Mass Spectrometry Research Articles

Brazilian AMS Radiocarbon Laboratory (LAC-UFF) and intercomparison of preliminary results with Sample Preparation Laboratory (LAPA14C – UFBA)

Abstract This study presents the initial results of carbon-14 dating after performing sample preparation and graphite production processes at the Federal University of Bahia (UFBA) in an intercomparison with the same processes performed at the Radiocarbon Laboratory of the Fluminense Federal University (LAC-UFF). Both laboratories are located in Brazil. The accelerator mass spectrometry (AMS) system at LAC-UFF was used for radiocarbon measurements. To verify any possible contamination sources during sample preparation, we initially performed swipe tests at UFBA, which were subsequently processed and the graphite samples were produced at LAC-UFF. After UFBA, several reference materials (IAEA-C1, -C2, -C6, -C9, and OXII standards) were prepared and converted into graphite. In addition, the sample material was first partially prepared at UFF and UFBA and then analyzed with the AMS system at LAC-UFF. Subsamples were prepared for additional measurements of the δ13C composition with an elemental analyzer coupled to an isotope ratio mass spectrometer (EA–IRMS) in LFNA-UFBA to study the isotopic fractionation and yield of the graphitization reaction. The obtained values closely aligned with the reference values, demonstrating reproducibility and quality and indicating minimal contamination during chemical and graphitization processes. In the future, samples from different matrices will be prepared at UFBA for application in paleoenvironmental and archaeological studies.

Cross-sectional study of proteomic differences between moderate and severe psoriasis

Although an ongoing understanding of psoriasis vulgaris (PV) pathogenesis, little is known about the proteomic differences between moderate and severe psoriasis. In this cross-sectional study, we evaluated the proteomic differences between moderate and severe psoriasis using data-independent acquisition mass spectrometry (DIA-MS). 173 differentially expressed proteins (DEPs) were significantly differentially expressed between the two groups. Among them, 85 proteins were upregulated, while 88 were downregulated (FC ≥ ± 1.5, P < 0.05). Eighteen DEPs were mainly enriched in the IL − 17 signalling pathway, Neutrophil extracellular trap formation, Neutrophil degranulation and NF − kappa B signalling pathway, which were associated with psoriasis pathogenesis. Ingenuity pathway Analysis (IPA) identified TNF and TDP53 as the top upstream up-regulators, while Lipopolysaccharide and YAP1 were the top potential down-regulators. The main active pathways were antimicrobial peptides and PTEN signalling, while the inhibitory pathways were the neutrophil extracellular trap pathway, neutrophil degranulation, and IL-8 signalling. 4D-parallel reaction monitoring (4D-PRM) suggested that KRT6A were downregulated in severe psoriasis. Our data identify Eighteen DEPs as biomarkers of disease severity, and are associated with IL − 17 signalling pathway, Neutrophil extracellular trap formation, NF − kappa B signalling pathway, and defence response to the bacterium. Targeting these molecules and measures to manage infection may improve psoriasis’s severity and therapeutic efficacy.

Ways to Measure Metals: From ICP-MS to XRF.

This review explores the use of Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and X-ray Fluorescence (XRF) for quantifying metals and metalloids in biological matrices such as hair, nails, blood, bone, and tissue. It provides a comprehensive overview of these methodologies, detailing their technological limitations, application scopes, and practical considerations for selection in both laboratory and field settings. By examining traditional and novel aspects of each method, this review aims to guide researchers and clinical practitioners in choosing the most suitable analytical tool based on their specific needs for sensitivity, precision, speed, and sample preparation. Recent studies highlight enhanced capabilities of both ICP-MS and XRF technologies, making them more adaptable to various analytical needs. ICP-MS is renowned for its unmatched sensitivity and precision in detecting ultra-trace metals and metalloids in complex biological samples, such as lead in plasma or seawater. XRF advancements include lower detection limits and reduced sample preparation time, enabling rapid, non-destructive analyses, ideal for quick field assessments. Portable XRF analyzers have revolutionized on-the-spot testing, providing robust data without traditional wet-lab constraints. Moreover, hybrid techniques combining ICP-MS and XRF features are emerging, offering rapid and precise metal analysis for environmental monitoring, clinical diagnostics, and epidemiological studies. Matching analytical methods to specific research demands is critical. ICP-MS is the gold standard for detailed quantitative analysis in laboratories, while XRF excels in non-destructive, immediate field applications. Selection should consider sample complexity, sensitivity, speed, and cost-efficiency. Integrating ICP-MS and XRF offers a versatile approach to metals analysis, transforming practices in environmental science and healthcare diagnostics. As these technologies evolve, they are promising to expand capabilities in detecting and understanding the roles of metals and metalloids in health and the environment.

Pharmacokinetics and pharmacodynamics of ciprofol after continuous infusion in elderly patients

BackgroundCiprofol, a novel intravenous anesthetic, which has primarily been used for the induction and maintenance of general anesthesia in adults, is characterized by rapid onset, short duration of action, and quick and smooth recovery. However, the pharmacokinetic characteristics of continuous infusions and the correlation between the plasma concentration and the bispectral index (BIS) in elderly patients are still unknown.MethodIn this randomized, controlled study, thirty elderly patients (62–78 years old) undergoing elective gastrointestinal tumor resection were treated with propofol (N = 15) or ciprofol (N = 15) as sedatives during anesthesia. After induction, ciprofol/propofol was continuously infused intravenously until the end of the operation. Perioperative vital signs, injection pain, adverse events (AEs), BIS values, eyelid reflex disappearance times, and recovery times were recorded. The plasma concentrations of ciprofol and propofol were measured by liquid chromatography tandem mass spectrometry (LC‒MS/MS) and the pharmacokinetics were determined by noncompartmental analysis.ResultsBoth drugs caused a decrease in blood pressure and heart rate after induction. Eight cases (53. 3%) of hypotension and 3 cases (20%) of bradycardia occurred in the propofol group, while 8 cases (53. 3%) of hypotension and 5 cases (33. 3%) of bradycardia occurred in the ciprofol group. At intubation, the ciprofol group experienced fewer fluctuations in blood pressure than the propofol group. Ciprofol resulted in only one case (6.7%) of mild injection pain, less than that produced by propofol (10/15, 66.7%) (P < 0.05). Anesthesia induction was successfully completed with both drugs, and there were no significant differences in eyelash reflex disappearance or recovery time between the two groups. The plasma concentrations during maintenance were relatively stable in both groups (propofol 1.78 ± 0.67 μg/mL, ciprofol 0.71 ± 0.23 μg/mL), and a suitable depth of sedation was achieved with a BIS of 40–60. The pharmacokinetic (PK) parameters for ciprofol are listed as follows: Maximum Plasma Concentration (Cmax) 6.02 ± 2.13 μg/ml; Time to Maximum Concentration (Tmax) 0.18 ± 0.62 min; Apparent Volume of Distribution (Vz) 3.96 ± 0.84 L/kg; Total Clearance (CL) 0.83 ± 0.14 L/h/kg; Half-life (t½) 3.47 ± 1.85 h; Area Under the Curve (AUC) 5000 ± 900 L/h/kg; Terminal Elimination Rate Constant (λz) 0.23 ± 0.07 1/h. Similar to propofol, the plasma concentration of ciprofol was linearly correlated with the BIS.ConclusionCiprofol, a novel intravenous anesthetic, can be safely and effectively used in elderly patient continuous infusion with minimal injection pain. Plasma concentrations of ciprofol correlate well with BIS values, helping control sedation depth. For elderly patients undergoing gastrointestinal tumor surgery, an optimal maintenance dose of 0.8 mg/kg/h is recommended.Trial registrationThis clinical trial (registration No: ChiCTR2100047580, https://www.chictr.org.cn. The pre-registration date was June 20, 2021, and the review approval and official case solicitation began in December 2021; Retrospectively registered) was conducted in accordance with the World Medical Congress Declaration of Helsinki and Good Clinical Practice guidelines. All study subjects provided written informed consent.

Revealing Molecular Connections between Dissolved Organic Matter in Surface Water Sources and Their Cytotoxicity Influenced by Chlorination Disinfection.

Dissolved organic matter (DOM) is the primary precursor of disinfection products (DBPs) during chlorination. However, the compositional characteristics of DOM transformation during the chlorination process in different source waters and its relationship to cytotoxicity remain understudied. Here, we used high-resolution mass spectrometry to evaluate chlorination-induced molecular-level changes in DOM derived from different surface water sources. We correlated DOM components with the cytotoxicity profiles of selected DBPs using new alternative methods with predictive toxicological assessments. Our findings indicate a selective chlorination of DOM in natural waters and a tendency for lignin and protein conversion during the manual chlorination process. The reactivity of bioactive compounds decreased in the order of lignin > protein > tannin or ConAC. The cytotoxicity of DOM from source waters is mainly attributed to lignin- and protein-like compounds within the CHO and CHNO groups. Additionally, mitochondrial damage is a highly sensitive indicator of DOM-induced cytotoxicity. The toxicity profiles of DBPs revealed 37 common toxicity-driving components characterized by low mass, medium H/C ratio, low O/C ratio, reduction state, and hydrophobicity. Our findings highlight the need to exploit the health effects of DOM and provide substantial experimental evidence for the necessity to remove potential toxicants.

Bio-synthesised nanoparticles employment for eliminating metals from wastewater via implementation of a three level Box-Behnken technique

The objective of the present study is to optimise the removal of metals such as aluminium, zinc, and copper from industrial wastewater using green-synthesised nanoadsorbents. To achieve this, the Box–Behnken experimental design and response surface methodology will be employed. We used inductively coupled plasma mass spectrometry to analyse the metals present in the wastewater. A three-factor, three-stage Box–Behnken design was used to maximise the removal of these metals from aqueous solution. This involved response surface modelling and quadratic programming based on 17 different experimental data from a batch study. The study focused on three independent variables: pH, contact time, and adsorbent amount. The nanoadsorbents were prepared using a combination of Citrus X sinensis peel and Musa Cavendish peel extract, which served as the reducing agents, to produce a combined peel extract-silver nanoparticle product. Field emission scanning electron microscopy imaging and UV–visible spectroscopic analysis unequivocally demonstrated the presence of nanoparticles, with a surface plasmon resonance at 438 nm. The optimal values of the selected variables were determined by solving the quadratic regression model and analysing the contour plots of the reaction surface. At the experimental conditions of pH = 5, contact time = 92.5 min, and adsorbent dosage = 0.1 g/L, the recovery efficiency of Al, Cu, and Zn was significantly reduced. The optimised parameters were successfully applied to wastewater collected, and the degradation of detected metal ions was tested. The experiment demonstrated an effective reduction in these metals.

Reaction mechanisms of Sn-based polarity-change copolymer resists with different counter anions, designed for extreme ultraviolet lithography

Abstract The development of high-resolution resists with a highly absorptive element for extreme ultraviolet (EUV) photons has attracted much attention for the next-generation lithographic applications. In this study, the radiation-induced reactions of polarity-change copolymer resists comprising tetraphenyltin (an EUV absorption unit) and phenyl dibenzothiophenium salts (polarity-change units) are investigated via electron-pulse radiolysis, electron-beam (EB) radiolysis, γ radiolysis, time-of-flight secondary-ion mass spectrometry (TOF-SIMS), quartz crystal microbalance (QCM) method, and contact angle measurement. Their lithographic performances are preliminary evaluated using a 125 keV EB writer. Trifluoromethanesulfonate, benzene sulfonate, and salicylate are used as counter anions for phenyl dibenzothiophenium cations. The effects of the counter anions on the radiation-induced reactions and yields of the main radiolytic products are small, whereas the resolution and sensitivity improve significantly with the increase in the pKa (or dipole moment) of corresponding acids for counter anions owing to the suppression of transient swelling layer formed during the development.

Hydride Formation and Decomposition on Cu(111) in HClO4.

Cu electrodeposition and the electrocatalysis of hydrogenation reactions thereupon involve significant interactions with adsorbed hydrogen. Electrochemical mass spectrometry (EC-MS) is used to explore the formation and decomposition of surface hydride on Cu(111) in 0.1 mol L-1 HClO4. Hydride formation is associated with two reduction waves that reflect the potential-dependent Hads coverage and its reconstruction. Voltammetric cycling reveals an additional oxidative and reductive feature at ≈ -0.05 V versus the reversible hydrogen electrode (RHE) that reflects the state of the 2D surface hydride. Extending the voltammetric window to more negative potentials results in an increase in Hads coverage and surface reconstruction that subsequently leads to accelerated hydride decomposition at positive potentials. Voltammetric and chronoamperometric analysis of hydride formation indicates a Hads coverage of ≈0.75 monolayers (ML) between -0.225 V vs RHE and -0.275 V vs RHE with further increases in Hads observed with the onset and acceleration of the HER at more negative potentials. Returning to more positive potentials, hydride decomposition begins above -0.05 V vs RHE. Recombination of Hads to form H2 accounts for desorption of ≈0.5 ML of Hads while its oxidation to H3O+ consumes between ≈0.15 and ≈0.4 ML of Hads, depending on the specific electrochemical conditions. The potential-dependent Hads coverage and surface reconstruction are congruent with trends identified in recent computational and electrochemical scanning tunneling microscopy studies. In contrast to perchloric acid, the presence of strongly adsorbing anions, such as sulfate or halides, favors hydride decomposition via the recombination pathway.

Screening potential antileukemia ingredients from sweet potato: integration of metabolomics analysis, network pharmacology, and experimental validation

BackgroundActive dietary flavonoids are a promising resource for novel drug discovery. Sweet potato, a widely cultivated functional crop, is abundant in flavonoids. However, the active ingredients associated with acute myeloid leukemia (AML) treatment and their underlying mechanisms have not been reported to date.ObjectiveThis study aims to identify novel drugs against AML from sweet potato by integrating metabolomics analysis, network pharmacology, and experimental validation.MethodsFirstly, ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed to analyze the major constituents in sweet potato. Then, nine active ingredients were selected for validation of their anti-leukemia effects. Subsequently, three of them underwent network pharmacology analyses and in vitro experimental verification. Finally, the anti-leukemia effect of cynaroside was further confirmed through in vivo experimental validation.ResultsFirstly, the flavonoid content of stem, leaves, flesh, and peel from 13 sweet potato cultivars was examined. The leaves of Nanshu 017 exhibited the highest flavonoid content of 2.27% dry weight (DW). Then, an extract derived from these leaves was employed for in vitro experiments, demonstrating significant inhibition of AML cell growth. Subsequently, based on the results of metabolomics analysis and network pharmacology, cynaroside, nepitrin, and yuanhuanin were identified as potential antileukemia agents present in sweet potato for the first time; while CASP3, KDR, EGFR, and SRC were recognized as pivotal targets of these three monomers against AML. Finally, the antileukemia effects of cynaroside, nepitrin, and yuanhuanin were confirmed through in vitro and in vivo experimental validation.ConclusionIn summary, sweet potato leaves extract possesses an antileukemic effect while cynaroside, nepitrin, and yuanhuanin demonstrate potential as treatments for AML.

Asiaticoside-nitric oxide synergistically accelerate diabetic wound healing by regulating key metabolites and SRC/STAT3 signaling

Abstract Background Diabetic wounds pose significant clinical challenges due to impaired healing processes, often resulting in chronic, non-healing ulcers. Asiaticoside (AC), a natural triterpene derivative from Centella asiatica, has demonstrated notable anti-inflammatory and wound-healing properties. However, the synergistic effects of nitric oxide (NO)—a recognized promoter of wound healing—combined with AC in treating diabetic wounds remain inadequately explored. Methods Ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was utilized to identify differential metabolites and dysregulated metabolic pathways associated with diabetic wounds. Molecular docking analyses were conducted to confirm the binding affinity of AC to key therapeutic targets. The effects of Asiaticoside-nitric oxide hydrogel (ACNO) on gene and protein expression were evaluated using RT-qPCR and western blotting. In vitro experiments using SRC agonists and inhibitors were performed to investigate the impact of ACNO therapy on the expression of SRC, STAT3, and other proteins in HaCaT cells. Results Metabolomic profiling revealed that diabetic wounds in mice exhibited marked metabolic dysregulation, which was attenuated by ACNO treatment. Key metabolites modulated by ACNO included mandelic acid, lactic acid, and 3-hydroxyisovaleric acid. The primary metabolic pathways involved were methyl histidine metabolism and the malate–aspartate shuttle. Immunofluorescence staining confirmed that ACNO therapy enhanced angiogenesis, promoted cellular proliferation, and facilitated diabetic wound closure. RT–qPCR data demonstrated that ACNO regulated the transcription of critical genes (SRC, STAT3, EGFR, and VEGFA). Notably, ACNO attenuated SRC/STAT3 pathway activation while concurrently upregulating EGFR and VEGFA expression. Conclusions These findings emphasize the therapeutic potential of ACNO hydrogel in diabetic wound healing through the modulation of metabolic pathways and the SRC/STAT3 signaling axis. By correlating altered metabolites with molecular targets, this study elucidates the pharmacodynamic foundation for ACNO’s pre-clinical application and provides valuable insights into the development of targeted therapies for diabetic wound management.

Two-Dimensional Liquid Chromatography-Isotope Ratio Mass Spectrometry Opens New Possibilities in the Field of Compound-Specific Stable Isotope Analysis.

Compound-specific stable isotope analysis (CSIA) using liquid chromatography-isotope ratio mass spectrometry (LC-IRMS) is a powerful tool for determining the isotopic composition of carbon in analytes from complex mixtures. However, LC-IRMS methods are constrained to fully aqueous eluents. Previous efforts to overcome this limitation were unsuccessful, as the use of organic eluents in LC-IRMS was deemed impossible. In our study, we developed a two-dimensional (2D) LC-IRMS method that, for the first time, enables the use of organic-containing eluents in an LC-IRMS setting. Initial experiments with caffeine were performed using a sample loop modulator with 20% methanol in the mobile phase of the first dimension, while separating the organic fraction from the analyte in the second dimension. Comparing results with one-dimensional (1D) LC-IRMS methods showed high precision with δ13C values in 2D measurements (-34.98 ± 0.04 ‰) closely matching 1D results (-34.95 ± 0.12 ‰). In the next step, incorporation of an at-column dilution (ACD) modulator allowed for the successful use of methanol concentrations up to 40% in the first dimension, with the ACD modulator effectively mitigating both peak fronting and carbon background interference, without losing any precision or accuracy of the measurements (δ13CCaffeine = -34.92 ± 0.03 ‰). All developed methods showed a method detection limit lower than 5 mg of carbon L-1 (mgC L-1), which is a major improvement compared with previous studies on caffeine analysis with LC-IRMS. This proof-of-concept study on 2D-LC-IRMS opens vast new possibilities for future CSIA research across diverse fields, including environmental science, pharmaceuticals, and food chemistry.

Metabolomic Exploration of Colorectal Cancer Through Amino Acids and Acylcarnitines Profiling of Serum Samples

Background/Objectives: Colorectal cancer (CRC) represents one of the most prevalent forms of cancer, with high mortality rates. The aim of this study was to observe and understand the metabolic changes in CRC through targeted metabolomics. Methods: Samples collected from 58 CRC patients and 35 healthy individuals have been analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), targeting two classes of metabolites: amino acids and acylcarnitines. Results: Statistical analysis revealed 26 significantly modified (p-value &lt; 0.01; |FC| &gt; 1.2) metabolites in CRC patients compared to the control group and 22 between colon cancer and control, whereas 8 metabolites differed only significantly between rectal cancer and healthy patients. Some of these significantly modified metabolites characterize cancer-specific adaptations, such as increased energy demand, increased tumor invasiveness, capabilities to promote amino acid synthesis, and tumor resistance against acute immune response. Moreover, receiver operator characteristic (ROC) analysis revealed that a set of two acylcarnitines (C6DC and C4-OH) can differentiate between CRC patients and healthy individuals with a high degree of confidence (AUC 0.837). Conclusions: By implementing a metabolomics approach targeting amino acids and acylcarnitines, several metabolic alterations induced by CRC have been highlighted. Even though these modifications are not specific enough to act as disease markers, they might prove useful for evaluating patient status.

Comprehensive Profiling of Illicit Amphetamines Seized in Poland: Insights from Gas Chromatography–Mass Spectrometry and Chemometric Analysis

The illicit production and distribution of amphetamines present significant challenges to public health and law enforcement, particularly in Europe, where these substances dominate the stimulant market. This study aimed to profile amphetamines consumed within a Polish community by employing gas chromatography–mass spectrometry (GC-MS) and chemometric techniques to analyze their chemical composition and associated impurities. The optimized GC-MS methodology facilitated the identification of synthesis markers, precursor origins, and distribution patterns. Impurity profiling provided critical insights into regional production trends, including the use of specific precursors and adulterants. Chemometric analysis further enabled the classification of samples into distinct groups, shedding light on their origins and distribution chains. These findings underscore the potential of extending amphetamine profiling to include distribution-related compounds, offering a powerful tool for tracking production trends and enhancing forensic investigations in the fight against drug trafficking.

Associations between circulating amino acids and metabolic dysfunction-associated steatotic liver disease in individuals living with severe obesity.

Metabolic dysfunction-associated steatotic liver disease (MASLD) describes liver diseases caused by the accumulation of triglycerides in hepatocytes (steatosis) as well as the resulting inflammation and fibrosis. Previous studies have demonstrated that accumulation of fat in visceral adipose tissue compartments and the liver is associated with alterations in the circulating levels of some amino acids, notably glutamate. This study aimed to investigate the associations between circulating amino acids, particularly glutamate, and MASLD. In addition, we hypothesized that liver steatosis, concomitant with visceral adiposity, could contribute to the association between circulating glutamate and visceral obesity. We studied a sample of 150 patients living with severe obesity who were non-diabetic and selected to represent a wide range of MASLD severity. Liver histological features were determined by a pathologist from a biopsy sample obtained at the time of bariatric surgery. Bulk RNA sequencing measured the hepatic mRNA expression level of selected genes related to the urea cycle and glutamate metabolism. Fasting plasma amino acid levels were measured by liquid chromatography coupled with tandem mass spectrometry. Patients with more advanced steatosis had larger visceral adipocytes, higher levels of circulating tyrosine, glutamate, and alanine as well as lower levels of serine. MASLD severity was significantly associated with the hepatic mRNA expression of glutamate metabolism genes such as GLS1, GLUL (positively), and NAGS (inversely). In individuals living with obesity, MASLD severity is associated with visceral adipocyte hypertrophy, higher circulating glutamate as well as potential alterations of hepatic amino acid and nitrogen metabolism.

Utilization of a Solid Waste Inhibitor for the Clean Flotation Enrichment of Phosphate Ores.

The accumulation of phosphogypsum (PG) in the phosphorus chemical industry poses significant environmental challenges. Therefore, developing a harmless utilization method is crucial for alleviating these burdens and promoting sustainable industry practices. In this study, PG was used as a flotation inhibitor, enabling the flotation separation of apatite and dolomite based on the main components and dissolution behavior of PG. A microflotation study revealed that 0.875 g/L PG selectively inhibited dolomite when the sodium oleate (NaOL) concentration was 1.5 × 10-4 mol/L, reducing dolomite recovery 76% to 10% at pH in the range of 7-11. Conversely, apatite recovery remained above 90% at pH 7-9 and was only slightly inhibited at pH in the range of pH 9-11. When CaSO4·2H2O and CaHPO4·2H2O were added as flotation inhibitors, they also inhibited dolomite, though their effects were weaker than PG. Measurements of contact angles, zeta potentials, and adsorption capacities indicated that PG enhanced the hydrophilicity of dolomite, hindering NaOL adsorption thereon, while it had little effect on the floatability of apatite. Atomic force and scanning electron microscopy revealed selective PG was adsorbed on the dolomite surface, altering its properties, while PG was weakly adsorbed on the apatite surface and had minimal impact on its properties. The solution chemical composition and microthermal results showed that CaSO4 and CaHPO4 are the effective components of PG inhibition. X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry confirmed that CaSO4 and CaHPO4 in PG were selectively adsorbed at Ca and Mg ion sites on the dolomite surface. Molecular dynamics simulations showed that CaSO4 interacts with the surface of dolomite, and CaHPO4 can promote the adsorption of CaSO4 on the surface of dolomite. Utilizing PG as a flotation inhibitor provides a novel approach for the environmentally safe use of PG resources.

Seasonal investigation of ultrafine-particle organic composition in an eastern Amazonian rainforest

Abstract. Reports on the composition of ultrafine particles (&lt;100 nm in diameter) in the Amazon are scarce, due in part to the fact that new-particle formation has rarely been observed near ground level. Ultrafine particles near the surface have nevertheless been observed, leaving open questions regarding the sources and chemistry of their formation and growth, particularly as these vary across seasons. Here, we present measurements of the composition of ultrafine particles collected in the Tapajós National Forest (2.857° S, 54.959° W) during three different seasonal periods: 10–30 September 2016 (SEP), 18 November–23 December 2016 (DEC), and 22 May–21 June 2017 (JUN). Size-selected (5–70 nm) particles were collected daily (for 22 h each day) using an offline sampler. Samples collected during the three time periods were compiled and analyzed using liquid chromatography coupled with Orbitrap high-resolution mass spectrometry. Our findings suggest a sustained influence of isoprene organosulfate chemistry on ultrafine particles from the different periods. We present chemical evidence that indicates that biological-spore fragmentation impacted ultrafine-particle composition during the late wet season (JUN), while chemical markers for biomass burning and secondary chemistry peaked during the dry season (SEP and DEC). Higher oxidation states and degrees of unsaturation were observed for organics in the dry season (SEP and DEC), suggesting greater extents of aerosol aging. Finally, applying a volatility parameterization to the observed compounds suggests that organic sulfur species are likely key drivers of new-particle growth in the region due to their low volatility compared to other species.

Antiproliferative Effect of Methanolic Extract of Vernonia greggii (Asteraceae) on Human Tumoral HeLa Cells Nanoencapsulated into PLGA-Nanoparticles

Vernonia greggii belongs to the Asteraceae family, and some members of this family have been reported to possess anticancer properties. This study evaluated the antiproliferative effect of V. greggii methanol extract (ME), both in its free form and encapsulated into poly(lactic-co-glycolide) (PLGA) nanoparticles (NPs), on human cervical cancer cells (HeLa) and human epidermal keratinocytes (HaCaT). The extract was subsequently sub-fractionated into n-hexane (F-He), methanol (F-Me), and distilled water (F-Ac) fractions, and their antiproliferative effects were assessed. Time-dependent toxicity on HeLa cells was observed for the free-form fractions, with the F-Me fraction showing the highest efficacy compared to the others. Additionally, an NP formulation based on PLGA and F-Me (NPs F-Me) was developed, achieving 64.21% encapsulation efficiency and 11.38% drug loading. The NPs had an average size of 146.9 nm, a polydispersity index (PDI) of 0.103, and a ζ-potential of 23.3 mV. NPs F-Me were tested on HeLa and HaCaT cells, with toxicity observed at concentrations of 300 and 500 μg/mL, affecting tumor cell morphology. Furthermore, the hemolytic activity of F-Me and NPs F-Me was evaluated. The major bioactive compounds in the F-Me fraction were identified using Liquid Chromatography–Mass Spectrometry (LC-MS). These findings suggest that the F-Me fraction of V. greggii exerts an antineoplastic effect both in its free form and when encapsulated in nanoparticles.

Properties of Uremic Solutes That Allow Their Effective Control by Hemodialysis.

If the GFR falls far enough, uremic symptoms such as anorexia and nausea prompt the initiation of dialysis. Thrice weekly hemodialysis can prevent recurrence of these symptoms even when patients become anuric. To accomplish this it must maintain the plasma levels of the uremic solutes which cause these symptoms lower than they were when dialysis was initiated. This study examined kinetic properties that solutes must possess for hemodialysis to accomplish this. We also sought to identify uremic solutes that possess these properties. Mathematical modeling analyzed how a solute's kinetic properties would determine the relation of its level in an anuric dialysis patients to its level when uremic symptoms prompt dialysis initiation. The previously unstudied solute methylurea was assayed by liquid chromatography tandem mass spectrometry (LC/MS/MS) in 13 participants on hemodialysis, 9 participants with advanced CKD, and 10 participants without kidney disease. Mathematical modeling showed that conventional dialysis can effectively control the plasma levels better than the failing native kidneys only of solutes which have a high dialytic clearance relative to their native kidney clearance and a large volume of distribution. LC/MS/MS measurements showed that methylurea has these properties. The dialytic clearance of methylurea was 255 ± 32 ml/min and its volume of distribution was 1.09 ± 0.25 times the body water volume in hemodialysis patients. The methylurea clearance was lower than the GFR in patients without kidney disease (fractional clearance 0.44 ± 0.19) and patients with advanced CKD (fractional clearance 0.53 ± 0.10). Literature review revealed that urea was the only solute previously known to possess these properties. A further search for solutes whose properties include a high dialytic clearance, a relatively low native kidney clearance, and a high volume of distribution could help identify solutes that contribute to uremic symptoms.

MsiFlow: automated workflows for reproducible and scalable multimodal mass spectrometry imaging and microscopy data analysis

Multimodal imaging by matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI MSI) and microscopy holds potential for understanding pathological mechanisms by mapping molecular signatures from the tissue microenvironment to specific cell populations. However, existing software solutions for MALDI MSI data analysis are incomplete, require programming skills and contain laborious manual steps, hindering broadly applicable, reproducible, and high-throughput analysis to generate impactful biological discoveries. Here, we present msiFlow, an accessible open-source, platform-independent and vendor-neutral software for end-to-end, high-throughput, transparent and reproducible analysis of multimodal imaging data. msiFlow integrates all necessary steps from raw data import to analytical visualisation along with state-of-the-art and self-developed algorithms into automated workflows. Using msiFlow, we unravel the molecular heterogeneity of leukocytes in infected tissues by spatial regulation of ether-linked phospholipids containing arachidonic acid. We anticipate that msiFlow will facilitate the broad applicability of MSI in multimodal imaging to uncover context-dependent cellular regulations in disease states.

Prominent Bump in the Two-Neutron Separation Energies of Neutron-Rich Lanthanum Isotopes Revealed by High-Precision Mass Spectrometry

Prominent Bump in the Two-Neutron Separation Energies of Neutron-Rich Lanthanum Isotopes Revealed by High-Precision Mass Spectrometry