Search Results (17,304)

Tongue squamous cell carcinoma (TSCC) is clinically heterogeneous, and patients with a similar TNM stage can experience markedly different outcomes. We systematically reviewed omics-driven studies to identify prognostic TSCC biomarkers. Although fundamentally prognostic, we discussed their theoretical translational relevance regarding future clinical decisions—such as treatment stratification or surveillance intensity—while strictly framing them as preliminary, hypothesis-generating targets. PubMed, Scopus, Web of Science, and Cochrane were searched for original human studies published between 2014 and 2024 using high-throughput genomic or transcriptomic profiling. Study selection followed referred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), data were extracted with a structured workbook, and risk of bias was assessed using QUIPS and PROBAST, with reporting completeness appraised using REMARK. Seventeen studies were included, identifying 85 distinct biomarkers. Across biomarkers supported by multivariable overall survival analyses, higher-risk associations were reported for NELL2, PDE4D, CTTN, HBEGF, and CA9, whereas lower-risk associations were reported for AC139530.1, LINC01711, CCDC96, CYP2J2, and SPAG16. Recurrent biological themes included IL-17 signaling, ECM-receptor interaction, and focal adhesion. CA9 was the only biomarker reported in more than one included study, supporting its prioritization for validation. Although the evidence remains heterogeneous and largely hypothesis-generating, these markers may support the future validation of response-oriented therapeutic stratification in TSCC. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells when the spike receptor-binding domain (RBD) engages angiotensin-converting enzyme 2 (ACE2). Cannabinoid scaffolds have recently been reported to bind S1/RBD, block spike-mediated membrane fusion, and modulate host inflammatory pathways, making them attractive candidates for entry inhibition. Here, we applied an integrated computational pipeline to prioritize cannabis-derived compounds as interfacial blockers of the RBD–ACE2 complex across variants. Eleven phytocannabinoids were docked into the wild-type (WT) RBD–ACE2 interface, identifying three cavities, with ligands preferentially occupying pocket 1. Complexes were subjected to triplicate 200 ns all-atom molecular dynamics (MD) simulations for WT, Delta, and Omicron BA.1 RBD–ACE2. Binding energetics were quantified using molecular mechanics/generalized Born surface area (MM/GBSA) and solvated interaction energy (SIE), and per-residue contributions were analyzed together with solvent-accessible surface area (SASA) and residue interaction networks. Among all compounds, cannabidiol (CBD) and cannabinol (CBN) were the only ligands that remained stably bound in pocket 1 for all variants. CBN showed the most favorable ligand–complex binding in WT, whereas CBD preserved favorable binding in Omicron BA.1 despite reduced interface burial, indicating that van der Waals/electrostatic complementarity and solvation, rather than surface coverage alone, govern affinity. Both ligands weakened modeled RBD–ACE2 binding by perturbing hot-spot residues centered on Y505 or N501Y in RBD and E37, A387, and R393 in ACE2. Overall, our results highlight CBD and CBN as tractable, variant-spanning interface disruptors and illustrate how MD-based free-energy calculations can support computational drug discovery against evolving viral protein–protein interfaces. Full article

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has revealed a complex interplay between respiratory and neurological manifestations. This study utilized K18-hACE2 transgenic mice to investigate the morphological, ultrastructural, and transcriptomic changes induced by SARS-CoV-2 infection in both lungs and brain tissues. Histopathological analysis at seven days post-infection revealed significant pulmonary damage characterized by interstitial pneumonia, alveolar septal thickening, with a marked inflammatory infiltrate predominantly consisting of neutrophils and lymphocytes, and an abnormal profile of type II pneumocytes. Concurrently, in the brain, we observed vasculitis, gliosis, and edema, indicating an inflammatory response and vascular compromise that can disturb the blood–brain barrier. In addition, gene expression in lung tissue presented increased CCL2, IL10, and GDDA45D in infected mice and the downregulation of proinflammatory genes. However, in brain tissue, the increased expression of CCL2, CASP1, IL6, IFNB1, and GDDA45G inflammatory genes was observed in infected K18-hACE2 mice. Full article

Acute coronary syndrome patients undergoing percutaneous coronary intervention remain at high risk for major adverse cardiovascular events (MACE: cardiovascular mortality, non-fatal myocardial infarction, and stroke). Inflammatory–oxidative stress biomarkers are potential prognostic tools; however, the influence of sampling timing—pre-procedural versus post-procedural—remains unclear. This meta-analysis evaluated six biomarkers: sST2, GDF-15, OPG, sLOX-1, H-FABP, and Galectin-3. Pooled Hazard Ratios (HRs) for time-to-event outcomes and Standardized Mean Differences (SMDs) between event and non-event groups were synthesized using random-effects models involving 40 studies (18,933 patients). Elevated pre-procedural levels of sST2 (HR = 3.32, p < 0.0001), GDF-15 (HR = 3.00, p < 0.0001), sLOX-1 (HR = 2.61, p = 0.0023), and OPG (HR = 1.79, p = 0.0206) significantly predicted MACE. Notably, pre-PCI sST2 strongly predicted heart failure hospitalization (HR = 6.30, p < 0.0001). Additionally, pre-PCI H-FABP demonstrated a moderate significant effect on adverse outcomes (SMD = 0.67, p < 0.0001). While pre-PCI Galectin-3 was not significant, its post-procedural levels showed a large significant effect (SMD = 1.15, p < 0.0001). In conclusion, inflammatory and oxidative stress biomarkers, particularly sST2 and GDF-15, demonstrate consistent associations with adverse outcomes in ACS patients undergoing PCI, offering more reliable baseline risk stratification than post-procedural measurements. Full article

Background/Objectives: Acute coronary syndromes (ACS) encompass a spectrum of clinical entities from unstable angina to non–ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI), all associated with significant morbidity and mortality. Inflammation plays a central role in the pathophysiology of ACS, contributing to atherosclerotic plaque destabilization, myocardial injury, and adverse clinical outcomes. Inflammatory biomarkers, together with N-terminal pro–B-type natriuretic peptide (NT-proBNP), are increasingly used for risk stratification, yet their prognostic value across different ACS presentations remains unclear. This study aimed to assess the prognostic value of inflammatory status in patients with acute coronary syndromes in a single-center cohort. Methods: This prospective observational study included 100 consecutive patients with ACS and elevated inflammatory biomarkers, enrolled in 2024–2025 at a tertiary cardiovascular center. Inflammatory status was assessed by using C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII); NT-proBNP was also measured. The primary endpoint was in-hospital MACE, defined as cardiovascular death, recurrent myocardial infarction, stroke, urgent coronary revascularization, or acute heart failure requiring escalation of therapy. Multivariable logistic regression and ROC analyses were performed. Results: Among the 100 ACS patients, half experienced in-hospital MACE. Compared with those without events, patients with MACE were older (p = 0.003) and had higher inflammatory biomarkers—CRP (p < 0.001; strongest association), NLR (p = 0.030), and SII (p = 0.042)—as well as higher NT-proBNP (p = 0.002). Patients with MACE also showed reduced renal function (p < 0.001) and lower left ventricular systolic function, reflected by reduced LVEF (p = 0.001), indicating concomitant renal impairment and ventricular dysfunction. Hypertension was more prevalent in the MACE group (p = 0.028), and new-onset atrial fibrillation was significantly more common among these patients (p < 0.001). In multivariable analysis, LVEF emerged as an independent predictor of short-term outcomes (OR 0.934 per 1% increase; p = 0.047). Conclusions: Inflammatory activation appears closely linked to the occurrence of in-hospital adverse events in patients with acute coronary syndromes. While left ventricular ejection fraction remained an independent determinant of short-term outcomes, inflammatory biomarkers may provide complementary insight into the inflammatory burden accompanying ACS. Full article

Background/Objectives: Allergic conjunctivitis (AC) is the most common inflammatory disease affecting the ocular conjunctiva. Tacrolimus (TCR), a potent calcineurin inhibitor, is limited by poor aqueous solubility and low ocular bioavailability. This study aimed to develop TCR-loaded cubosomes (TCR-Cubs) incorporated into HPMC/PVP K90 dissolving microneedles (MNs) to enhance their therapeutic efficacy. Methods: TCR-Cubs were prepared using a modified top-down fragmentation method with glyceryl monooleate and poloxamer 407, optimized via Box–Behnken design, and incorporated into dissolving MNs. The system was evaluated in vitro, ex vivo, and in vivo using a rabbit model of allergic conjunctivitis. Results: The optimized formulation exhibited the smallest particle size (210 ± 0.91 nm), polydispersity index (0.29 ± 0.03), zeta potential (−21 ± 0.87 mV), and the highest entrapment efficiency (% 93.3 ± 0.45). The optimized formulation was incorporated into MNs via micro molding. Scanning electron microscopy (SEM) confirmed well-defined, sharp microneedles, with low height reduction (<10%) by mechanical testing and high penetration efficiency (>85–90%). In vitro release studies revealed sustained drug release of (~75–80%) over 24 h, compared to (~40%) from the TCR suspension, following diffusion-controlled kinetics. Ex vivo permeation studies showed a (~2–3-fold) enhancement in corneal drug flux. In vivo pharmacodynamic evaluation using an ovalbumin-induced allergic conjunctivitis model demonstrated significant reductions in inflammatory mediators, including inflammatory markers (TNF-α, IL-1β, IL-6, NLRP3), which were reduced by (~50–75%), with modulation of CPA3, BCL2, and TGF-β1 by qRT-PCR. Histopathology and TLR4 analysis confirmed reduced inflammation without irritation. Conclusions: This dual-delivery system offers a promising, non-invasive platform for enhanced ocular delivery of tacrolimus with superior anti-inflammatory efficacy in allergic conjunctivitis. Full article

In recent years, typhoon activity over the South China Sea (SCS) has intensified, and interactions between typhoons and mesoscale eddies profoundly regulate the regional oceanic environment and air–sea energy exchange. To systematically investigate the position- and polarity-dependent eddy responses to typhoon forcing, we developed a typhoon–eddy spatial matching algorithm and analyzed the global mesoscale eddy dataset (2006–2020) combined with China Meteorological Administration (CMA) best-track typhoon records. Composite and correlation analyses were employed to examine variations in the eddy surface available potential energy (SAPE) and sea-surface temperature (SST) within a 7-day window before and after typhoon passage, with the typhoon power dissipation index (PDI) used to quantify storm intensity. Composite results reveal distinct dual-asymmetric responses: (1) Energetically, eddies on the left side of typhoon tracks exhibit overall weakening, with anticyclonic eddies (ACEs) showing more pronounced energy decay; in contrast, right-side eddies undergo significant intensification, and cyclonic eddies (CEs) display stronger enhancement than ACEs. (2) Thermally, all eddy types experience net cooling after typhoon passage, with right-side eddies showing stronger SST reductions than left-side ones, and CEs exhibiting more intense cooling than ACEs. Time-scale correlation analyses further demonstrate that the eddy energy change rate (EECR) of left-side CEs, right-side CEs, and right-side ACEs is positively correlated with PDI, whereas left-side ACEs show no significant correlation. For the SST change rate (SSTCR), all types of eddy events exhibit significant negative correlations with PDI, with weaker correlations for CEs and stronger correlations for ACEs. This study demonstrates that the track-relative position of tropical cyclones and the polarity of pre-existing mesoscale eddies exert a systematic control on the observed eddy responses to tropical cyclone forcing in the SCS. These results provide observational constraints on the asymmetric oceanic responses induced by tropical cyclones and offer insights into the interpretation of typhoon–ocean interaction diagnostics in marginal seas. Full article

The development of novel antiviral nanomaterials is an important approach for addressing emerging viral threats. In this study, glycyrrhizic acid-modified gold nanoparticles (GA-Au NPs) were successfully synthesized and characterized, and their inhibitory effects against porcine reproductive and respiratory syndrome virus (PRRSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus were systematically evaluated. At non-cytotoxic concentrations, GA-Au NPs showed inhibitory activity against PRRSV in vitro. Stage-specific assays suggested that intracellular replication-related events were prominently affected, with additional inhibitory effects observed during adsorption, invasion, and release, whereas no direct virucidal activity was detected under the tested conditions. Furthermore, GA-Au NPs dose-dependently reduced SARS-CoV-2 pseudovirus infection-associated reporter signals in HEK-293T-ACE2 cells, supporting inhibitory activity in an additional viral model. In conclusion, GA-Au NPs represent a biocompatible antiviral nanomaterial with multi-stage inhibitory activity against PRRSV and inhibitory effects in a SARS-CoV-2 pseudovirus model, supporting their further evaluation as antiviral nanomaterials in enveloped virus-related models. Full article

Soil salinity severely constrains strawberry production by disrupting ion homeostasis and provoking oxidative injury. This study investigated whether soluble silicon (Si) and activated carbon (AC) act to enhance salt tolerance in strawberry (Fragaria × ananassa). Under NaCl stress, plants showed pronounced growth inhibition, increased Na⁺ accumulation and a deteriorated K⁺/Na⁺ balance, accompanied by elevated reactive oxygen species (ROS) and lipid peroxidation. In contrast, combined AC + Si treatment consistently provided the strongest protection, improving seedling vigor and survival. Relative to NaCl alone, AC + Si increased shoot and root fresh weight by 67.5% and 78.5%, reduced shoot Na⁺ by 59.1%, and lowered shoot H₂O₂ and MDA by 62.6% and 66.5%, respectively, indicating marked improvement in ion–redox homeostasis. Beyond plant responses, AC-containing treatments alleviated salt-induced increases in soil electrical conductivity, coinciding with a clear restructuring of the rhizosphere bacterial community and enrichment of putatively beneficial taxa. Transcriptome profiling further supported coordinated reprogramming of ion transport, redox control and stress-responsive signaling pathways under the AC + Si regime. Collectively, the results indicated that Si and AC co-application enhances strawberry salt tolerance through an integrated soil–plant–microbiome mechanism that stabilizes ion homeostasis and reinforces redox homeostasis. Full article

Rising population pressures have intensified the need to reuse wastewater, which increases exposure to microbial and heavy metal contamination, negatively impacting ecosystems and human health. Heavy metals in wastewater present a major environmental concern. This study examines the adsorption capacities and efficiencies of individual and combined adsorbents—activated carbon (AC), biochar (BC), and kaolinite (KA)—for removing heavy metals, organic matter, salinity, and pathogens from wastewater. Wastewater samples were treated in column adsorption systems and analyzed before and after treatment using physicochemical and microbiological methods. The composite adsorbent (AC + BC + KA) performed best, reducing electrical conductivity by 75% (from 4.0 to 1.0 mS/cm), total dissolved solids from 2560 mg/L to 915.2 mg/L, and sodium adsorption ratio from 27.14 to 7.06. The pH remained within the optimal irrigation range (7.66). The system removed up to 85.87% of heavy metals (Cu²⁺, Cd²⁺, Mn²⁺, Zn²⁺) and 100% of pathogenic bacteria (E. coli, Shigella spp., and B. cereus). The microporous structure of AC provides large surface areas for pollutant trapping through adsorption, while BC introduces functional groups that enhance contaminant capture. The combination of these materials offers an eco-friendly and effective method for wastewater purification. Full article

This work uses battery-coupled power electronic converter systems and distributed backstepping controllers to improve the reliability of electrical distribution networks. The motivation is to prevent blackouts such as the 28 April 2025 outage in Spain, Portugal, and the south of France. It is now accepted that a rapid rise in solar power injections caused AC overvoltage above grid code limits, triggering photovoltaic (PV) park disconnections as overvoltage self-protection. This case study considers near-Zero-Energy Buildings (nZEBs) connected to the Madeira Island isolated microgrid, where PV power installation is increasing excessively. The main university facility will be upgraded as an nZEB, using roughly 3000 m² of unshaded rooftops plus coverable parking areas to install PV panels. Optimizing the profits/energy cost ratio, a PV power system of around 560 kW can be planned, and the Battery Storage System (BSS) energy capacity can be estimated. The BSS is connected to the university nZEB via backstepping-controlled multilevel converters to manage PV and BSS, enabling the building to contribute to voltage and frequency regulation. Distributed multilevel converters inject renewable energy into the medium-voltage network, regulating active and reactive power to prevent overvoltages shutting down the PV inverters. This removes sustained overvoltage and maximizes PV penetration while augmenting AC grid reliability and resilience. When there is excess solar power and reactive power is insufficient to reduce voltage, controllers slightly curtail PV active power to eliminate overvoltage, maintaining operation with minimal revenue loss while preventing long interruptions, thereby improving grid reliability and power quality. Full article

The dynamic modulus of asphalt mixtures is a key design parameter in pavement design, which significantly impacts the mechanical properties of asphalt pavements. This study simulated dynamic modulus tests of asphalt mixtures using the three-dimensional (3D) discrete element method (DEM) to investigate mechanical behaviors such as the loading-bearing ratio of individual aggregates. Fine-grained AC-13 and medium-grained AC-20 asphalt mixture models were randomly constructed in the DEM program using user-defined methods. The dynamic modulus and phase angle values of the asphalt mixtures were predicted. By comparing laboratory experiments with DEM simulation results, the model was validated, and the effects of temperature and loading frequency on the dynamic modulus were explored. Further exploration was conducted on the loading-bearing ratio and mechanical interactions among aggregates of different sizes within the mixtures. The results show that the 3D DEM model can accurately predict the dynamic modulus and phase angle of asphalt mixtures. Temperature and frequency have an impact on these parameters, and the increase in gradation has an impact on the loading-bearing ratio, due to the proportion of coarse aggregates. Full article

Background: National guidelines recommend adjuvant chemotherapy (AC) following resection for all stages of pancreatic cancer (PDAC), but the benefit of AC in Stage IA disease remains unclear. The objective of this study was to identify a subgroup of patients with Stage IA PDAC that could possibly forego AC. Study Design: The National Cancer Database (NCDB) was queried to identify all patients with Stage IA PDAC diagnosed from 2010 to 2021. Patients who received AC were compared to those who did not. Multivariable analysis was conducted to identify risk factors associated with overall survival (OS). Results: There were 1421 patients eligible for analysis. On multivariable analysis, we found nine factors associated with worse overall OS: advanced age (p = 0.0414), lower median income (p = 0.0148), Medicare (p = 0.0180), higher-grade tumor histology (p = 0.0182), LVI (p = 0.0028), positive surgical margins (p = 0.0027), examination of fewer than 12 lymph nodes (p = 0.0395), and a length of stay greater than 7 days (p < 0.0001). OS was negatively correlated with an increased number of risk factors. Improved OS was observed following AC in patients with three (∆OS = +54 months; p = 0.0016) or four or more risk factors (∆OS = +11.4 months; p = 0.0250). However, patients with fewer than three risk factors did not experience improvement in OS following AC. Conclusions: AC does not appear to benefit Stage IA PDAC patients with fewer than three risk factors indicating that it may be safe to omit AC in these individuals. Full article

Background/Objectives: Enterococcus spp. are important indicators of AMR and potential opportunistic pathogens. Urban green spaces, frequented by dogs and humans, may serve as reservoirs for resistant bacteria. This study assessed the occurrence, AMR profiles, and virulence traits of Enterococcus spp. in dog feces from urban green spaces in Porto (Portugal). Methods: In December 2023 and May 2024, 240 dog fecal samples were collected from 12 urban green spaces across Porto. Enterococcus spp. were isolated using selective culture, identified to species level, and tested for antimicrobial susceptibility following CLSI guidelines. PCR screening was performed for resistance genes (vanA, vanB, erm(A/B/C), vatD/E, tet(M/O/L/K)) and virulence genes (gelE, ace). Environmental and socioeconomic features, including vegetation density (NDVI), presence of water features, and neighborhood deprivation (EDI), were recorded to explore associations with bacterial occurrence and traits. Results: Thirty-two isolates were recovered, mainly E. faecium (n = 9) and E. faecalis (n = 7). High resistance rates were observed to tetracycline (56.3%) and quinupristin/dalfopristin (37.5%), with lower rates for vancomycin, teicoplanin, and ciprofloxacin (3.1%), and imipenem (6.3%). Tet(M) was the most prevalent resistance gene (40.6%), and gelE and ace were frequently detected, often co-occurring with resistance determinants. Distribution of resistance and virulence genes varied across green spaces, with widely used parks showing more isolates. Vegetation density and water features were not directly associated with bacterial recovery. Conclusions: Dog feces in urban green spaces contribute to localized AMR hotspots, acting as potential reservoirs of resistant and potentially pathogenic Enterococcus spp. These findings highlight the importance of One Health strategies for urban sanitation and AMR surveillance. Full article

With the growing trend toward insulator hybridization, higher requirements are imposed on the synergistic improvement of interfacial durability and pollution flashover performance. Machining annular grooves at the green-body stage and embedding silicone rubber enables the construction of an embedded structure with improved durability, forming hydrophilic/hydrophobic alternating surfaces. However, the outdoor insulation characteristics of such hybrid surfaces remain insufficiently investigated, and their engineering feasibility requires further validation. In this study, a series of hydrophilic/hydrophobic alternating surfaces were fabricated, and artificial pollution tests were conducted. The results show that the AC pollution flashover voltage exhibits a saturated increasing trend as the hydrophobic interfaces become more dispersed. When twenty 4 mm wide hydrophobic interfaces were distributed along a 16 cm creepage distance, the flashover voltage was 12.4% higher than that of a fully hydrophobic surface. These results indicate that appropriate design of hydrophobic interface distribution can achieve excellent pollution flashover performance even at relatively low hydrophobic coverage (≤50%). High-speed imaging combined with infrared thermography reveals the discharge mechanism governed by hydrophobic interface distribution from an electro–thermal coupling perspective. The coexistence of multiple dry bands induced by discrete hydrophobic interfaces is identified as the key factor enhancing flashover withstand capability. A static pollution flashover model was established to quantitatively estimate the AC flashover voltage, confirming the external insulation feasibility of the embedded hybrid concept. Full article