Virginia Innovation Partnership Corporation

Various rounded turn designs in Structures for Lossless Ion Manipulation (SLIM) were explored via ion trajectory simulations. The optimized design was integrated into a SLIM ion mobility (IM) system coupled with a time-of-flight (TOF) mass spectrometer (MS) for further experimental investigation. The SLIM-TOF IM-MS system was assessed for IM resolution and ion transmission efficiency across a wide m/z range using various RF frequencies and buffer gas combinations. High ion transmission efficiency and high resolution ion mobility (HRIM) separation were achieved for Agilent tune mix ions through a ∼12.8 m serpentine separation path in both nitrogen and helium. In helium, ion transmission for low m/z ions was enhanced at higher RF trapping frequency, enabling the detection of ions with m/z below 50 and all 17 amino acids from a standard mixture. Lossless ion transmission was observed for glycine (m/z 76) in both passthrough and HRIM modes. HRIM resolution was benchmarked using L-isoleucine, L-leucine, and various other isobaric and isomeric metabolites with m/z values of 60-89. This work demonstrates a rounded turn SLIM design that enables HRIM measurements for small molecule analytes, with a particular focus on metabolomics, where IM offers a means to enhance the speed, robustness, and specificity of analytical workflows.

Colonization of the human stomach with Helicobacter pylori strains producing active forms of the secreted toxin VacA is associated with an increased risk of peptic ulcer disease and gastric cancer, compared with colonization with strains producing hypoactive forms of VacA. Previous studies have shown that active s1m1 forms of VacA cause cell vacuolation and mitochondrial dysfunction. In this study, we sought to define the cellular metabolic consequences of VacA intoxication. Untargeted metabolomic analyses revealed that several hundred metabolites were significantly altered in VacA-treated gastroduodenal cells (AGS and AZ-521) compared with control cells. Pathway analysis suggested that VacA caused alterations in taurine and hypotaurine metabolism. Treatment of cells with the purified active s1m1 form of VacA, but not hypoactive s2m1 or Δ6-27 VacA-mutant proteins (defective in membrane channel formation), caused reductions in intracellular taurine and hypotaurine concentrations. Supplementation of the tissue culture medium with taurine or hypotaurine protected AZ-521 cells against VacA-induced cell death. Untargeted global metabolomics of VacA-treated AZ-521 cells or AGS cells in the presence or absence of extracellular taurine showed that taurine was the main intracellular metabolite significantly altered by extracellular taurine supplementation. These results indicate that VacA causes alterations in cellular taurine metabolism and that repletion of taurine is sufficient to attenuate VacA-induced cell death. We discuss these results in the context of previous literature showing the important role of taurine in cell physiology and the pathophysiology or treatment of multiple pathologic conditions, including gastric ulcers, cardiovascular disease, malignancy, inflammatory diseases, and other aging-related disorders.

Drug enantiomers can possess vastly different pharmacological properties, yet they are identical in their chemical composition and structural connectivity. Thus, resolving enantiomers poses a great challenge in the field of separation science. Enantiomer separations necessitate interaction of the analyte with a chiral environment─in mass spectrometry-based analysis, a common approach is through a three-point interaction with a chiral selector commonly introduced during sample preparation. In select cases, the structural difference imparted through noncovalent complexation results in enantiomer-specific structural differences, facilitating measurement using a structurally selective analytical technique such as ion mobility-mass spectrometry (IM-MS). In this work, we investigate the direct IM-MS differentiation of chiral drug compounds using mononuclear copper complexes incorporating an amino acid chiral selector. A panel of 20 chiral drugs and drug-like compounds were investigated for separation, and four l-amino acids (l-histidine, l-tryptophan, l-proline, and l-tyrosine) were evaluated as chiral selectors (CS) to provide the chiral environment necessary for differentiation. Enantiomer differentiation was achieved for four chiral molecule pairs (R/S-thalidomide, R/S-baclofen, R/S-metoprolol, and d/l-panthenol) with two-peak resolution (Rp-p) values ranging from 0.7 (>10% valley) to 1.5 (baseline separation). Calibration curves relating IM peak areas to enantiomeric concentrations enabled enantiomeric excess quantitation of racemic thalidomide and metoprolol with residuals of 5.7 and 2.5%, respectively. Theoretical models suggest that CuII and l-histidine complexation around the analyte chiral center is important for gas-phase stereoselectivity. This study demonstrates the potential of combining enantioselective noncovalent copper complexation with structurally selective IM-MS for differentiating chiral drugs and drug-like compounds.

High-resolution ion mobility (resolving power > 200) coupled with mass spectrometry (MS) is a powerful analytical tool for resolving isobars and isomers in complex samples. High-resolution ion mobility is capable of discerning additional structurally distinct features, which are not observed with conventional resolving power ion mobility (IM, resolving power ~ 50) techniques such as traveling wave IM and drift tube ion mobility (DTIM). DTIM in particular is considered to be the “gold standard” IM technique since collision cross section (CCS) values are directly obtained through a first-principles relationship, whereas traveling wave IM techniques require an additional calibration strategy to determine accurate CCS values. In this study, we aim to evaluate the separation capabilities of a traveling wave ion mobility structures for lossless ion manipulation platform integrated with mass spectrometry analysis (SLIM IM-MS) for both lipid isomer standards and complex lipid samples. A cross-platform investigation of seven subclass-specific lipid extracts examined by both DTIM-MS and SLIM IM-MS showed additional features were observed for all lipid extracts when examined under high resolving power IM conditions, with the number of CCS-aligned features that resolve into additional peaks from DTIM-MS to SLIM IM-MS analysis varying between 5 and 50%, depending on the specific lipid sub-class investigated. Lipid CCS values are obtained from SLIM IM (TW(SLIM)CCS) through a two-step calibration procedure to align these measurements to within 2% average bias to reference values obtained via DTIM (DTCCS). A total of 225 lipid features from seven lipid extracts are subsequently identified in the high resolving power IM analysis by a combination of accurate mass-to-charge, CCS, retention time, and linear mobility-mass correlations to curate a high-resolution IM lipid structural atlas. These results emphasize the high isomeric complexity present in lipidomic samples and underscore the need for multiple analytical stages of separation operated at high resolution.Graphical abstract

Geotechnical properties of clayey soils are not only influenced by the chemical composition of clay, but also the geological formation. Construction of coastal transportation infrastructure (highways, bridges, rails, and harbors), shallow and deep foundations for the super structures, and buried structures including tunnels and pipelines require detailed investigation and information of the geotechnical properties of the soils. This study is focused on the geostatistical analyses of the strength and index properties of a deltaic clayey soil based on 1,070 bore-hole data collected up to a depth of 23 m and covering an area of over 25,000 m2. Also, marine clay data collected from around the world were analyzed. For the deltaic clay soils, based on the statistical analyses of over 3,700 liquid limit data and 3,700 plastic limit data, the statistical distribution was lognormal with positive skewness. The statistical distribution of the undrained shear strength for the CH and CL deltaic soils was lognormal. The liquid limit range and plastic limit range for the marine CH soils were much higher than the deltaic CH soils. In addition, geotechnical property correlations between undrained shear strength and index properties were investigated based on over 1,180 data of deltaic clay soils. In this study, a total of over 12,500 data were used.

In society, people live in a social reality where multiculturalism is an increasingly relevant and prevalent topic in their contexts. Facing this, caring for multicultural patients in an emergency service or intensive care unit setting requires a high level of cultural competence due to the complexity, vulnerability of the patient, rapid changes in hemodynamic status, involvement of the family, their informational needs. To map the strategies for nursing care of critically ill multicultural patients. A Scoping Review was conducted following the Joanna Briggs Institute's recommendations, with the research question: What are the strategies for nursing care of critically ill multicultural patients? The study was guided by PRISMA. The research was conducted through the EBSCOHost platform, SciELO, Portugal's Open Access Scientific Repository, the Virtual Health Library and a search in grey literature. This was achieved by combining the descriptors DECS/MESH: cultural competence; critical care; emergency room; intensive care; and natural words: cultural care; nurs* interventions; nurs* strategies; within the time frame from 2012 to 2024. The study screening was performed by three independent reviewers through the reading of titles, abstracts and full texts, applying exclusion criteria. The study results were then subjected to content analysis, from which categories emerged. The selected articles highlight various strategies that contribute to the improvement of nursing care for critically ill multicultural patients, focusing on care practice and cultural diversity training for both nurses and nursing students. Nurses with cultural competence possess more knowledge and strategies to provide tailored care for multicultural critically ill patients, thereby enhancing the quality of care delivered and contributing to the humanization of healthcare. Nurses need to have knowledge of existing strategies for caring for multicultural critically ill patients. No direct patient or public contribution to the review.

Ion mobility (IM) is an important analytical technique for increasing identification coverage of metabolites in untargeted studies, especially when integrated into traditional liquid chromatography-mass spectrometry workflows. While there has been extensive work surrounding best practices to obtain and standardize collision cross section (CCS) measurements necessary for comparing across different IM techniques and laboratories, there has been little investigation into experimental factors beyond the mobility separation region that could potentially influence CCS measurements. The first-principles derived CCS of 15 chemical standards were evaluated across 27 aqueous:organic solvent compositions using a high-precision drift tube instrument. A small but measurable dependency of the CCS on the solvent composition was observed, with the larger analytes from this study (m/z > 400) exhibiting a characteristic increase in CCS at the intermediate (40-60%) solvent compositions. Parallels to the behavior of solvent viscosity and protonation site tautomers (protomers) were noted, although the origin of these solvent-dependent CCS trends is as yet unclear. Taken together, these findings document a solvent dependency on CCS, which, while minor (<0.5%), identifies an important need for reporting the solvent system when utilizing CCS in comparative ion mobility studies.