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Per- and polyfluoroalkyl substances (PFAS) are known to bioaccumulate in aquatic organisms, such as shellfish, and have been linked to adverse human health outcomes. Increasing attention has been focused on method development for the detection of PFAS in various media; however, these methods are typically tedious, require high solvent volumes, and are time consuming. The present method used a Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) extraction approach and analysis by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) to detect 28 PFAS in Eastern oyster (Crassostrea virginica) tissue. This method was validated using limit of detection, limit of quantitation, and precision and accuracy studies. Limits of detection ranged from 0.2 to 5.8 ng g−1, limits of quantitation ranged from 0.66 to 19.2 ng g−1, and recoveries spanned 52.1–105.9% at the 100 ng mL−1 analyte level. Analysis of 12 unknown oyster composite samples revealed the detection of PFHxA, PFPeS, PFOA, PFHpA and PFOS and at least two compounds were detected in each oyster sample. This validated method proved to be an efficient and environmentally friendly sample preparation method for PFAS analysis in complex tissue media, such as oysters. [ABSTRACT FROM AUTHOR]

As a common pharmaceutical plant, Angelica sinensis (called Danggui (DG) in Chinese) is widely used in food, pharmaceuticals, and cosmetics and frequently processed with rice wine. Eight batches of rice wine-processed (WDG) samples and unprocessed DG were prepared to compare the chemical component differences. High-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS) was combined with a molecular network strategy. The 140 components were identified, thereby providing a comprehensive characterization of DG and WDG. Chemometrics was used to compare the variations in these components, and the results revealed higher abundances of certain amino acids and organic acids in WDG. These differences may explain the higher efficacy of WDG. This study shows the differences between DG and WDG included variation in the content, which provides a basis for the study of WDG and support for the standardization of Chinese medicine processing. [ABSTRACT FROM AUTHOR]

The analysis of gangliosides and glycosphingolipids is crucial for understanding cellular membrane structure and function as well as to accurately diagnose certain inborn errors of metabolism. GM2-gangliosidosis represents a rare and fatal group of lysosomal storage disorders characterized by accumulation of GM2 gangliosides in various tissues and organs. These disorders arise due to deficiency or functional impairment of the β-hexosaminidase A or B enzymes, which are responsible for degradation of GM2 ganglioside. Deficient enzyme activity primarily leads to the accumulation of GM2 gangliosides within the lysosomes of cells. Accurate and rapid diagnostic methods that detect increased levels of GM2 gangliosides in patients with GM2-gangliosidosis can play a significant role in early diagnosis and appropriate treatment of this condition. To address this need, we developed a multiplexed liquid chromatography-tandem mass spectrometry method targeting 84 species of gangliosides and other glycosphingolipids involved in ganglioside metabolism. Reproducibility, linearity, extraction efficiency, and sample stability were evaluated and proof-of-concept data obtained from analysis of serum samples from confirmed cases of GM2-gangliosidosis. This method has the potential to simultaneously monitor the biosynthesis of gangliosides and the lysosomal catabolic pathway serving as a valuable tool for screening and diagnosing an important group of lysosomal storage disorders. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The endolichenic Fusarium solani (EF5), known to show induced metabolite production when exposed to red and green lights, was selected for characterization of their putative light-regulated bioactive compounds. To achieve this, fractionation was first performed for crude extracts from cultures of F. solani (EF5) incubated in green, red, white-fluorescent light and dark conditions. The extract yielded 12 (dark condition) to 15 (exposed to green, red, and white-fluorescent lights) fractions, and each of the fractions was tested for antimicrobial activities. The fraction (fraction 5) that showed the most promising antimicrobial activity was then subjected to high-performance liquid chromatography (HPLC) and liquid chromatography–mass spectrometry (LC-MS) to identify the bioactive compounds. Results revealed detection of two new metabolites from endolichenic F. solani, putatively identified as 8-deoxyjavanicin and fusolanone A, which are known to have antimicrobial properties. This study revealed that red and green lights trigger the production of 8-deoxyjavanicin and fusolanone A, which likely contributed to the antimicrobial properties demonstrated by endolichenic F. solani. [ABSTRACT FROM AUTHOR]

The contents and distribution of different collagen types in bones, skins, and guts of salmon and cod were assessed by chemical and mass spectroscopic methods. The highest levels of collagen were found in the skin (89–98%), followed by the bones (79–89%), and the guts (25–36%). A variety of different collagen α-chain proteins were detected in the assessed tissues, with proteins from 12 to 6 different collagen types quantified in salmon and cod, respectively. The less well-known collagen IV was found in significant levels in all tissues, and the most diverse collagen composition was found in the bones. [ABSTRACT FROM AUTHOR]

Kasugamycin (KSM), an aminoglycoside antibiotic, has been widely used as a natural fungicide to control plant diseases, particularly for managing rice blast. However, its uptake mechanism and transport in rice remain to be explored. In this article, rice seedlings were treated by the foliar spraying method, and the content of KSM in rice leaves, stems and roots under different treatments was detected by high‐performance liquid chromatography tandem mass spectrometry (HPLC‐MS/MS), respectively. Results showed that leaf‐applied KSM could be transported to the phloem and migrate to roots and stems after uptake by leaves. Concentration, temperature and pH had significant effects on the uptake of KSM. Compared with the control, the competitive inhibitors d‐glucose and phlorizin both inhibited the uptake of KSM, demonstrating that sugar transporter proteins were involved in the uptake process. The energy inhibitors dinitrophenol (DNP) and carbonyl cyanide chlorophenylhydrazone (CCCP) also significantly inhibited the uptake of KSM, indicating that the uptake of KSM required energy consumption. Thus, the uptake of KSM by rice was an active process involving sugar transporter proteins, and it could migrate downward through the phloem. This study contributes to the promotion of the scientific application of antibiotics and the biological control of crop diseases. It will also provide a theoretical basis for the development of root‐targeted pesticides and transport pesticides with phloem mobility. [ABSTRACT FROM AUTHOR]

Dating silk mounting textiles is important for understanding their condition and susceptibility to degradation. Amino acid racemization is a technique currently used for this purpose. The research presented here aimed to clarify when this technique is reliable and when it is not. Silk fibers taken from a cocoon and from Japanese mounting textiles were studied using optical microscopy to document surface roughness. Chiral capillary electrophoresis mass spectrometry for amino acid racemization dating (AAR), liquid chromatography mass spectrometry for dye analysis, and FTIR for analysis of sericin and other materials adhering to the silk were also used. A change from rough fiber surfaces (greater than a hundred years old) to smooth fiber surfaces (less than a hundred years) was found. This correlated with the time of the introduction of Western degumming methods in Japan. Synthetic dyes were not found on the earlier silk fibers with rough surfaces. AAR dating measurements on rough surfaced fibers with remaining sericin correlated better with the estimated age of the silk fabrics than fibers with smooth surfaces, suggesting the technique should only be used for silk fibers with rough surfaces. A screening method for fibers for AAR analysis was outlined. [ABSTRACT FROM AUTHOR]

The reuse of the same chromatography resin to purify multiple products is of high economic and ecologic interest in the pharmaceutical industry. An effective cleaning program to ensure no product carryover from one product to the subsequent is key to enable a multi-product use strategy. The methods utilised to assess product carryover during resin lifetime studies for a given product are not specific enough to detect carryover to support multi-product use. Here the proposed use of liquid chromatography coupled to mass spectrometry (LC-MS) is the analytical method of choice due to its high sensitivity and selectivity. A proof-of-concept study using protein A resin and two distinct IgG product streams produced by CHO cell lines was conducted. The experimental design was developed to determine any carryover from previous products after a multiple product Protein A resin reuse process, using LC-MS and capillary electrophoresis (CE). The capability of LC-MS coupled with bioinformatic analysis to detect carryover where CE with UV detection was not able to detect any carryover was demonstrated. The findings from this approach suggest that the acceptance of chromatographic resin reuse for multiple products will be dependent on the development of analytical/bioinformatics tools such as those proposed in this work. [Display omitted] • A multiple product Protein A resin reuse process was designed. • Capillary electrophoresis with UV detection was not able to detect any carryover. • LC-MS coupled with bioinformatic analysis did detect carryover. • These data provide leverage for chromatographic resin reuse for biopharmaceuticals. [ABSTRACT FROM AUTHOR]

Lipopeptides have favorable biological activity and thus have great potential to serve as replacements. Whole genome sequencing was used in this work to pinpoint the gene clusters in Bacillus subtilis that code for secondary metabolites that have antibacterial qualities. Afterwards, the metabolic pathways responsible for the production of these compounds were clarified, and the lipopeptides were separated and identified using a combination of chromatography and spectroscopy methods, such as High-Performance Liquid Chromatography (HPLC), Fourier Transform Infrared Spectroscopy (FTIR), and Liquid Chromatography-Mass Spectrometry (LC-MS). Bacillus subtilis mainly synthesized surfactin homologs with carbon chain lengths ranging from C13 to C16 ([M+H]+: 994.6418; 1008.6586; 1022.6730; 1036.6896) and fengycin homologs with carbon chain lengths of C15 and C16 ([M+H]+: 1449.7937, 1463.8046). The isolated lipopeptides exhibited strong inhibitory effects against Escherichia coli and Staphylococcus aureus , with minimum inhibitory doses of 12.50 mg/L and 6.25 mg/L, respectively. Furthermore, lipopeptides demonstrated a dose-dependent inhibition of E. coli and S. aureus. The findings from SEM and SYTO 9/PI staining demonstrate that lipopeptides function by compromising the integrity of bacterial cell membranes. The results demonstrate the effectiveness of lipopeptides as antibacterial agents against foodborne pathogens, indicating their potential as substitutes for traditional antibiotics. [Display omitted] • Lipopeptides in the secondary metabolites of B. subtilis was predicted by WGS. • Different lipopeptides families were obtained by characterization. • Lipopeptides have antibacterial activity against E. coli and S.aureus. • Lipopeptides has the potential to work as a new type of antibacterial agent. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are effective procedures to treat and manage type 2 diabetes (T2D). However, the underlying metabolic adaptations that mediate improvements in glucose homeostasis remain largely elusive. The purpose of this study was to identify metabolic signatures associated with biochemical resolution of T2D after medical therapy (MT) or bariatric surgery. RESEARCH DESIGN AND METHODS: Plasma samples from 90 patients (age 49.9 ± 7.6 years; 57.7% female) randomly assigned to MT (n = 30), RYGB (n = 30), or SG (n = 30) were retrospectively subjected to untargeted metabolomic analysis using ultra performance liquid chromatography with tandem mass spectrometry at baseline and 24 months of treatment. Phenotypic importance was determined by supervised machine learning. Associations between change in glucose homeostasis and circulating metabolites were assessed using a linear mixed effects model. RESULTS: The circulating metabolome was dramatically remodeled after SG and RYGB, with largely overlapping signatures after MT. Compared with MT, SG and RYGB profoundly enhanced the concentration of metabolites associated with lipid and amino acid signaling, while limiting xenobiotic metabolites, a function of decreased medication use. Random forest analysis revealed 2-hydroxydecanoate as having selective importance to RYGB and as the most distinguishing feature between MT, SG, and RYGB. To this end, change in 2-hydroxydecanoate correlated with reductions in fasting glucose after RYGB but not SG or MT. CONCLUSIONS: We identified a novel metabolomic fingerprint characterizing the longer-term adaptations to MT, RYGB, and SG. Notably, the metabolomic profiles of RYGB and SG procedures were distinct, indicating equivalent weight loss may be achieved by divergent effects on metabolism. [ABSTRACT FROM AUTHOR]

Astragalus membranaceus is a traditional Chinese medicine with multiple pharmacological activities. Modern pharmacological research has found that Astragalus membranaceus extract has an inhibitory effect on α-glucosidase, however, which component can inhibit the activity of α-glucosidase and its degree of inhibition are unknown. To address this issue, this study used affinity ultrafiltration screening combined with UPLC-ESI-Orbitrap-MS technology to screen α-glucosidase inhibitors in Astragalus membranaceus. Using affinity ultrafiltration technology, we obtained the active components, and using UPLC-ESI-Orbitrap-MS technology, we quickly analyzed and identified them. As a result, a total of 8 ingredients were selected as α-glucosidase inhibitors. [ABSTRACT FROM AUTHOR]

A new coumarin (1) and a new flavonoid (2) were isolated from the air-dried flower buds of Ochrocarpus longifolius, together with ten known compounds (3–12). The structures of two new compounds were established by 1D and 2D NMR and MS data. In addition, the new compound 2 showed significant proliferation inhibitory activity on Eca-109 and MGC-803 cells. The results of this study may enrich the diversity of compounds from O. longifolius and provide a basis for further research on its natural products and pharmacological activities. [ABSTRACT FROM AUTHOR]

Pesticide residues were extracted using the QuEChERS method, followed by detection by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The non-carcinogenic health risk in adult and child consumers was calculated by target hazard quotient (THQ) and total target hazard quotient (TTHQ) in the Monte Carlo Simulation (MCS) method. The rank order of pesticides detected by UHPLC-MS/MS based on median concentration in onion was tebuconazole (0.004551 mg/kg) > imidacloprid (0.00233 mg/kg) > boscalid (0.00211 mg/kg) > diazinon (0.00079 mg/kg) > thiabendazole (0.00075 mg/kg) > acetamiprid (0.00052 mg/kg) > thiophanate-methyl (0.00052 mg/kg) > dichlorvos (0.000349 mg/kg) > fenitrothion (0.000132 mg/kg) > penconazole (0.00005 mg/kg). The median of TTHQ in adults and children's consumers were 4.00E–3 and 2.00E–2, respectively. TTHQ in adults and children's consumers was lower than 1 value. Hence, consumers were in the acceptable range (TTHQ <1). Consequently, onion consumption cannot endanger consumers' health status due to the pesticide residues. [ABSTRACT FROM AUTHOR]

Clozapine (CLZ) -related accidents or crimes are common in the world. Oral fluid drug detection is a convenient measure of dealing with things like that. There has not been any literature reported detailedly the representation rule of clozapine and its metabolites in oral fluid so far. The study aimed to describe the pharmacokinetics of CLZ and its metabolites N-desmethylclozapine and clozapine-N-oxide in human oral fluid after a single 12.5 mg oral dose of CLZ. Twenty-nine volunteers, including 20 males and 9 females, were recruited, and 2 mL oral fluid was collected from each participant at post-consumption time-points of prior (zero), 0.5, 1.5, 3, 5, 8, 12, 24, 36, 51, 82, and 130 h, respectively. Analytes of interest were extracted with solid-phase extraction and analyzed with liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters were calculated using the pharmacokinetic software DAS according to the non-compartment model. The maximum concentration, the time of maximum concentration, oral clearance, and the elimination half-life of clozapine were 16.57 ± 9.63 ng/mL, 4.53 ± 3.61 h, 57.65 ± 23.77 L/h and 53.58 ± 52.28 h, respectively. The maximum concentration, the time of maximum concentration, and the elimination half-life of the metabolite N-desmethylclozapine were 3.08 ± 1.19 ng/mL, 9.38 ± 9.33 h and 62.67 ± 82.57 h, respectively; of clozapine-N-oxide were 1.15 ± 0.36 ng/mL, 4.53 ± 2.19 h and 19.15 ± 23.11 h, respectively. It was the first study on the pharmacokinetics of CLZ and its metabolites in the oral fluid of Chinese healthy volunteers, and it provided a basis for the therapeutic drug monitoring and toxicological interpretation in clozapine-related cases. [ABSTRACT FROM AUTHOR]

[Display omitted] • A panel of seven lipids increased c-statistic by an increment of 0.077, the greatest added value for prediction of incident CVD ever achieved by prospective lipidomics studies to the best of our knowledge. • Considerable mediations were observed through SM 41:1b, presumably SM(d18:1/23:0), in the associations between established cardiovascular risk factors and CHD risk, diabetes in particular. • CHD risk associated with increased levels of PC 36:0a, SM 41:1b, LPC 18:0 and LPC 20:3, and decreased levels of CE 18:2 were aggravated by long-term exposure to ambient air pollution. Previous lipidomics studies have identified various lipid predictors for cardiovascular risk, however, with limited predictive increment, sometimes using too many predictor variables at the expense of practical efficiency. To search for lipid predictors of future coronary heart disease (CHD) with stronger predictive power and efficiency to guide primary intervention. We conducted a prospective nested case-control study involving 1,621 incident CHD cases and 1:1 matched controls. Lipid profiling of 161 lipid species for baseline fasting plasma was performed by liquid chromatography-mass spectrometry. In search of CHD predictors, seven lipids were selected by elastic-net regression during over 90% of 1000 cross-validation repetitions, and the derived composite lipid score showed an adjusted odds ratio of 3.75 (95% confidence interval: 3.15, 4.46) per standard deviation increase. Addition of the lipid score into traditional risk model increased c-statistic to 0.736 by an increment of 0.077 (0.063, 0.092). From the seven lipids, we found mediation of CHD risk from baseline diabetes through sphingomyelin (SM) 41:1b with a considerable mediation proportion of 36.97% (P < 0.05). We further found that the positive associations of phosphatidylcholine (PC) 36:0a, SM 41:1b, lysophosphatidylcholine (LPC) 18:0 and LPC 20:3 were more pronounced among participants with higher exposure to fine particulate matter or its certain components, also to ozone for LPC 18:0 and LPC 20:3, while the negative association of cholesteryl ester (CE) 18:2 was attenuated with higher black carbon exposure (P < 0.05). We identified seven lipid species with greatest predictive increment so-far achieved for incident CHD, and also found novel biomarkers for CHD risk stratification among individuals with diabetes or heavy air pollution exposure. [ABSTRACT FROM AUTHOR]

In our previous research, microporous packaging combined with chitosan active coating (MP-CH) treatment extended the shelf life of passion fruit at 25 °C to 12 days by regulating water loss and physiological metabolism. However, proteomic investigation and metabolic changes in passion fruit by MP-CH treatment are unclear. In this study, tandem mass tag (TMT) labeling combined with two-dimensional liquid chromatography tandem mass spectrometry (2D LC‒MS/MS) was used to monitor the metabolic changes in passion fruit treated with the MP-CH group and the control group. A total of 730 differentially expressed proteins (DEPs) were identified. Compared with the control group stored for 12 days, there were 359 DEPs in the MP-CH group, including 179 upregulated proteins and 180 downregulated proteins. The upregulated DEPs were mainly involved in the processes of L-ascorbic acid biosynthesis, anthocyanin-containing compound biosynthesis, aspartate family amino acid biosynthesis, and regulation of protein stability. The downregulated DEPs were mainly involved in oxaloacetate metabolism, carbohydrate metabolism, organic substance metabolism, cellular lipid metabolism, pectin catabolism, and galacturonan metabolism. Results showed that the expression of antioxidant enzymes in the MP-CH group was upregulated, which could enhance the antioxidant capacity and stress resistance of passion fruit. In addition, the expression of cell wall-degrading enzymes was downregulated, which could delay the degradation of cell wall components and maintain the relative stability of its cell wall structure, making for a further extended shelf life of passion fruit. [ABSTRACT FROM AUTHOR]

Due to their widespread use, testing for direct oral anticoagulants (DOACs) has become urgent in certain clinical situations. Screening based on widely available, rapid, and simple hemostasis assays such as prothrombin time, activated partial thromboplastin time, or even diluted Russel Viper venom time may provide sufficient evidence of "over-coagulation" and could be used "in small/peripheral/spoke laboratories" as an emergency strategy, but is not thought to be reliable for driving clinical decision making. Given their good correlation with plasma concentration, urine dipsticks may be considered a valuable alternative for emergency screening, although their performance is dependent on renal function, may vary depending on the time since the last urination, and there may be problems of interfacing with the laboratory/hospital information system. Separation methods based on liquid chromatography and mass spectrometry may be clinically questionable, since they measure the concentration rather than the actual inhibitory effect of DOACs, are relatively expensive, cumbersome and time consuming, and therefore seem unsuitable for most conditions requiring urgent clinical decision making. A proposed approach therefore involves establishing a network of routine clinical laboratories, designating a reference center where DOAC tests could be available 24/7, establishing a clear diagnostic care pathway for ordering the tests from the laboratory and standard operating procedures for performing them, the use of the diluted thrombin time for dabigatran and anti-FXa assays (drug-calibrated) for rivaroxaban, apixaban, and edoxaban, as well as providing expert advice throughout the testing process, from ordering to interpretation of results. [ABSTRACT FROM AUTHOR]

Trastuzumab is a potent targeted therapy drug for HER2-positive cancer patients. A comprehensive understanding of trastuzumab's mechanism of action, pharmacokinetic (PK) parameters, and steady-state exposure in different treatment regimens and administration routes is essential for a thorough evaluation of the drug's safety and effectiveness. Due to the distinctive pharmacokinetics, indications, and administration methods of trastuzumab, this understanding becomes crucial. Drug exposure can be assessed by measuring trastuzumab's peak concentration, trough concentration, or area under the curve through assays like enzyme-linked immunosorbent assay (ELISA) or liquid chromatography-tandem mass spectrometry (LC-MS/MS). The dose-response (D-R) and exposure-response (E-R) relationships establish the correlation between drug dosage/exposure and the therapeutic effect and safety. Additionally, various covariates such as body weight, aspartate transaminase, and albumin levels can influence drug exposure. This review provides a comprehensive overview of trastuzumab's mechanism of action, data on steady-state concentration and PK parameters under multiple administration routes and indications, discussions on factors influencing PK parameters, and evaluations of the effectiveness and safety of E-R and D-R in diverse HER2-positive cancer patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: The nutritional intake of formula‐fed newborns is often limited to a single source, so it must be supplemented with essential nutrients for the growth and proper development of infants. Taurine, l‐carnitine, and choline are considered conditionally essential nutrients especially in newborns and infants. RESULTS: In this work, a simple routine hydrophilic interaction liquid chromatography‐electrospray ionization‐tandem mass spectrometry (HILIC‐ESI‐MS/MS) method was developed and validated for the simultaneous determination of these semi‐essential nutrients in infant and adult/pediatric milk formulas. The extraction recoveries were between 90% and 114%. Precision of the method offered relative standard deviation below 5% and 7% for intra‐day and inter‐day precision, respectively. The proposed method was successfully applied to quantification of taurine, l‐carnitine, and choline in milk formula. The contents found were in good agreement with those provided on the product label for almost all samples. CONCLUSION: In view of these results, it can be concluded that the developed method can be a useful approach for the simultaneous determination of taurine, l‐carnitine and choline in powdered milk samples, so it can be useful in the routine quality control of this kind of samples. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Beehive products, particularly pollen, are among the foodstuffs that may contain pyrrolizidine alkaloids (PAs), prompting concern due to their negative effects on humans, such as hepatotoxic potential. Based on these aspects, this study represents the first investigation into eight PAs present in samples of bee bread (n = 16) and commercial pollens (n = 15) from Brazil utilizing liquid chromatography coupled to mass spectrometry in tandem. Our findings showed the presence of at least two PAs in all samples analyzed (n = 31), with monocrotaline, senecionine, senecionine N-oxide, and retrorsine emerging as the most frequently abundant in the Brazilian samples. The PAs sum varied widely (from 268 to 263,849 µg kg−1), with 77.4% of the samples exceeding the maximum limit established by the European Union (500 µg kg−1). Therefore, this study demonstrates that bee pollen and bee bread are foods with high levels of PAs and highlights that further studies related to PAs and beehive products are necessary so that actions are taken to minimize risks to consumers and safeguard the beekeeping industry. [ABSTRACT FROM AUTHOR]

This study investigates the changes in hippocampal proteomic profiles during demyelination and remyelination using the cuprizone model. Employing two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry for protein profiling, we observed significant alterations in the expression of ketimine reductase mu-crystallin (CRYM) and protein disulfide isomerase A3 precursor (PDIA3) following exposure to and subsequent withdrawal from cuprizone. Immunohistochemical staining validated these protein expression patterns in the hippocampus, revealing that both PDIA3 and CRYM were downregulated in the hippocampal CA1 region during demyelination and upregulated during remyelination. Additionally, we explored the potential protective effects of CRYM and PDIA3 against cuprizone-induced demyelination by synthesizing cell-permeable Tat peptide-fusion proteins (Tat-CRYM and Tat-PDIA3) to facilitate their crossing through the blood–brain barrier. Our results indicated that administering Tat-CRYM and Tat-PDIA3 mitigated the reduction in proliferating cell and differentiated neuroblast counts compared to the group receiving cuprizone alone. Notably, Tat-PDIA3 demonstrated significant effects in enhancing myelin basic protein expression alongside phosphorylation of CREB in the hippocampus, suggesting its potential therapeutic role in the prevention or treatment of demyelination, and by extension, in conditions such as multiple sclerosis. [ABSTRACT FROM AUTHOR]

This document provides information about the synthesis and characterization of various compounds, including indazoles and pyrazolopyridines. The compounds were synthesized using specific reactions and purification techniques, and their structures were confirmed using various spectroscopic techniques. The document includes data such as chemical shifts, yields, melting points, and spectroscopic data for each compound. The authors acknowledge the support of the Central Laboratory of Pharmacy at Ankara University and declare no conflicts of interest. [Extracted from the article]

Field trials were conducted in two consecutive years to evaluate the terminal residue levels, dissipation trend of cupric nonyl phenolsulfonate in citrus and soil. Analyses were carried out using QuEChERS (Quick, Easy, Cheap, Effective, Rugged, Safe) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the concentration of cupric nonyl phenolsulfonate in citrus and soil. The results showed a good linear relationship within the range of 0.01 to 5.0 mg·L−1 (R2 = 0.9999). Average recoveries were 77.70%-105.25% for cupric nonyl phenolsulfonate at the spiked levels of 0.01, 0.1,1, and 5 mg·kg−1, the relative standard deviations (RSDs) were 2.23–7.22%. Half-lives (t1/2) of cupric nonyl phenolsulfonate were 2.76–5.87 and 1.27–3.22 days in citrus and soil, respectively. The results showed that the final contents of cupric nonyl phenolsulfonate in citrus peel were the highest while that of citrus pulp were the lowest. As for soil, the final contents range from < 0.010 to 4.081 mg·kg−1. The dietary risk assessment of citrus was evaluated with risk quotients. The risk quotient values were found to be significantly < 100%, indicating that using recommended doses of cupric nonyl phenolsulfonate in citrus fruits poses risks to human health within acceptable risk levels. The results of this study contribute to the guidance of safe and reasonable use of cupric nonyl phenolsulfonate. [ABSTRACT FROM AUTHOR]

Alpinia monopleura is one of the endemic plants of Sulawesi, and it has an extensive distribution in the region. Research on chemical compounds and biological activities of A. monopleura is essential to continue as an effort to support the utilization of native plants for medicine. The extract was obtained using the maceration method. The chemical compounds in the extract were identified using Liquid Chromatography Mass Spectrometry (LCMS). Bovine Serum Albumin (BSA) and molecular docking methods were used to evaluate the anti-inflammatory activity. Ten compounds contained in the extract were successfully identified, E-para-coumaric acid (1), trans-ferulaldehyde (2), 3,5,6-trihydroxy-4',7-dimethoxyflavone (3), nevadensin (4), malvalic acid (5), ent-16α,17-hydroxy-19-kauranoic acid (6), 3',5-dihydroxy-7,4'-dimethoxy flavone (7), saurufuran B (8), 5-hydroxy-7,8,2'-trimethoxyflavanone (9) and dehydroabietic acid (10). The anti-inflammatory activity of extracts from rhizomes and stems of A. monopleura were 8.62 and 10.59 mg/L, respectively. Some flavonoids (9 and 7) can bind strongly to specific residues around the COX-2 active site, such as Ser530, thereby interfering with the function of the COX-2 enzyme and reducing the production of pro-inflammatory prostaglandins. Thus, A. monopleura extract has the potential to inhibit inflammatory responses through molecular regulation of the COX-2 enzyme. [ABSTRACT FROM AUTHOR]

• Predictive models using immune-based biomarkers perform well in discerning bipolar and schizophrenic patients from controls. • IL-6, TNF-ɑ, IFN-γ QUINO and PICO are identified as key markers for schizophrenia and bipolar disorder classification. • Challenges in differentiating schizophrenia from bipolar disorder highlight shared immunological mechanisms. • Larger multi-centric studies and multi-domain models are needed for enhanced generalizability and clinical translation. Schizophrenia and bipolar disorder frequently face significant delay in diagnosis, leading to being missed or misdiagnosed in early stages. Both disorders have also been associated with trait and state immune abnormalities. Recent machine learning-based studies have shown encouraging results using diagnostic biomarkers in predictive models, but few have focused on immune-based markers. Our main objective was to develop supervised machine learning models to predict diagnosis and illness state in schizophrenia and bipolar disorder using only a panel of peripheral kynurenine metabolites and cytokines. The cross-sectional I-GIVE cohort included hospitalized acute bipolar patients (n = 205), stable bipolar outpatients (n = 116), hospitalized acute schizophrenia patients (n = 111), stable schizophrenia outpatients (n = 75) and healthy controls (n = 185). Serum kynurenine metabolites, namely tryptophan (TRP), kynurenine (KYN), kynurenic acid (KA), quinaldic acid (QUINA), xanthurenic acid (XA), quinolinic acid (QUINO) and picolinic acid (PICO) were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS), while V-plex Human Cytokine Assays were used to measure cytokines (interleukin-6 (IL-6), IL-8, IL-17, IL-12/IL23-P40, tumor necrosis factor-alpha (TNF-ɑ), interferon-gamma (IFN-γ)). Supervised machine learning models were performed using JMP Pro 17.0.0. We compared a primary analysis using nested cross-validation to a split set as sensitivity analysis. Post-hoc, we re-ran the models using only the significant features to obtain the key markers. The models yielded a good Area Under the Curve (AUC) (0.804, Positive Prediction Value (PPV) = 86.95; Negative Prediction Value (NPV) = 54.61) for distinguishing all patients from controls. This implies that a positive test is highly accurate in identifying the patients, but a negative test is inconclusive. Both schizophrenia patients and bipolar patients could each be separated from controls with a good accuracy (SCZ AUC 0.824; BD AUC 0.802). Overall, increased levels of IL-6, TNF-ɑ and PICO and decreased levels of IFN-γ and QUINO were predictive for an individual being classified as a patient. Classification of acute versus stable patients reached a fair AUC of 0.713. The differentiation between schizophrenia and bipolar disorder yielded a poor AUC of 0.627. This study highlights the potential of using immune-based measures to build predictive classification models in schizophrenia and bipolar disorder, with IL-6, TNF-ɑ, IFN-γ, QUINO and PICO as key candidates. While machine learning models successfully distinguished schizophrenia and bipolar disorder from controls, the challenges in differentiating schizophrenic from bipolar patients likely reflect shared immunological pathways by the both disorders and confounding by a larger state-specific effect. Larger multi-centric studies and multi-domain models are needed to enhance reliability and translation into clinic. [ABSTRACT FROM AUTHOR]

This phase 1/2 study aimed to evaluate the safety and preliminary efficacy of combining disulfiram and copper (DSF/Cu) with radiation therapy (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM). Patients received standard RT and TMZ with DSF (250-375 mg/d) and Cu, followed by adjuvant TMZ plus DSF (500 mg/d) and Cu. Pharmacokinetic analyses determined drug concentrations in plasma and tumors using high-performance liquid chromatography-mass spectrometry. Thirty-three patients, with a median follow-up of 26.0 months, were treated, including 12 IDH -mutant, 9 NF1 -mutant, 3 BRAF -mutant, and 9 other IDH -wild-type cases. In the phase 1 arm, 18 patients were treated; dose-limiting toxicity probabilities were 10% (95% CI, 3%-29%) at 250 mg/d and 21% (95% CI, 7%-42%) at 375 mg/d. The phase 2 arm treated 15 additional patients at 250 mg/d. No significant difference in overall survival or progression-free survival was noted between IDH - and NF1 -mutant cohorts compared with institutional counterparts treated without DSF/Cu. However, extended remission occurred in 3 BRAF -mutant patients. Diethyl-dithiocarbamate-copper, the proposed active metabolite of DSF/Cu, was detected in plasma but not in tumors. The maximum tolerated dose of DSF with RT and TMZ is 375 mg/d. DSF/Cu showed limited clinical efficacy for most patients. However, promising efficacy was observed in BRAF -mutant GBM, warranting further investigation. [ABSTRACT FROM AUTHOR]

Our aim was to evaluate whether alcohol use is associated with changes in the circulating metabolite profile similar to those present in persons with depression. If so, these findings could partially explain the link between alcohol use and depression. We applied a targeted liquid chromatography mass spectrometry method to evaluate correlates between concentrations of 86 circulating metabolites and self-reported alcohol use in a cohort of the non-depressed general population (GP) (n = 247) and a cohort of individuals with major depressive disorder (MDD) (n = 99). Alcohol use was associated with alterations in circulating concentrations of metabolites in both cohorts. Our main finding was that self-reported alcohol use was negatively correlated with serum concentrations of hippuric acid in the GP cohort. In the GP cohort, consumption of six or more doses per week was associated with low hippuric acid concentrations, similar to those observed in the MDD cohort, but in these individuals it was regardless of their level of alcohol use. Reduced serum concentrations of hippuric acid suggest that already-moderate alcohol use is associated with depression-like changes in the serum levels of metabolites associated with gut microbiota and liver function; this may be one possible molecular level link between alcohol use and depression. • We studied both the general population and individuals with major depressive disorder. • Targeted LC-MS-based metabolomics was used to measure metabolite profile. • Correlations between alcohol use and serum metabolite levels were calculated. • In GP, moderate alcohol use was associated with decreased levels of hippuric acid. • Decreased hippuric acid levels were seen in MDD regardless of alcohol use. [ABSTRACT FROM AUTHOR]

Trichothecenes (deoxynivalenol, 3- and 15-acetyl-deoxynivalenol) and zearalenone are toxic secondary metabolites produced by Fusarium species. Although managing these mycotoxins simultaneously is crucial, current analytical methods differ because of their distinct properties. In this study, food matrix extraction conditions were established and applied to cereal-based foods (n = 90). The optimal conditions were developed by utilizing fragment ions and precursors, following the guidelines established by the Association of Official Agricultural Chemists (AOAC). The developed method demonstrated high accuracy and reliability within 20 min, even for samples with low concentrations. Consequently, the recovery range of the fat-oil-processed products and cereal sirup improved from 27.0% to 98.3% and 27.6% to 97.8%, respectively. This improved extraction method offers a more convenient and rapid approach for the analysis of various matrices. Furthermore, these optimized methods can be extended to monitor the co-occurrence of mycotoxins in cereal-based foods, providing valuable assistance to the food industry and regulatory agencies for detecting and monitoring mycotoxins that may pose potential health risks. [ABSTRACT FROM AUTHOR]

Farfarae Flos (FF), also known as "Kuandonghua" in Chinese, is a commonly used traditional Chinese medicine (TCM) with various therapeutic properties, including antitussive, expectorant, antioxidant, and anti-inflammatory effects. Despite the widespread consumption of processed FF, there has been limited progress in improving quality control measures for both raw FF and honey-processed Farfarae Flos (PFF). This study aimed to establish a comprehensive strategy for quality evaluation and distinguish between FF and PFF by integrating high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis with chemometric techniques. Additionally, the antioxidant activities of FF and PFF were assessed using radical-scavenging experiments. The spectrum-effect relationship is the association of chemical composition information of the fingerprint with antioxidant activity, which was used to predict the primary active components that influence the antioxidant activity of FF. The results indicated that FF and PFF samples showed a clear distinction, and the most potent pharmacologically active ingredients were hyperoside, quercetin, caffeic acid, isoquercitrin, neochlorogenic acid, rutin, cryptochlorogenic acid, and isochlorogenic acid C. Moreover, the comprehensive efficacy of the honey-processed FF was better than for raw FF. In conclusion, the findings of this study provide a scientific foundation for future evaluation of the quality, further research, and practical use of FF herbs. [ABSTRACT FROM AUTHOR]

A novel strontium-iron-based perovskite-type material (SrFeO3) has been successfully synthesized and characterized as a promising photocatalyst for degrading diclofenac sodium (DCF). The catalyst was synthesized using the sol–gel method, resulting in a material with distinctive features, including a dense structure and a uniform distribution of metal components on the catalytic surface. The degradation efficiency of SrFeO3 was compared to that of titanium dioxide (TiO2), a well-established photocatalyst known for its effectiveness in degrading emerging contaminants. Under identical experimental conditions, SrFeO3 achieved a degradation efficiency of 68% over 150 min, while TiO2 reached 70%. Additionally, phytotoxicity tests performed on the post-treatment solution demonstrated a reduction in toxicity compared to the initial solution for both catalysts, indicating that SrFeO3 has promising characteristics for the aqueous treatment of DCF. These results suggest that SrFeO3 exhibits performance comparable to TiO2 and could be a viable alternative for future water treatment applications. Furthermore, liquid chromatography-mass spectrometry (LC–MS) analysis was employed to identify intermediate products and propose a plausible degradation pathway for DCF, highlighting SrFeO3's potential in facilitating DCF removal from aqueous environments. [ABSTRACT FROM AUTHOR]

Per‐ and polyfluoroalkyl substances (PFAS) accumulate at the air–water interface of the surface microlayer (SML) on marine and freshwater bodies. In order to determine if including the SML when sampling bulk surface water leads to a high bias in measured PFAS concentrations, a pilot study and a full field study were conducted. The pilot study conducted at two sites was aimed at determining the analytical precision and small‐scale (~1 m) spatial variability in concentrations of PFAS in bulk water and the SML. The full field study was performed at 11 sites, where three commonly used bulk surface water sampling methods were compared: (1) a peristaltic pump with tubing that excludes the SML, (2) a fully submerged sample bottle that excludes the SML, and (3) a partially submerged sample bottle that allows inclusion of the SML. The SML was sampled using the glass plate method. The samples were analyzed by liquid chromatography tandem mass spectrometry. The pilot study indicated that sampling variation was greater than analytical variation (although Levene's tests indicated that the differences were not statistically significant) and that relatively small differences in the mean concentration among sampling methods could be detected. The full investigation indicated that there was no evidence of high bias of PFAS concentrations in bulk surface water resulting from inclusion of SML using the partially submerged bottle sampling method. Unexpectedly, there was evidence that samples collected using the partially submerged bottle had slightly lower PFAS concentrations, particularly for less hydrophobic PFAS, than bulk water samples that excluded the SML. Additionally, the PFAS enrichment factor in the SML increased with increasing retention time, although the increase was not evident at all sampling sites for all PFAS. Integr Environ Assess Manag 2024;20:2271–2282. © 2024 SETAC Key Points: PFAS enrichment in the surface microlayer of small, freshwater lakes and ponds did not result in high bias of bulk water PFAS concentrations collected using a partially submerged sample bottle.For some PFAS, water samples collected with a partially submerged bottle that entrains the enriched surface microlayer had slightly lower PFAS concentrations compared with samples collected from approximately 10–15 cm using a peristaltic pump or a fully submerged bottle. [ABSTRACT FROM AUTHOR]

Context Women with hypopituitarism remain at increased risk of morbidity and mortality. Insufficient replacement of sex steroids has been suggested as a contributing factor, but sex steroid levels in women with hypopituitarism have not been comprehensively mapped. Objective To quantify sex steroids in women with hypopituitarism by a high-sensitivity assay. Methods Using a combination of clinical and biochemical criteria, women with hypopituitarism (n = 104) who started GH replacement in 1995 to 2014 at a single center were categorized as eugonadal or having hypogonadotropic hypogonadism (HH). A population-based cohort of women (n = 288) served as controls. Eugonadal women and controls were categorized as pre-/postmenopausal and HH women as younger/older (≤ or >52 years). Dehydroepiandrosterone (DHEA), androstenedione, testosterone, dihydrotestosterone, progesterone, 17αOH-progesterone, estradiol, and estrone were analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Results Among both premenopausal/younger and postmenopausal/older women, women with HH had lower levels of sex steroid precursors (DHEA, androstenedione) and androgens (testosterone and dihydrotestosterone) than controls. Progesterone, 17αOH-progesterone, estrone, and estradiol showed similar patterns. Women with HH and ACTH deficiency had markedly lower concentrations of all sex hormones than those without ACTH deficiency. Conclusion This study demonstrates for the first time a broad and severe sex steroid deficiency in both younger and older women with HH, particularly in those with combined gonadotropin and ACTH deficiency. The health impact of low sex steroid levels in women with hypopituitarism requires further study, and women with combined gonadotropin and ACTH deficiency should be a prioritized group for intervention studies with sex hormone replacement. [ABSTRACT FROM AUTHOR]

Ayahuasca is a brew traditionally prepared with a mixture of Psychotria viridis leaves and Banisteriopsis caapi vine and has demonstrated therapeutic properties for depression. Knowledge of the brew composition is important to improve the therapeutic potential and decrease side effects if ayahuasca becomes an option for refractory depression treatment. Ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) was applied to analyze 126 ayahuasca samples collected from different ayahuasqueiro groups and geographic origins. We were able to observe a differentiation in the metabolite composition of ayahuasca samples prepared by diverse ayahuasqueiro groups. These samples presented different antioxidant effects based on FRAP and ORAC assays. Exploratory statistical analysis demonstrated a trend of separating the samples according to the religious group. The most important identified compounds for differentiation of the brew prepared by distinct religious groups are glycosylated and/or phenolic compounds. The comparison based on the mode of ayahuasca preparation presented more variability than the comparison based on the botanical variety of B. caapi used. We conclude that ayahuasca samples prepared with “caupuri” or “tucunacá” separately exhibited differences in the analysis of L-glutamate and the metabolism of arginine and proline. This suggests that a possible variation in this pathway could explain the occurrence of swollen stem nodes in “caupuri,” one of the B. caapi varieties. [ABSTRACT FROM AUTHOR]

Background: Skin commensal bacteria (Staphylococcus epidermidis) can help defend against skin infections, and they are increasingly being recognized for their role in benefiting skin health. This study aims to demonstrate the activities that Myristica fragrans Houtt. seed extracts, crude extract (CE) and essential oil (EO), have in terms of promoting the growth of the skin commensal bacterium S. epidermidis and providing metabolites under culture conditions to disrupt the biofilm formation of the common pathogen Staphylococcus aureus. Methods: The culture supernatant obtained from a co-culture of S. epidermidis with M. fragrans Houtt. seed extracts in either CE or EO forms were analyzed using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS), in silico investigations, and applied to assess the survival and biofilm formation of S. aureus. Results: The combination of commensal bacteria with M. fragrans Houtt. seed extract either CE or EO produced metabolic compounds such as short-chain fatty acids and antimicrobial peptides, contributing to the antimicrobial activity. This antimicrobial activity was related to downregulating key genes involved in bacterial adherence and biofilm development in S. aureus, including cna, agr, and fnbA. Conclusion: These findings suggest that using the culture supernatant of the commensal bacteria in combination with CE or EO may provide a potential approach to combat biofilm formation and control the bacterial proliferation of S. aureus. This may be a putative non-invasive therapeutic strategy for maintaining a healthy skin microbiota and preventing skin infections. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been extensively documented as posing significant health risks to human populations. However, there is a lack of research of their impact on endangered species, which significantly affects the effectiveness of conservation efforts and maintenance of these populations. In this study, we examined the levels of PFAS pollution in adults and juveniles of the vulnerable Saunders's gull (Larus saundersi), along with their various food sources using ultra high-performance liquid chromatography-tandem mass spectrometry and Ecopath model. Long-chain PFAS, predominantly composed of perfluorooctanoic acid (accounting for 51.4% of the total), were identified as the main pollutants in the gull, its food, and the environment. Saunders's gulls showed significant bioaccumulation and magnification of PFAS, with contamination levels significantly above those recorded in other species. Mean PFAS levels between juveniles (904.26 ng/g wet weight) and adults (407.40 ng/g wet weight) revealed a significant disparity, indicating that PFAS pollution may severely threaten these birds. Among the food sources analyzed, bivalves and polychaetes emerged as the primary contributors to PFAS contamination in Saunders's gulls, with high transfer efficiency. The fundamental cause of PFAS pollution in benthic organisms and the gulls appears to be baseline environmental pollution, which was highly consistent across all examined pollutant types. Moreover, chemical plants close to breeding areas may cause severe environmental pollution, threatening organisms at various trophic levels through the food web. We suggest enhancing the pollution monitoring of important biological habitats for timely prediction and early warning of chemical risks. Additionally, ecological restoration of key habitats should be strengthened to ensure the effectiveness of biodiversity conservation. [ABSTRACT FROM AUTHOR]

The fungal pathogen Magnaporthe oryzae causes devastating blast disease in various cereals, including rice (Oryza sativa), wheat (Triticum aestivum), maize (Zea mays), and barley (Hordeum vulgare). Despite previous reports on fungal host specificity, the mechanisms underlying differential host infection strategies remain unclear. This study aimed to identify differentially abundant proteins (DAPs) in the apoplast of rice, barley, and wheat following infection with two M. oryzae pathovars using liquid chromatography-tandem mass spectrometry (LC–MS/MS). LC–MS/MS analysis revealed an enrichment of both M. oryzae and host proteins in the apoplast during the compatible reaction compared to the incompatible reaction. DAPs from M. oryzae involved in the host interaction included secreted extracellular enzymes (e.g., hydrolases), which were significantly increased in the M. oryzae Oryzae (MoO)-infected rice apoplast. Among host proteins, the proportion of protein-modifying enzymes increased in the M. oryzae Triticum (MoT)-infected rice and MoO-infected wheat apoplastic fluids, particularly rice glycosidases, peroxidases, and serine proteases, as well as wheat serine proteases. Furthermore, DAPs from MoL-infected rice were enriched in carbohydrate metabolism, suggesting that carbohydrate metabolism-related proteins may play a vital role in rice resistance to MoL. Additionally, protein-modifying and cytoskeletal proteins, as well as stress-responsive proteins, were enriched in the MoO-infected wheat apoplastic fluid. Finally, DAPs from both MoO- and MoL-infected barley were enriched in hydrogen peroxide catabolism, suggesting that peroxidases may be vital for barley resistance to M. oryzae. The identification of DAPs from both M. oryzae strains and the three host plants offers valuable insights into the host specificity mechanisms of M. oryzae in cereal crops. [ABSTRACT FROM AUTHOR]

In the elderly population, coronary heart disease (CHD) often coexists with hypertension. However, excessive blood pressure reduction can paradoxically increase the incidence of adverse events. Understanding the molecular mechanisms underlying hypertension and CHD in aged populations is crucial for developing targeted therapies and improving clinical outcomes. In this study, we constructed myocardial infarction (MI) and transverse aortic constriction (TAC) modelsY in aged mice to simulate the disease states of CHD and hypertension, respectively. Using integrated proteomic and phosphoproteomic analyses, we investigated the molecular signatures associated with MI and TAC in these models. Our aim was to identify key molecules involved in these conditions and to understand their unique and shared characteristics. Through our comprehensive proteomic and phosphoproteomic analysis, we identified a total of 1583 proteins and 232 phosphorylated proteins. We observed significant upregulation of heart disease markers such as Myh7, Xirp2, and Acta1, indicating the successful establishment of the MI and TAC models. The overlapped differentially expressed proteins (DEPs) and differentially phosphorylated proteins (DPPs) in MI and TAC were involved in heart failure‐related processes including cardiac muscle contraction and hypertrophic cardiomyopathy, further supporting the validity of the models. Among the DEPs, Ppme1 was upregulated in the TAC model but downregulated in the MI model, while Sec31a and Gm56451 displayed the opposite expression patterns. Among the DPPs, Ablim1 and Atp2a2 were found to be significantly upregulated in the TAC model, whereas their expression was markedly reduced in the MI model. In addition, five other DPPs, including REV_Q3TAY5, Cbx3, PITPNB, Eif4b, and A0A1Y7VP73, were elevated in the MI model but decreased in the TAC model. In conclusion, these findings suggest that MI and TAC not only share certain molecular features but also retain their unique characteristics, providing potential biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusions Exposure to environmental contaminants is globally universal. However, communities vary in the specific combination of contaminants to which they are exposed, potentially contributing to variation in human health and creating “locally situated biologies.” We investigated how environmental exposures differ across environments by comparing exposure profiles between two contexts that differ markedly across political, economic, and sociocultural factors—Namqom, Formosa, Argentina, and New Haven, Connecticut, United States.We collected infant urine, maternal urine, and human milk samples from mother–infant dyads in Formosa (n = 13) and New Haven (n = 21). We used untargeted liquid chromatography with high‐resolution mass spectrometry (LC‐HRMS) to annotate environmental contaminants and endogenous metabolites in these samples, and we analyzed the data using exposome‐wide association studies (EWAS) followed by pathway enrichment.We found statistically significant differences between the chemical exposure profiles of the Argentinian and US mothers, mostly involving pesticides; however, we observed similarities in the infant urine and human milk environmental contaminant profiles, suggesting that the maternal body may buffer infant exposure through human milk. We also found that infants and mothers were exposed to contaminants that were associated with alterations in amino acid and carbohydrate metabolism. Infants additionally showed alterations in vitamin metabolism, including vitamins B1, B3, and B6.Differences in chemical exposure profiles may be related to structural factors. Despite variation in the composition of exposure profiles between the two study sites, environmental contaminant exposure was associated with similar patterns in human physiology when we considered contaminants comprehensively rather than individually, with implications for metabolic and cardiovascular disease risk as well as infant cognitive development. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionDrug use in Danish prisons has previously not been investigated in detail using confirmatory, laboratory analysis. The objective of the present quality study, initiated by the Danish Prison and Probation Service, was to i) evaluate the performance of an initial, on-site drug screening strategy; ii) gain insights into emerging drug trends; and iii) suggest evidence-based strategies for future drug testing.Over a two-year period, routine urine samples (n = 1952 from 710 inmates) from three Danish prisons were subjected to comprehensive drug testing. Immunoassay screening was conducted on-site. A parallel sample aliquot was forwarded to laboratory analysis by confirmatory methods: High-performance liquid chromatography and tandem mass spectrometry (LC-MS/MS) and gas chromatography and mass spectrometry (GC-MS) targeting 56 drugs-of-abuse/medical drugs, 26 key metabolites, 41 new psychoactive substances (NPS), including specific biomarkers for heroin, crack cocaine, or ethanol (a total of 123 target analytes/sample).The on-site immunoassay method showed a sensitivity from 66 to 100%; specificity was above 98%; accuracy was above 95%. Laboratory analysis detected compounds not screened for including tramadol, oxycodone, buprenorphine, ketamine, MDMA, 4-fluoroamphetamine, and GHB. The prevalence of drug use was in the order: cannabis > ethanol > cocaine > benzodiazepines > amphetamine.The performance of the immunoassay was found acceptable; however, the screening program was inadequate for detecting other significant substances. Based on these findings, a broader screening method will be implemented in future at Danish Prisons to minimize false negative results. The data did not indicate a trend of using NPS in Danish prisons. [ABSTRACT FROM AUTHOR]

Neovascular age-related macular degeneration (nAMD) is characterized by abnormal blood vessel growth from the choroid, leading to complications and eventual blindness. Despite anti-VEGF therapy, subretinal fibrosis remains a major concern, as VEGF/VEGF receptor-2 (VEGFR2) signaling can contribute to both angiogenesis and fibrosis. For the identification of the aqueous humor proteome, we performed liquid chromatography with tandem mass spectrometry analysis. To investigate the potential therapeutic effects of targeting the VEGF signaling pathway using apatinib, a highly selective VEGFR2 tyrosine kinase inhibitor, this study employed in vitro (THP-1 conditioned media-treated ARPE-19 cells) and in vivo (laser-induced choroidal neovascularization mouse) models of nAMD. This study revealed elevated VEGFR2 protein levels in the aqueous humor of nAMD patients, suggesting a potential target to mitigate neovascularization and fibrosis in nAMD. Apatinib effectively reduced VEGFA and αSMA levels in both in vitro and in vivo models. Moreover, apatinib showed improvement in laser-induced subretinal hyper-reflective lesions. The action mechanism was linked to the inhibition of VEGFR2 activation, leading to the suppression of both angiogenesis and fibrosis through the downregulation of STAT3 phosphorylation. Therefore, the VEGFR2 signaling pathway appears to play a central role in the development of nAMD by regulating both angiogenesis and fibrosis. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a life-threatening disease with a poor prognosis, and metabolic abnormalities play a critical role in its development. This study used metabolomics, machine learning algorithms and bioinformatics to screen for potential metabolic biomarkers associated with the diagnosis of PAH. In this study, plasma samples were collected from 17 patients diagnosed with idiopathic pulmonary arterial hypertension (IPAH) and 20 healthy controls. Plasma metabolomic profiling was performed by high-performance liquid chromatography-mass spectrometry. Gene profiles of PAH patients were obtained from the GEO database. Key differentially expressed metabolites (DEMs) and metabolism-related genes were subsequently identified using machine learning algorithms. Twenty differential plasma metabolites associated with IPAH were identified (VIP score > 1 and p < 0 0.05), and enrichment analysis revealed the arginine biosynthesis pathway as the most altered pathway. Using machine learning models, including least absolute shrinkage and selection operator (LASSO), random forest (RF) and support vector machine (SVM), we extracted key metabolites that correlated with clinical phenotypes. Our results suggested that five metabolites, kynurenine, homoserine, tryptophan, AMP, and spermine, are potential biomarkers for IPAH. Bioinformatics analysis also identified 3 metabolism-related genes, MAPK6, SLC7A11 and CDC42BPA, that are strongly correlated with pulmonary hypertension, demonstrating strong predictive power and clinical relevance. Our findings revealed some key genes associated with metabolism in PH, and provided crucial information about complex metabolic reprogramming signals and may lead to the identification of useful metabolic biomarkers for the diagnosis of PAH. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma is a highly heterogeneous tumor with bile acid metabolism involving in its development. The aim of this study was to characterize bile acid metabolism and identify specific subtypes to better stratify cholangiocarcinoma patients for individualized treatment and prognostic assessment. Methods: A total of 30 bile acids were quantified using the ultra-performance liquid chromatography tandem mass spectrometry. Using Consensus clustering, the molecular subtypes related to bile acid metabolism were identified. The prognosis, clinicopathologic characteristics, immune landscape, and therapeutic response were compared between these subtypes. The single-cell RNA sequencing (scRNA-seq) analysis and preliminary cell experiment were also conducted to verify our findings. Results: The altered bile acid profile and genetic variation of bile acid metabolism-related genes in cholangiocarcinoma were demonstrated. The cholangiocarcinoma was categorized into bile acid metabolism-active and -inactive subtypes with different prognoses, clinicopathologic characteristics, tumor microenvironments (TME) and therapeutic responses. This categorization was reproducible and predictable. Specifically, the bile acid metabolism-active subtype showed a poor prognosis with an immunosuppressive microenvironment and an inactive response to immunotherapy, while the bile acid metabolism-inactive subtype showed the opposite characteristics. Moreover, the scRNA-seq revealed that immunotherapy altered bile acid metabolism in TME of cholangiocarcinoma. Finally, a prognostic signature related to bile acid metabolism was developed, which exhibited strong power for prognostic assessment of cholangiocarcinoma. Consistently, these results were verified by immunohistochemistry, cell proliferation, migration, and apoptosis assays. Conclusion: In conclusion, a novel cholangiocarcinoma classification based on bile acid metabolism was established. This classification was significant for the estimation of TME and prognosis. [ABSTRACT FROM AUTHOR]

Purpose: Newborn screening using dried blood spot (DBS) samples for the targeted measurement of metabolites and nucleic acids has made a substantial contribution to public healthcare by facilitating the detection of neonates with genetic disorders. Here, we investigated the applicability of non-targeted quantitative proteomics analysis to newborn screening for inborn errors of immunity (IEIs). Methods: DBS samples from 40 healthy newborns and eight healthy adults were subjected to non-targeted proteomics analysis using liquid chromatography-mass spectrometry after removal of the hydrophilic fraction. Subsequently, DBS samples from 43 IEI patients were analyzed to determine whether patients can be identified by reduced expression of disease-associated proteins. Results: DBS protein profiling allowed monitoring of levels of proteins encoded by 2912 genes, including 1110 listed in the Online Mendelian Inheritance in Man database, in healthy newborn samples, and was useful in identifying patients with IEIs by detecting reduced levels of disease causative proteins and their interacting proteins, as well as cell-phenotypical alterations. Conclusion: Our results indicate that non-targeted quantitative protein profiling of DBS samples can be used to identify patients with IEIs and develop a novel newborn screening platform for genetic disorders. [ABSTRACT FROM AUTHOR]

The R programming language, RStudio, and open-source software solutions for analysis of liquid chromatography-mass spectrometry (LC–MS) data have been used with user-written R-based custom quantification programs (CQP) for semi-quantification of triacylglycerols (TAGs) in bovine milk lipid extracts. Using the peak-finding capabilities of the package "xcms" in RStudio, peaks were integrated, and retention times aligned, normalized, and then used for semi-quantitative analysis of a custom set of four extraction internal standards (EISs) and 29 TAG regioisomers using the choice of four analytical internal standards (AISs). Alternating stereospecific numbering (sn) 1,3 TAG regioisomers (standards 1, 3, and 5 of six calibration standards) and sn-1,2 TAG regioisomers (standards 2, 4, and 6 of six standards) were used to make a set of six calibration standards, which were used for quantification using a linear fit model, polynomial fit model, power fit model, level-bracketed linear fit, replicate-bracketed polynomial fit, replicate-bracketed power fit, and replicate- and level-bracketed linear fit and response factors. For example, the linear fit for EIS1 gave an unacceptable coefficient of determination (CoD), r2 = 0.9616, whereas the polynomial fit gave r2 = 0.9908 and the power fit gave r2 = 0.9928, while the double-bracketed linear fit gave CoDs of r2 = 0.9960, 0.9848, and 0.9781 for the three brackets, yet gave the least % difference to known calibration concentrations. For unparalleled transparency, the CQP produced webpages that allowed every step in the data processing and quantification sequence to be verified and reproduced, and contained interactive figures. The data are publicly available using a digital object identifier (DOI). The R code can be downloaded and used with the downloadable data to reproduce the results, to modify the code and further customize the results, or to copy and paste and adapt the code to other quantification applications. [ABSTRACT FROM AUTHOR]

Glycosphingolipids (GSL) are a highly heterogeneous class of lipids representing the majority of the sphingolipid category. GSL are fundamental constituents of cellular membranes that have key roles in various biological processes, such as cellular signaling, recognition, and adhesion. Understanding the structural complexity of GSL is pivotal for unraveling their functional significance in a biological context, specifically their crucial role in the pathophysiology of various diseases. Mass spectrometry (MS) has emerged as a versatile and indispensable tool for the structural elucidation of GSL enabling a deeper understanding of their complex molecular structures and their key roles in cellular dynamics and patholophysiology. Here, we provide a thorough overview of MS techniques tailored for the analysis of GSL, emphasizing their utility in probing GSL intricate structures to advance our understanding of the functional relevance of GSL in health and disease. The application of tandem MS using diverse fragmentation techniques, including novel ion activation methodologies, in studying glycan sequences, linkage positions, and fatty acid composition is extensively discussed. Finally, we address current challenges, such as the detection of low-abundance species and the interpretation of complex spectra, and offer insights into potential solutions and future directions by improving MS instrumentation for enhanced sensitivity and resolution, developing novel ionization techniques, or integrating MS with other analytical approaches for comprehensive GSL characterization. [ABSTRACT FROM AUTHOR]

In recent years, instrumental improvements have enabled the spread of mass spectrometry–based lipidomics platforms in biomedical research. In mass spectrometry, the reliability of generated data varies for each compound, contingent on, among other factors, the availability of labeled internal standards. It is challenging to evaluate the data for lipids without specific labeled internal standards, especially when dozens to hundreds of lipids are measured simultaneously. Thus, evaluation of the performance of these platforms at the individual lipid level in interlaboratory studies is generally not feasible in a time-effective manner. Herein, using a focused subset of sphingolipids, we present an in-house validation methodology for individual lipid reliability assessment, tailored to the statistical analysis to be applied. Moreover, this approach enables the evaluation of various methodological aspects, including discerning coelutions sharing identical selected reaction monitoring transitions, pinpointing optimal labeled internal standards and their concentrations, and evaluating different extraction techniques. While the full validation according to analytical guidelines for all lipids included in a lipidomics method is currently not possible, this process shows areas to focus on for subsequent method development iterations as well as the robustness of data generated across diverse methodologies. [ABSTRACT FROM AUTHOR]

Paris polyphylla is an important traditional medicinal plant of the Himalayan region. It is extensively used for the production of natural steroidal saponins and flavonoids. Although seed dormancy of wild plants can be broken to be artificially maintained and regenerated through micropropagation in the laboratory, the success of secondary metabolite production in higher quantities and the synthesis of superior plant metabolites have been very limited. In this study, we present differential metabolic profiling of P. polyphylla plants maintained for 8 years in natural and greenhouse conditions. Untargeted profiling of the metabolites through ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS), followed by statistical analysis, identified secondary metabolites that were enriched in the naturally occurring plant roots compared with the greenhouse plant roots. A multivariate statistical analysis revealed the differential distribution of the compounds between the two groups. Overall, we identified 1,182 secondary metabolites, with 116 metabolites being differentially upregulated and 256 metabolites being downregulated. Moreover, 810 metabolites showed no significant variation under both growing conditions. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the naturally forest-grown P. polyphylla plants were significantly enriched in steroidal saponins, lipids, vitamins, flavonoids, and flavonols. An analysis of the top 10 differentially upregulated secondary metabolites indicated a significantly enriched quantity of spirost-5-en-3,12-diol and kaempferol synthesis pathways, which are known to reduce the effect of free radicals scavengers inside the cell. In addition, veratramine alkaloids were also enriched under natural conditions. Our findings indicated that naturally maintained P. polyphylla plants are suitable for the extraction of medicinally important compounds. Our study established a causal relationship between the metabolic composition of the roots and their natural growth condition. This study highlighted the importance of environmental conditions in the biosynthesis of secondary metabolites of plants. [ABSTRACT FROM AUTHOR]

Insomnia and depression are psychiatric disorders linked to substantial health burdens. The gut microbiome and metabolomic pathways are increasingly recognized as key contributors to these conditions' pathophysiology. Suanzaoren Decoction (SZRD), a traditional Chinese herbal formulation, has demonstrated significant therapeutic benefits for both insomnia and depression. This study aims to elucidate the mechanistic effects of SZRD on insomnia and depression by integrating gut microbiome and metabolomic analyses and to assess the differential impacts of SZRD dosages. Using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS), we identified 66 chemical constituents within SZRD. Behavioral assays indicated that low-dose SZRD (LSZRD) significantly ameliorated insomnia symptoms in rat models, whereas high-dose SZRD (HSZRD) markedly improved depressive behaviors. 16S rRNA sequencing revealed that SZRD modulated gut microbiome dysbiosis induced by insomnia and depression, characterized by an increased abundance of short-chain fatty acid (SCFA)-producing genera. Metabolomic profiling demonstrated reduced plasma amino acid metabolites and disrupted γ-aminobutyric acid (GABA) and L-glutamic acid metabolism in the hippocampus of affected rats. SZRD administration restored fecal SCFA levels and ameliorated metabolic imbalances in both plasma and hippocampal tissues. These findings underscore the pivotal role of gut microbiome modulation and metabolic regulation in the therapeutic effects of SZRD, providing a scientific basis for its use in treating insomnia and depression. [ABSTRACT FROM AUTHOR]