Search Results (11,048)

This study established novel and high-throughput strategies for the simultaneous analysis of 30 fluorinated emerging pollutants in different matrices from the shrimp aquaculture system in eastern China using UHPLC-MS/MS. The parameters of SPE for analysis of water samples and of QuEChERS methods for sediment and shrimp samples were optimized to allow the simultaneous detection and quantitation of 17 per- and polyfluoroalkyl substances (PFASs) and 13 fluoroquinolones (FQs). Under the optimal conditions, the limits of detection of 30 pollutants for water, sediment, and shrimp samples were 0.01–0.30 ng/L, 0.01–0.22 μg/kg, and 0.01–0.23 μg/kg, respectively, while the limits of quantification were 0.04–1.00 ng/L, 0.03–0.73 μg/kg, and 0.03–0.76 μg/kg, with satisfactory recoveries and intra-day precision. The developed methods were successfully applied to the analysis of multiple samples collected from aquaculture ponds in eastern China. PFASs were detected in all samples with concentration ranges of 0.18–0.77 μg/L in water, 0.13–1.41 μg/kg (dry weight) in sediment, and 0.09–0.96 μg/kg (wet weight) in shrimp, respectively. Only two FQs, ciprofloxacin and enrofloxacin, were found in the sediment and shrimp. In general, this study provides valuable insights into the prevalence of fluorinated emerging contaminants, assisting in the monitoring and control of emerging contaminants in aquatic foods. Full article

Background: The issue of Helicobacter pylori (H. pylori) resistance to clarithromycin (CLR) has consistently posed challenges for clinical treatment. Hence, a rapid susceptibility testing (AST) method urgently needs to be developed. Methods: In the present study, 35 isolates of H. pylori were isolated from 203 gastritis patients of the Guangzhou cohort, and the antimicrobial resistance phenotypes were associated with their genomes to analyze the relevant mutations. Based on these mutations, a rapid detection system utilizing high-resolution melting (HRM) curve analysis was designed and verified by the Shenzhen cohort, which consisted of 38 H. pylori strains. Results: Genomic analysis identified the mutation of the 2143 allele from A to G (A2143G) of 23S rRNA as the most relevant mutation with CLR resistance (p < 0.01). In the HRM system, the wild-type H. pylori showed a melting temperature (Tm) of 79.28 ± 0.01 °C, while the mutant type exhibited a Tm of 79.96 ± 0.01 °C. These differences enabled a rapid distinction between two types of H. pylori (p < 0.01). Verification examinations showed that this system could detect target DNA as low as 0.005 ng/μL in samples without being affected by other gastric microorganisms. The method also showed a good performance in the Shenzhen validation cohort, with 81.58% accuracy, and 100% specificity. Conclusions: We have developed an HRM system that can accurately and quickly detect CLR resistance in H. pylori. This method can be directly used for the detection of gastric microbiota samples and provides a new benchmark for the simple detection of H. pylori resistance. Full article

Background: We aimed to explore the predictive role of soluble urokinase plasminogen activator receptor (suPAR) in patients undergoing coronary angiography by systematically evaluating its association with adverse cardiovascular events at 10 years follow-up. Methods: The KORONEF study was a single-center, observational, prospective study with 492 subjects included. In the multivariable Cox regression model, we checked the impact of suPAR, neutrophil elastase, myeloperoxidase, and DNase 1 on long-term outcomes. Results: The mean study population age was 64.4 ± 9.9 years, and there were 37.2% women. We divided the population into tertiles of suPAR levels (T1 0.793–2.135 ng/mL; T2 2.136–2.868 ng/mL; and T3 2.872–8.677 ng/mL). Patients with higher suPAR concentrations were more often females (tertile 1 vs. tertile 3: 27.4% vs. 50.6%, p < 0.001) and older age (60.8 ± 8.7 years vs. 68.8 ± 9.5 years, p < 0.001). They also characterized higher incidence of diabetes (17.7% vs. 38.0%, p < 0.001), previous myocardial infarction (22% vs. 44.8%, p < 0.001), and chronic kidney disease (3% vs. 18.4%, p < 0.001), but lower incidence of dyslipidemia (54.3% vs. 35.6%). The 10-year all-cause death rates were 14.6% vs. 34.1%, HR 2.68, 95% CI 1.66–4.33, p < 0.001 for tertile 2, and 14.6% vs. 39.9%, HR 3.24, 95% CI 2.03–5.17, p < 0.001 for tertile 3. The optimal cut-off suPAR value of 2.39 ng/mL provided a sensitivity of 66.9% and a specificity of 54.6% in predicting all-cause death. Conclusions: The association of elevated suPAR with increased mortality risk suggests its potential relevance in predicting long-term outcomes and may help inform more individualized management strategies for high-risk patients. Full article

Background/Objectives: Currently, the prediction of disease recurrence after radical prostatectomy (RP) in localized prostate cancer (PCa) relies on clinicopathological parameters, which lack accuracy in predicting clinical outcomes. This study focused on evaluating the utility of cfDNA levels and fragmentation patterns as prognostic biomarkers in progressive prostate-specific antigen (PSA) patients, including those with persistent PSA and biochemical recurrence (BR), after primary treatment in localized PCa patients. Methods: Twenty-nine high-risk localized PCa patients were enrolled in the study between February 2022 and May 2023. Blood samples were obtained before robotic RP. cfDNA concentration and fragment size were quantified using the Quant-it PicoGreen dsDNA Assay kit and Agilent 2200 TapeStation System, respectively. Results: The mean PSA value at diagnosis was 9.4 ng/mL. Seven patients (24.1%) had stage pT2 and 22 (75.9%) pT3. Nine patients (31%) had detectable PSA at the first PSA control six weeks after surgery, and four patients (20%) had BR during a mean follow-up of 18.4 months. No associations were found between cfDNA levels or fragmentation patterns and clinicopathological data. Although not statistically significant, patients with detectable PSA levels post-surgery exhibited higher cfDNA levels and shorter fragments compared with those with undetectable PSA. Conclusions: Our study indicated a tendency toward more fragmented cfDNA levels in PCa patients with persistent PSA. Strikingly, biochemical recurrent PCa patients exhibited similar cfDNA levels and fragmentation patterns compared to non-recurrent patients. Further studies exploring liquid biopsy-derived biomarkers in localized PCa patients are needed to elucidate their clinical utility in predicting PSA persistence. Full article

The co-ensiling technique is widely used to improve silage quality; however, it remains unclear as to what high-quality silages can be made by co-ensiling Napier grass (NG) with Sugarcane top (ST). The aim of this study was to evaluate the fermentation characteristics, chemical composition, and microbiological profile of silage produced from mixtures of NG and ST in varying ratios. Silage was prepared using a small-scale fermentation system, and treatments were designed as control silage (NG ensiled alone) or with 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100%ST on a fresh matter basis with six replicates, respectively. Increasing ST in the silage reduced the contents of crude protein, ash, acetic acid, butyric acid, ammonia-N, as well as pH, but increased the contents of dry matter, ether extract, neutral detergent fiber, acid detergent fiber, water-soluble carbohydrate, lactic acid, and lactic acid bacteria. Lactobacillales and Enterobacterales were the dominant orders, with Lactiplantibacillus and Weissella as the dominant genera. Co-ensiling NG with ST enhanced microbial diversity and richness. ST, as a local by-product, is a viable additive to improve NG silage quality and nutrition. This study suggests that good-quality silages can be produced with NG: ST ratios of 40:60 to 20:80 and that these silages offer an opportunity to optimize the nutrient supply for ruminants. Full article

Background: Benign prostatic hyperplasia (BPH) is a growing issue due to an ageing population. Our study investigated the possible associations between BPH and ageing hallmarks, including the telomere length (TL) and mitochondrial genome copy number (mtDNA CN), along with genetic variations in the TP53 gene and mtDNA. Methods: Prostate tissue samples were obtained from 32 patients with BPH, together with 30 blood samples. As a healthy control group, age-matching blood DNA samples were used. For the comparison of mtDNA sequence data, 50 DNA samples of the general Latvian population were used. The full mtDNA genome was analyzed by using Next-Generation Sequencing (NGS), the TP53 gene by Sanger sequencing, and the mtDNA copy number (mtDNA CN) and telomere length (TL) byqPCR assay. Results: The results showed that in BPH patients, telomeres in the prostate tissue were significantly longer than in blood cells, while the TL in blood cells of the healthy controls was the shortest. Also, the mtDNA amount in the prostate tissue of BPH patients was significantly greater in comparison with blood cells, and controls had the smallest mtDNA CN. We did not find any mutations in the TP53 gene that could be linked to BPH; however, in mtDNA, we found several unique mutations and heteroplasmic changes, as well as genetic changes that have been previously associated with prostate cancer. Conclusions: In conclusion, prolonged telomeres and changes in the mtDNA amount might be involved in the molecular mechanisms of BPH. Some of the heteroplasmic or homoplasmic mtDNA variants might also contribute to the development of BPH. Additional studies are needed to substantiate these findings. Full article

The efficacy and cost-effectiveness of Multigene Panel Next-Generation Sequencing (NGS) in directing patients towards genomically matched therapies remain uncertain. This study investigated metastatic colorectal cancer (mCRC) patients who underwent NGS analysis on formalin-fixed paraffin-embedded tumor samples. Data from 179 patients were analyzed, revealing no mutations in 39 patients (21.8%), one mutation in 83 patients (46.4%), and two or more mutations in 57 patients (31.8%). KRAS mutations were found in 87 patients (48.6%), including KRAS G12C mutations in 5 patients (2.8%), PIK3CA mutations in 40 patients (22.4%), and BRAF mutations in 26 patients (14.5%). Less common mutations were identified: ERBB2 in five patients (2.8%) and SMO in four patients (2.2%). Additionally, MAP2K1, CTNNB1, and MYC were mutated in three patients (2.4%). Two mutations (1.1%) were observed in ERBB3, RAF1, MTOR, JAK1, and FGFR2. No significant survival differences were observed based on number of mutations. In total, 40% of patients had druggable molecular alterations, but only 1.1% received genomically guided treatment, suggesting limited application in standard practice. Despite this, expanded gene panel testing can identify actionable mutations, aiding personalized treatment strategies in metastatic CRC, although current eligibility for biomarker-guided trials remains limited. Full article

(1) Mercury (Hg) is a persistent, ubiquitous contaminant that readily biomagnifies into higher trophic level species in aquatic environments across the globe. It is crucial to understand the movement of environmentally relevant concentrations of Hg in impacted freshwater streams to minimize risks to ecological and human health. (2) The bioconcentration kinetics of aqueous Hg exposure (20, 100, and 200 ng/L) in the invasive Asian Clam, Corbicula fluminea, were measured. A toxicokinetic model, the first parameterized for Hg accumulation in freshwater clams, was developed to estimate uptake and efflux parameters and compared to previous parameter values estimated for other mollusk species. (3) Results demonstrated that even at low Hg concentrations, Corbicula record signals of contamination through bioconcentration, and both direct measurement and toxicokinetic models demonstrate large Hg bioconcentration factors (as high as 1.34 × 10⁵ mL/g dry tissue), similar to partitioning coefficients seen in engineered Hg sorbents. (4) Our study found that Corbicula accumulated Hg at aqueous concentrations relevant to impacted streams, but well below regulatory drinking water limits, demonstrating their utility as a sensitive sentinel species and potential bioremediator. Full article

We assessed the anti-inflammatory activity of the TSPO ligand 2-Cl-MGV-1. Lipopolysaccharide (LPS) was used to induce inflammatory response in a murine RAW264.7 macrophage model (LPS: 100 ng/mL) and a mouse model (C57BL/6) of lung inflammation (LPS: 5 mg/kg). In the macrophage model, the presence of 2-Cl-MGV-1 (25 µM) caused the LPS-induced elevation in nitrite levels to decrease by 70% (p < 0.0001) and interleukin (IL)-6 by 50% (p < 0.05). In the mouse model, 2-Cl-MGV-1, administered 30 min before, or co-administered with, an LPS injection, significantly inhibited the elevation in serum IL-5 levels (both by 65%; p < 0.001 and p < 0.01, respectively). 2-Cl-MGV-1 administration to mice 30 min before LPS injection and 1 h thereafter significantly inhibited the elevation in IL-1β serum levels (both by 63%, p < 0.005). IL-6 elevation was inhibited by 73% (p < 0.005) when 2-Cl-MGV-1 was administered 30 min before LPS, by 60% (p < 0.05) when co-administered with LPS, and by 64% (p < 0.05) when administered 1 h after LPS. All cytokine assessments were conducted 6 h post LPS injection. Histological analyses showed decreased leukocyte adherence in the lung tissue of the ligand-treated mice. 2-Cl-MGV-1 administration 30 min prior to exposure to LPS inhibited inflammation-induced open field immobility. The beneficial effect of 2-Cl-MGV-1 suggests its potential as a therapeutic option for inflammatory diseases. Full article

Simple development of an electrochemiluminescence (ECL) immunosensor for convenient detection of tumor biomarker is of great significance for early cancer diagnosis, treatment evaluation, and improving patient survival rates and quality of life. In this work, an immunosensor is demonstrated based on an enhanced ECL signal boosted by nanochannel-confined Au nanomaterial, which enables sensitive detection of the tumor biomarker—carcinoembryonic antigen (CEA). Vertically-ordered mesoporous silica film (VMSF) with a nanochannel array and amine groups was rapidly grown on a simple and low-cost indium tin oxide (ITO) electrode using the electrochemically assisted self-assembly (EASA) method. Au nanomaterials were confined in situ on the VMSF through electrodeposition, which catalyzed both the conversion of dissolved oxygen (O₂) to reactive oxygen species (ROS) and the oxidation of a luminol emitter and improved the electrode active surface. The ECL signal was enhanced fivefold after Au nanomaterial deposition. The recognitive interface was fabricated by covalent immobilization of the CEA antibody on the outer surface of the VMSF, followed with the blocking of non-specific binding sites. In the presence of CEA, the formed immunocomplex reduced the diffusion of the luminol emitter, resulting in the reduction of the ECL signal. Based on this mechanism, the constructed immunosensor was able to provide sensitive detection of CEA ranging from 1 pg·mL⁻¹ to 100 ng·mL⁻¹ with a low limit of detection (LOD, 0.37 pg·mL⁻¹, S/N = 3). The developed immunosensor exhibited high selectivity and good stability. ECL determination of CEA in fetal bovine serum was achieved. Full article

Patients with systemic lupus erythematosus (SLE) are known to frequently suffer from comorbid cardiovascular diseases (CVDs). There are abundant data on cytokine levels and their role in the pathogenesis of SLE, while growth factors have received much less attention. The aim of this study was to analyze growth factor levels in SLE patients and their association with the presence of comorbid CVDs. The serum concentrations for the granulocyte-macrophage colony-stimulating factor (GM-CSF), nerve growth factor β (NGFβ), glial cell line-derived neurotrophic factor (GDNF), and neuregulin-1 β (NRG-1β) were determined in the SLE patients (n = 35) and healthy individuals (n = 38) by a Luminex multiplex assay. The NGFβ and NRG-1β concentrations were shown to be significantly higher in the total group of SLE patients (median [Q1–Q3]: 3.6 [1.3–4.5] and 52.5 [8.5–148], respectively) compared with the healthy individuals (2.9 [1.3–3.4] and 13.7 [4.4–42] ng/mL, respectively). The GM-CSF and GDNF levels did not differ. Interestingly, elevated NRG-1β levels were associated with the presence of CVDs, as SLE patients with CVDs had significantly higher NRG-1β levels (99 [22–242]) compared with the controls (13.7 [4.4–42]) and patients without CVDs (19 [9–80] ng/mL). The model for the binary classification of SLE patients with and without CVDs based on the NRG-1β level had an average predictive ability (AUC = 0.67). Thus, altered levels of growth factors may be associated with comorbid CVDs in SLE patients. Full article

Chronic Lymphocytic Leukemia (CLL) is the most frequent type of leukemia in Western countries. In recent years, there have been important advances in the knowledge of molecular alterations that underlie the disease’s pathogenesis. Very heterogeneous prognostic subgroups have been identified by the mutational status of immunoglobulin heavy variable genes (IGVH), FISH analysis and molecular evaluation of TP53 mutations. Next-generation sequencing (NGS) technologies have provided a deeper characterization of the genomic and epigenomic landscape of CLL. New therapeutic targets have led to a progressive reduction of traditional chemoimmunotherapy in favor of specific biological agents. Furthermore, in the latest clinical trials, the minimal residual disease (MRD) has emerged as a potent marker of outcome and a guide to treatment duration. This review focuses on recent insights into the understanding of CLL biology. We also consider the translation of these findings into the development of risk-adapted and targeted therapeutic approaches. Full article

Background and Objectives: Seliciclib (SEL) is the first selective, orally bioavailable potential drug containing cyclin-dependent kinase inhibitors. Preclinical studies showed antitumor activity in a broad range of human tumor xenografts, neurodegenerative diseases, renal dysfunctions, viral infections, and chronic inflammatory disorders. To support the pharmacokinetics and aid in therapeutic monitoring of SEL following its administration for therapy, an efficient analytical tool capable of quantifying the concentrations of SEL in blood plasma is needed. In the literature, there is no existing method for quantifying SEL in plasma samples. This study introduces the first HPLC method with a photodiode array (PDA) detector for the quantitation of SEL in plasma. Materials and Methods: The chromatographic resolution of SEL and linifanib as an internal standard (IS) was achieved on Zorbax Eclipse Plus C18 HPLC column (150 mm length × 4.6 mm internal diameter, 5 µm particle size), with a mobile phase composed of acetonitrile–ammonium acetate, pH 5 (50:50, v/v) at a flow rate of 1.0 mL min⁻¹. Both SEL and IS were detected by PDA at 230 nm. The method was validated according to the ICH guidelines for bioanalytical method validation. Results: The method exhibited linearity in concentrations ranging from 50 to 1000 ng mL⁻¹, with a limit of quantitation of 66.1 ng mL⁻¹. All remaining validation parameters satisfied the ICH validation criteria. The environmental sustainability of the method was verified using three extensive tools. The proposed HPLC-PDA method was effectively utilized to study the pharmacokinetics of SEL in rats after a single oral administration of 25 mg/kg. Conclusions: The proposed method stands as a valuable tool for studying SELs for pharmacokinetics in humans. It aids in achieving the targeted therapeutic advantages and safety of treatment with SEL by optimizing the SEL dosage and dosing schedule. Full article

During the growth process of weaned piglets, digestive problems such as gastrointestinal disorders and diarrhea are common. Farmers usually use antibiotics to help piglets grow smoothly. However, the overuse of antibiotics can lead to antibiotic resistance issues. Therefore, this study chose to use plant extracts as feed additives to explore their potential as alternatives to antibiotics. Additionally, Tilmicosin was used as the antibiotic because it is widely used in treating respiratory infections in piglets. Since traditional Chinese medicine often uses natural products, we selected Guizhi Li-Zhong (GLZ) extract as an alternative to antibiotics. The experiment involved 126 piglets, each 4 weeks old, which were randomly assigned to one of four groups: the sham group (basal diet without supplements, 10.3 ± 0.4 kg, n = 31), the low-dose GLZ group (basal diet with 0.05% GLZ, 10.9 ± 0.4 kg, n = 32), the regular-dose GLZ group (basal diet with 0.2% GLZ, 10.6 ± 0.4 kg, n = 32), and the regular-dose Tilmicosin antibiotic group (basal diet with 0.2% Tilmicosin, 10.2 ± 0.3 kg, n = 31). We recorded and compared the survival rate, growth rate, feed conversion ratio, and diarrhea incidence among four groups of weaned piglets from the 4th to the 10th weeks of age. Then, we examined the oxidative stress, inflammation, and apoptosis in small intestine tissue (jejunum and ileum) through immunohistochemistry and Western blot and compared the gut microbiota in large intestine tissue (colon and rectum) through a next-generation sequencing (NGS) analysis. Our results showed that weaned piglets supplemented with 0.05% and 0.2% GLZ had better survival rates, growth rates (p < 0.01), and feed conversion ratios (p < 0.01) compared to those receiving sham treatment. Even weaned piglets supplemented with 0.2% GLZ performed better than those supplemented with 0.2% Tilmicosin antibiotics (p < 0.05). Furthermore, the incidence of diarrhea and small intestine injury (indicated by oxidative stress-, inflammation-, and apoptosis-related proteins) in piglets supplemented with 0.05% and 0.2% GLZ was lower than in piglets receiving sham treatment (p < 0.05). Even piglets supplemented with 0.2% GLZ had less injury than those supplemented with 0.2% Tilmicosin antibiotics (p < 0.05). The NGS results further showed that GLZ treatment significantly improved beneficial bacteria in weaned piglets (p < 0.05), while antibiotic treatment reduced beneficial bacteria (p < 0.05). In summary, we recommend adding GLZ to the feed as an alternative to antibiotics. This not only effectively reduces intestinal damage but also improves the gut microbiota, thereby promoting the growth of weaning piglets. Full article

Individuals with chronic diseases are more vulnerable to environmental inhalation exposures. Although metabolic syndrome (MetS) is increasingly common and is associated with susceptibility to inhalation exposures such as particulate air pollution, the underlying mechanisms remain unclear. In previous studies, we determined that, compared to a healthy mouse model, a mouse model of MetS exhibited increased pulmonary inflammation 24 h after exposure to AgNPs. This exacerbated response was associated with decreases in pulmonary levels of specific specialized pro-resolving mediators (SPMs). Supplementation with specific SPMs that are known to be dysregulated in MetS may alter particulate-induced inflammatory responses and be useful in treatment strategies. Our current study hypothesized that administration of resolvin E1 (RvE1), protectin D1 (PD1), or maresin (MaR1) following AgNP exposure will differentially regulate inflammatory responses. To examine this hypothesis, healthy and MetS mouse models were exposed to either a vehicle (control) or 50 μg of 20 nm AgNPs via oropharyngeal aspiration. They were then treated 24 h post-exposure with either a vehicle (control) or 400 ng of RvE1, PD1, or MaR1 via oropharyngeal aspiration. Endpoints of pulmonary inflammation and toxicity were evaluated three days following AgNP exposure. MetS mice that were exposed to AgNPs and received PBS treatment exhibited significantly exacerbated pulmonary inflammatory responses compared to healthy mice. In mice exposed to AgNPs and treated with RvE1, neutrophil infiltration was reduced in healthy mice and the exacerbated neutrophil levels were decreased in the MetS model. This decreased neutrophilia was associated with decreases in proinflammatory cytokines’ gene and protein expression. Healthy mice treated with PD1 did not demonstrate alterations in AgNP-induced neutrophil levels compared to mice not receiving treat; however, exacerbated neutrophilia was reduced in the MetS model. These PD1 alterations were associated with decreases in proinflammatory cytokines, as well as elevated interleukin-10 (IL-10). Both mouse models receiving MaR1 treatment demonstrated reductions in AgNP-induced neutrophil influx. MaR1 treatment was associated with decreases in proinflammatory cytokines in both models and increases in the resolution inflammatory cytokine IL-10 in both models, which were enhanced in MetS mice. Inflammatory responses to particulate exposure may be treated using specific SPMs, some of which may benefit susceptible subpopulations. Full article