Recent advances in understanding the roles of d-amino acids (d-AAs) in nervous and endocrine systems have highlighted their emerging significance in cell-to-cell signaling, particularly in diabetes, where d-AAs are localized in specific islet cell types. In type 1 diabetes (T1D), the autoimmune-mediated destruction of β-cells and the consequent reduction of insulin production impact the disease onset and progression. The presence of d-AAs in T1D serum allows us to understand if they are misregulated in T1D. Correlations between serum d-AAs, glycated hemoglobin (HbA1c), C-peptide levels, and disease duration in T1D patients are investigated. d/l-alanine, -proline, -aspartate, -serine, and -glutamate are quantified using chiral liquid chromatography-tandem mass spectrometry with a multiple-reaction-monitoring approach (LC-MRM-MS/MS). Additionally, d-cysteine levels are determined through a luciferase assay and confirmed via d-amino acid oxidase enzyme degradation. Positive correlations between d-glutamate and d-aspartate levels and C-peptide levels are observed. Obtained results demonstrate positive correlations between d-alanine, d-proline, and d-cysteine levels and disease duration, and a negative correlation with d-aspartate and d-glutamate. These findings suggest the involvement of a range of d-AAs and that serum d-AA levels may be indicators of T1D progression.

High-throughput single-cell mass spectrometry is a rapidly evolving field that requires innovative sampling and ionization techniques to balance speed, sensitivity, and reliability for metabolomic and lipidomic analyses. This study provides a comparative analysis of two cutting-edge ionization platforms for single-cell analysis: Liquid Vortex Capture (LVC) and Rapid Droplet Sampling Interface (RDSI). The performance was benchmarked by testing pharmaceuticals, EquiSPLASH, and single-cell experiments. RDSI demonstrated up to 100-fold improvements in sensitivity for drugs and lipids such as propranolol, amiodarone, atorvastatin, and phosphocholines in water and phosphate-buffered solutions. This was attributed to its low-flow rate operation (3 μL/min) and reduced dilution. Conversely, LVC excelled in handling higher liquid volumes with greater reproducibility due to its higher solvent flow rate (200 μL/min), enabling increased dilution, solubility, and cleaning. Single-cell uptake of atorvastatin incubated for 10 min, or amiodarone incubated for 24 h in HepG2 cells, similarly revealed up to 85-fold enhancement in sensitivity by RDSI for drugs and lipids. These findings highlight the potential of RDSI for enhancing sensitivity in single-cell drug monitoring and lipidomics.

This study demonstrates ion focusing at ambient pressure and increased ion signal by creating a voltage difference from a field-free region to a detector, thereby improving the detection of chemicals ...

Pancreatic cancer remains one of the most challenging malignancies to diagnose and treat due to the late development of symptoms and limited early diagnostic options. Intraductal papillary mucinous ne...

Fetal development is a vulnerable period for exposure to per- and polyfluoroalkyl substances (PFAS). However, certified analytical standards do not exist for many PFAS, limiting our ability to quantify overall exposure burden to PFAS as a chemical class. PFAS-focused nontargeted analysis (NTA) enables detection of PFAS for which chemical standards may not exist. The overall objectives of this study were to provide a more comprehensive picture of PFAS exposure in cord blood, develop cumulative exposure burden scores for the PFAS detected, and evaluate differences in the infant’s PFAS burden score with respect to mother’s parity. We measured PFAS using targeted and NTA methods in cord blood samples collected between 2003 and 2006 in the HOME Study (Cincinnati, Ohio). Using NTA, we putatively identified 42 PFAS in cord blood, 4 of which were also detected in targeted analysis. We summarized an infant’s overall prenatal exposure burden to PFAS using item response theory methods. We constructed two scores, one based on PFAS concentrations from targeted analysis (“PFAS exposure burden scores”), and one based on relative abundance from NTA (“PFAS-omics scores”). As expected, infants with multiparous mothers had significantly lower PFAS exposure burden scores than those with nulliparous mothers, but these disparities were not present when comparing their PFAS-omics scores. Our results show that infants are exposed to a wide range of PFAS, including perfluorinated chemicals, polyfluorinated chemicals, and fluorotelomers, before birth. Further, PFAS-focused NTA can help estimate total exposure to PFAS. Lastly, reported disparities in PFAS exposure burden across parity may depend on the panel of assessed PFAS and their half-lives.

Branched-chain fatty acids (BCFAs) are key components of the bacterial lipidome, playing a role in regulating membrane fluidity and permeability. In mammals, BCFAs occur at much lower concentrations, and their functions remain largely unexplored. Conventional lipid analysis methods, employing collision-induced dissociation (CID)-tandem mass spectrometry (MS/MS), often fail to locate methyl branching, as fragmentation rarely occurs around the branching site. Here, we introduce a bifunctional derivatization reagent, 1-(8-methoxy-5-quinolinyl) methanamine (MeO-QN), for pinpointing methyl branching in BCFAs with high sensitivity. MeO-QN enhances ionization efficiency of derivatized BCFAs in positive ion mode due to its quinoline moiety and serves as a precursor for radical-directed dissociation (RDD). Upon CID, the quinoline-O radical (QN-O•) is generated, which subsequently induces RDD along the fatty acyl chain and forms a characteristic 28 Da spacing indicative of the branching point. By integrating this MS/MS method with reversed-phase liquid chromatography, we have developed a sensitive analytical workflow, detecting BCFAs at sub-nM levels in mammalian samples. We detected the rarely reported n-5 methyl branched fatty acid (FA 16:0;12Me) in pooled human plasma. We also observed significantly reduced even-chain isobranched fatty acids in breast cancer cells (MDA-MB-468) versus normal breast cells (MCF-10A), suggesting its potential in cancer biomarker discovery.

Single-cell native mass spectrometry (MS) holds immense potential for highly sensitive in situ analysis of biological events within individual live cells. Herein, we present a significant advancement ...

The biotransformation of the dietary supplement ingredient 5α-hydroxy-laxogenin was investigated using human HepG2 cells, the rat and in silico using the online software Next-gen E-Resource for Drug ...

This study examines the isomeric composition of PEth reference materials and compares it with the natural variation in isomer distribution found in blood samples.

The objective of this study was to evaluate rapid evaporative ionization mass spectrometry (REIMS) as a rapid method to measure biochemical markers of…

Metabolic function plays a key role in our understanding of both biological and pathophysiological processes. Metabolism is a complex combination of intrinsic processes and environmental cues across a...

This work summarizes the criteria for a useful reagent for ion/ion proton transfer in an electrodynamic ion trap with specific emphasis on proton transfer to high mass multiply-charged analyte ions. A...

Background The rising incidence of Salmonella-induced diarrhea highlights the critical need for judicious antibiotic use to ensure effective treatment outcomes. Methods This study presents an inno...

This study presents a sustainable approach utilizing activated carbon derived from hazelnut shells as an adsorbent for the simultaneous quantitative analysis of 48 different volatile organic compounds...

Dissolved organic matter (DOM) cycling across the land-ocean continuum is highly complex, and our limited understanding of DOM molecular transformations hinders a full assessment of land-ocean connect...

Untargeted tandem mass spectrometry (MS/MS)-based metabolomics enable broad characterization of small molecules in complex samples, yet the majority of spectra in a typical experiment remain unannotated, limiting biological interpretation. Reference data-driven (RDD) metabolomics addresses this gap by contextualizing spectra through comparison to curated, metadata-annotated reference data sets, allowing inference of spectrum origins without requiring exact structural identification. Here, we present an open-source RDD metabolomics platform comprising a user-friendly web application and a Python software package that performs RDD analyses directly from molecular networking outputs generated by GNPS. The tools support visualization and statistical analysis of RDD results, including interactive bar plots, heat maps, principal component analysis, and Sankey diagrams. We illustrate the approach using a hierarchical reference data set of 3500 food items to derive dietary patterns from stool metabolomics data of omnivore and vegan participants. The analysis reveals clear dietary group separation, demonstrating how RDD metabolomics can extract biologically meaningful patterns from otherwise unannotated spectra. Thus, the RDD metabolomics platform removes technical barriers for the metabolomics community to adopting RDD analysis, with the functionality freely available at https://github.com/bittremieuxlab/gnps-rdd and https://gnps-rdd.bittremieuxlab.org/.

Here we present CleaveScope, a lightweight standalone software tool for rapid and flexible analysis of protease specificity using LC-MS/MS data. The program accepts XML output files from the Mascot se...

The graphical abstract summerizes the Investigation of the phytochemical profile and biological activities of the roots and flowers of D. tortuosa and D. triradiata. Plant materials were extracted us...

Exenatide and H-GLP-1 belong to the GLP-1 agonist class of potential therapeutic agents. A robust multienzyme peptide-mapping workflow combined with LC-HRMS/MS enables high-resolution sequence covera...

Background Recurrent implantation failure (RIF) is a significant clinical challenge in assisted reproduction, yet its underlying molecular mechanisms remain poorly understood. This study aimed to char...

Abstract. Seronegative rheumatoid arthritis (negRA) is difficult to diagnose due to the absence of rheumatoid factor and anticitrullinated peptide antibodi

Abstract. Diabetic kidney disease (DKD) is a complication of diabetes and the leading cause of kidney failure among diabetic patients. Unfortunately, it is

Cyanobacteria are highly taxonomically and ecologically diverse species that have survived for billions of years. Here, authors show key structural features have remained within their light harvesting...

Four famous freshwater fish in China are renowned for their high production among freshwater species and are much-prized as sought-after delicacies. H…

There is a growing need for rapid, low-cost analytical tools to screen water supplies for persistent contaminants. Due to their ubiquitous presence in the environment and their detrimental effects on ...