Search Results (123)

In Gram-negative bacteria, lipopolysaccharides (LPSs, also known as endotoxin) can induce extensive immune responses that will enable victims to produce severe septic shock syndrome. Because of the high mortality of sepsis in the face of standard treatment, advance detoxification schemes are urgently needed in clinics. Herein, we described a supramolecular detoxification approach via direct host–guest complexation by a giant macrocycle. Cationic pentaphen[3]arene (CPP3) bearing multiple quaternary ammonium groups was screened as a candidate antidote. CPP3 exhibited robust binding affinity toward LPS with an association constant of (4.79 ± 0.29) × 10⁸ M⁻¹. Co-dosing with an equivalent amount of CPP3 has been demonstrated to decrease LPS-induced cytotoxicity on a cellular level through inhibiting ROS generation and proinflammatory cytokine expression. In vivo experiments have further proved that post-treatment by CPP3 could significantly improve the survival rate of LPS-poisoned mice from 0 to 100% over a period of 3 days, and inflammatory abnormalities and tissue damage were also alleviated. Full article

Background/Objectives: Being overweight and obesity are major public health concerns that demand effective nutritional strategies for weight and body composition management. Beyond excess weight, these conditions are closely linked to chronic inflammation, oxidative stress, and gut dysbiosis, all of which contribute to cardiometabolic risk. Polyphenols—bioactive compounds in plant-based foods—may support improvements in body composition and metabolic health by modulating gut microbiota, reducing oxidative stress, and suppressing inflammation. This systematic review and meta-analysis aimed to evaluate the effects of polyphenol-rich interventions on gut microbiota composition, in combination with either oxidative stress or inflammatory biomarkers, and their potential impact on body composition in overweight or obese adults. Methods: A systematic search of PubMed, Scopus, Cochrane, and Web of Science was conducted through May 2025. Eligible randomized controlled trials included adults (BMI ≥ 25 kg/m²) receiving polyphenol-rich interventions, with reported outcomes on gut microbiota and at least one inflammatory or oxidative stress biomarker. Standardized mean differences (SMDs) were pooled using a random-effects model. Results: Thirteen trials (n = 670) met inclusion criteria. Polyphenol supplementation significantly reduced circulating lipopolysaccharides (LPSs; SMD = −0.56; 95% CI: −1.10 to −0.02; p < 0.04), indicating improved gut barrier function. Effects on cytokines (IL-6, TNF-α) and CRP were inconsistent. Catalase activity improved significantly (SMD = 0.79; 95% CI: 0.30 to 1.28; p < 0.001), indicating enhanced antioxidant defense. Gut microbiota analysis revealed increased butyrate (SMD = 0.57; 95% CI: 0.18 to 0.96; p < 0.001) and acetate (SMD = 0.42; 95% CI: 0.09 to 0.75; p < 0.01), supporting prebiotic effects. However, no significant changes were observed in BMI or body weight. Conclusions: Polyphenol supplementation in overweight or obese adults may reduce metabolic endotoxemia, boost antioxidant activity, and promote SCFAs production. Effects on inflammation and body weight remain unclear. Further long-term trials are needed. Full article

The rapid progress of Large Language Models (LLMs) has intensified the demand for flexible evaluation frameworks capable of accommodating diverse user needs across a growing variety of applications. While numerous standardized benchmarks exist for evaluating general-purpose LLMs, they remain limited in both scope and adaptability, often failing to capture domain-specific quality criteria. In many specialized domains, suitable benchmarks are lacking, leaving practitioners without systematic tools to assess the suitability of LLMs for their specific tasks. This paper presents LLM PromptScope (LPS), a customizable, real-time evaluation framework that enables users to define qualitative evaluation criteria aligned with their domain-specific needs. LPS integrates a novel LLM-as-a-Judge mechanism that leverages multiple language models as evaluators, minimizing human involvement while incorporating subjective preferences into the evaluation process. We validate the proposed framework through experiments on widely used datasets (MMLU, Math, and HumanEval), comparing conventional benchmark rankings with preference-driven assessments across multiple state-of-the-art LLMs. Statistical analyses demonstrate that user-defined evaluation criteria can significantly impact model rankings, particularly in open-ended tasks where standard benchmarks offer limited guidance. The results highlight LPS’s potential as a practical decision-support tool, particularly valuable in domains lacking mature benchmarks, offering both flexibility and rigor in model selection for real-world deployment. Full article

Sepsis remains a global health emergency, demanding timely and accurate diagnostics to reduce morbidity and mortality. This review critically assesses the recent progress (2020–2025) in the development of electrochemical aptamer-based biosensors for sepsis detection. These biosensors combine aptamers’ high specificity and modifiability with the sensitivity and miniaturization potential of electrochemical platforms. The analysis highlights notable advances in detecting key sepsis biomarkers, such as C-reactive protein (CRP), procalcitonin (PCT), interleukins (e.g., interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)), lipopolysaccharides (LPSs), and microRNAs using diverse sensor configurations, including a field-effect transistor (FET), impedance spectroscopy, voltammetry, and hybrid nanomaterial-based systems. A comparative evaluation reveals promising analytical performance in terms of the limit of detection (LOD), rapid response time, and point-of-care (POC) potential. However, critical limitations remain, including variability in validation protocols, limited testing in real clinical matrices, and challenges in achieving multiplexed detection. This review underscores translational barriers and recommends future directions focused on clinical validation, integration with portable diagnostics, and interdisciplinary collaboration. By consolidating current developments and gaps, this work provides a foundation for guiding next-generation biosensor innovations aimed at effective sepsis diagnosis and monitoring. Full article

Background: Sepsis-induced acute lung injury (ALI) is a serious disease constituting a heavy burden on society due to high mortality and morbidity. Inflammation and oxidative stress constitute key pathological mechanisms in ALI caused by sepsis. LL-37 can improve the survival of septic mice. Nevertheless, its function and underlying mechanism in sepsis-evoked ALI is elusive. Methods: The human A549 alveolar epithelial cell line was treated with LL-37 or ZBP1 recombinant vector under LPS exposure. Then, the effects on cell oxidative stress injury, inflammatory response, and autophagy were analyzed. RNA-seq analysis was performed to detect the differentially expressed genes (DEGs) between the LPS and LPS/LL-37 groups. Furthermore, the effects of LL-37 on cecal ligation and the puncture (CLP)-constructed ALI model were explored. Results: LL-37 attenuated LPS-evoked oxidative injury in human alveolar epithelial cells by increasing cell viability and suppressing ROS, malondialdehyde, and lactate dehydrogenase levels and apoptosis. Moreover, LPS-induced releases of pro-inflammatory IL-18, TNF-α, and IL-1β were suppressed by LL-37. Furthermore, LPS’s impairment of autophagy was reversed by LL-37. RNA-seq analysis substantiated 1350 differentially expressed genes between the LPS and LPS/LL-37 groups. Among them was ZBP1, a significantly down-regulated gene with the largest fold change. Moreover, LL-37 suppressed LPS-increased ZBP1 expression. Importantly, ZBP1 elevation restrained LL-37-induced autophagy in LPS-treated cells and abrogated LL-37-mediated protection against LPS-evoked oxidative injury and inflammation. LL-37 ameliorated abnormal histopathological changes, tissue edema, the lung injury score, oxygenation index (PaO2/FiO2), and glycemia contents in the CLP-constructed ALI model, which were offset through ZBP1 elevation via its activator CBL0137. Additionally, LL-37 suppressed inflammation and oxidative stress in lung tissues, concomitant with autophagy elevation and ZBP1 down-regulation. Conclusions: LL-37 may alleviate the progression of sepsis-evoked ALI by attenuating pulmonary epithelial cell oxidative injury and inflammatory response via ZBP1-mediated autophagy activation, indicating a promising approach for the therapy of ALI patients. Full article

Loess–palaeosol sequences (LPSs) are continuous records of palaeoenvironmental and palaeoclimatic conditions during the Quaternary. This study includes 17 LPS located in the NE of the Iberian Peninsula, irregularly distributed, associated with different river basins: the Ebro Basin, the Mora Basin, and the Ter sub-basin. The soils developed on these loess deposits present a loam–sandy texture, coarser than the typical loess, ochre in colour, with variable thickness (1–12 m), calcareous composition (20–45% CaCO₃ eq.), very low or null organic matter (OM), and basic pH. These deposits have been classified as desert LPS, whose pedogenesis is mainly associated with the redistribution of calcium carbonate and, in some cases, gypsum. Several methodologies have been applied to determine their mineralogical, physical, and chemical characteristics and date them by luminescence techniques. In addition, some relevant pedofeatures (porosity, CaCO₃, gypsum, etc.) have been characterised in detail. The aims of the present study have been to know the pedogenic development of the LPS by defining the main soil-forming factors that have affected them in order to associate these factors with the characteristic palaeoclimatic and palaeoenvironmental conditions reported in this area over time and to improve the understanding of soil evolution. Full article

The Kashmir Valley, characterized by its rich loess–palaeosol sequences (LPSs), provides a unique geo-archive for reconstructing Late Quaternary climate dynamics. This study presents an extensive multi-proxy study, integrating high-resolution lithostratigraphy, geochemical analyses, stable isotope analysis of soil organic matter (δ¹³C-VPDB), and radiocarbon (¹⁴C) chronology of a sediment sequence approximately 200 cm thick, to unravel the complex interplay of climatic, pedogenic and environmental processes shaping the region spanning the Pleistocene–Holocene transition. The results establish a precise chronology of the sediment sequence between 13.4 ka and 7.2 ka, covering the transition from the Pleistocene to the Holocene Epoch. The results reveal distinct climatic and environmental conditions during this Epoch. The study reveals substantial loess deposition during the cold and dry glacial climate towards the end of the Pleistocene, followed by a shift to a warmer and wetter interglacial climate at the onset of the Holocene Epoch. This climatic shift led to the development of soil units with pronounced fluvial characteristics around 10 ka, eventually transitioning to fluvial deposition. Geochemical indices such as Ca/Ti, Al/Ti, Si/Ti, and K/Ti indicate low weathering intensity prior to 11 ka, followed by a noticeable increase around 11 ka, possibly driven by enhanced precipitation. δ¹³C values, ranging from −26.2‰ to −22.5‰, suggest C₃-dominated vegetation during the Late Pleistocene, indicating wetter climatic conditions. This study provides valuable insights into the intricate interactions between climate, soil development, and vegetation dynamics during the critical Late Pleistocene–Holocene transition in the Kashmir Valley. Full article

To address the time-variant reliability (TVR) issue during a structure’s life cycle, we propose an innovative Kriging method named EDFK-FCTP. This active-learning TVR analysis is based on an error distance function (EDF) and the first crossing time point (FCTP). We employ Latinized partially stratified sampling (LPSS) to estimate the first four-order origin moments of the FCTP surrogate model. The convergence condition for establishing the optimal surrogate model for the FCTP is determined by the geometric mean of the probability density of training samples and the maximum error of the first four-order origin moments across two adjacent iterations. Utilizing the optimal surrogate model, the probability density function (PDF) of the FCTP is solved using kernel density estimation (KDE), thereby deriving the failure probability of the structure throughout its life cycle. Example analyses demonstrate that the calculation accuracy of our proposed method fulfills engineering requirements. Notably, it presents certain advantages over alternative methods, particularly in regions of low failure probability. For complex performance functions, our method offers significant computational efficiency benefits compared to other approaches. Full article

Background/Objectives: Clinical experience indicates that the determination of interleukin 6 (IL-6) in human blood can vary depending on time span between sample collection and centrifugation. Here, we evaluated confounding effects in various blood specimens. Methods: The blood of healthy individuals and critically ill patients was collected in EDTA-, heparin-, and serum collection tubes. Tubes were facultatively incubated (20 °C, 24–48 h) before centrifugation, and IL-6 was measured in the supernatant. Results: The preincubation of the blood collection tubes increased the IL-6 values in heparin plasma (in 17/20 samples up to 50-fold) and serum (in 17/20 samples up to 12-fold). These changes were relevant since the normal values were thereby lifted above the upper confidence limit in 12/20 heparin plasma samples and 4/20 serum samples. These IL-6 increases were probably due to in vitro synthesis as opposed to the release of preformed IL-6 from blood cells because subjecting uncentrifuged collection tubes to mechanical cell lyses had negligible effects on IL-6, while incubation with microbial stimulators dramatically increased these values. In the case of EDTA blood, collection tube preincubation induced IL-6 decreases in 17/20 samples from healthy individuals and 20/23 samples from critically ill patients. Conclusions: IL-6 determination in heparin plasma and serum is compromised by delayed centrifugation. This effect is relevant for normal values. It increased the number of false high results by >50%. The delayed centrifugation of EDTA blood decreased the IL-6 values, which caused a single false-negative result in 1/43 healthy and critically ill people. The false-negative rate is possibly higher in EDTA blood from non-critically ill out-patients, exhibiting moderately increased IL-6 levels. Full article

The accurate detection of small ships based on images or vision is critical for many scenarios, like maritime surveillance, port security, and navigation safety. However, achieving accurate detection for small ships is a challenge for cost-efficiency models; while the models could meet this requirement, they have unacceptable computation costs for real-time surveillance. We propose YOLO-LPSS, a novel model designed to significantly improve small ship detection accuracy with low computation cost. The characteristics of YOLO-LPSS are as follows: (1) Strengthening the backbone’s ability to extract and emphasize features relevant to small ship objects, particularly in semantic-rich layers. (2) A sophisticated, learnable method for up-sampling processes is employed, taking into account both deep image information and semantic information. (3) Introducing a post-processing mechanism in the final output of the resampling process to restore the missing local region features in the high-resolution feature map and capture the global-dependence features. The experimental results show that YOLO-LPSS outperforms the known YOLOv8 nano baseline and other works, and the number of parameters increases by only 0.33 M compared to the original YOLOv8n while achieving 0.796 and 0.831 AP^50:95 in classes consisting mainly of small ship targets (the bounding box of the target area is less than 5% of the image resolution), which is 3–5% higher than the vanilla model and recent SOTA models. Full article

Objectives: Metabolic dysfunction-associated steatohepatitis (MASH) lacks effective therapies. This study aimed to evaluate the therapeutic potential of compound 3d, a novel elafibranor derivative, focusing on its dual mechanisms of PPAR pathway activation and p38 MAPK signaling inhibition. Methods: Integrated in vitro and in vivo approaches were employed. In vitro, free fatty acid (FFA)-induced lipid accumulation in L02 hepatocytes and lipopolysaccharides (LPSs)-stimulated inflammatory responses in RAW264.7 macrophages were used to evaluate lipid metabolism and anti-inflammatory effects. In vivo, a high-fat diet (HFD)-induced MASH model in C57BL/6 mice assessed serum biochemical parameters (triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), aspartate transaminase (AST), tumor necrosis factor-α (TNF-α), nitric oxide (NO), and interleukin-6 (IL-6)), liver histopathology (H&E, Oil Red O, Masson staining), and proteomic profiling. Gut microbiota composition was analyzed via 16S rRNA sequencing. Western blotting quantified PPAR isoforms (γ/δ), downstream targets (Acox1, EHHADH, Acaa1), and p38 MAPK pathway proteins (p-p38, caspase-8, Bcl-2). Results: In vitro, 3d significantly reduced lipid accumulation (reduction in TG, p < 0.01) and inflammation (decrease in ALT activity, p < 0.05) in hepatocytes, while suppressing LPSs-induced TNF-α (63% reduction), NO (51% decrease), and IL-6 (48% reduction) in macrophages (p < 0.01). In vivo, 3d (30 mg/kg) lowered serum TG (39% decrease), TC (32% reduction), LDL-C (45% decline), and TNF-α (57% reduction) in HFD-fed mice (p < 0.05 vs. model), normalized AST/ALT levels, and ameliorated hepatic steatosis, ballooning, and fibrosis. Proteomics demonstrated PPARγ/δ activation (2.3–3.1-fold upregulation of Acox1, EHHADH, Acaa1; p < 0.001) and p38 MAPK pathway inhibition (54% reduction in p-p38, 61% decrease in caspase-8; 1.8-fold increase in Bcl-2; p < 0.01). Gut microbiota analysis revealed enrichment of beneficial taxa (Lactobacillus: 2.7-fold increase; Bifidobacterium: 1.9-fold rise) and reduced pathogenic Proteobacteria (68% decrease, p < 0.05). Conclusions: Compound 3d alleviates MASH via PPAR-mediated lipid metabolism enhancement and p38 MAPK-driven inflammation/apoptosis suppression, with additional gut microbiota modulation. These findings highlight 3d as a multi-target therapeutic candidate for MASH. Full article

Adult congenital heart disease (ACHD) represents a significant portion of congenital anomalies, and with improved treatments leading to an increased life expectancy, its prevalence has been increasing over the past few decades. Nonetheless, a considerable number of patients with ACHD require cardiac rhythm management devices during their lifetime. Traditionally, transvenous pacemaker placement has been the standard mode of treatment for these patients. However, some patients with ACHD have anatomical barriers that obscure this mode of treatment. Leadless pacing systems (LPSs) have changed the field of pacing. Currently, two different LPSs are available. In a real-world setting, implanting an LPS in patients after tricuspid valve (TV) surgery seems to be a straightforward procedure with a low risk of complications, with patients showing no valvular dysfunction after the intervention. LPS implantation is an option to avoid device-related complications in patients with previous TV surgery. Moreover, it has been demonstrated that even the jugular approach seems as safe as the femoral approach and could be considered an alternative implantation method for LPSs. The Aveir VR leadless pacemaker is a helix LPS with unique features, such as its capacity as a dual-chamber leadless pacemaker, the ability to map electrical parameters before releasing the device, and its possibility of being retrievable. Hereby, we present the case of Ebstein’s anomaly, atrial septal defect closure, and previous TV surgery with symptomatic intermittent advanced atrioventricular block. This case illustrates that a transjugular approach for LPSs is also feasible in patients with ACHD. Full article

Klebsiella oxytoca bacilli co-form the human intestinal microbiota, but in favorable conditions, they may also affect immunocompromised individuals, causing urinary tract infections, bacteremia, or antibiotic-associated hemorrhagic colitis. The growing numbers of clinical outbreaks of K. oxytoca infections make these bacteria an emerging pathogen, which is still masked by the predominant K. pneumoniae isolates. Thus, it is very important to advance knowledge on K. oxytoca pathogenicity. This work aims to characterize a urine isolate, K. oxytoca 0.062, from central Poland, which appears to present a multidrug-resistant and extended-spectrum β-lactamases-positive phenotype. The structural experiments include sugar and methylation analyses, mass spectrometry, and ¹H and ¹³C Nuclear Magnetic Resonance (NMR) spectroscopy. Additionally, ¹H,¹H ROESY, and ¹H,¹³C HMBC experiments were carried out on the high-molecular-weight O polysaccharide fraction of K. oxytoca lipopolysaccharides (LPSs). These analyses led to the detection of two polysaccharide antigens: one neutral, containing a linear trisaccharide unit called mannan, and one acidic, which is built up of a branched tetrasaccharide unit containing two mannopyranose (α-Manp) residues, one galactopyranose (β-Galp) residue, and one galacturonic acid (α-GalpA) residue. The GalpA residue seems to be a potential minor epitope, recognized by the selected Proteus antisera in the serological studies. Full article

3-O-Methyl-D-chiro-inositol (pinitol) has been reported to possess insulin-like effects and is known as one of the anti-diabetic agents for improving muscle and liver function. However, the beneficial effects of pinitol on human dermal microvascular endothelial cells (HDMECs) are not well understood. In this study, we investigated whether pinitol could protect HDMECs from damage induced by lipopolysaccharides (LPSs), which cause various cell defects. We observed that pinitol enhanced wound healing for LPS-damaged HDMECs. We found that pinitol significantly downregulated the LPS-induced upregulation of reactive oxygen species (ROS). Pinitol also significantly restored the mitochondrial membrane potential in these cells. Immunofluorescence analysis revealed that pinitol notably reduced the nuclear localization of NF-κB in LPS-damaged HDMECs. Furthermore, we demonstrated that pinitol decreased the phosphorylation levels of the MAPK family in LPS-damaged HDMECs. Interestingly, we observed that pinitol improved tube formation in LPS-damaged HDMECs. Taken together, we suggest that pinitol exerts several beneficial effects on LPS-damaged HDMECs and may be a promising therapeutic agent for improving vascular-related skin diseases. Full article

Background/Objectives: Intestinal alkaline phosphatase (IAP) is an enzyme expressed in the intestinal brush border, which may exert anti-inflammatory effects by detoxifying lipopolysaccharides (LPSs), thereby preventing metabolic disorders. Various food components have been reported to influence IAP activity. However, few studies have evaluated the effects of fermented milk on IAP activity. In this study, we aimed to investigate fermented milk with high IAP-activating capacity and investigate its effect. Methods: We screened a skim milk culture (SC), a fermented milk model, using differentiated Caco-2 cells. We investigated the effect of SC on IAP activity and gene expression in the Drosophila midgut. Quantitative PCR and immunoblot assays were conducted to examine gene and protein levels. Results: Among the SC samples from different lactic acid bacteria or bifidobacteria, the SC of Lactobacillus johnsonii SBT0309 (LJ0309 SC) demonstrated a particularly strong capacity to activate IAP in Caco-2 cells, demonstrated by significantly increased IAP gene expression and protein levels in Caco-2 cells. Additionally, LJ0309 SC inhibited increased secretion of IL-8 in LPS-stimulated Caco-2 cells. Finally, in Drosophila melanogaster fed LJ0309 SC, we observed an increase in both IAP activity and gene expression in the midgut. Conclusions: LJ0309 SC increased IAP activity and gene expression in both Caco-2 cells and the Drosophila midgut, and inhibited the inflammatory response in LPS-stimulated Caco-2 cells. Although further in vivo studies are required, LJ0309 SC might help to ameliorate LPS-induced inflammation and disease via IAP activation. Full article