Search Results (12,791)

Hepatocellular carcinoma (HCC) represents one of the most lethal malignancies worldwide and is characterized by profound metabolic reprogramming during its development. Paraoxonase 1 (PON1), a liver-synthesized secretory protein involved in lipid metabolism, has an incompletely defined role in cancer biology. This study aimed to systematically investigate the expression pattern, clinical features, and biological function of PON1 in HCC through an integrated approach combining data mining, RNA-seq and experimental verification. Our results demonstrated that PON1 expression is significantly downregulated in HCC tissues compared with adjacent tissues. Clinically, significant disparities were observed in gender (χ² = 19.305, p < 0.0001), tumor stage (χ² = 18.030, p = 0.0004), and tumor grade (χ² = 13.391, p = 0.0039) between patients with high and low PON1 expression in HCC. Low PON1 expression was associated with poor prognosis (TCGA_LIHC, log-rank: χ² = 9.290, p = 0.0023; ICGC_LIRI, log-rank: χ² = 8.469, p = 0.0036; GSE14520, log-rank: χ² = 9.746, p = 0.0018). Univariate and multivariate Cox regression analyses revealed PON1 as an independent prognostic biomarker. Pathway analysis showed that PON1-positively correlated genes enriched in pathways such as peroxisome and fatty acid degradation, whereas PON1-negatively correlated genes mainly in the cell cycle pathway. Functional experiments confirmed that knockdown of PON1 promoted HCC cell proliferation, migration, invasion and inhibited apoptosis, whereas overexpression of PON1 reversed these malignant phenotypes. Mechanistically, we uncovered that PON1 exerts its tumor-suppressive effects by negatively regulating TANK and CXCL3, key molecules of the NOD-like receptor signaling pathway. In summary, our findings identify PON1 as an independent prognostic biomarker in HCC and demonstrate the tumor-suppressive role of PON1, indicating its potential as a therapeutic target for HCC. Full article

Background/Objectives: Biofilms are a form of defense that enables bacteria to withstand antibiotic pressure and demonstrate antibiotic resistance. It is crucial to develop anti-biofilm strategies in order to combat chronic and persistent multidrug-resistant (MDR) infections. Methods: In this study, we developed 3D biofilms of single-, dual-, and poly-species MDR ESKAPE components, including the pathogens P. aeruginosa S. aureus and K. pneumoniae, in CF Mu3Gel. We evaluated the efficacy of using a phage, a di-hetero phage cocktail or a poly-hetero phage cocktail in combination with ciprofloxacin to eliminate mature biofilm biomass after 72 h or one week in a single treatment. Results: The phage components mostly exhibited synergistic behavior when combined with ciprofloxacin and with each other in di- and poly-hetero-cocktails. The reduction in 72-h dual- and poly-species biofilms was one log higher than that of one-week biofilms treated with the phage–antibiotic combination. The greatest reductions were observed in the 72-h single-species biofilm with combination therapy, at 1.4–3.0 log. Reductions of 2.16 and 1.6 log were observed in the dual-species P. aeruginosa and S. aureus biofilm and the poly-species biofilm, respectively. Conclusions: This study examined how a single application of phages or phage cocktails, either alone or in combination with ciprofloxacin, impacted established biofilm models, and how this affected the proportion of microcolonies of different species within each model. These insights will facilitate the development of strategies for multiple follow-up treatments, as well as the reordering of phages, phage cocktails, and combinations with antibiotics, to improve outcomes. The 3D biofilm models developed here could be used to screen phages or phage cocktails either on their own or alongside other therapies. This would facilitate the application of in vitro findings to real physiological settings. Full article

Background/Objectives: This study evaluates the prognostic value of baseline inflammatory biomarkers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), and pan-immune-inflammation value (PIV) in advanced cutaneous melanoma treated with first-line immunotherapy. Methods: This multicenter retrospective study included 162 patients with unresectable stage III/IV cutaneous melanoma treated with first-line pembrolizumab, nivolumab, or nivolumab plus ipilimumab. Biomarkers were calculated from complete blood counts obtained within 30 days before treatment start. Cut-offs were defined by ROC analysis. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier and Cox regression. Response was assessed by RECIST v1.1. Results: Higher baseline NLR, PLR, MLR, SII, and PIV were more common in patients with adverse baseline features, including liver metastases, elevated LDH, and poorer ECOG performance status. Patients with biomarker values below the cut-offs had significantly longer PFS and OS. In biomarker-specific multivariable models adjusted for selected clinical covariates, PIV retained the most consistent association with PFS and OS, while MLR was associated with PFS, and PLR with OS. Conclusions: Baseline inflammatory biomarkers from routine blood counts provide useful prognostic information in advanced melanoma treated with first-line ICIs. PIV showed the most consistent association with survival outcomes and may support initial risk stratification alongside LDH, ECOG, and metastasis pattern. However, prospective validation in independent cohorts is needed before routine clinical implementation. Full article

Electrocatalytic oxidation technology demonstrates significant potential in treating refractory industrial wastewater, playing a crucial role in industrial pollution control. This paper established an electrocatalytic oxidation system using Ti/IrO₂–RuO₂ as the anode for pretreating high-salinity, refractory pesticide and chemical membrane concentrate. The optimal conditions were identified through a systematic investigation of key parameters including salt concentration, current density, initial pH, and electrode spacing as follows: salt concentration of 15 g/L, current density of 43.69 mA/cm², initial pH of 5.0, and electrode spacing of 2.0 cm, achieving a maximum COD removal rate of 93.45% with energy consumption of 0.191 (kW h)/kg COD. The results indicated that this system effective degraded organic compounds in membrane concentrate. These findings provided innovative approaches for the efficient treatment of refractory organic wastewater from pesticide and chemical industries. Full article

River water quality assessments are commonly conducted under conventional anthropogenic pressures; however, the long-term environmental impacts of armed conflicts remain insufficiently understood. This study addresses this gap by evaluating the persistence of war-related heavy metal contamination and its associated human health risks in the Tigris River, Mosul, a post-conflict urban system. The results revealed that Cd, Pb, Cr, and Ni concentrations exceeded WHO guideline values across most sites, while Zn remained within acceptable limits. The highest contamination levels were observed in the central urban zone (Zone 3), which was directly affected by military activities. Hazard quotient (HQ) values for Cd and Pb exceeded the safe threshold (HQ > 1) at all sites, identifying them as dominant contributors to toxicity. The cumulative hazard index (HI) reached extremely high levels (>300 in 2022 and >200 in 2023), indicating severe non-carcinogenic health risks despite a slight temporal improvement. Spatially, contamination increased from upstream to downstream, with midstream and downstream areas acting as critical hotspots. Temporally, although pollutant levels declined in 2023, they remained significantly above safe limits, demonstrating limited natural recovery. Overall, the findings provide clear evidence of the long-term persistence of conflict-related contamination and its sustained risks to human health. This study highlights the need for targeted remediation strategies and offers a transferable framework for assessing water quality in conflict-affected river systems.: Full article

Electronic components play a fundamental role in critical missions, performing functions such as data processing, measurement of physical variables, data storage, communication, power generation and storage, and algorithm computation. However, their performance can be compromised in harsh environments like those encountered in aerospace applications, where components are exposed to extreme conditions including radiation, temperature variations, and vibrations. To ensure reliability, electronic components used in aerospace missions must comply with strict specifications, typically requiring space- or military-grade standards. These components are significantly more expensive than commercial alternatives and often involve long development and design times for custom platforms. The use of COTS (Commercial-Off-The-Shelf) components has emerged as a viable solution for aerospace applications where cost and development time are critical factors. This paper presents a state-of-the-art review of COTS components used in aerospace missions. After an extensive literature review and document screening process, the results indicate that COTS components are commonly employed in critical missions, representing 44% of the studies analyzed. Furthermore, approximately 81% of the reviewed projects focused on space applications, with validation performed in space (22%), ground (75%), and air (3%) environments. Among the systems validated for space missions, half used CubeSat-based payload structures, while the rest relied on other platforms. Most launches were conducted using spacecraft (96%), with the remainder using balloons. Full article

Conventional fired clay brick production is energy-intensive and associated with significant carbon emissions due to kiln firing and mass molding processes. In this context, extrusion-based additive manufacturing (AM), particularly Direct Ink Writing (DIW), has emerged as a potential alternative for shaping clay-based building units, enabling reduced material waste, the use of locally sourced clays and recycled additives, and the fabrication of complex geometries with enhanced thermal and structural performance. However, despite these advantages, the application of AM to clay bricks remains limited, as key challenges persist in terms of material rheology, interlayer bonding, production scalability, and the continued need for high-temperature firing, which constrains its environmental benefits. This study presents a scoping review of AM technologies applied to clay brick manufacturing, focusing on their technical feasibility, material requirements, and sustainability implications in comparison with conventional processes. Furthermore, current research trends are analyzed to identify existing gaps, particularly regarding industrial scalability and life cycle assessment (LCA), and to outline future research directions required for the development of a new generation of sustainable clay bricks. Full article

This work explores the organization of a supply system within a military transportation network. The nodes of the studied network, comprising suppliers and recipients of supplies (representing delivery and collection points), were geographically identified, as well as the volume of cargo transported in each connection. The idea was to improve the efficiency of supply within the network, understood as minimizing total transportation costs. Calculations were performed using three methods: North–West Corner Method (N-WCM), least cost in the matrix method (LCMM), and Vogel’s Approximation Method (VAM). As a result of the calculations, basic feasible solutions (BFS) were obtained for each method, satisfying the constraint conditions. Each BFS was degenerate, because each contained m + n − 1 basic (non-zero) elements. In accordance with the calculation methodology, optimization was performed for each BFS using the potential method. For N-WCM and LCMM, up to five iterations were required, while for VAM, only one iteration was sufficient, confirming the best performance for this method. In addition to the total transport costs, additional criteria such as total distance, fuel consumption and CO₂ emissions were considered. Full article

In this study, we investigated the interaction of a dapagliflozin-containing medicinal product (the commercial drug Forxiga^®) with human serum albumin (HSA) at different temperatures using steady-state fluorescence spectroscopy, competitive displacement assays, UV–Vis absorption spectroscopy, and thermodynamic analysis. Increasing concentrations of Forxiga induced a gradual, concentration-dependent quenching of the intrinsic fluorescence of HSA (${\lambda }_{\mathrm{ex}}=284$ nm; ${\lambda }_{\mathrm{em}\max }\approx 334$–339 nm), indicating perturbation of the microenvironment surrounding Trp-214 located in subdomain IIA. Stern–Volmer analysis showed that the quenching constants were temperature-dependent. Meanwhile, the high apparent bimolecular quenching constants suggested a predominantly static quenching mechanism associated with ground-state complex formation. By performing a modified Scatchard-type double-logarithmic analysis, we identified a primary binding site, particularly at lower temperatures. Van’t Hoff analysis revealed negative enthalpy and entropy changes. This indicates that the interaction was spontaneous and exothermic, mainly driven by hydrogen bonding and van der Waals forces. The competitive displacement assays confirmed preferential binding at Sudlow’s site I, in proximity to Trp-214. Additionally, the UV–Vis spectroscopy, supported by ligand-induced perturbation of aromatic residues, confirmed the absence of significant inner-filter effects. Differential scanning calorimetry suggested partial thermal stabilization of HSA upon ligand binding. This finding is consistent with the formation of a stabilized protein–ligand complex. These results suggest that Forxiga forms a relatively stable ground-state complex with HSA, primarily at Sudlow’s site I, and that the interaction is influenced by temperature-dependent conformational changes in the protein. Full article

Preterm birth is a major cause of neonatal morbidity and mortality, and many spontaneous cases remain idiopathic. Increasing evidence suggests that intrauterine inflammation may occur in the absence of detectable infection, leading to the recognition of sterile intrauterine inflammation as an important mechanism contributing to threatened preterm labor and spontaneous preterm birth. This review summarizes current knowledge regarding the role of damage-associated molecular patterns (DAMPs), alarmins, pattern recognition receptors, inflammasome activation, cellular senescence, and pyroptosis in the initiation of sterile inflammatory pathways associated with labor. Key mediators including HMGB1, IL-1α, fetal cell-free DNA, platelet-activating factor, and S100 proteins appear to promote inflammatory activation within fetal membranes and the amniotic cavity. The review also discusses the emerging contribution of fetal immune activation, maternal–fetal immune dysregulation, maternal microchimerism, and epigenetic mechanisms to idiopathic preterm birth. Current diagnostic and therapeutic options remain limited, and no targeted treatment for sterile intrauterine inflammation has yet been established. Future approaches may include precision biomarkers, multiomics-based risk stratification, targeted immunomodulatory therapies, and modulation of maternal–fetal immune interactions. Improved understanding of sterile inflammatory mechanisms may ultimately support development of personalized strategies to prevent preterm birth and improve perinatal outcomes. Full article

High-resolution, commercially acquired satellite imagery has been shown to be a powerful tool for documentation and analysis of damage to archaeological sites, particularly in conflict zones where ground-based observations are impractical or dangerous. Using this approach, previous investigations have reported widespread looting and other forms of damage to archaeological sites in Syria during the early years of the civil war (2011–2016). Relying on an expanding suite of satellite imagery resources, this paper presents a renewed analysis of looting and archaeological site damage in Syria over the past decade. The results reveal: (1) severe damage to many sites in northern Syria from a novel form of mechanized looting, (2) intensified impacts from the establishment of military facilities or refugee camps on many prominent sites, and (3) rampant incidents of small-scale looting across all areas of the country. These results highlight the importance of ongoing imagery-based heritage monitoring efforts and will support emerging mitigation, stabilization, and damage assessment efforts in Syria going forward. Full article

To address the challenge of accurately reconstructing multi-depth targets using single-photon Light Detection and Ranging (LiDAR) under few-frame conditions in high-precision applications such as autonomous driving perception, remote sensing, and military reconnaissance, this paper proposes a computational imaging method named the Jensen–Shannon Divergence Weighted Pixel Fusion Constant False Alarm Rate (JSWPF-CFAR) approach. First, the proposed method utilizes the Jensen–Shannon (JS) divergence to characterize the statistical similarity between adjacent pixels, thereby constructing adaptive weights to achieve the effective fusion of echo signals. The key innovation lies in the formulation of a JS divergence-based weighting factor, which fully exploits the inherent spatial correlation within 3D target structures to optimize the pixel fusion process and enhance the signal statistics of target echoes. Subsequently, a CFAR detection model tailored for Geiger-mode Avalanche Photodiode (GM-APD) multi-depth echo signals is constructed to estimate the noise photon count within a local sliding window; this estimate is then used to calculate a photon counting threshold for identifying and extracting high-confidence target intervals. Finally, a peak-picking method is employed to perform the 3D reconstruction of multi-depth targets. Compared with existing techniques such as matched filtering and Reversible Jump Markov Chain Monte Carlo (RJMCMC), the proposed method exhibits superior reconstruction quality under few-frame and low Signal-to-Background Ratio (SBR) conditions. The experimental results demonstrate that the proposed method achieves an improvement in target restoration degree (RD) of at least 21.16% and a relative variance (Var) optimization of at least 62.90% over the matched filtering and RJMCMC baselines. These results indicate that the proposed approach effectively enhances the multi-depth estimation performance of single-photon LiDAR in complex scenes. Full article

Background: It is important to note that motherwort (Leonurus cardiaca) has especially calming properties, partly due to its chlorogenic acid (CLA) content. While the concentration of this acid in alcoholic or water–alcoholic extracts has been determined in the literature, there is no knowledge about the content of CLA in water extracts. Therefore, the aim of this study was primarily to assess the CLA content in infusions prepared in four different ways and to estimate the actual CLA intake with these infusions. An additionally aim was to assess the content of phenols and their antioxidant properties. Methods: A capillary electrophoresis device equipped with a DAD detector was used to determine CLA in dried motherwort herb, and the DPPH test and the Folin–Ciocâlteu method were used to determine antioxidant properties. Results: The median CLA content in the infusions was 527.26 µg/100 mL. In turn, the total phenol content per glass was 32.88 mg. The mean median DPPH test expressed as Trolox equivalent was 33.65 mg/L TE. Conclusions: The method of preparing infusions affects the content of CLA and phenols in water infusions. However, these changes did not significantly affect the antioxidant properties of the prepared extracts. Full article

To realize the real-time structural health and operational safety monitoring of military and industrial devices, such as hypersonic vehicles, aero-engine blades, and thermal power plant boilers, at operating temperatures up to and beyond 1400 °C, this study presents a miniaturised, integrated, high-thermal-stability wireless sensor device. This study investigated the influence of temperature on the interdigital electrodes (IDEs) of surface acoustic wave (SAW) temperature sensors for three configurations: bare electrode, single-layer protective film, and multilayer composite film. While the exposed electrode exhibited thermal stability at 1000 °C, it underwent structural failure at 1250 °C. To achieve health monitoring at temperatures exceeding 1400 °C, an Al₂O₃/AlN/Al₂O₃ multilayer protective architecture was developed. The device demonstrated functionality up to 1400 °C with a temperature coefficient of frequency (TCF) of −40.03 ppm/°C, yielding a sensitivity of 12.0 kHz/°C at a center frequency of ~300 MHz. The electrode protection structure elevated the maximum operating temperature. A hybrid heterogeneous integration of high-temperature co-fired ceramic (HTCC) inverted-F antenna and a Langasite (LGS) SAW device with a multilayer composite film was realised. The wireless device maintained functionality from room temperature to 1400 °C and withstood 1400 °C for 2 h, exhibiting a maximum repeatability error of 12.67% (corresponding to a temperature measurement error of ~177.4 °C at 1400 °C). This integrated design enables the miniaturization of high-temperature wireless sensors, making them suitable for harsh environments. Full article

Recently, a new generalization of hyperbolic functions called para-hyperbolic functions has been introduced. However, properties of the para-hyperbolic functions have not been investigated yet. In this paper, we derive the correct explicit formulas of the para-hyperbolic sine and cosine, study elementary properties of these functions, and explore which of the inequalities that hold for trigonometric and hyperbolic functions find their counterparts for para-hyperbolic functions. Namely, we prove a Wilker type inequality, Cusa-Huygens and Lazarević type inequality, Wu-Debnah modification of Wilker type inequality and Shafer type inequality for para-hyperbolic functions. Our results provide the first thorough exploration of para-hyperbolic functions which establishes groundwork for further discoveries and applications. Full article