Mass Analysis Research Articles

Challenging the Astral mass analyzer to quantify up to 5,300 proteins per single cell at unseen accuracy to uncover cellular heterogeneity.

Despite significant advancements in sample preparation, instrumentation and data analysis, single-cell proteomics is currently limited by proteomic depth and quantitative performance. Here we demonstrate highly improved depth of proteome coverage as well as accuracy and precision for quantification of ultra-low input amounts. Using a tailored library, we identify up to 7,400 protein groups from as little as 250 pg of HeLa cell peptides at a throughput of 50 samples per day. Using a two-proteome mix, we check for optimal parameters of quantification and show that fold change differences of 2 can still be successfully determined at single-cell-level inputs. Eventually, we apply our workflow to A549 cells, yielding a proteome coverage ranging from 1,801 to a maximum of >5,300 protein groups from a single cell depending on cell size and search strategy used, which allows for the study of dependencies between cell size and cell cycle phase. Additionally, our workflow enables us to distinguish between in vitro analogs of two human blastocyst lineages: naive human pluripotent stem cells (epiblast) and trophectoderm-like cells. Our data harmoniously align with transcriptomic data, indicating that single-cell proteomics possesses the capability to identify biologically relevant differences within the blastocyst.

Effect of electronic cigarette atomising power and flavour on aerosol size-segregated metal concentration and inhalation risk

IntroductionAlthough numerous studies have estimated the inhalation dose of metals emitted from electronic cigarettes (e-cigs), the impact of factors including aerosol size and the atomising power of e-cig aerosols on...

Sarcopenia and Cardiogeriatrics: The Links Between Skeletal Muscle Decline and Cardiovascular Aging

Sarcopenia, an age-related decline in skeletal muscle mass, strength, and function, is increasingly recognized as a significant condition in the aging population, particularly among those with cardiovascular diseases (CVD). This review provides a comprehensive synthesis of the interplay between sarcopenia and cardiogeriatrics, emphasizing shared mechanisms such as chronic low-grade inflammation (inflammaging), hormonal dysregulation, oxidative stress, and physical inactivity. Despite advancements in diagnostic frameworks, such as the EWGSOP2 and AWGS definitions, variability in criteria and assessment methods continues to challenge standardization. Key diagnostic tools include dual-energy X-ray absorptiometry (DXA) and bioimpedance analysis (BIA) for muscle mass, alongside functional measures such as grip strength and gait speed. The review highlights the bidirectional relationship between sarcopenia and cardiovascular conditions such as heart failure, aortic stenosis, and atherosclerotic cardiovascular disease, which exacerbate each other through complex pathophysiological mechanisms. Emerging therapeutic strategies targeting the mTOR pathway, NAD+ metabolism, and senescence-related processes offer promise in mitigating sarcopenia’s progression. Additionally, integrated interventions combining resistance training, nutritional optimization, and novel anti-aging therapies hold significant potential for improving outcomes. This paper underscores critical gaps in the evidence, including the need for longitudinal studies to establish causality and the validation of advanced therapeutic approaches in clinical settings. Future research should leverage multi-omics technologies and machine learning to identify biomarkers and personalize interventions. Addressing these challenges is essential to reducing sarcopenia’s burden and enhancing the quality of life for elderly individuals with comorbid cardiovascular conditions. This synthesis aims to guide future research and promote effective, individualized management strategies.

Progress in Tandem Mass Spectrometry Data Analysis for Nucleic Acids.

Mass spectrometry (MS) has become a critical tool in the characterization of covalently modified nucleic acids. Well-developed bottom-up approaches, where nucleic acids are digested with an endonuclease and the resulting oligonucleotides are separated before MS and MS/MS analysis, provide substantial insight into modified nucleotides in biological and synthetic nucleic. Top-down MS presents an alternative approach where the entire nucleic acid molecule is introduced to the mass spectrometer intact and then fragmented by MS/MS. Current top-down MS workflows have incorporated automated, on-line HPLC workflows to enable rapid desalting of nucleic acid samples for facile mass analysis without complication from adduction. Furthermore, optimization of MS/MS parameters utilizing collision, electron, or photon-based activation methods have enabled effective bond cleavage throughout the phosphodiester backbone while limiting secondary fragmentation, allowing characterization of progressively larger (~100 nt) nucleic acids and localization of covalent modifications. Development of software applications to perform automated identification of fragment ions has accelerated the broader adoption of mass spectrometry for analysis of nucleic acids. This review focuses on progress in tandem mass spectrometry for characterization of nucleic acids with particular emphasis on the software tools that have proven critical for advancing the field.

Static Analysis of Gelatin-like Simulation Mass as a Subsoil in Scale Physical Modeling

Static Analysis of Gelatin-like Simulation Mass as a Subsoil in Scale Physical Modeling

Microwave-Assisted Synthesis of Bis-1,2,3-Triazole Based Benzophenones, In Vitro Antimicrobial Activity and Molecular Docking Studies.

In this work, we have adopted an easy route to synthesizing bis-1,2,3-triazole-based benzophenone compounds via a 1,3-dipolar cycloaddition reaction (Click Chemistry). All the target compounds achieved better yields though the microwave-assisted method than the conventional method. Target compounds structure were confirmed based on the IR, 1H NMR, 13C NMR and HR Mass analysis. Additionally, we have carried out in vitro antibacterial and antifungal activities with Ciprofloxacin and Fluconazole standard drugs, respectively. The compounds 5b, 5f, 5i, 5k and 5n antibacterial, 5a, 5e, 5g, 5i, and 5k showed promising antifungal activity with respect to standard drugs. Further, molecular docking study performed against DNA gyrase and Lanosterol 14-alpha demethylase envisioned promising binding interactions with a good docking score.

A Carbazole Acrylonitrile Substituted Turn-On Fluorescence Chemosensors for Cyanide Ion and its Application to Real Sample Analysis.

An efficient probe (E)-2-(benzo[d]thiazol-2-yl)-3-(9-ethyl-9H-carbazol-3-yl)acrylonitrile (CZ-BTZ) for selective fluorescence "turn-on" response with cyanide (CN-) ion sensor was developed by simple Knoevenagel condensation of 9-ethyl-9H carbazole-3-carbaldehyde with 2-(benzo[d]thiazol-2-yl) acetonitrile. The sensing ability of probe CZ-BTZ was tested with different inorganic anions through spectrophotometric and spectrofluorimetric methods. The UV-vis and fluorescence spectral studies show the formation of a new adduct between CZ-BTZ and CN- by appearing with a new absorbance band at 350nm and "turn-on" fluorescence at 535nm in CH3CN: H2O (8:2, v/v, pH 7.2). The absorbance and fluorescence study reveals the formation of 1:1 (CZ-BTZ: CN-) stoichiometry adducts with an estimated association constant of 2.04 × 105 M-1. The probe CZ-BTZ could detect CN- down to 4.19 nM without much interference, much lower than the WHO limit (1.9 µM) in drinking water. The sensing mechanism of CZ-BTZ with CN- ions was studied using FTIR, ESI mass analysis, and DFT calculation. Further, the probe was applied to analyse CN- ions' real-time food sample analysis.

Efficient Coupling of Structures for Lossless Ion Manipulations with Ion Trap Mass Analyzers Using Phase Modulation.

Phased structures for lossless ion manipulation offer significant improvements over the scanning second gate method for coupling with ion trap mass analyzers. With an experimental run time of under 1 min for select conditions and an average run time of less than 4 min, this approach significantly reduces experimental time while enhancing the temporal duty cycle. The outlined SLIM system connects to an ion trap mass analyzer via a PCB stacked ring ion guide, which replaces the commercial ion optics and capillary inlet. By applying a discrete and repeating injection pulse and solving a series of algebraic equations, the system reconstructs an arrival time distribution with a minimal degree of error with enhanced ion throughput. To demonstrate the feasibility of this approach, the 3.4-m SLIM system resolves gas-phase conformers for various small peptides and proteins. This system and methodology also enable direct implementation between SLIM and ion trap mass analyzers traditionally interfaced with front separation systems such as liquid chromatography.

To image or not to image: Use of imaging mass spectrometry in biomedical lipidomics.

Lipid imaging mass spectrometry (LIMS) allows for establishing the bidimensional distribution of lipid species within a tissue section. One of the main advantages is the generation of spatial information on lipid species distribution at a spatial (lateral) resolution bordering on single-cell resolution with no need to isolate cells. Thus, LIMS images demonstrate, with a level of detail never described before, that lipid profiles are highly sensitive to cell type and pathophysiological state. The wealth and relevance of the information conveyed by LIMS makes up for the lack of a separation stage before sample injection into the mass analyzer, which can somehow be circumvented by other means. Hence, the possibility of describing the lipidome at the cellular level while preserving the microenvironment offers an incomparable opportunity to investigate physiological and pathological contexts. However, to fully grasp the biological implications of the lipid profiles, it is essential to contextualize LIMS data within the broader multiscale 'omic' landscape, entailing genomics, epigenomics, and proteomics, each offering a unique window into the regulatory layers of the cell. In this line, the number of techniques that can be combined with LIMS to delve into the molecular mechanisms underlying differential lipid profiles is continuously increasing. Herein, we aim to describe the key features of LIMS analyses, from sample preparation to data interpretation, as well as the current methodologies to enrich and complete the final outcome. While the field is rapidly advancing, we consider there is solid evidence to foresee the incorporation of LIMS into clinical environments.

Disruption of a potential disulfide bond of Cys65-Cys141 on the structure and stability of globin X from zebrafish.

Globin X is a newly discovered member of the globin family, while its structure and function are not fully understood. In this study, we performed protein modelling studies using Alphafold3 and molecular dynamics simulations, which suggested that the protein adopts a typical globin fold, with the formation of a potential disulfide bond of Cys65 and Cys141. To elucidate the role of this unique disulfide in protein structure and stability, we constructed a double mutant of C65S/C141S by mutating the two cysteine residues to serine. As suggested by protein mass, ultraviolet-visible (UV-Vis) and circular dichroism (CD) spectroscopy analyses, the potential disulfide bond has minimal effect on the overall protein structure, but its absence reduces the protein stability. Electron paramagnetic resonance (EPR) analysis also revealed an increase in the proportion of high-spin state heme iron, which accelerates the rate of heme degradation in reaction with H2O2. This study highlights the critical role of the Cys65-Cys141 in maintaining the stability of globin X and the bis-His heme coordination state, providing insights into the structure-function relationship of the newly discovered globin.

Spatiotemporal variability in benthic-pelagic coupling on the Oregon-Washington shelf

Continental shelf sediments are sinks for dissolved oxygen (DO) and sources of many major and minor nutrients required for oceanic surface primary production, resulting in a strong coupling between benthic and pelagic biogeochemical cycling. In this study, we present paired benthic flux and bottom water biogeochemical data collected from two Oregon shelf sites sampled approximately quarter-annually between 2017 and 2019, and from nine other shelf sites, located off central Oregon to southern Washington, and sampled in either July or September 2022. The benthic fluxes were determined using a novel set-up for ex situ core incubations. When fluxes were normalized to the respective measured sediment DO flux, ratios aligned well with ratios of past flux estimates from the region which were determined using in situ benthic chambers; however, the ex situ flux magnitudes are generally lower. Our findings demonstrate sediments acting as net sinks for DO and nitrate, and sources for phosphate, silicate, and ammonium. Shelf-wide estimates of the relative contribution of sediment-remineralized phosphate and silicate to surface waters on the Oregon shelf, indicate that shelf sediments supplied at least 5 ± 7 % and 37 ± 7 % of the available phosphate and silicate during recent summer upwelling seasons, with similar, respective estimates of 2 ± 9 % and 35 ± 11 % during the spring. Remineralization ratios of C:N:P:O2 corroborate increased denitrification during the summer and weak denitrification during the winter due to a more oxygenated water column in support of previous studies. A multi-tracer water mass analysis also exhibited an increased watercolumn nitrate deficit during the summer and fall. Benthic denitrification rates, estimated from benthic fluxes, were between 0.2 and 1.8 mmol N m-2 day-1 and in the range of past assessments during the upwelling season. A simple model, applied to further constrain the contributions to bottom water fixed nitrogen (N) loss under assumptions of benthic boundary layer height and residence time, showed that although sediment denitrification could readily account for total bottom water N losses during the summer, additional water column denitrification is indicated by the strength of early fall deficits at some stations. Constraining water column and benthic contributions to fixed N deficits is important for understanding how N-limited primary productivity in this region will respond to projected ocean deoxygenation under anticipated global warming. These results demonstrate the interplay of sediment and water column remineralization processes across the OR-WA shelf. As in most shallow marine systems, the two are integral to the ecosystem dynamics and responses to environmental change.

Smartphone-assisted colorimetric detection of nickel(II) ions using a novel benzothiazole-quinoline dyad in semi-aqueous media.

In this study, we present three different approaches for the colorimetric detection of Ni2+ ions using a specifically designed benzothiazole-quinoline dyad (L) synthesized via the Knoevenagel condensation reaction in high yield. The unique properties of L enable a rapid and selective response to Ni2+ ions, making it an ideal probe for practical applications. The probe L shows a pale yellow color under normal conditions. Upon interaction with Ni2+ ions, L undergoes a significant color change from pale yellow to bright orange, allowing for visual detection in semi-aqueous media. This rapid colorimetric response enables real-time monitoring of Ni2+ concentrations. The absorption maximum of L undergoes a bathochromic shift in the presence of Ni2+ ions due to ligand-to-metal charge transfer (LMCT). The probe L could form a 2 : 1 [L : Ni2+] stoichiometric complex, confirmed through Job's plot and ESI mass analysis with an estimated association constant of 2.61 × 106 M-2. The probe L could detect Ni2+ concentration down to 61 nM, 106 nM, and 129 nM via a UV-Vis spectrophotometer, smartphone-assisted RGB method, and test paper strip analysis. The binding mechanism of probe L with metal ions was studied using 1H NMR, ESI mass spectrometry, and DFT calculations. The zeta potential analysis showed a potential of -28.38 mV for the free ligand and +12.09 mV upon complexation with Ni2+. More importantly, the potential application of probe L includes the quantification of Ni2+ ions in various water samples through all three sensing approaches.

Effects of electroosmosis and entropy generation on a particulate-fluid suspension through peristaltic motion of Prandtl fluid: a numerical investigation

In thermodynamics, engineering, and environmental science, entropy generation are useful for comprehending complicated phenomena like heat transfer and fluid dynamics, analysing irreversibility, and optimising energy systems. Particulate-fluid flow with chemical reactions are employed in pharmaceutical manufacturing, catalytic converters, and combustion processes. This study provides insights into mass and thermal transmission analysis and influences of electroosmosis on flow of the Prandtl fluid in peristaltic micro-channel. The flow is also investigated considering the multiphase phenomenon influenced by chemical reaction. The flow problem modelling utilises lubrication theory with lengthy wavelengths and creeping flow assumptions. Furthermore, using Debye linearisation, the Poisson equation is simplified. The consequent structures for coupled ordinary differential equations have been handled by numerical solutions computed by using a highly efficient shooting technique with the help of NDSolve tool in Mathematica. It is concluded graphically that the profile of velocity declines with the increasing variation of porosity factor while enhances with the rise in Helmholtz-Smoluchowski velocity parameter. Thermal distribution increases with higher values of solid particle concentration and porous surface. It is evident that the concentration profile diminishes with the porosity coefficient but rises with the Helmholtz-Smoluchowski velocity factor.

Breeding estimation of initial alfalfa material according to green mass productivity and quality

Breeding of perennial grasses is the foundation for developing a forage base to produce high-quality livestock products. The purpose of the current study was to estimate the variability of phenotypic traits of alfalfa collection populations, as well as to identify the most promising ones in terms of possession of important agronomic traits for developing varieties that meet modern requirements of agricultural production. There have been estimated economically valuable traits of 80 alfalfa populations of various ecological and geographical origins from the collection of the FSBSI “ARC “Donskoy” for the period 2019–2023. The variety ‘Rostovskaya 90’ was used as a standard. There was determined a biochemical analysis of the green mass of alfalfa collection samples, including content of protein, fat, ash, fiber, and NFE, and there was carried out a statistical analysis of the experimental data. As a result of the research, there were identified the samples ‘Smuglyanka’ (Ukraine) – 7.9 kg/m2 , ‘Rambler’ (Canada) – 7.7 kg/m2 and ‘Stavropolskaya 430’ (Russia) – 7.6 kg/m2 with large productivity of green mass. The samples with high indicators of green mass quality ‘Tibetskaya’ (Kazakhstan), ‘Sinegibridnaya 1316’ (Russia), ‘Stavropolskaya 430’ (Russia), ‘Rhizoma’ (Canada), ‘Rambler’ (Canada), ‘VNIIOZ-16’ (Russia), ‘Smuglyanka’ (Ukraine), ‘Karlygash’ (Kazakhstan), ‘Prowler’ (USA), ‘Sarga’ (Russia), ‘G-4’ (Russia), ‘Donskaya 5’ (Russia), ‘Sin 4’ (Russia), ‘Sin 5’ (Russia) and ‘Sin 6’ (Russia) have been recommended for breeding programs to develop alfalfa varieties with large productivity of green mass and nutritional properties of dry matter.

CAR WEIGHT AS A FUNDAMENTAL CRITERION IN THE WORK OF A FORENSIC EXPERT. A PRACTICAL VIEW

Forensic medical examination of injuries in traffic accidents is very important, because these cases remain one of the main causes of mortality among the working-age population. Determining the mechanisms and circumstances of injury, especially in the absence of witnesses or video recording of the accident, requires the use of new methods of analysis. The mass of the vehicle, which directly affects the intensity and nature of the injuries received, is an important but insufficiently studied criterion, justifying the need to improve approaches to forensic medical research in this area. The aim of the study: to analyze injuries sustained by drivers and passengers as a result of frontal collisions with incomplete overlap in class B vehicles, and to assess the impact of vehicle mass on the spectrum and nature of injuries sustained. Material and methods. The object of the study was 179 “Acts of forensic medical examination of corpses” and “Expert conclusions” regarding traffic accidents accompanied by injury and death of people. The study used anthropometric, morphometric, photographic, criminalistic and statistical methods of analysis. The description of injuries was carried out in accordance with the Abbreviated Injury Scale standards, taking into account the anatomical areas of injury. Results. The analysis showed that with the right incomplete overlap, the number of injuries was slightly higher compared to the left. The total number of injuries among drivers was 194 cases, which is more than among passengers — 166 cases. The most common injuries were fractures of the lower extremities, chest, and soft tissue injuries. This confirms the dependence of the nature of injuries on the location of the victims in the car, the direction of the collision, and the mass of the car. Conclusions. The mass of the vehicle and its class have a significant impact on the spectrum and severity of injuries resulting from traffic accidents. Therefore, the introduction of vehicle mass analysis as a mandatory parameter in forensic medical examinations will contribute to increasing the accuracy of determining injury mechanisms.

Understanding the Formation Dynamics and Physical Properties of Nanocapsules Using Charge Detection Mass Spectrometry.

Characterizing the size, structure, and composition of nanoparticles is vital in predicting and understanding their macroscopic properties. In this work, charge detection mass spectrometry (CDMS) was used to analyze nanocapsules (∼10-200 MDa) consisting of a liquid oleic acid core surrounded by a dense silica outer shell. CDMS is an emerging method for nanoparticle analysis that can rapidly measure the mass and charge of thousands of individual nanoparticles. We find that increasing the feed volume of the tetraethylorthosilicate (TEOS) precursor added to form the silica shell of the nanocapsules yielded both higher and broader nanocapsule mass distributions with differentiable densities. A two-dimensional mass versus charge analysis also revealed the formation of two distinct populations of nanocapsules. These two nanocapsule morphologies were also present in transmission electron microscopy (TEM) images and exhibited low-density spherical cores and crescent-shaped cores where the remainder of the core volume was "filled in" by more dense silica. Nanocapsule shell growth kinetics over a ∼48-h synthesis period were also monitored by sampling the reaction mixture at various times, quenching the sampled aliquots, and then characterizing these time-resolved samples by CDMS. The CDMS data reveal three distinct growth phases in nanocapsule formation; rapid initial nucleation, an "inverted" distribution of silica growth, and a final slow growth phase where the rate of mass increase and final nanocapsule masses are dictated by the initial TEOS feed volumes. CDMS-enabled understanding of the diverse nanocapsule sizes, morphologies, and growth dynamics will allow us to better predict nanocapsule properties while reducing the experimental burden in optimizing nanocapsules for real-world applications.

Mass-Guided Single-Cell MALDI Imaging of Low-Mass Metabolites Reveals Cellular Activation Markers.

Single-cell MALDI mass spectrometry imaging (MSI) of lipids and metabolites >200Da has recently come to the forefront of biomedical research and chemical biology. However, cell-targeting and metabolome-preserving methods for analysis of low mass, hydrophilic metabolites (<200Da) in large cell populations are lacking. Here, the PRISM-MS (PRescan Imaging for Small Molecule - Mass Spectrometry) mass-guided MSI workflow is presented, which enables space-efficient single cell lipid and metabolite analysis. In conjunction with giant unilamellar vesicles (GUVs) as MSI ground truth for cell-sized objects and Monte Carlo reference-based consensus clustering for data-dependent identification of cell subpopulations, PRISM-MS enables MSI and on-cell MS2-based identification of low-mass metabolites like amino acids or Krebs cycle intermediates involved in stimulus-dependent cell activation. The utility of PRISM-MS is demonstrated through the characterization of complex metabolome changes in lipopolysaccharide (LPS)-stimulated microglial cells and human-induced pluripotent stem cell-derived microglia. Translation of single cell results to endogenous microglia in organotypic hippocampal slice cultures indicates that LPS-activation involves changes of the itaconate-to-taurine ratio and alterations in neuron-to-glia glutamine-glutamate shuttling. The data suggests that PRISM-MS can serve as a standard method in single cell metabolomics, given its capability to characterize larger cell populations and low-mass metabolites.

Body size and evolutionary rate analyses reveal complex evolutionary history of Alvarezsauria.

Some of the smallest examples of dinosaurian body size are from alvarezsaurians, an enigmatic group of maniraptoran coelurosaurians with a peculiar combination of anatomical features unique among theropods. Despite the large number of alvarezsaurian species described worldwide and the increased understanding this has provided, the body-size macroevolution of alvarezsaurians has received little attention. Here we reconstruct and analyse directional trends of alvarezsaurian body-size evolution through an integrated analysis of body mass, ontogenetic age, and morphological rate data enabled by a comprehensively revised phylogeny. Our analyses identify four periods of high morphological rate evolution (Bathonian-Callovian, Hauterivian-early Berriasian, early Cenomanian, and late Cenomanian-Turonian) that we link to the key effects of animal body-size changes for the first time, including morphological novelty, structural reduction and simplification, elevated homoplasy, and behavioral changes associated with miniaturization. In doing so, this study provides a holistic example of miniaturization in a Mesozoic vertebrate group that offers a framework for other detailed studies of animal body-size evolution, including in more disparate groups.

Synthesis, Characterization and Biological Evaluation of N [3-Chloro-2 (aryl)-4-oxoazitidin-1-y] pyridine-4-carboxamide

Isoniazid on addition with different aromatic aldehyde gives Schiff’s bases. The Schiff base so formed on treatment with chloroacetyl chloride and triethyl amine as a base catalyst in 1-4 Dioxan gives product 2a-2n.The synthesized compounds characterized by spectral analysis like IR, NMR &amp; Mass and elemental analysis. The compounds were screened by anticonvulsant and antimycobacterial activity.

Advances in Single Particle Mass Analysis.

Single particle mass analysis methods allow the measurement and characterization of individual nanoparticles, viral particles, as well as biomolecules like protein aggregates and complexes. Several key benefits are associated with the ability to analyze individual particles rather than bulk samples, such as high sensitivity and low detection limits, and virtually unlimited dynamic range, as this figure of merit strictly depends on analysis time. However, data processing and interpretation of single particle data can be complex, often requiring advanced algorithms and machine learning approaches. In addition, particle ionization, transfer, and detection efficiency can be limiting factors for certain types of analytes. Ongoing developments in the field aim to address these challenges and expand the capabilities of single particle mass analysis techniques. Charge detection mass spectrometry is a single particle version of mass spectrometry in which the charge (z) is determine independently from m/z. Nano-electromechanical resonator mass analysis relies on changes in a nanoscale device's resonance frequency upon deposition of a particle to directly derive its inertial mass. Mass photometry uses interferometric video-microscopy to derive particle mass from the intensity of the scattered light. A common feature of these approaches is the acquisition of single particle data, which can be filtered and concatenated in the form of a particle mass distribution. In the present article, dedicated to our honored colleague Richard Cole, we cover the latest technological advances and applications of these single particle mass analysis approaches.