Search Results (41,200)

Biliverdin (BV) and bilirubin (BR) are established endogenous antioxidants and immune modulators in other organ systems; however, their roles in the male genital tract remain undefined. The aim of this study was to quantify both bile pigments in human seminal plasma using a fluorescent protein biosensor and to examine their associations with basic semen parameters. We analyzed forty-two semen samples from men undergoing infertility evaluation. Biliverdin predominated over bilirubin in 88.1% of samples. Biliverdin concentration ranged from 51.8 to 611.2 nM, whereas bilirubin ranged from 19.7 to 240.7 nM. The mean total amounts per ejaculate were 1054 pmol for biliverdin and 280 pmol for bilirubin. The total amount of bilirubin in the ejaculate was positively correlated with total sperm count (Rs = 0.47; p = 0.028), whereas biliverdin showed no significant association (Rs = 0.21; p = 0.723). Oligozoospermic samples had significantly lower bilirubin concentrations (p < 0.001) and lower total bilirubin amounts (p < 0.005). Teratozoospermic samples exhibited significantly higher biliverdin concentrations (p < 0.05). This study provides the first simultaneous quantification of biliverdin and unconjugated bilirubin in human seminal plasma and identifies distinct associations with sperm quality. These findings suggest that bile pigments may reflect localized redox-related processes in the male genital tract and may influence male fertility potential. Full article

Background/Objective: The identification of novel non-invasive diagnostic and prognostic biomarkers is urgently needed in pleural mesothelioma (PM). While soluble mesothelin-related peptides (SMRP) are the most established circulating biomarker, their prognostic value is limited. A wide range of microRNAs (miRs) play diverse roles in regulating gene expression in PM. MiR-21 has been shown to be upregulated in mesothelioma tissue; nevertheless, the diagnostic and prognostic utility of miR-21 in the circulation and its association with survival in PM have not been extensively investigated to date. The objective of the current study was to evaluate miR-21 as a potential blood-based diagnostic and prognostic biomarker in PM. Methods: Plasma samples from PM patients (n = 94) were collected at the time of diagnosis, prior to treatment. Sex- and age-matched healthy individuals (n = 30) served as controls. MiR-21 levels were measured using quantitative RT-PCR and normalized to miR-16, and potential correlations with clinicopathological data were analyzed. Serum SMRP levels were measured in matched patients (n = 84), and a direct comparative analysis of miR-21 and SMRP was conducted. In situ hybridization (ISH) was used to confirm the presence of miR-21 in tumor cells. Results: Plasma miR-21 levels were significantly elevated in PM patients compared to healthy controls (p < 0.001), demonstrating good diagnostic performance (AUC 0.81). The localization of miR-21 in PM cells was confirmed by ISH. High miR-21 levels were associated with significantly shorter median overall survival (12.4 vs. 24.3 months, p < 0.001). Elevated SMRP levels were also associated with reduced survival (12.4 vs. 19.5 months, p = 0.032); however, SMRP did not retain independent prognostic significance in multivariable analysis. In contrast, high-circulating miR-21 was confirmed as an independent predictor for poor survival (HR 3.12, p < 0.001). Conclusions: Our findings highlight that circulating miR-21 is a potential non-invasive biomarker with both diagnostic and independent prognostic value in pleural mesothelioma and outperforms SMRP in multivariable survival analysis. Further research is warranted to validate its role in the biology of this disease and to assess its correlation with outcome and treatment responses. Full article

Industrial emissions of large amounts of CO₂ have seriously affected human health, making it imperative to reduce atmospheric CO₂ concentrations. However, carbon capture technologies such as chemical absorption and membrane separation are still limited by high regenerative energy costs, corrosion, and low efficiency in diluting flue gas. Within this technological landscape, physical adsorption separation technology, due to its advantages such as a wide operating temperature range, low equipment corrosivity, and low regeneration energy consumption, has gradually become a research hotspot in carbon capture technology. The core of physical adsorption lies in finding high-quality adsorbents. Metal–organic frameworks (MOFs), with their ultra-high specific surface area, tunable pore structure, and abundant functionalization sites, are considered highly promising next-generation CO₂ adsorbent materials. This review summarizes strategies for modifying MOFs to improve CO₂ adsorption performance, focusing on aperture adjustment, doped metal ions, functional group doping, and computational screening. Performance enhancements are mechanism-dependent rather than simply additive. Moderate aperture adjustment and defect engineering can improve gas selectivity and CO₂ capture capacity, while excessively narrow pores sacrifice available pore volume and gas diffusion. Doped metal ions, particularly in MOF-74 and related materials, can enhance CO₂ capture capacity while controlling framework integrity and dopant composition. Functional group Doping remains an effective method for capturing low-partial-pressure CO₂. Computational screening is shifting from ranking based on single adsorption capacity to a comprehensive consideration that includes humidity tolerance, stability, and regenerability. Overall, under industrial conditions, modified MOFs should be evaluated by balancing affinity, selectivity, capacity, stability, and energy efficiency. This review provides guidance for the rational design of MOF-based carbon capture adsorbents. Full article

Background: Cardiovascular diseases remain important causes of morbidity and potential premature mortality in children. Although clinical imaging and electrophysiologic testing have advanced, early, minimally invasive biomarkers that can both detect myocardial injury and help differentiate among overlapping pediatric phenotypes are still limited. Circulating microRNAs (miRNAs; miRs) are becoming attractive biomarker candidates because many are abundant in the heart, actively released into the circulation, and remarkably stable in plasma. The study aimed to assess the expression of miR-1-3p, miR-let-7b-5p, miR-21-5p, and miR-26b-5p in children with cardiovascular disease. Methods: Children aged 10–18 years with cardiac arrhythmias, myocarditis, or cardio-myopathies were recruited. The control group consisted of healthy age- and sex-matched children. For each participant, peripheral venous blood was collected for plasma isolation and miRNA profiling. The expression of miR-1-3p, miR-let-7b-5p, miR-21-5p, miR-26b-5p, and UniSp6 molecules was analyzed using the comparative cycle threshold delta Ct (ΔCt) method. A p-value ≤ 0.05 was considered statistically significant. Results: miR-26b-5p was significantly downregulated in patients with cardiac disease compared with healthy controls. miR-21-5p and miR-26b-5p were downregulated in patients with ventricular arrhythmia. Moreover, miR-26b-5p was downregulated in arrhythmia in general. We found no significant difference in the expression of miR-1-3p, miR-let-7b-5p, miR-21b-5p, and miR-26b-5p between patients with and without myocarditis, as well as with and without hypertrophic cardiomyopathy. Conclusions: miR-26b-5p may distinguish young patients with cardiovascular disease and those with arrhythmias from healthy individuals. miR-21-5p and miR-26b-5p may also be seen as potential biomarkers of ventricular arrhythmia. Further studies involving a larger sample size are required to obtain sufficient data and validate these findings. Full article

We report a diagnostically challenging case of a 79-year-old man who presented with mediastinal lymphadenopathy, hepatosplenomegaly, and renal enlargement, raising suspicion for clinical lymphoma. However, the histological evaluation of a submandibular gland excision revealed fibrosis, a dense IgG4-positive plasma cell infiltrate (>100/HPF), and an IgG4:IgG ratio > 40%, supportive of IgG4-related disease (IgG4-RD) in the appropriate clinicopathologic context. This case illustrates an important but well-recognised diagnostic pitfall in which IgG4-RD may clinically and radiologically mimic lymphoma. PET-CT demonstrated multiorgan involvement with diffuse FDG uptake, but definitive diagnosis required the integration of clinical, radiologic, serologic, and pathologic findings. The patient’s laboratory profile, including hypocomplementemia and elevated inflammatory markers, supported the proliferative phenotype of IgG4-RD—recently proposed in the literature as a clinically distinct subgroup with systemic involvement and steroid responsiveness. Rather than representing a novel presentation, this case reinforces the importance of integrated assessment in distinguishing IgG4-RD from haematolymphoid malignancy. PET-CT served as a useful adjunct for identifying multiorgan disease and guiding diagnostic evaluation, but tissue evaluation remained essential to avoid misdiagnosis and inappropriate treatment. Recognition of this entity is vital to avoid misdiagnosis and inappropriate treatment. Full article

Background/Objectives: Women and girls, particularly in sub-Saharan Africa, face high risks for both HIV and unintended pregnancy. Inconsistent condom use underscores the need for new multipurpose prevention technologies (MPTs) that combine HIV pre-exposure prophylaxis (PrEP) and contraception. Long-acting (LA) injectables are especially promising. To this end, an LA cabotegravir (CAB)/medroxyprogesterone acetate (MPA) in situ-forming implant (ISFI) has been developed. We report pharmacokinetic (PK) modeling to characterize CAB and MPA disposition and absorption to support the development of the MPT ISFI. Methods: Female BALB/c mice received single intravenous (IV) or subcutaneous (SQ) bolus doses of CAB or MPA. Sparse plasma samples were collected (~3 mice/timepoint) for PK analysis by LC-MS/MS. Noncompartmental analysis assessed SQ bioavailability. Macroparameterized compartmental PK models were fit to IV data to derive unit impulse responses (UIRs) for each drug. Results: CAB and MPA exhibited 61% and 42% bioavailability, respectively. CAB IV PK was best described by a two-compartment model with macroconstant parameters: A = 16,621 ng/mL, α = 4.52 h⁻¹, B = 30,206 ng/mL, and β = 0.053 h⁻¹. MPA IV PK was also best described by a two-compartment model, with A = 2506 ng/mL, α = 10.5 h⁻¹, B = 439 ng/mL, and β = 0.65 h⁻¹. These values define the UIR for CAB and MPA. Conclusions: Our IV PK modeling framework fully characterizes CAB/MPA disposition in mouse, enabling downstream deconvolution-based estimation of absorption from controlled-release formulations. This provides a foundation for in vitro–in vivo correlation, facilitating preclinical evaluation of long-acting formulations such as ISFIs. Full article

Activated carbons are usually prepared from natural precursors (e.g., fruit stones or nutshells) by carbonization and activation processes carried out at 400–1000 °C. They exhibit well-developed porosity, and chemical activation introduces hydrophilic functional groups on their surface, providing excellent sorption properties. However, the high temperatures required during thermal treatment increase production costs. In this work, cost-reducing methods for preparing carbon sorbents are proposed. Carbonization of H₃PO₄ activated waste pistachio nutshells was performed using classical pyrolysis (500 or 550 °C, 30 min, N₂ atmosphere) and microwave treatment (power 1000 W, 20 min). The properties of the synthesized carbons were characterized using thermogravimetry and spectroscopic techniques including infrared (ATR), Raman, photoelectron (XPS) spectroscopies, and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS). Porous structure parameters were determined using nitrogen adsorption experiments. The efficiency of Pb²⁺ removal from spiked ultrapure, tap and river water was evaluated by batch sorption experiments and inductively coupled plasma–mass spectrometry. The most porous carbons were those prepared at 500 and 550 °C, with specific surface areas of 910 and 256 m²/g, respectively. Surface phosphates increased the Pb²⁺ sorption efficiency to 99% from ultrapure water, at an initial concentration of 300 µg Pb²⁺/L. The material obtained with the microwave method was not fully carbonized and remained nonporous, but it also exhibited 99% Pb²⁺ uptake from ultrapure water due to the presence of oxygen-containing surface groups. The Pb²⁺ removal from spiked tap and river water reached up to 84% and 94%, respectively, at the spiking level of 300 µg Pb²⁺/L. Full article

To improve the adhesion and tribological performance of diamond-like carbon (DLC) coatings on steel substrate, a Ti-enhanced plasma nitriding (PNTi) layer was formed on the surface of 38CrMoAl steel, followed by deposition of a Cr-based interlayer (mainly CrN) and then a W interlayer. Finally, a DLC coating was deposited, resulting in a novel PNTi/DLC coating. For comparison, a conventional PN/DLC coating was prepared under the same processing conditions. Optical microscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman spectroscopy, hardness tests, and tribological experiments were performed to systematically investigate the effect of TiN-enriched PNTi supporting layer on the performances of the PNTi/DLC composite coating. The results show that comparing with PN/DLC composite coating, the critical load (Lc₂) of the PNTi/DLC coating was increased from 28.89 N to 43.25 N—about a 50% enhancement. The microhardness was increased from 2650 HV_0.05 to 4400 HV_0.05 (corresponding to 28.2 GPa to 44.1 GPa). The friction coefficient was decreased from 0.28 to 0.11, about a 60% reduction, and the wear rate declined more than 40%, from 4.81 × 10⁻⁶ to 2.90 × 10⁻⁶ mm³·N⁻¹·m⁻¹. The introduction of Ti promoted the in situ formation of TiN phase in the nitrided layer, which significantly improved the compactness of the nitrided layer and the adhesion at the film–substrate interface. Consequently, the PNTi/DLC composite coating exhibited excellent wear resistance and friction stability under high-load and severe tribological conditions. This study provides a promising perspective for engineering applications of steel-based DLC coatings in harsh service environments. Full article

This study systematically investigates the influence of CeO₂ content (0–0.6 wt.%) on the microstructure and mechanical properties of Stellite6/WC composite coatings fabricated by plasma spray welding. The phase composition and microstructure of the coatings were characterized using X-ray diffraction (XRD) and scanning electron microscopy (SEM), while microhardness and tribological performance were evaluated using a semi-automatic Vickers microhardness tester and a ball-on-disk tribometer. The results indicate that the coating with 0.4 wt.% CeO₂ exhibits the optimal combination of mechanical and tribological properties, achieving a maximum microhardness of 1107.62 HV_0.3—a 50.5% improvement over the unmodified coating—and a minimum wear mass loss of 1.4 mg, corresponding to a 78.1% reduction compared to the CeO₂-free counterpart. These findings demonstrate that appropriate CeO₂ addition significantly enhances both the microhardness and wear resistance of Stellite6/WC coatings, offering an effective strategy to mitigate surface degradation and extend the service life of 45 steel substrates under demanding operating conditions. Full article

Background: Chronic endometritis (CE) is a subtle, often asymptomatic endometrial inflammation marked by CD138⁺ plasma cell infiltration and linked to recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), and unexplained infertility. Emerging evidence implicates endometrial microbiome dysbiosis in CE. Objective: To systematically review and conduct meta-analysis on the association between CE and endometrial microbiome alterations and their reproductive implications. Methods: We searched MEDLINE, Embase, Web of Science, Scopus, Cochrane CENTRAL, and Google Scholar for studies diagnosing CE via CD138 immunostaining, assessing microbiota with molecular techniques. Data extraction, quality assessment, and meta-analysis were performed. Results: Twenty-two studies including 4022 women were analyzed. CE was associated with reduced prevalence of Lactobacillus-dominated microbiota and increased detection of non-Lactobacillus species, particularly Streptococcus spp., Enterococcus spp., Escherichia coli, Staphylococcus spp., Ureaplasma spp., and Gardnerella vaginalis. In the meta-analysis (2947 women), Enterococcus spp. and Ureaplasma spp. were significantly more prevalent in women with CE, whereas Streptococcus spp., E. coli, Staphylococcus spp. and G. vaginalis showed non-significant trends. Only E. coli and Streptococcus spp. showed significant heterogeneity between-studies. Conclusions: CE is linked to microbial dysbiosis with reduced Lactobacillus dominance and enrichment of potentially pathogenic taxa, notably Enterococcus and Ureaplasma spp. These findings suggest that the endometrial microbiome contributes to chronic inflammation and adverse reproductive outcomes, yet heterogeneity and limited evidence call for standardized diagnostics and robust trials before clinical implementation. Full article

Atherosclerosis remains the leading cause of death worldwide and imposes a major healthcare burden. Physiologically, elimination of cholesterol from the arterial wall depends on reverse cholesterol transport (RCT). RCT requires access to HDL and apolipoprotein A-I (ApoA-I) to lesional macrophages/foam cells. The endothelial glycocalyx is a dynamic and injury-sensitive layer of proteoglycans and glycosaminoglycans (including hyaluronan). It contributes to vascular barrier properties, leukocyte adhesion, mechanotransduction, and macromolecular transport. In atherosclerosis, glycocalyx structure and function are altered; this may facilitate entry/retention of atherogenic lipoproteins and may also alter transport conditions relevant to cholesterol efflux pathways. This article presents a mechanistic hypothesis: short, transient, systemic hyaluronidase exposure could temporarily remodel glycocalyx/extracellular matrix components and thereby facilitate conditions permissive for regulated transport processes relevant to RCT. However, the proposed link between glycocalyx remodeling and improved lesional cholesterol efflux remains theoretical. Direct in vivo evidence that the endothelial glycocalyx is a dominant barrier limiting HDL- or ApoA-I-mediated cholesterol efflux from plaque macrophages is currently limited. Moreover, glycocalyx degradation is widely associated with endothelial dysfunction, increased permeability, inflammation, and thrombosis, all of which could aggravate rather than ameliorate atherosclerosis. Human pharmacokinetic data indicate a very short plasma half-life of circulating hyaluronidase activity, suggesting that any systemic enzymatic effect is brief. Nevertheless, the biological consequences of repeated degradation–regeneration cycles, especially in high-risk states such as diabetes, inflammation, oxidative stress, or chronic kidney disease, remain incompletely understood. Evidence supporting clinical benefit in atherosclerosis is currently limited to heterogeneous animal experiments, historical uncontrolled reports, and a small number of anecdotal case observations, whereas randomized trials have only been performed in other settings such as acute myocardial infarction and do not establish efficacy for plaque regression. We therefore provide a balanced evaluation of knowns, uncertainties, alternative interpretations, potential risks, dosing unknowns, and a translational research agenda including mechanistic preclinical studies, biomarker development, imaging, and carefully designed early-phase clinical investigation. Full article

This study presents a comparative Failure Modes and Effects Analysis (FMEA) of electro-hydraulic braking (EHB) and electro-mechanical braking (EMB) systems within brake-by-wire architectures. The analysis integrates both the conventional Risk Priority Number (RPN) approach and the AIAG–VDA Action Priority (AP) methodology, enabling a structured comparison of risk prioritization strategies applied to identical failure modes. A consistent system-level framework is developed to harmonize severity (S), occurrence (O), and detection (D) assessments across both architectures, allowing direct evaluation of methodological differences. The results demonstrate systematic divergences between RPN and AP approaches, particularly in high-severity scenarios, where AP provides more safety-oriented prioritization. The study further identifies key limitations of traditional RPN-based evaluation in safety-critical systems and highlights the advantages of rule-based prioritization frameworks. In addition, corrective measures are proposed and their impact on occurrence and detection ratings is quantified, illustrating practical pathways for risk reduction. Beyond methodological comparison, the work introduces a novel integration of reliability engineering with advanced manufacturing strategies, demonstrating how laser and plasma-based surface engineering can mitigate failure mechanisms by reducing occurrence and improving system robustness. The proposed approach establishes a conceptual and physically grounded bridge between system-level risk assessment and material-level optimization, contributing to the development of more reliable next-generation brake-by-wire systems. Full article

Background: Pre-eclampsia (PE) is a significant cause of maternal and perinatal morbidity and mortality globally and is characterized by impaired endothelial function and disturbances in coagulation pathways. The effects of Human Immunodeficiency Virus (HIV) on the immune and coagulation systems have been investigated during pregnancy, but there are few reports on anticoagulant factors in pregnant women who are infected with HIV and develop PE. This investigation compares plasma protein C levels in pregnant women with pre-eclampsia and those without pre-eclampsia, and compares the results based on their HIV status. Methods: A hospital-based cross-sectional study design was used for the current research, which was carried out at Charlotte Maxeke Johannesburg Academic Hospital, South Africa. A total of 83 pregnant women participated in the study and were categorized into one of four groups: normotensive HIV-negative (n = 36); normotensive HIV-positive (n = 18); pre-eclamptic HIV-negative (n = 21); and pre-eclamptic HIV-positive (n = 8). Data collected included demographic information and clinical characteristics that were abstracted from maternity records. Plasma protein C concentrations were determined by ELISA (enzyme-linked immunosorbent assay). Nonparametric statistical methods were used to compare the mean values of plasma protein C between each of the four groups, and significance was set at p < 0.05. Subgroup analyses, particularly for the pre-eclamptic HIV-positive group (n = 8), were considered exploratory due to small sample sizes. Results: As would be anticipated, both systolic and diastolic blood pressure values were significantly elevated in the pre-eclamptic group when compared to the normotensive control subjects (p < 0.0001). There were no statistically significant differences in plasma protein C concentration between the normotensive and pre-eclamptic groups, nor between the HIV-negative and HIV-positive groups. Similarly, there were no significant differences in plasma protein C concentration when comparing all four study groups (Kruskal–Wallis test p = 0.2295). Conclusions: Plasma protein C concentrations did not vary significantly according to the presence of pre-eclampsia or HIV status in this cohort. These findings suggest that protein C concentrations were not measurably altered between groups within this study population. However, due to the small sample size in key subgroups, these findings should be considered preliminary and interpreted with caution. Larger, adequately powered studies are required to further investigate potential associations between HIV infection, pre-eclampsia, and anticoagulant pathways during pregnancy. Full article

Extracellular vesicles (EVs) mediate intercellular communication by delivering proteins and RNAs, with their molecular cargo often reflecting the biological context of their source. Perinatal tissues are promising sources of EV-related biomaterials with potential dermatologic applications. In this study, we compared EV-related molecular cargo from two umbilical cord-associated sources, umbilical cord mesenchymal stem cell (UCMSC)-derived EVs and cord blood plasma (CBP), to investigate whether these materials exhibit distinct functional effects on melanogenesis. UCMSC-derived EVs were isolated from conditioned culture medium and characterized using nanoparticle tracking analysis (NTA), cryo-electron microscopy (cryo-EM), and canonical EV marker detection, while cord blood samples were processed to obtain plasma following centrifugation and filtration, containing EVs together with soluble plasma components. Functional assays in the murine melanocyte cell line B16F10 demonstrated that UCMSC-derived EVs suppressed melanin production, whereas CBP treatment enhanced melanogenesis. Integrative omics analyses combining microRNAs (miRNAs) microarray profiling and proteomic characterization revealed distinct molecular signatures between UCMSC-derived EVs and CBP samples. Functional validation using miRNA mimic assays showed that selected miRNAs, including miR-6862-5p, miR-3622b-5p, miR-7847-3p, miR-6774-5p, and miR-4685-5p, reduced melanin production, whereas others, including miR-203a-3p, miR-126-3p, miR-139-5p, and miR-15b-5p, increased melanin levels. Pathway analysis using Ingenuity Pathway Analysis (IPA) (QIAGEN Inc.) associated these miRNA subsets with signaling pathways involved in melanogenesis. Together, these findings indicate that UCMSC-derived EVs and CBP exhibit opposite functional effects on melanogenesis and possess distinct miRNA and protein cargo profiles, providing potential molecular targets for modulating pigmentation and supporting the development of EV-related therapeutic strategies for pigmentation disorders. Full article