been elucidated. This study aims to investigate the effect and mechanism of JGTC on UC. Methods: The chemical compositions of JGTC were examined using ultra-high-performance liquid chromatography with quadrupole time-of-fight mass spectrometry. The anti-UC effect of JGTC was evaluated by assessing the disease activity index (DAI), colon length, intestinal barrier recovery, and inflammatory factors in a dextran sulfate sodium (DSS)-induced colitis model. Mechanisms were investigated through fecal 16S rDNA sequencing, metabolomics analysis, enzyme-linked immunosorbent assay (ELISA), Western blotting, and network pharmacology analysis. Results: JGTC significantly reduced the DAI scores in UC mice, increased their body weight and colon length (p < 0.001), repairing damaged intestinal tissue. It decreased the levels of inflammatory cytokines TNF-α, IL-6, IL-1β, and LPS (p < 0.01, p < 0.001), alleviating intestinal inflammation. It also raised the expression of tight junction proteins ZO-1, Claudin-1, and Occludin (p < 0.05, p < 0.001), thereby enhancing intestinal barrier function. Fecal metabolomic analysis revealed that the favorable alterations in amino acid and lipid metabolites were more pronounced. Heat maps showed strong correlations between pharmacological indicators and gut microbiota, as well as between the main differential metabolites and gut microbial communities. UPLC-QTOF-MS detection yielded 33 components of JGTC, and network pharmacology analysis based on these components predicted pathways of action of JGTC in UC. Functional pathways closely associated with significantly differential metabolites and metabolic pathways were also investigated. The PI3K-AKT-mTOR pathway was one of them, which is consistent with the conclusions drawn from network pharmacology. JGTC significantly modulated key factors in this pathway, inhibiting the expression of PI3K, Akt, PDK1, and mTOR, while augmenting the expression of PTEN (p < 0.05, p < 0.01, p < 0.001). It also mitigated the levels of related oxidative stress factors MDA, MPO, and D-LA, and raised SOD levels (p < 0.01, p < 0.001). Conclusions: JGTC improved the excessive inflammatory response in UC by regulating intestinal flora and metabolic disorders, affecting the PI3K-AKT-mTOR signaling pathway, restoring intestinal tissue damage and intestinal barrier, and inhibiting inflammatory and oxidative stress factors. Full article

Background/Objectives: During oral and gut microbiota dysbiosis, lipopolysaccharides (LPSs) of major bacteria, such as Porphyromonas gingivalis and Escherichia coli, translocate into the bloodstream and lead to endotoxemia. Cerebral endothelial cells are targets of LPSs that may aggravate inflammation and cerebrovascular disorders. This study aimed to evaluate the protective role of the characterized polyphenol-rich extract of the Dodonaea viscosa medicinal plant and a predominant component, epicatechin, on murine bEnd.3 cerebral endothelial cells exposed to P. gingivalis or E. coli LPSs. Methods: The effects of LPSs and polyphenols were assessed on cell viability (MTT, trypan blue exclusion assays) and inflammatory, redox, vasoactive and permeability markers (RT-qPCR, Western blot, ELISA, FITC-Dextran test). Results: The data show that LPSs activated the TLR2-4/NFĸB signaling pathway and promoted IL-1β, IL-6, TNF-α, MCP-1, COX-2, iNOS, ICAM-1, VCAM-1 and E-selectin production without affecting cell viability. LPSs induced oxidative stress by elevating intracellular ROS levels and altering the expression of genes encoding NOX2-4, SOD, catalase, GPx, HO-1 and Nrf2. LPSs imbalanced NO vasodilator and ET-1 vasoconstrictor levels and reduced the production of occludin and ZO-1 tight junction proteins. Meanwhile, LPSs raised the permeability to FITC-Dextran, suggesting cell integrity loss. The extent of endothelial dysfunction caused by LPSs depended on their bacterial origin. Importantly, plant polyphenols and epicatechin exerted anti-inflammatory and antioxidant effects, and attenuated LPSs’ deleterious action on vasoactive and permeability markers. Conclusions: This study shows that polyphenols limit cerebral endothelial cell dysfunction under inflammatory conditions mediated by LPSs, highlighting their therapeutic potential in protecting brain homeostasis during oral and gut microbiota dysbiosis. Full article

Background: Microplastics and nanoplastics, as pervasive and persistent environmental pollutants, are raising growing concerns regarding their potential risks to reproductive health, particularly pregnancy outcomes. Although the reproductive toxicity of polystyrene nanoplastics (PS-NPs) has been reported, the specific mechanisms underlying their effects on placental development and offspring health following gestational exposure remain unclear. Method: This study aimed to investigate the effects of gestational exposure to PS-NPs of different sizes (50 and 200 nm) and concentrations (1, 3, and 10 mg/mL) on placental function and embryonic development in ICR mice. An exposure model was established via tail vein injection, and samples were collected on embryonic Day 14.5 (E14.5). Results: the exposed groups tended towards increased embryo weight, embryo length, and embryo head circumference. Transcriptomic analysis revealed that PS-NP exposure significantly downregulated the expression of Ndufa5 (a subunit of mitochondrial respiratory chain complex I) and mt-CO1 (a core subunit of complex IV), but upregulated the expression of the genes Cldn1 (tight junction protein) and Erbb3 (receptor tyrosine kinase) in the placenta. Differentially expressed genes were enriched primarily in pathways related to oxidative phosphorylation, the tricarboxylic acid (TCA) cycle, and ErbB signalling. Conclusions: These changes collectively led to decreased mitochondrial ATP production, increased oxidative stress in the placenta, and potentially altered placental barrier function and trophoblast cell proliferation signalling. This study reveals a novel mechanism by which PS-NPs disrupt placental development and embryonic growth through impairment of placental energy metabolic homeostasis and key signalling pathways, thus providing crucial experimental evidence for assessing the reproductive and developmental toxicity of nanoplastics. Full article

Background/Objectives: Circular RNAs (circRNAs) are emerging players in human diseases, with functions as part of competing endogenous networks. Given the importance of messenger RNA (mRNA) regulation in human diseases and the potential of circRNAs in this regulation, we studied the circRNA–mRNA couple in blood within a cohort of 712 patients suspected of having hereditary colorectal cancer (CRC) and 249 matched controls. Methods: The circRNA–mRNA couple was studied by SEALigHTS (Splice and Expression Analyses by exon Ligation and High-Throughput Sequencing) with a panel of 23 genes involved in CRC predisposition, comprising 788 probes designed at exon ends, enabling the exploration of all exon–exon junctions. Following reverse transcription and probe hybridization on cDNA, nearby probes were ligated, and the number of ligations was quantified using unique molecular identifiers and sequencing. Results: We identified 220 circular junctions, including 47 novel ones. The circRNA/mRNA ratio was 2.42-fold higher in patients compared to controls (p < 10⁻¹⁶), irrespective of age at cancer onset. This increase was mainly driven by POLD1 (fold change 3.84) and a single circPOLD1(3,2) with oncogenic potential Conclusions: This study supports the existence of a physiological balance between circRNA and mRNA that can be disrupted under pathological conditions. It rules out a competitive mechanism between circular and linear transcripts in CRC predisposition and raises questions about the role of specific circRNAs in the development of CRC, either as a cause or a consequence. Full article

Background: X-linked hypophosphatemic rickets (XLH) is a rare hereditary disorder characterized by renal phosphate wasting and impaired bone mineralization. Oral manifestations such as spontaneous periapical lesions and dental abscesses in the absence of caries or trauma may precede systemic features in XLH due to underlying dentin hypomineralization and enamel–dentin junction defects, and could serve as early diagnostic indicators. Case Report: We report on the case of a 4-year-old boy referred to our pediatric dental unit with recurrent intraoral fistulas persisting over the past year. Clinical examinations and an orthopantomogram revealed extensive root resorption and periapical pathology affecting multiple primary molars without evident caries or trauma. Laboratory investigations showed hypophosphatemia, elevated renal phosphate loss, and raised inflammatory markers (CRP (C-reactive protein) and granulocytes). Genetic testing of the child and his mother confirmed a diagnosis of X-linked hypophosphatemic rickets. Management: Due to behavioral challenges, treatment proceeded with difficulty over multiple visits. Endodontic treatment was initiated using a formalin–resorcinol technique; however, several primary molars developed progressive necrosis and required extraction. Orthodontic space maintainers were placed to preserve arch integrity and support future eruption. The patient remains under follow-up and is currently awaiting Burosumab therapy. Despite systemic management, spontaneous necroses of the primary molars persist, highlighting the refractory nature of dental involvement in XLH. Conclusions: This case underscores the pivotal role of pediatric dentists in recognizing systemic diseases through oral findings and demonstrates the challenges of managing XLH-related dental pathology, even under targeted systemic therapy. Early interdisciplinary collaboration is essential to optimize both dental and systemic outcomes in affected children. Full article

Background: Radiotherapy (RT) combined with immune checkpoint inhibitors (ICIs) has shown therapeutic benefits, and the potential for enhanced immune activation has raised concerns about increased immune-related adverse events (irAEs). The immunological implications of mediastinal RT combined with ICI therapy remain unclear. Methods: We conducted an exploratory retrospective review of 58 patients with esophageal oresophagogastric junction cancer who received ICIs between 2021 and 2024. Patients were categorized into RT (+) and RT (-) groups based on whether they underwent mediastinal RT. The incidence and severity of irAEs were compared using chi-square testing. Subgroup analyses included treatment sequence (RT before vs. after ICI), interval between RT and ICI (<90 vs. ≥90 days), and ICI regimen (nivolumab [N], pembrolizumab [P], or nivolumab plus ipilimumab [NI]). Results: irAEs occurred in 28.6% of RT (+) and 39.1% of RT (-) (p = 0.42). Severe irAEs were uncommon in both groups. Treatment sequence and RT-ICI interval did not significantly influence irAE incidence. irAEs were more frequent in the NI group (85.7%) than in N (22.9%) or P (31.2%) (p = 0.01). Mediastinal RT itself did not increase irAE risk. Conclusions: Although RT combined with ICIs has been hypothesized to elevate irAEs through enhanced immune activation, mediastinal RT did not increase irAEs in this cohort. However, given the exploratory and small patient cohort, these findings suggest, with caution, that mediastinal irradiation may attenuate systemic immune activation through lymphocyte depletion, potentially balancing ICI-induced immune responses. Full article

Foodborne botulism is a potentially fatal disease caused by Clostridium botulinum neurotoxins (BoNTs). These spore-forming bacteria are ubiquitous in the environment and can contaminate various food products, especially raw vegetables. During the preparation of home-made preserves, favorable conditions of anaerobiosis, temperature, salinity, and pH can lead to spore germination and toxin production. BoNTs can reach neuromuscular junctions where they block the release of acetylcholine. In this study, we present a case of foodborne botulism associated with the consumption of chili peppers preserve containing BoNT/B. The isolated strains were characterized through Whole Genome Sequencing, confirming the strains involved in the outbreak. This work increases the understanding of the epidemiology and the ecology of C. botulinum, highlighting the importance of raising medical awareness and making timely clinical diagnoses for the effective management of botulism outbreaks. Full article