High-performance Liquid Chromatography-mass Spectrometry Research Articles

Downstream Effects of the Pandemic? Spatiotemporal Trends of Quaternary Ammonium Compounds in Suspended Particulate Matter of German Rivers

During the SARS-CoV-2 pandemic, the preventive use of antimicrobials such as quaternary ammonium compounds (QACs) surged worldwide. As cationic and surface-active biocides, QACs are only partly removed during wastewater treatment and may cause adverse ecological effects in the downstream environment. To understand the environmental consequences of increased disinfectant use during the pandemic, we investigated spatiotemporal QAC concentration trends in the suspended particulate matter (SPM) of three diverse German rivers. Covering pooled annual SPM samples from 2006-2021 and monthly samples from 2018-2021 collected by the German Environmental Specimen Bank, 31 QACs were quantified by high performance liquid chromatography–mass spectrometry.∑QAC concentrations in annual samples differed by more than tenfold between rivers in the order Saar (average 6.7µg/g) > Rhine (0.9µg/g) > Mulde (0.3µg/g). The strongest potential pandemic imprint was however observed in the Mulde (+67%) and Rhine (+22%). Besides pandemic dynamics, also seasonal variation and mineral content of SPM tentatively affected QAC concentrations. Exceedance of predicted no-effect concentrations for sediment suggest ecotoxicological risks for long-chained QACs already before the pandemic. Our study thus highlights the importance of monitoring the environmental effects of antimicrobial use during pandemics and calls for an urgent minimization of non-essential applications. Environmental implicationThe SARS-CoV-2 pandemic caused a global surge in disinfectant use, including quaternary ammonium compounds (QACs). This raises concerns about their environmental residues, aquatic toxicity and contribution to the (co)selection of antimicrobial resistance in pathogens. To assess these ecotoxicological risks, we investigated spatiotemporal QAC concentration trends in suspended particulate matter of German rivers. While seasonal and spatial fluctuations exceed a potential pandemic “imprint” by a factor of 10, concentrations of some QACs reach ecotoxicological effect levels. This highlights the need to consider particle-associated QAC concentrations, the widespread use of QAC, as well as the environmental implications of chemical public health interventions.

Investigation of the Role of Chemical Analysis in Causality Assessment of Herbal and Dietary Supplement-Induced Liver Injury.

The attribution of drug-induced liver injury (DILI) to specific herbal and dietary supplements (HDS) is confounded by inaccurate labels and undisclosed ingredients. The US Drug-Induced Liver Injury Network (DILIN) determines the attribution of injury to an agent through its structured expert opinion causality assessment process, but without the use of chemical analysis data of HDS. We aimed to determine the impact of chemical analysis of HDS products on prior causality assessment scores. Obtained samples of HDS consumed by DILIN-enrolled patients were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Chemical analysis data were compared to label accuracy and detect whether the product contained botanical and non-botanical compounds. A comparison of the causality scores reassessed with chemical analysis was compared with the original scores. A total of 54 previously adjudicated cases with chemical analysis available were reassessed for causality with chemical analysis data; reviewers were blinded to original causality scores. Using the chemical analysis data, 37% (n = 20) of the 54 cases were scored with a higher likelihood of DILI compared with the original causality scores; 14 of the 20 (70%) moved from probable to highly likely; 52% had no change in causality score; and 11% of cases were scored as a lower likelihood of DILI. Our study demonstrates that there is value in using HDS chemical analysis data in the causality assessment process for DILI. In more than a third of cases, chemical analysis of products led to an increased confidence in DILI attribution to HDS. These findings suggest that chemical analysis is an important tool in causality assessment for HDS agents, specifically in challenging situations, and further studies are needed to confirm its applicability in clinical practice.

Exploring of Chemical Profile and Biological Activities of Three Ocimum Species From Comoros Islands: A Combination of In Vitro and In Silico Insights.

Ocimum species have a great interest in different traditional medicinal systems. This study examined the chemical composition, antioxidant properties, enzyme inhibitory effects, and antibacterial and antifungal activities of the aerial parts of Ocimum gratissimum, Ocimum americanum, and Ocimum basilicum from the Comoros Islands. The extracts were analyzed using high-performance liquid chromatography-mass spectrometry (HPLC-MS) to determine their chemical composition. Antioxidant activity was assessed using 2,2-Diphenyl-1-picrylhydrazyl (DPPH), 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), cupric reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant power (FRAP), chelating ability, and phosphomolybdenum radical scavenging assays. Enzyme inhibitory activities against acetylcholinesterase (AChE), butrylcholinesterase (BChE), tyrosinase, amylase, and glucosidase were evaluated using spectrophotometric methods. Antibacterial and antifungal activities were tested using the broth microdilution method against selected pathogenic microorganisms. The selected enzymes and proteins were evaluated using in silico methods with biomolecules from these plants. In addition, 111 different metabolites were identified in the tested extracts using advanced HPLC/MS techniques. The most significant number of detected compounds were derivatives of hydroxycinnamic acids, followed by flavonoid glycosides and aglycones and derivatives of hydroxybenzoic acids. All three Ocimum species exhibited significant antioxidant activities, O. gratissimum exhibited the best-reducing abilities in CUPRAC and FRAP assays. In addition, enzyme inhibitory assays revealed that O. americanum had the most potent inhibitory effect on tyrosinase (48.01 ± 3.89 mg kojic acid equivalent [KAE]/g), and amylase (1.08 ± 0.02 mmol acarbose equivalent [ACAE]/g). Antibacterial and antifungal tests demonstrated that the extracts possess broad-spectrum activity. Molecular docking results showed that compounds exhibited remarkable binding energies with target enzymes and proteins. The molecular dynamics simulations identified chicoric acid with MurE of Staphylococcus aureus complex as the most promising drug candidate. These findings support their traditional medical and nutraceutical uses and suggest possibilities for natural functional applications.

Insoluble proteomics analysis of acute intracranial large vessel occlusive thrombus

BackgroundAcute large vessel occlusion (LVO) stroke is highly prevalent and severe. Despite thrombolytic therapy, many patients experience substantial complications. Understanding the origins, constituents, and pathologic processes involved in thrombus formation in acute intracranial large artery occlusion is crucial. ObjectivesTo identify the characteristics of insoluble proteins from different sources of cerebral thrombus. MethodsThis study included 13 patients with cardiogenic embolic (CE) thrombus and 15 with large artery atherosclerotic (LAA) thrombus. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry were used to analyze insoluble proteins in thrombi. Bioinformatics analyses explored differential proteins and associated functional pathways. Least absolute shrinkage and selection operator and random forest identified biomarkers for diagnosing thrombus sources, validated by parallel reaction monitoring. ResultsWe constructed an insoluble protein atlas of cerebral thrombi, identifying 6975 insoluble proteins, including 143 extracellular matrix (ECM)-related proteins. The enrichment pathways considerably varied between thrombi from different sources. Inflammation-related pathways, such as acute inflammatory response, along with ECM-related pathways such as laminin interactions, were notably upregulated in LAA compared with CE. Additionally, 2 biomarkers (IDH2 and HSPG2) exhibited strong diagnostic performance (area under the curve = 1) and robustness. ConclusionIn the insoluble proteomics of thrombus, we highlighted the crucial roles of immune responses and ECM proteins in thrombus formation, providing new insights into its mechanisms and potential drug development. Additionally, we identified 2 biomarkers that offer new methods for determining thrombus sources in patients with LVO.

Identification of bioactive compounds in Amphipterygium adstringens branch bark

Background: Cuachalalate (Amphipterygium adstringens) is one of Mexico’s most commercialised medicinal plants, and its natural populations are mainly found in this country. The high demand for stem bark (SB) has risked its survival, making it necessary to develop sustainable strategies.Aim: This study aimed to identify bioactive compounds in branch bark (BB) and evaluate their antipathogenic and antivirulence capacities.Setting: The study was conducted in the low deciduous forest (LDF) of the State of Puebla, Mexico.Methods: Bioactive metabolites in BB were profiled by high-performance thin-layer chromatography (HPTLC). The chemical composition of aqueous bark extracts was scrutinised by high-performance liquid chromatography-mass spectrometry (HPLC-EM-SQ-TOF system) and molecular network analysis. The folk method’s antipathogenic capacity was determined in a burn model in mice infected with Pseudomonas aeruginosa. Finally, the antivirulence properties of bark organic extracts were determined.Results: The BB contained masticadienoic, 3α-hydroxymasticadienoic and anacardic acids, also present in SB. The aqueous extracts showed the presence of flavonoids, catechins and saponins in both barks. The folk method using BB extracts significantly reduced mouse mortality and prevented sepsis development. This might be related to the capability of extracts to block the production of bacteria virulence factors.Conclusion: The similarity in bioactive metabolites and biological activity between SB and BB of cuachalalate suggests that using BB as a medicinal agent could be a practical and sustainable strategy. This approach could potentially prevent the overexploitation of cuachalalate’s SB, contributing to its conservation.Contribution: This study proposes a sustainable strategy for using cuachalalate as a medicinal agent using BB, a renewable source.

Threonine In Different Phenotypes Of Chronic Heart Failure With Preserved Ejection Fraction

Background — Chronic heart failure with preserved ejection fraction (CHFpEF) develops as a result of many diseases that lead to significant metabolic disorders. Given the heterogeneity of this group of patients, therapeutic options for this syndrome are extremely limited. In this regard, it seems promising to study the metabolomic profile in patients with CHFpEF to identify biomarkers, examine their roles in the pathogenesis of the syndrome, and search for potential targets for targeted therapy. Objective — The study aimed at testing the correlation between the threonine level and the features of the clinical course of CHFpEF. Methods — The study included a total of 154 patients: 82 with CHFpEF, 45 with hypertension and/or coronary artery disease (comparison group), and 27 healthy volunteers (control group). Threonine levels were assessed using high-performance liquid chromatography-mass spectrometry. Results — The threonine concentration was significantly reduced in patients with CHFpEF (1) vs. comparison group (2) and control group (3): p<0.001; p1-3<0.001; p2-3=0.037). A reduction in the threonine level was characteristic for patients with diabetes mellitus vs. patients without it (p=0.029). Conclusion — Given the importance of threonine in energy metabolism and significant changes in its level in various pathophysiological processes, it should be considered as an additional diagnostic and prognostic criterion for CHFpEF. Additional studies are needed to better understand the role of threonine in the pathophysiology of cardiovascular diseases.

Storing liquid chromatographic separations on surface energy traps: decoupling the LC and the mass spectrometer.

We report a micro-fractionation device for high performance liquid chromatography-mass spectrometry to archive chromatographic separations on an array of optimized surface energy traps (SETs). The method has the potential to significantly alter nanoflow LC-MS workflow, decoupling separation and analysis. The wetting characteristics of the SETs cause the HPLC eluent stream to spontaneously split into droplet microfractions. The droplet mirofractions are then dried down to enable facile storage and transport of the archived separation. Discontinuously dewetting array parameters were explored to maximize array volume and resolution using a combination of SET design, shape, size, and spacing. Mass spectrometry analysis is performed utilizing a liquid micro-junction surface sampling probe to extract dried analytes from the surface of the SETs followed by electrospray ionisation. A reverse phase separation of pharmaceutical compounds is "recorded" using the micro-fractionation device followed by "reading" the chromatographic trace with a mass spectrometer 24 hours after the separation was performed/archived, demonstrating a true decoupling of LC, and MS. Additionally, we demonstrate the ability to collect microfractions with sub-one-second integration time, approaching the scan time of a mass spectrometer or UV-Vis detector. With further improvements to the device, sub-1-second micro-fractionation may enable seamless reconstruction of archived chromatograms indistinguishable from online LC-MS data, while also providing the benefits of easy storage and transport of archived separations.

Selective oxidation of organic pollutants by unactivated and carbonate-activated peroxymonosulfate (PMS): Mechanism, kinetics, and transformation pathway

Although the activation mechanisms of peroxymonosulfate (PMS) by various homogeneous and heterogeneous catalysts have been reported, the chemistry of PMS in catalyst-free systems and its interaction with background oxygenated anions remains poorly understood. In this study, the unactivated PMS and carbonate-activated PMS (CO32–/PMS) systems for removal of various organic pollutant (including oxytetracycline (OTC), metronidazole (MNZ), methylene blue (MB), and acid orange G (OG)) were investigated. The results showed that 74.5 %, 90.21 %, 1.22 %, and 2.25 % of OTC, MB, OG, and MNZ were removed, respectively within 180 min in the unactivated PMS system due to the formation of ·OH and 1O2. 95.88 %, 100 %, 100 %, and 6.09 % of OTC, MB, OG, and MNZ were removed, respectively in the CO32–/PMS system, which is primary due to the generation of 1O2. The removal efficiencies of these four pollutants were significantly improved under alkaline conditions. In addition, the TOC removal rates were 21.88 % for MB and 26.53 % for OTC within 180 min in the CO32–/PMS system. The presence of Cl− and SO42− can greatly enhance the OTC removal efficiency both in the unactivated and CO32–/PMS systems. Through the high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis, OTC degradation products in the unactivated PMS and CO32–/PMS systems were identified, revealing six different reaction mechanisms, including hydroxylation (+16 Da), decarbonylation (−28 Da), demethylation (−14 Da), secondary alcohol oxidation (−2 Da), deamination (−15 Da), and dehydration (−18 Da). This study provides insight into the reaction mechanism of catalyst-free PMS systems and may promote the application of unactivated PMS and CO32–/PMS systems for the remediation of organic contaminated water.

Introducing oxygen cacancies to tune Cu2O by Sn ion-doped for high-effective photocatalytic degradation of norfloxacin in wastewater

Photocatalytic materials have attracted considerable attention owing to its positive environmental impact and efficiency in wastewater treatment. Herein, tin (Sn)-doped copper oxide (Cu2O) photocatalysts were successfully synthesized via a facile hydrothermal approach. The doping of Sn ions into the Cu2O lattice promoted the formation of more oxygen vacancies, which increased the separation efficiency of photogenerated carriers and enhanced photocatalytic activity. Moreover, the presence of Sn ions enhanced light absorption and the specific surface area of Cu2O, and reduced photogenerated carriers recombination. The synergistic effect of the abovementioned advantages, induced excellent photocatalytic activity to the as-prepared catalysts. Tin chloride (30 mg)-doped Cu2O showed optimal photocatalytic properties with the highest norfloxacin degradation rate of 83.9 % in 140 min under visible light irradiation. Hydroxy radicals played a major role during degradation as demonstrated by the capturing of active species experiment and EPR testing. Photocatalytic mechanisms and possible degradation pathways were proposed based on Perdew-Burke-Ernzerhof and high-performance liquid chromatography-mass spectrometry techniques. The toxicity analyses of the intermediates proved their low toxicity. Repeated cycling experiments confirmed the excellent stability of the catalysts. This work provides a feasible strategy for fabricating high-performance Cu2O-based photocatalysts.

Improved adsorption and charge transfer capacity by coupling g-C3N4 and NH2-MIL-125 for efficient degradation of sulfamethoxazole in water: Characterization, degradation efficiency, influence factors, and mechanism

Photocatalysis is an advanced oxidation process that shows excellent promise in degrading organic pollutants present in water. However, electrons and holes tend to combine easily during the transfer process, and the adsorption capacity of single-phase photocatalytic materials is weak, resulting in a low degradation rate. Therefore, a new composite semiconductor photocatalyst g-C3N4/NH2-MIL-125 was constructed using a two-step solvothermal method. The morphology, elemental composition, structure, photoelectric properties, and photocatalytic activity of g-C3N4/NH2-MIL-125 were characterized. The photocatalytic degradation of Sulfamethoxazole (SMX) in water was also carried out. Results indicated that g-C3N4/NH2-MIL-125 had been synthesized successfully, and g-C3N4/NH2-MIL-125 had a broader photoresponse range, higher adsorption capacity, and higher separation efficiency of photogenerated carriers. When pH was 4.0 and catalyst dosage was 0.15 g/L, g-C3N4/NH2-MIL-125 showed the highest degradation rate for SMX. It was confirmed that the main active groups in SMX degradation were OH, h+, and O2−. 15 kinds of intermediates of SMX and the possible degradation pathways were identified by high-performance liquid chromatography-mass spectrometry and DFT calculation. Toxicity analysis revealed that the intermediate products have a lower developmental toxicity than SMX. This work demonstrated that g-C3N4/NH2-MIL-125 has great potential in eliminating antibiotics from water.

Eupatorium adenophorum Spreng root extract as an efficient inhibitor for the corrosion of steel in sulfamic acid solution

Eupatorium adenophorum Spreng root extract (EASRE) was prepared using a reflux extraction method with 40 % ethanol (C2H5OH) as the extractant solvent. The corrosion inhibitory impact of EASRE on cold rolled steel (CRS) in 0.10 M sulfamic acid (NH2SO3H) solution was explored through gravimetric tests, potentiodynamic polarization curves, and electrochemical impedance spectroscopy (EIS) methods. Metallographic microscopy (MM), scanning electron microscopy (SEM), atomic force microscopy (AFM), and confocal laser scanning microscopy (CLSM) were employed to examine the micrographs of CRS specimens. The adsorbed chemical substances on the inhibited CRS surface were examined via X-ray photoemission spectroscopy (XPS). And the main chemical constituents of EASRE were analysed by high performance liquid chromatography-mass spectrometry (HPLC-MS). The results of the study showed that EASRE at a concentration of 500 mg L−1 in 0.10 M NH2SO3H at 30 °C for 12 h had a significant inhibitory effect on CRS, with a maximum inhibitory efficiency of 89.7 %. At all set temperatures, the adsorption of EASRE onto CRS surface adheres to Langmuir isotherm. EASRE functions as a mixed-type inhibitor through a “geometric covering effect”. EIS show that the addition of EASRE significantly improves the charge transfer resistance at the steel/sulfamic acid interface, and the charge transfer resistance increases with increasing inhibitor concentration. XPS analysis confirm the presence of a “protective film” generated by EASRE on the CRS surface, and it consists of O-H, N-H, C-O, C-H, CC, CN, CO. Microscopic graphs of MM, SEM, AFM and CLSM reveal that EASRE efficiently alleviates the corrosion on the CRS surface. The HPLC-MS suggest that the main components of EASRE are flavonoids and phenylpropanoid compounds.

Anemarrhena asphodeloides Bunge total saponins lower lipid via modulating MAOA activity to enhance defense mechanisms in mice and C. elegans

Ethnopharmacological relevanceWithin Anemarrhena asphodeloides Bunge (AAB), the pivotal bioactive constituents are identified as Anemarrhena asphodeloides Bunge total saponins (ABS). In traditional pharmacology, ABS has exhibited notable anti-inflammatory, hypoglycemic, and cardioprotective properties. Despite these observed effects, the specific protective mechanisms of ABS against metabolic diseases and improving the endocrine system remain largely uncharted. Aim to studyThis work intends to shed light on the effects and intrinsic mechanisms of ABS on metabolic diseases. Materials and methodsThe characterization of ABS components was achieved through High-Performance Liquid Chromatography/Mass Spectrometry (HPLC/MS). To evaluate ABS's anti-inflammatory efficacy, mouse macrophages underwent analysis using the Griess method. Induced differentiation of mouse fibroblasts was assessed through Oil Red O staining. In an obesity model with C57BL/6 N mice, ABS administration prompted measurements of glucose and insulin tolerance. Western blot analysis quantified lipolysis and anti-inflammatory protein expression. Nile red staining gauged body fat content in C. elegans post-ABS treatment. The mechanism of ABS action was elucidated through mRNA sequencing, further validated using RNA interference technology, and nematode mutants. ResultsABS showcased the ability to diminish Nitric Oxide (NO) production in inflammatory macrophages and shrink adipocyte lipid droplets. In mice experiments, ABS was effective in alleviating fat accumulation and affecting serum lipid metabolism in diabetic mice. It enhanced oral glucose tolerance and insulin tolerance while increasing lipolysis-associated protein expression. ABS notably reduced fat content in C. elegans. Mechanistically, ABS downregulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and monoamine oxidase A (MAOA) expression while enhancing UGT, ilys-2, and ilys-3. Lipolysis emerged as a pivotal pathway for ABS in the therapeutic intervention of metabolic diseases. ConclusionsOur investigation has revealed that ABS exert a role in combating metabolic diseases by enhancing the body's defense mechanisms. ABS activate the NLRP3-neurotransmitter-visceral adipose pathway in mice, thereby bolstering resistance and diminishing fat accumulation. In C. elegans, ABS downregulated the expression of MAOA, bolstered resistance, and augmented glucuronidase activity, consequently leading to a reduction in fat content.

A multifunctional natural treasure based on a “one stone, many birds” strategy for designing health-promoting applications: Tordyliumapulum

Wild plants provide important bioactive compounds, and their analysis relies heavily on selecting the right extraction techniques and solvents. This study was conducted to determine the phenolic content and biopharmaceutical potential of four different extracts (ethyl acetate, ethanol, 70% ethanol, and water) from the aerial parts of wild plant Tordylium apulum L. The biochemical profile of the extract was screened using high performance liquid chromatography -mass spectrometry (HPLC-MS) analysis. The total phenolic and flavonoid content was examined using the Folin-Ciocalteu assay and the aluminium trichloride assay, respectively. The antioxidant activity was evaluated through several tests, including 2,2-Diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), cupric reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant power (FRAP), phosphomolybdenum (PBD), and metal chelating activity (MCA). Five types of enzyme inhibition activity were tested against acetylcholinesterase (AChE), butrylcholinesterase (BChE), tyrosinase, α-amylase, and α-glucosidase. Additionally, For the first time, the inhibitory activity of T. apulum extract against human carbonic anhydrase isoenzymes I and II (hCA-I and hCA-II) was evaluated. Fifty-five compounds for negative ionization mode, and twenty-eight compounds for positive ionization mode were recorded in HPLC-MS analysis and they were polyphenolic, flavonoids, carbohydrates, sugar alcohol and amino acids. These results indicate that different solvents extract varying levels of antioxidants from T. apulum, with ethanol and water extracts generally exhibiting superior antioxidant activities. The ethanol extract of T. apulum exhibited the maximum contents of total phenolics measuring 33.71 mg gallic acid equivalent (GAE)/g. The ethanol extract exhibited the highest inhibition of AChE with 2.28 mg galanthamine equivalent (GALAE)/g. The ethyl acetate and ethanol extracts also showed the highest hCA-I and hCA-II inhibition potential, respectively. The ethanol-water and water extracts acted on the biofilm of E. coli (49.93% and 45.22%, respectively), and the biofilm of P. aeruginosa (50.68% and 44.46%, respectively). The extracts were tested on different cell lines for cytotoxic potentials and in particular the water extract induced the apoptotic pathways in cervical cancer (HELA) cell lines. In conclusion, T. apulum exhibit multidirectional biological properties and it could be considered as a versatile agent for the development of health-promoting applications.

Investigation into temporal changes in the human bloodstain lipidome.

Bloodstains are crucial pieces of physical evidences found at violent crime scenes, providing valuable information for reconstructing forensic cases. However, there is limited data on how bloodstain lipidomes change over time after deposition. Hence, we deployed a high-throughput high-performance liquid chromatography-mass spectrometry (HPLC-MS) approach to construct lipidomic atlases of bloodstains, whole blood, plasma, and blood cells from 15 healthy adults. A time-course analysis was also performed on bloodstains deposited for up to 6months at room temperature (~ 25°C). The molecular levels of 60 out of 400 detected lipid species differed dramatically between bloodstain and whole blood samples, with major disturbances observed in membrane glycerophospholipids. More than half of these lipids were prevalent in the cellular and plasmic fractions; approximately 27% and 10% of the identified lipids were uniquely derived from blood cells and plasma, respectively. Furthermore, a subset of 65 temporally dynamic lipid species arose across the 6-month room-temperature deposition period, with decreased triacylglycerols (TAGs) and increased lysophosphatidylcholines (LPCs) as representatives, accounting for approximately 8% of the total investigated lipids. The instability of lipids increased linearly with time, with the most variability observed in the first 10days. This study sheds light on the impact of air-drying bloodstains on blood components at room temperature and provides a list of potential bloodstain lipid markers for determining the age of bloodstains.

Fully Integrated Recognition and Enrichment Electrospray Ionization Source for High-Sensitivity Mass Spectrometry Determination of Bioamine.

The development of a highly specific recognition electrospray ionization source presents a major challenge for achieving rapid ambient mass spectrometry (AMS) detection of trace harmful substances in complex samples. In this study, we constructed a molecular imprinting nanofiber electrospinning membrane-coated steel substrate (MINMCS) based on the electrospinning strategy. This was designed as a highly specific recognition and enrichment electrospray ionization source module for AMS, where the molecular imprinting nanofiber membrane served as an excellent extraction and enrichment layer. The prepared ionization source demonstrated a sufficient loading capacity for three bioamines (BAs): histamine (HIS), tyramine (TYR), and tryptamine (TRY). With simplified sample pretreatment, this ionization source exhibited sensitivity comparable to that of high performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Moreover, the entire analysis process could be completed within 1 min with acceptable recoveries (83.21-101.80%). In brief, this study introduces a new integrated recognition and enrichment electrospray ionization source for the detection of harmful substances such as bioamines, showcasing significant commercial potential for the rapid detection of foodborne harmful compounds.

TiO2/Ti3C2Tx gel microsphere for efficient photocatalytic degradation of organic pollutant with excellent recycling stability

Enhancing the recycling stability of photocatalysts is crucial for practical applications. The significant loss of powder catalyst materials during the recycling process hampers its degradation rate and results in a low reuse rate. Herein, the in-situ prepared TiO2/Ti3C2Tx (TOTC) heterojunction is embedded in gel microsphere (GMS) as a recyclable photocatalyst TOTC@GMS for efficient photocatalytic degradation of Congo red (CR). The experimental results show that the removal rate can reach 99 % in 120 min without any co-catalysts or sacrificial reagents. The GMS can be recycled after rinsing in deionized water for only 2 min, and the removal rate still maintains over 90 % after 25 cycles. Additionally, under natural sunlight exposure, TOTC@GMS achieves a removal rate of 90 % for CR in real water samples. The degradation mechanism is elucidated through hydroxyl radicals (OH) and superoxide radicals (O2−) as the main reactive species, as confirmed by free radical scavenging and electron paramagnetic resonance (EPR) experiments. The degradation products are further analyzed using high-performance liquid chromatography-mass spectrometry (LC-MS), allowing for the deduction of degradation pathways of CR. Furthermore, a phytotoxicity test confirms the non-toxicity of the organic micromolecules generated after degradation. This study presents a practical strategy to improve the recycling stability of photocatalysts, thereby effectively reducing the cost of wastewater treatment.

Aspirin hypersensitivity diagnostic index (AHDI): Invitro test for diagnosing of N-ERD based on urinary 15-oxo-ETE and LTE4 excretion.

15-oxo-eicosatetraenoic acid (15-oxo-ETE), is a product of arachidonic acid (AA) metabolism in the 15-lipoxygenase-1 (15-LOX-1) pathway. 15-oxo-ETE was overproduced in the nasal polyps of patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). In this study we investigated the systemic biosynthesis of 15-oxo-ETE and leukotriene E4 (LTE4) and assessed their diagnostic value to identify patients with N-ERD. The study included 64 patients with N-ERD, 59 asthmatics who tolerated aspirin well (ATA), and 51 healthy controls. A thorough clinical characteristics of asthmatics included computed tomography of paranasal sinuses. Plasma and urinary 15-oxo-ETE levels, and urinary LTE4 excretion were measured using high-performance liquid chromatography and tandem mass spectrometry. Repeatability and precision of the measurements were tested. Plasma 15-oxo-ETE levels were the highest in N-ERD (p < .001). A receiver operator characteristic (ROC) revealed that 15-oxo-ETE had certain sensitivity (64.06% in plasma, or 88.24% in urine) for N-ERD discrimination, while the specificity was rather limited. Modeling of variables allowed to construct the Aspirin Hypersensitivity Diagnostic Index (AHDI) based on urinary LTE4-to-15-oxo-ETE excretion corrected for sex and the Lund-Mackay score of chronic rhinosinusitis. AHDI outperformed single measurements in discrimination of N-ERD among asthmatics with an area under ROC curve of 0.889, sensitivity of 81.97%, specificity of 87.23%, and accuracy of 86.87%. We confirmed 15-oxo-ETE as a second to cysteinyl leukotrienes biomarker of N-ERD. An index based on these eicosanoids corrected for sex and Lund-Mackay score has a similar diagnostic value as gold standard oral aspirin challenge in the studied group of patients with asthma.

Chemical Composition and Antioxidant Activity of Ganoderma lingzhi and Ganoderma lucidum Fruiting Body Extracts

INTRODUCTION. Ganoderma spp. have been used as a traditional oriental medicine and a bioactive dietary supplement. These fungi are a promising source of effective antioxidants. Currently, there is no regulatory framework to control the quality of this herbal drug and its bioactive components in the Russian Federation and the Republic of Belarus. Therefore, it is essential to study the chemical composition and pharmacological activity spectrum of G. lingzhi and G. lucidum extracts.AIM. The aim of this study was to determine the chemical composition and antioxidant activity of G. lingzhi and G. lucidum fruiting body extracts.MATERIALS AND METHODS. The study focused on pure cultures of G. lingzhi and G. lucidum obtained from the fungal species collection of the Forest Institute of the National Academy of Sciences of Belarus. Fungal biomass was grown using two substrates, including alder sawdust (1–3 mm fraction) and oak shavings (5–10 mm fraction). The fungal biomass was extracted using repeated maceration with 70% ethanol. The study tested the free radical-scavenging activity of the extracts in reactions with the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the radical cation derived from 2,2’-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS). The chemical composition was analysed by high-performance liquid chromatography–mass spectrometry (HPLC–MS). The assays for phenols, steroids, and triterpenes used spectrophotometry.RESULTS. The extract of G. lucidum strain 334 cultivated on the alder substrate demonstrated the highest free radical-scavenging activity (IC50 =3.1±0.2 μg/mL (DPPH), IC50 =3.7±0.2 μg/mL (ABTS)), the highest phenolic content (326.2±16.5 μmol/g), and the highest triterpene content (2.00±0.11 mmol/g) of all the studied extracts. The antioxidant activity of the extracts of G. lingzhi and G. lucidum may be attributed to the content of ganoderic acid D, lucidenic acid D, naringenin, and other phenolic compounds.CONCLUSION. The high yield of extracts with a significant radical-scavenging activity makes artificially cultivated G. lingzhi and G. lucidum mushrooms a promising source of natural antioxidants.

Pharmacokinetics and Bioavailability Study of a Novel Smoothened Inhibitor TPB15 for Treatment of Triple-Negative Breast Cancer in Rats by High Performance Liquid Chromatography-Mass Spectrometry.

Smoothened (SMO), a key component of the hedgehog signaling pathway, represents a therapeutic target for triple negative breast cancer(TNBC), yet the chemotherapy response rate in TNBC patients is only 40-50%, underscoring the urgent need for the development of novel drugs to effectively treat this condition. The novel compound TPB15, an SMO inhibitor derived from [1,2,4] triazolo [4,3-α] pyridines, demonstrated superior anti-TNBC activity and lower toxicity compared to the first SMO inhibitor vismodegib in both in vitro and in vivo. However, the compound's pharmacokinetic properties remain unclear. The present work aims to develop a simple HPLC-MS/MS method to profile the pharmacokinetics and bioavailability of TPB15 in rats as a ground work for further clinical research. Separation was performed on an Agilent ZORBAX StableBond C18 column by gradient elution using acetonitrile and 0.1% formic acid as mobile phase at a flow rate of 0.3mL/min. Multiple reaction monitoring(MRM) in positive mode with the transitions of m/z 454.2 → 100.0, 248.1 → 121.1 was employed to determine TPB15 and internal standard tinidazole, respectively. The specificity, intra- and inter- day precision and accuracy, extraction recovery, stability, matrix effect, dilution integrity and carryover of the method was validated. The pharmacokinetics and bioavailability studyof TPB15 were carried out on rats through intravenous injection at the dose of 5 mg/kg and oral gavage at the dose of 25 mg/kg, and the pharmacokinetics parameters were calculated by the non-compartment analysis using the pharmacokinetics software DAS 2.1.1. The values of specificity, intra- and inter- day precision and accuracy, extraction recovery, stability, matrix effect, dilution integrity and carryover satisfied the acceptable limits. The lower limit of quantification of this method was 10 ng/mL with a linear range of 10-2000ng/mL. The validated method was then applied to pharmacokinetics and bioavailability studies in rat by dosing with gavage (25mg/kg) and intravenous injection(5mg/kg), and the oral bioavailability of TBP15 in rat was calculated as 16.4 ± 3.5%. The pharmacokinetic parameters were calculated as following: maximum of plasma concentration (Cmax) (PO: 2787.17 ± 279.45µg/L), Time to maximum plasma concentration (Tmax) (PO: 4.20 ± 0.90 h), the area under the concentration-time curve 0 to time (AUC0-t) (PO: 17,373.03 ± 2585.18 ng/mL·h, IV: 21,129.79 ± 3360.84ng/mL·h), the area under the concentration-time curve 0 to infinity (AUC0-∞) (PO: 17,443.85 ± 2597.63 ng/mL·h, IV: 17,443.85 ± 2597.63ng/mL·h), terminal elimination half-life (t1/2) (PO: 7.26 ± 2.16h, IV: 4.78 ± 1.09h). TPB15, a promising candidate for treating TNBC, hasdemonstrated outstanding efficacy and safety in vitro and in vivo. This study established a simple, sensitive, and rapid HPLC-MS/MS bioanalytical method, developed and validated in accordance with FDA and EMA guidelines, for conducting pharmacokinetic and bioavailability studies of TPB15. The results revealed a favorable pharmacokinetic profile owing to its long t1/2. Nevertheless, the next phase of research should include formulation screening to enhance bioavailability, as well as clinical trials, metabolism pathway analysis, and assessment of potential drug-drug interactions.

Regulating facet exposure and sulfur vacancy in magnetic greigite nanosheet for boosting heterogeneous Fenton-like reaction towards efficient degradation of metronidazole under visible light irradiation: Synergistic enhancement effect, DFT calculations and mechanism insight

Environmentally friendly iron catalysts have attracted widespread attention in the heterogeneous Fenton-like reaction based on peroxymonosulfate (PMS) for the degradation of emerging pollutants in water, while it has always suffered from the disadvantage of low catalytic activity. Herein, we successfully prepared the magnetic greigite (Fe3S4) nanosheet with the exposed {011} facet and rich sulfur vacancies (FS-1) through a simple solvothermal method. The degradation rate of metronidazole by the FS-1 activating PMS under visible light irradiation was 2.93, and 4.48 more than those of the Fe3S4 nanosheet with the exposed {011} facet and poor sulfur vacancies, and Fe3S4 nanobulk with the exposed {112} facet, respectively. The result of electrochemical analysis and theoretical calculation indicated that the exposed {011} facet of prepared FS-1 offered more active sites to adsorb PMS, and the rich sulfur vacancies on the surface accelerated the electron transfer between oxidants and catalyst. This collaborative effect significantly lowered the energy barrier associated with PMS activation, leading to an increased generation of singlet oxygen. Additionally, the degradation mechanism and pathway of metronidazole, including hydroxyethyl cracking, denitrification, and hydroxylation, were explored in detail through theoretical calculations and high-performance liquid chromatography-mass spectrometry, respectively. This work offers insight into boosting the catalytic performance of environmentally friendly iron-based catalysts.