Serranowilhelmsen1897

From the liver lipidomic analysis, we found that PFOS exposure mainly affected glycerophospholipid metabolism and sphingolipid metabolism. The up-regulated ceramide and lysophosphatidylcholine (LPC) might lead to liver cell apoptosis, and the decrease in liver triglyceride (TG) content might result in insufficient energy in mice and cause liver morphological damage. Phosphatidylcholine (PC) synthesis via phosphatidylethanolamine N-methyltransferase (PEMT) pathway might be a mechanism of self-protection in animals against PFOS induced inflammation. This study might provide new insight into underlying toxicity mechanism after exposure to PFOS.Carbon quantum dots (CQDs) are considered as good chromatographic separation materials. However, due to the hydrophily of the synthesized CQDs, their applications in HPLC are limited to HILIC for separating strong polar compounds only. In this work, a novel amphipathic CQDs with both hydrophobicity and hydrophily is developed as mixed-mode stationary phase for RPLC/HILIC. To give CQDs certain hydrophobicity, 1,8-diaminooctane is chosen as one of the carbon sources for introducing alkyl chain into CQDs. The amphipathic CQDs modified silica (CQDs/SiO2) stationary phase has typical characteristic of RPLC/HILIC. Both hydrophobic and hydrophilic compounds including alkylbenzenes, polycyclic aromatic hydrocarbons, nucleosides and bases, amino acids, β-adrenoceptor blockers and agonists, sulfonamides, antibiotics and alkaloids obtain satisfactory separation on this CQDs/SiO2 column. 14 nucleosides and bases commonly existing in living organisms achieve good separation on this amphipathic CQDs/SiO2 column within 25 min and the resolutions reach 1.33-13.83 with an average column efficiency of 18,800. The retention mechanism of this novel CQDs/SiO2 column is investigated by linear solvation energy relationship model. It is found that hydrophobic interaction, π-π stacking, hydrogen-bonding and electrostatic interactions are main retention interactions under RPLC mode. This work provides a new approach for synthesis of amphipathic CQDs. Also, it indicates that amphipathic CQDs with versatile functional properties have great prospect in separation science.Nucleic acid detection is of great importance in a variety of areas, from life science and clinical diagnosis to environmental monitoring and food safety. Unfortunately, nucleic acid targets are always found in trace amounts and their response signals are difficult to be detected. Amplification mechanisms are then practically needed to either duplicate nucleic acid targets or enhance the detection signals. Polymerase chain reaction (PCR) is one of the most popular and powerful techniques for nucleic acid analysis. But the requirement of costly devices for precise thermo-cycling procedures in PCR has severely hampered the wide applications of PCR. Fortunately, isothermal molecular reactions have emerged as promising alternatives. The past decade has witnessed significant progress in the research of isothermal molecular reactions utilizing hairpin DNA probes (HDPs). Based on the nucleic acid strand interaction mechanisms, the hairpin DNA-mediated isothermal amplification (HDMIA) techniques can be mainly divided into three categories strand assembly reactions, strand decomposition reactions, and strand creation reactions. In this review, we introduce the basics of HDMIA methods, including the sensing principles, the basic and advanced designs, and their wide applications, especially those benefiting from the utilization of G-quadruplexes and nanomaterials during the past decade. We also discuss the current challenges encountered, highlight the potential solutions, and point out the possible future directions in this prosperous research area.In recent years, the development of peptide drugs and alternative routes of administration, such as buccal and sublingual routes, has become increasingly important to the pharmaceutical industry. Performing experiments under physiologically relevant conditions is still a challenge that has not yet been fully mastered. The requirements associated with these alternative administration routes (e.g. permeation testing for buccal administration) push common analytical detection systems in pharmaceutical technology to their limits, especially with regard to large molecules and peptides. An HPLC-coupled coaxial liquid-core waveguide fluorescence detector has been developed and evaluated within this study to overcome these limits by achieving a more sensitive detection. Desmopressin acetate was selected as the peptide drug with the aim of investigating its permeation behavior during the clinically relevant application period of one hour. Based on the detector system, a complete validation according to the requirements of international guidelines was successfully performed. The results of the validation showed an increase in sensitivity resulting in a limit of detection of 4.7 ng/mL and a lower limit of quantification of 9.5 ng/mL. click here Moreover, it has been demonstrated that the permeation of desmopressin can be observed in clinically relevant dosages and time periods of up to one hour using this innovative detector system.Paprika is considered a high-quality product being one of the most consumed spices in the world. Contamination with mycotoxins may appear due to inappropriate practices during processing or resulting from invading mould in the final manufactured products. A sample treatment based on dispersive magnetic solid-phase extraction (DMSPE) has been proposed for emerging mycotoxin determination, enniatins (ENNs) and beauvericins (BEAs), in paprika. Different magnetic nanoparticles were tested, and cellulose-ferrite nanocomposite was selected for the extraction and preconcentration of the mycotoxins. Nanocomposite was characterised using field emission scanning electron microscopy and energy dispersive X-ray spectroscopy in terms of morphology and elemental composition. High-resolution mass spectrometry allowed the quantification of the five main emerging mycotoxins and the monitoring of unexpected members of this class of toxic fungal secondary metabolites. The method has been validated, obtaining limits of quantification between 9.5 and 9.9 μg kg-1 and testing its trueness through recovery studies, with satisfactory values of between 89.5 and 97.7%. Relative standard deviations were calculated to evaluate the intra- and inter-day precision and values lower than 8% were obtained in all cases. The analysis of 26 samples, including conventional and organic, demonstrated the presence of ENNB1 at 12.0 ± 0.6 μg kg-1 in one of the samples studied. Other analogues ENNs and BEAs were not detected.Many phosphoprotein biomarkers have been proved to exist in body fluids such as serum and urine, however, there is absence of rapid and efficient separation and identification method. In this study, we proposed to combine metal oxide affinity chromatography (MOAC), molecular imprinting technology (MIT) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to establish an effective approach to solve this problem. To verify the feasibility of this approach, we selected a typical phosphoprotein lysozyme (Lys) as template and magnetic TiO2 as substrate to prepare the molecularly imprinted nanoparticles (denoted as Fe3O4@TiO2@Lys MIPs). A point worth noting is that polydopamine (PDA) as polymer layer made Fe3O4@TiO2@Lys MIPs more hydrophilic and biocompatible. Thanks to the recognition sites of phosphate and the template-shaped cavities, Fe3O4@TiO2@Lys MIPs showed great sensitivity (0.01 ng*μL-1) and selectivity (Lysozyme BSA β-casein = 1100100, mass ratio) in standard phosphoprotein solution. At the end, the Fe3O4@TiO2@Lys MIPs showed great separation ability to lysozyme phosphoprotein in both human serum and urine samples. Therefore, the MOAC-based molecularly imprinted approach is worthy to be expected in effective separation of phosphoprotein biomarker in complex body fluid, which will be a promising one in future.The preparation of well-defined new hydrophilic molecularly imprinted polymer (MIP) microspheres and their use as the dispersive solid-phase microextraction (dSPME) sorbents for direct and selective drug (i.e., propranolol) capture from the undiluted bovine serum are described. These MIPs have surface-grafted dense poly(2-hydroxyethyl methacrylate) (PHEMA) brushes with different molecular weights and grafting densities. They were readily prepared via the facile reversible addition-fragmentation chain transfer (RAFT) coupling chemistry. Both the molecular weights and grafting densities of PHEMA brushes showed significant influence on their complex biological sample-compatibility, and only those MIPs bearing PHEMA brushes with high enough molecular weights and grafting densities could selectively recognize propranolol in the undiluted pure milk and bovine serum. In particular, they have proven to be highly versatile dSPME sorbents for directly and selectively capturing propranolol from the undiluted bovine serum with satisfactory recoveries (85.2-97.4%) and high accuracy (RSD = 2.3-3.7%), even in the presence of one analogue of propranolol. The limit of detection was 0.002 μM with a linear correlation coefficient of 0.9994 in the range of 0.01-100 μM. Excellent precision was verified by both the intraday and interday analytical results. Their good reusability was also confirmed. This work demonstrates the high potential of such hydrophilic MIP-based dSPME sorbents for rapid, accurate, and reliable drug determination in complex biological samples.Electrochemical conversion of fesoterodine to one of its oxidation products was evaluated with the application of the wall-jet flow cell. A traditional, "static" mode of electrolysis was compared with the "dynamic" mode of cell performance. For statistical assessment of the data, experiments were planned and performed with the application of design of experiments approach, namely Taguchi L18 design. After screening phase, the experimental settings were broadened or adjusted according to the results and optimization was performed. All of the samples were electrolysed with the use of chronoamperometric method in a three electrode system. The electrolysed samples were analysed using UHPLC-PDA-QDA method. The chromatographic run was performed in gradient elution with the application of C8 column. The response was expressed as % area of the main peak found with the PDA detection method whereas QDA detector was used in positive SIM mode for structural confirmation. All data obtained for both screening and optimization were treated together and linear models were adjusted. The use of large-surface glassy carbon electrode along with pH~7 were found to be the most significant factors influencing electrochemical oxidation of fesoterodine in both modes. The major differences were identified in terms of voltage applied to the electrodes which yielded the highest amounts of oxidation product. Evolution of electrochemical methods may serve as complementary technique in stress degradation studies in pharmaceutical industry.Therapeutic drug monitoring (TDM) of tyrosine kinase inhibitors (TKIs) in cancer therapy offers the potential to improve treatment efficacy while minimizing toxicity. Therefore, a high-throughput, sensitive LC-MS/MS method was developed and validated, to be used for personalized treatment of hematologic malignancies. The assay allows the simultaneous quantification in plasma (EDTA and heparin) and whole blood of eight TKIs, including bosutinib, dasatinib, gilteritinib, ibrutinib, imatinib, midostaurin, nilotinib and ponatinib, which are used in the treatment of chronic and acute myeloid leukemia (CML, AML) and chronic lymphocytic leukemia (CLL). The procedure involves simple protein precipitation of 50 μL of sample, a 4-min chromatographic separation by applying gradient elution on a standard reverse phase column, and tandem mass spectrometric detection. The method was successfully validated based on international guidelines in terms of calibration curves, precision (within-run CV 0.74-16.4%; between-run CV 1.