Search Results (125,340)

5-Aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) is one of the treatment modalities for oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC). However, the role of ferroptosis in ALA-PDT for OLK and OSCC remains unclear. Therefore, this study aimed to investigate whether ALA-PDT can induce ferroptosis in OLK and OSCC. We detected relative cellular dehydrogenase activity (CCK-8 assay), long-term proliferative viability, reactive oxygen species (ROS) generation, glutathione levels, and mitochondrial morphology after ALA-PDT. The expression of ferroptosis-related proteins was detected using Western blot. A tongue OSCC model was established in male BalB/c nude mice, and then ALA-PDT was performed. Immunohistochemical staining of Ki67, GPX4 and FTH1 was conducted to evaluate the effect of ALA-PDT. Subsequently, OLK and OSCC cells were pre-treated with ferrostatin-1 (Fer-1) before ALA-PDT. Relative cellular dehydrogenase activity, ROS generation, lipid peroxidation, Fe²⁺ levels, and ferroptosis-related protein expression were measured. Finally, OLK and OSCC cells were treated with a combination of ALA-PDT and erastin, and mitochondrial function was evaluated. In vitro study showed that ALA-PDT increased ROS generation and decreased GSH/GSSG ratio in OLK and OSCC cells. After ALA-PDT, mitochondrial morphology exhibited typical characteristics of ferroptosis. In vivo experiments showed that immunohistochemistry (IHC) scores of Ki67, GPX4 and FTH1 in the tissues decreased after ALA-PDT. Moreover, pre-treatment with Fer-1 could reverse ROS levels, lipid peroxidation and intracellular Fe²⁺ accumulation in OLK and OSCC cells after ALA-PDT. Additionally, Fer-1 pre-treatment reversed the changes in protein expression induced by ALA-PDT. The combination of ALA-PDT and erastin significantly reduced mitochondrial O₂•⁻ production and decreased mitochondrial membrane potential. Above all, ALA-PDT can induce ferroptosis in OLK and OSCC. The use of ferroptosis agonists may enhance the therapeutic efficacy of ALA-PDT for OLK and OSCC. Full article

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to α-galactosidase A deficiency, accumulation of globotriaosylceramide (Gb3), and progressive multiorgan involvement. Increasing evidence indicates that oxidative stress plays a central role in disease pathogenesis. This review aims to synthesize current knowledge on the molecular mechanisms underlying oxidative stress, the relevance of oxidative damage biomarkers, and potential therapeutic implications. A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar using terms related to Fabry disease, Gb3 metabolism, mitochondrial and endothelial dysfunction, inflammatory signaling, and oxidative stress markers. Clinical, experimental, and translational studies were included. Available data demonstrate that Gb3 accumulation disrupts mitochondrial function and activates NADPH oxidase, NF-κB, and MAPK signaling pathways, resulting in excessive production of reactive oxygen species. These processes contribute to cellular injury, particularly within the cardiovascular, renal, and nervous systems. Biomarkers such as malondialdehyde, 8-hydroxy-2′-deoxyguanosine, glutathione redox status, and antioxidant enzyme activities appear useful for assessing oxidative burden and monitoring therapeutic responses. Overall, current evidence underscores the pivotal role of oxidative stress in the progression of Fabry disease and highlights the need for further research into targeted antioxidant and disease-modifying therapeutic strategies. Full article

Compact antennas with ultra-wideband operation and stable radiation are essential for portable and airborne ground-penetrating radar (GPR), yet miniaturization in the sub 3 GHz region is strongly constrained by the wavelength-driven aperture requirement and often leads to impedance discontinuity and radiation instability. This paper presents a compact aperture-slot antipodal Vivaldi antenna (AS-AVA) designed under a radiation stability-driven co-design strategy, where the miniaturization features are organized along the energy propagation path from the feed to the flared aperture. The proposed structure combines (i) aperture-slot current-path engineering with controlled meandering to extend the low-frequency edge, (ii) four tilted rectangular slots near the aperture to restrain excessive edge currents and suppress sidelobes, and (iii) back-loaded parasitic patches for coupling-based impedance refinement to eliminate residual mismatch pockets. A fabricated prototype on FR-4 (thickness 1.93 mm) occupies $111.15\times 156.82$ mm² and achieves a measured $S_{11}$ below $-10$ dB from 0.63 to 2.03 GHz (fractional bandwidth 105.26%). The measured realized gain increases from 2.1 to 7.5 dBi across the operating band, with stable far-field radiation patterns; the group delay measured over 0.6–2.1 GHz remains within 4–8 ns, indicating good time-domain fidelity for stepped-frequency continuous-wave (SFCW) operation. Finally, the antenna pair is integrated into an SFCW-GPR testbed and validated in sandbox and outdoor experiments, where buried metallic targets and a subgrade void produce clear B-scan signatures after standard processing. These results confirm that the proposed AS-AVA provides a practical trade-off among miniaturization, broadband matching, and radiation robustness for compact sub 3 GHz GPR platforms. Full article

Background: Cancer-related fatigue (CRF) is one of the most common and burdensome symptoms faced by patients with cancer, yet effective drug-based treatments remain limited. In recent years, phytotherapeutic agents have drawn attention as complementary options, supported by plausible anti-inflammatory, antioxidant, and immunomodulatory mechanisms. Methods: We performed a systematic review and meta-analysis to quantitatively synthesize randomized controlled trial evidence on the efficacy of phytotherapeutic interventions for cancer-related fatigue and to assess the certainty of evidence. Databases were searched from inception, with the final search update completed in October 2025. Eligible studies included adults with CRF and compared herbal interventions with placebo controls. Standardized mean differences (SMDs) were pooled using a DerSimonian–Laird random-effects model. We also evaluated risk of bias (RoB 2), publication bias, and certainty of evidence using GRADE. This systematic review and meta-analysis was conducted in accordance with the PRISMA 2020 guidelines. Results: Fourteen trials were included, studying agents such as Paullinia cupana, Panax ginseng, multi-herbal Traditional Chinese Medicine formulations, and other botanical extracts. Overall, phytotherapy provided a modest improvement in CRF (SMD = 0.31; 95% CI, 0.08–0.53; p = 0.022), though heterogeneity was substantial (I² = 56.7%). In subgroup analyses, only the group of “other formulations” demonstrated significant benefit; ginseng and guaraná did not demonstrate statistically significant effects. Most trials had high or unclear risk of bias, and the certainty of evidence was rated very low. Conclusions: Current evidence does not firmly support phytotherapeutic agents as effective treatments for CRF, hindered largely by methodological weaknesses, heterogeneous interventions, and imprecise effect estimates. Even so, the biological rationale and the variability in clinical responses point toward an opportunity for the emerging field of precision herbal oncology. Well-designed, multicenter trials are essential to determine whether phytotherapy can meaningfully contribute to CRF management. Full article

Ultra-high-performance concrete (UHPC) is a sophisticated construction material known for its exceptional strength and durability. Conventional UHPC generally self-consolidates, which makes it unsuitable for roof and bridge deck rehabilitation applications due to its thin layers and inclined surfaces. UHPC overlay construction generally requires a highly thixotropic material that responds well to vibration and remains stable on slopes. Despite the complex rheological properties of thixotropic UHPC, there are limited testing methods for effectively assessing the workability of overlay mixes. Therefore, this paper provides a comprehensive evaluation of the workability of overlay UHPC using existing and newly developed tests. Besides the commonly used static and dynamic flow tests, this study introduces Patting Response (PR) and Vibration-Slope Stability (VSS) tests, designed to evaluate different qualities of UHPC overlay mixtures. Seven groups of mixtures with varying binder content, water-to-binder ratio (w/b), fiber reinforcement, and admixture dosages were prepared and tested. A lab-scale sloped slab was constructed to validate the buildability of the most promising mixtures. These tests and mixtures support effective overlay solutions for roof slab and bridge deck repairs, providing protection against infrastructure deterioration and improving overall performance by introducing a dense, durable UHPC overlay. Results indicate that mixtures with static flow below 6 in. and dynamic flow between 7 and 8 in. consistently passed both PR and VSS tests, demonstrating stable vibration response and slope retention. The constructability evaluation confirmed the effectiveness of the new testing methods. Additionally, the correlation between different tests, particularly flow and VSS, was examined. Recommendations for appropriate ranges for various workability tests were established based on the performance of the developed mixtures. The proposed static and dynamic flow ranges are performance-based and are expected to be broadly applicable to thixotropic UHPC overlay systems exhibiting comparable workability and rheological behavior under vibration and sloped placement conditions. Overall, these tests and thixotropic UHPC mixtures facilitate effective repair of roof slabs and bridge decks, providing overlay protection against deterioration and potentially enhancing structural capacity through composite behavior. Full article

Introduction: Mounting evidence indicates that the p53 Pro72Arg single-nucleotide polymorphisms (SNPs) may play a role in modulating hepatocarcinogenesis in the setting of chronic HBV infection. However, there is currently a lack of studies focusing on this genetic variant in Indonesia, a country characterized by its diverse genetic landscape comprising over 1300 distinct ethnic groups. We aimed to investigate the association between the p53 Pro72Arg polymorphism and the risk of hepatocellular carcinoma (HCC) among Indonesian patients with chronic HBV infection. Methods: A total of 140 patients with chronic hepatitis B (CHB) were recruited, including 79 with HCC and 61 without HCC serving as controls. We used direct sequencing of DNA extracted from peripheral blood to analyze the SNPs of p53 codon 72. Results: The distribution of p53 Pro72Arg genotypes among Indonesian CHB patients was 12.9% for proline homozygotes (Pro/Pro), 31.4% for arginine homozygotes (Arg/Arg), and 55.7% for proline/arginine heterozygotes (Pro/Arg). Despite the lack of association between the SNPs and HCC risk in the overall population, both the Pro/Arg and Arg/Arg genotypes demonstrate an increased susceptibility to HCC compared to Pro/Pro genotypes exclusively in the Madurese ethnic group. Additionally, we discovered that in those with decompensated cirrhosis, the heterozygote Pro/Arg was more likely to develop HCC than the homozygous Pro/Pro. No significant association was found between the SNPs of p53 Pro72Arg and the clinicopathological characteristics of HCC. Conclusions: The p53 Pro72Arg polymorphism might contribute to hepatocarcinogenesis in Indonesian chronic hepatitis B patients, particularly Madurese and those with liver decompensation. Full article

The impact of a quarter-circle corner crack on an adjacent parallel semi-elliptical surface crack (SESC) located in a semi-infinite solid subjected to in-plane bending is studied using a 3-D finite element analysis. The stress intensity factor (SIF) distributions along the front of the SESC are evaluated to determine said impact. The SESC’s semi-major axis ranged from a₁ = 10 mm to 30 mm with ellipticities of b₁/a₁ varying from 0.1 to 1.0 for a constant quarter-circle corner crack length of a₂ = 15 mm. Furthermore, several crack configurations are considered where the normalized vertical and horizontal gaps between the two cracks are taken to be H/a₂ = 0.4 and 1.2 and S/a₂ = −0.5 and 1.0, respectively. The results show that the effect of the quarter-circle corner crack on the SESC can be considerable both in amplifying and in attenuating the SIFs along the semi-elliptical surface crack front. Moreover, these opposite effects can occur simultaneously, but in different sections of the SESC’s crack front. The magnitude and pattern of these effects depend on the length and ellipticity of the SESC. It is further concluded that when considering the fitness-for-service of a critical real mechanical component, a complete 3-D analysis is needed to provide a reliable solution for such crack configurations. Full article

The simultaneous HPLC method for quantifying Quercetin (Que), Thymoquinone (Thy), and Pterostilbene (Pte) aims at the precise measurement of these polyphenols alone or in complex mixtures, targeting their therapeutic potential in disorders such as diabetes and epilepsy. The method focuses on quantifying Que, Thy, and Pte, utilizing optimized reversed-phase HPLC conditions as per ICH Q2(R1) standards. Key validation aspects include linearity, specificity, precision, and accuracy, ensuring compliance for quality control in nanomedicine and nutraceuticals, and the method’s applications support pharmacokinetic studies and stability testing, contributing to personalized medicine and addressing pharmaco-resistance. The HPLC method development and validation were performed on a phenyl column using the mobile phase consisting of solvent A (0.1% orthophosphoric acid in HPLC water) and solvent B (acetonitrile) at a ratio of 55:45 in an isocratic elution mode at a flow rate of 1 mL/min and at a column temperature of 35 °C. Ultraviolet detection was measured at 254 nm. Moreover, the method was validated for accuracy, precision, linearity, specificity, and sensitivity. The retention time for tested Que, Thy, and Pte was observed at 4.15 min, 8.70 min, and 10.75 min, respectively. Limits of detection for Que, Thy, and Pte were 1.55 μg/mL, 2.40 μg/mL, and 70.79 µg/mL, whereas limits of quantification were 4.69 μg/mL, 7.28 μg/mL, and 214.52 µg/mL, respectively. Linearity and correlation coefficients for Que, Thy, and Pte were found in the range of 50–250 μg/mL (0.9999), 50–250 μg/mL (0.9999), and 620–3100 μg/mL (0.9996), respectively. A reasonable level of accuracy was indicated by the tested method suggesting extremely high recovery levels (98–102%). The separation of tested compounds was achieved within 11 min. The developed and validated RP-HPLC–UV method was successfully applied for the identification and quantification of Que, Thy, and Pte for their combined estimation in complex formulations. From the validation study, it was found that the tested method is specific, accurate, precise, reliable, and reproducible. Full article

Cardiac transplantation remains an important therapy for end-stage heart failure, although allograft rejection continues to pose significant clinical challenges. This review evaluates both established and emerging blood-based biomarkers for noninvasive monitoring of rejection in heart transplant recipients. Donor-derived cell-free DNA (ddcfDNA) and gene expression profiling (GEP) represent well-validated, commercially available molecular tools that demonstrate strong discriminative capacity for acute rejection episodes. Additionally, microRNAs (miRs) and extracellular vesicles (EVs) show considerable potential as novel biomarkers, although further validation is required. In contrast, conventional biomarkers such as B-type natriuretic peptide (BNP), cardiac troponins, and creatine kinase-MB (CK-MB) offer limited specificity in the context of rejection. This review synthesizes current evidence on the clinical utility, methodological challenges, and integration strategies of these biomarkers, highlighting a shift toward molecular-based approaches for improving post-transplant surveillance and patient outcomes. Full article

Halide perovskites have many advantages in environmental remediation. The photocatalytic performance of halide perovskites is often hindered by low specific surface area and rapid photogenerated carrier recombination. The aim of this work is to prepare a green, novel photocatalyst in the form of biochar-anchored Cs₃Bi₂Br₉ perovskite composites. The rose-petal-derived biomass carbon (RC) provides adsorption sites and high electrical conductivity, while the perovskite Cs₃Bi₂Br₉ can efficiently capture visible right and degrade pollutants, and the reciprocal effect can enhance the photocatalytic efficiency of the composite. The results of scanning electron microscopy (SEM) showed the Cs₃Bi₂Br₉ particles were loaded on the surface of RC. Compared with bare Cs₃Bi₂Br₉, Cs₃Bi₂Br₉/RC composite has a more perfect structure, higher specific surface area, enhanced ability to absorb visible light, and reduced bandgap value. As visible-light-driven photocatalysts, the prepared Cs₃Bi₂Br₉/RC composites can enhance the removal efficiency of Rhodamine B. The Cs₃Bi₂Br₉/RC–0.2 composite displays the highest degradation efficiencies for RhB (10 mg/L), reaching 98% within 60 min. And the rate constant (k) is 1.9 times that of bare Cs₃Bi₂Br₉. The results of electrochemical impedance spectroscopy (EIS) show that the interaction between RC and Cs₃Bi₂Br₉ speeds up charge carrier separation and transfer. During photocatalytic process, holes (h⁺) and superoxide radicals (·O₂⁻) played major roles. The composites also showed excellent stability. It is meaningful to deal with a large number of withered rose petals to make them high-value products. This work not only provides a guideline for the construction of perovskite composites materials but also shows the promising prospects of biochar composites in deep treatment for contaminated water. Full article

Background: Mycoplasma pneumoniae pneumonia (MPP) is a common community-acquired pneumonia in children. Increasing drug resistance highlights the need for more effective treatments with fewer side effects. The Qingfei Tongluo Jiedu formula (QTJD) has demonstrated clinical efficacy against MPP; however, its underlying mechanisms remain unclear. This study aimed to explore the mechanism of QTJD on MPP using network pharmacology and in vitro experiments. Methods: Network pharmacology was used to identify the active compounds and signaling pathways of QTJD in MPP. QTJD-containing serum was prepared, and primary mouse lung and bone marrow cells were isolated to examine the effects of QTJD on macrophage polarization through butyric acid. Cell viability assays, flow cytometry, and quantitative reverse transcription-polymerase chain reaction were performed. GPR109^−/− cells were used to confirm the receptor mediating butyric acid’s action, and Western blotting was employed to assess the MAPK signaling pathway. Results: QTJD promoted macrophage polarization and alleviated the inflammatory response caused by Mycoplasma pneumoniae. High-performance liquid chromatography-electrospray ionization mass spectrometry combined with network pharmacology identified 20 active compounds. Protein-protein interaction analysis revealed 10 core target, including JUN and Tumor Necrosis Factor (TNF), while enrichment analysis highlighted pathways such as Mitogen-Activated Protein Kinase (MAPK) and Phosphoinositide 3-Kinase-Protein Kinase B. Experimental validation demonstrated that QTJD reduced M1 markers (CD86, CXCL10) by increasing butyrate levels (p < 0.01) and enhanced M2 markers (CD206, Arg-1, MRC-1), promoting M2 polarization. QTJD inhibited ERK1/2, p38, and JNK1/2 (p < 0.01). In GPR109A^−/− mice macrophages, QTJD suppressed p38 and JNK1/2 (p < 0.01) but showed no effect on ERK1/2 (p > 0.05), confirming involvement of the butyrate-GPR109A-MAPK pathway. Conclusions: QTJD effectively alleviates MPP by regulating macrophage polarization through the butyrate-GPR109A-MAPK pathway. Future studies should explore how QTJD modulates pulmonary immunity through gut microbiota and butyrate production and elucidate its immunoregulatory mechanisms along the gut-lung axis using multi-omics approaches. Full article

The total cavopulmonary anastomosis (Fontan procedure), a palliative procedure for single-ventricle congenital heart disease, improves survival but is associated with progressive multiorgan complications and high long-term morbidity. Prior blood-based proteomic studies in adults have been limited to targeted antibody-based panels or focused on methodological comparisons. Systemic molecular alterations in younger, clinically heterogeneous patients, particularly in untargeted pathways, remain incompletely characterized. Serum samples from 48 Fontan patients and 48 age- and sex-matched healthy controls were analyzed using mass spectrometry with TMT labeling. 2228 proteins were quantified, of which 124 were significantly differentially abundant (fold change > 1.5 or <0.67, FDR-adjusted p < 0.05). Network analysis identified three major functional clusters: extracellular matrix (ECM) organization (predominantly increased), actin cytoskeleton organization, and platelet-related pathways (both predominantly decreased). Stratified analyses showed reduced ECM protein abundance in high-risk patients, suggesting a shift from active remodeling toward a more established fibrotic state, and uniquely elevated cytochrome b5 reductase 3 (CYB5R3), implicating altered redox homeostasis, nitric oxide metabolism, and cellular aging. Overall, our findings extend prior targeted analyses, reveal potential biomarkers such as CYB5R3 and underscore the complexity of the Fontan circulation, with implications for risk stratification and therapeutic targeting. Full article

Background/Objectives: In severe peripheral artery disease (PAD) with limb ischemia, hypercholesterolemia (HC) is associated with impaired neovascularization. Extracellular vesicles (EVs) are present within ischemic muscles, and they contain microRNAs (miRs) involved in several biological functions, including angiogenesis and neovascularization. Methods: We used a mouse model of PAD and compared the response to hindlimb ischemia in hypercholesterolemic ApoE^−/− vs. normocholesterolemic mice. Next-generation sequencing (NGS) was used to perform full miR expression profiling in ischemic skeletal muscles and in EVs of varying sizes—large EVs (lEVs) and small EVs (sEVs)—within these muscles. Results: We identified several miRs with potential pro-angiogenic effects (angiomiRs) that are reduced by HC in lEVs (Let-7b-5p, miR-151-3p, Let-7c-5p) or sEVs (miR-21a-5p, miR-196b-5p, miR-340-5p). As proof of principle, we showed that the overexpression of Let-7b-5p in lEVs, or miR-21a-5p in sEVs, can significantly increase the angiogenic capacity of these EVs in vitro. HC also impaired the enrichment of specific angiomiRs in lEVs (miR-100-5p), sEVs (miR-142a-3p), or in both lEVs and sEVs (miR-146b-5p). In silico approaches, including the prediction of miR targets, pathway unions, and gene unions, identified the resulting predictive effects of HC-modulated miRs in EVs on processes with key roles in the modulation of angiogenesis and neovascularization, such as the regulation of the actin cytoskeleton and focal adhesion and the HIF-1, MAPK, AMPK, and PI3K-Akt signaling pathways. Conclusions: Our results constitute an important first step towards the identification of specific miRs that could be targeted to improve EV angiogenic function in hypercholesterolemic conditions and reduce tissue ischemia in patients with severe PAD. Full article

This study investigates the improvement of Ni/SiO₂-Al₂O₃ catalysts in the dry reforming of methane (DRM) process by detailed adjustments of calcination temperature (600–900 °C) and duration (1–9 h). N₂ physisorption, H₂-TPR, XRD, TGA, and TEM show that elevated calcination temperatures result in increased surface roughness and reduced specific surface areas. The present investigation indicates that the ideal calcination parameters are 900 °C and 3 h. This helps the catalyst work better. This condition gave the best initial activity (54% CH₄ conversion and 61% CO₂ conversion) and the best long-term stability and resistance to carbon deposition. Using MATLAB R2025b (ODE45) for kinetic analysis, it was found that these factors have a big effect on activation energy. Shorter calcination of 1 h gave high initial activity, but it quickly lost its effectiveness. On the other hand, a longer calcination time of 9 h made the material more stable but less able to condition convert because it sintered too much. These results show that it is very important to carefully control the conditions of calcination in order to make long-lasting, high-performance catalysts for making syngas. Moreover, a 20-h DRM stability run of the optimum catalyst exhibited nearly constant activity, highlighting its strong structural integrity and superior ability to alleviate rapid coke formation. Full article

This article describes a field- and laboratory-based framework that can be used to monitor the C balance in Mediterranean pine forest ecosystems under different management practices that determine their structure and function. By jointly monitoring stand structure, gas exchange, litter, and decomposition dynamics, this protocol enables the assessment of how management-driven changes regulate carbon uptake, turnover, and losses, thereby affecting carbon sequestration potential. As an example, we suggest the implementation of the protocol at ten (10) permanent monitoring plots across three study areas located in Greece. The first group of plots represents a post-fire chronosequence in pine stands with no management interventions. The second group includes pine stands that exhibit variation in overstory and understory density driven by differences in microclimate and management history. The third group consists of peri-urban pine stands subjected to thinning of varying intensity. The monitoring protocol is implemented across all plots and the collected data can be classified into three analytical domains: (a) demography, encompassing measurements of tree growth and mortality; (b) litter and decomposition dynamics, involving the quantification of litterfall and its seasonality and the estimation of its decomposition rates; and (c) gas exchange, focusing on measurements of leaf photosynthesis and respiration (including relevant leaf functional traits) and monitoring of soil respiration. These three data domains can be used to comparatively consider the effect of forest management on key ecosystem processes and to constrain local-scale vegetation dynamics models. Full article