High-resolution Mass Spectrometry Research Articles

Clinical formulation Zhigan Oral Liquid intervenes in alcoholic liver injury by regulating the intestinal flora and PI3K\\AKT\\NF-κB pathway

Introduction: Zhigan Oral Liquid (ZOL) was developed from the empirical formulation of Professor Zhao Wenxia, a nationally renowned practitioner of Chinese medicine, and it has been used in Chinese medicine for many years for the effective treatment of alcoholic liver damage (ALD). However, the interventional mechanism of action of the dosage indications for different stages of ALD pathogenesis is not clear. Methods: The main chemical components of ZOL were qualitatively analyzed by ultra-high performance liquid chromatography (UHPLC-Q-Orbitrap HRMS) in tandem with quadrupole electrostatic field orbital well high resolution mass spectrometry and quantitatively analyzed by high-performance liquid chromatography (HPLC). Network pharmacological analysis was performed to predict the targets and pathways of the potential pharmacodynamic components. The pharmacodynamic effects and potential target mechanisms were verified in a murine model of ALD. To observe the effect of ZOL on the intestinal flora, 16s rDNA sequencing was performed on ALD mice. Results: ZOL can achieve alcohol detoxification by increasing the activity of ALDH and other detoxification enzymes and can intervene in the process of alcoholic liver injury and liver fibrosis by regulating the alcohol-induced bacterial dysbiosis, increasing the level of antioxidants, and inhibiting the activation of the PI3K\\AKT\\NF-κB signaling pathway. Kakkalide, Luteolin, Puerarin, tectoridin, and dihydromyricetin are related to the flavonoids that may be the main pharmacodynamic components that exert their medicinal effects. Conclusions: The findings have significant implications for the development of Empirical treatments for alcoholic liver injury. Furthermore, the study contributes to promoting development and utilization of new dosage forms of hospital preparations by emphasizing the composition identification and animal experimental efficacy of ZOL. Overall, this study provides valuable insights into establishing an alcohol-induced liver injury model, and demonstrates the potential of ZOL as a common treatment for alcoholic liver injury a rich source.

Associations between volatile organic compounds exposure and multiple oxidative damage biomarkers: Method development, human exposure, and application for e-waste pollution prediction

Atmospheric monitoring studies reveal substantial health risks from exposure to volatile organic compounds (VOCs) for workers and nearby children in e-waste recycling areas (ERA), yet internal exposure risks are seldom examined. To address this, we developed a method to simultaneously analyze 12 urinary VOC metabolites (mVOCs) and oxidative damage biomarkers (ODBs) in workers and children from ERA and general adults from control areas using ultrahigh performance liquid chromatography coupled with quadrupole/orbitrap high-resolution mass spectrometry (UPLC-Orbitrap-HRMS). The results showed that e-waste workers exhibited significantly higher levels of VOC exposure and ODBs than e-waste children and control adults. Exceeding 91.1 %, 69.1 %, 20.8 %, 19.7 %, and 3.26 % of e-waste workers faced non-carcinogenic risk from exposure to acrolein, acrylonitrile, acrylamide, 1,3-butadiene, and 1,2-dichloroethane, respectively. The weighted quantile sum, quantile g-computation, and Bayesian kernel machine regression models consistently indicated significant positive associations between these VOC mixtures and cholesterol ODB levels (i.e., glycocholic acid, cholic acid, and glycochenodeoxycholic acid), highlighting the necessity for improved protective measures for occupational workers. Interestingly, cholesterol ODBs significantly mediated the association between VOCs exposure and nucleic acid ODBs, accounting for 12.0–26.0 % of the association with 8-hydroxy-2′-deoxyguanosine (an oxidative DNA damage biomarker) and 25.4–53.4 % with 8-hydroxyguanosine (an oxidative RNA damage biomarker). This suggests that cholesterol ODBs potentially serve as better indicators of health risks from VOC exposure than nucleic acid ODBs. Additionally, the combination of mVOCs and ODBs (Mean AUC: 0.906, ACC: 0.821) as exposure fingerprints outperformed either mVOCs (Mean AUC: 0.878, ACC: 0.802) or ODBs (Mean AUC: 0.843, ACC: 0.768) alone in predicting the presence of e-waste pollution, underscoring the importance of integrating exposure and effect biomarker fingerprints to accurately capture e-waste pollution characteristic. Our findings offer a novel approach for screening e-waste pollution in unknow e-waste recycling sites and provide a foundation for developing high-precision prediction models for other polluting industries.

Dispersive solid phase extraction of 18 PFAS from environmental water samples using a novel MOF-polymeric monolith composite followed by High-Resolution mass spectrometry analysis

Metal-organic frameworks (MOFs) have been broadly coupled with many pretreatment techniques due to their remarkable attributes including high porosity, significantly increased specific surface area, and chemical stability, but their nanoscale dimensions make their handling challenging. To overcome this, a novel MOF-polymeric monolith composite was synthesized and studied as a novel sorbent material in an analytical technique. A rapid and efficient method for the extraction of a mixture of 18 per- and poly-fluoroalkyl (PFAS) compounds from environmental water samples was established based on MOF-polymeric monolith composite assisted dispersive solid phase extraction (d-SPE). The analytical methodology was carried out with the aid of liquid chromatography tandem high-resolution mass spectrometry. Several parameters influencing the extraction efficiency were comprehensively evaluated and optimized. The optimization was based on two processes: the one-variable-at-a-time approach (OVAT) and the central composite design (CCD). Preliminary studies were conducted and the extraction and elution time, as well as the sample volume were evaluated by adopting OVAT approach. The optimal parameters were found to be 15 min for extraction time, 5 min for the elution time and 10 mL as sample volume. Under the optimum conditions, the sample pH, sorbent amount and eluent volume were all evaluated under the design of experiments (DoE). ANOVA demonstrated the suitability of the suggested model with a p-value of less than 0.05 and various diagnostic tests validate the well-fitting results. The software extracted the optimal conditions which were pH = 7, sorbent amount = 10 mg and eluent volume = 750 μL. The method was subsequently validated with respect to accuracy, linearity detection limits and reproducibility. The proposed method presented recoveries over 70 %, method detection limits 1–46 ng/L and relative standard deviations <20 %. Before the implementation of the method in real samples, the “green” character was evaluated using the ComplexGAPI index, indicating the satisfactorily “green” character of the new MOF-based dSPE-LC-HRMS method. Finally, the efficacy of the method for determining PFASs in four environmental water matrices was tested using several matrices of varying complexity, including wastewater effluent, river water, marine water, and runoff.

Associations of per- and polyfluoroalkyl substances with human milk metabolomic profiles in a rural North American cohort.

Per- and polyfluoroalkyl substances (PFAS) are a class of persistent synthetic chemicals that are found in human milk and are associated with negative health effects. Research suggests that PFAS affect both lactation and the human metabolome. We measured perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) in the milk of 425 participants from the New Hampshire Birth Cohort Study using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A nontargeted metabolomics assay was performed using LC with high-resolution MS, and metabolites were identified based on in-house database matching. We observed six metabolic profiles among our milk samples using self-organizing maps, and multinomial logistic regression was used to identify sociodemographic and perinatal predictors of these profiles, including infant sex, parity, participant body mass index, participant age, education, race, smoking status, gestational weight gain, and infant age at time of milk collection. Elevated PFOA was associated with profiles containing higher amounts of triglyceride fatty acids, glycerophospholipids and sphingolipids, and carnitine metabolites, as well as lower amounts of lactose and creatine phosphate. Lower concentrations of milk PFOS were associated with lower levels of fatty acids. Our findings suggest that elevated PFOA in human milk is related to metabolomic profiles consistent with enlarged milk fat globule membranes and altered fatty acid metabolism. Further, our study supports the theory that PFAS share mammary epithelial membrane transport mechanisms with fatty acids and associate with metabolic markers of reduced milk production.

When subcellular chemical imaging enlightens our understanding on intestinal absorption, intracellular fate and toxicity of PFOA in vitro

Perfluorooctanoic acid (PFOA) is a persistent organic pollutant that accumulates in the human body, leading to major health issues. Upon oral uptake, the gastrointestinal tract is the first biological barrier against PFOA. However, the localization of PFOA and its impact on the intestinal wall are largely unknown. Here we achieve a breakthrough in the knowledge of intestinal absorption, intracellular fate and toxicity of PFOA using in vitro assays combined with novel analytical imaging techniques. For the first time, we localized PFOA in the cytosol of Caco-2 cells after acute exposure using high spatial resolution mass spectrometry imaging, and we estimated the PFOA cytosolic concentration. Knowing that PFOA enters and accumulates in the intestinal cells, we also performed common toxicity assays assessing cell metabolic activity, membrane integrity, oxidative stress response, and cell respiration. This study integrating powerful analytical techniques with widely used toxicology assays provides insightful information to better understand potential negative impacts of PFOA and opens new opportunities in toxicology and life science in general.

Fluorotelomer Alcohol (FTOH) Emission Rates from New and Old Rain Jackets to Air Determined by Iodide High-Resolution Chemical Ionization Mass Spectrometry

Per- and polyfluoroalkyl substances (PFAS), which include fluorotelomer alcohols (FTOHs), are synthetic chemicals used in consumer products because of their water-, stain-, and grease-repellent properties; thus, PFAS are commonly found in functional clothing such as rain jackets. To date, emissions of PFAS from products to indoor air have not been well characterized, although many PFAS-containing products are used and stored indoors. We used a test chamber connected to a high-resolution time-of-flight chemical ionization mass spectrometer equipped with iodide as a reagent ion (I-HR-ToF-CIMS) to measure emission rates for four FTOHs from 10 rain jackets and one backpack cover. The materials were categorized as old/used, new, or “PFAS-free”, and they were tested under two different scenarios, i.e., immediately out of package and after airing out. We observed real-time FTOH emissions from all materials. Under the out-of-package scenario, emissions of 6:2, 8:2 and 10:2 FTOH showed characteristics that indicate mass transfer is limited by internal diffusion, with a high initial peak followed by a lower steady-state emission rate. Peak emission rates correlated well with material-phase concentrations determined by an offline extractive gas chromatography-mass spectrometry (GC-MS) method. Our results further suggest that the old, used jackets had, on average, higher peak emission rates and higher material-phase concentrations than the new jackets, largely driven by 8:2 FTOH. “PFAS-free” materials had the overall lowest emission rates and material-phase concentrations. After airing out, emission rates were on average an order of magnitude lower than peak emission rates. Our findings emphasize the importance of considering consumer products like rain jackets as sources of indoor exposure to PFAS.

Effects of relative humidity on atmospheric organosulfur species derived from photooxidation and nocturnal chemistry in a forest environment

The molecular composition of organic aerosols in ambient PM2.5 was investigated at the northern foothills of Qinling Mountain region in central China during the summer of 2022. The molecular characteristics of organic matter were analyzed using ultrahigh performance liquid chromatography coupled with high-resolution Orbitrap mass spectrometry. The number of molecular formula assignments was dominated by organosulfur species (OrgS, on average 28–47% in total). Both the number and peak area of OrgS increased significantly with higher relative humidity (RH), while those of CHO and CHON species decreased, indicating the different impacts of RH on individual organic groups. The entire study period was divided into two distinct stages, including a low RH and a high RH period (LRH and HRH). The enhanced formation of CHOS with O>7 in HRH was primarily attributed to photochemical oxidation, whereas the increase in CHONS with O>7 was driven by enhanced NO3 radical-initiated oxidation under elevated RH conditions. Nearly 50% of OrgS presented only in HRH had aliphatic structures with C≥9. Although isoprene-derived organosulfates dominated the peak area across the entire period, the monoterpenes and long-chain alkanes-derived organosulfates largely increased in HRH. The strong correlations between aerosol liquid water content and OrgS containing high oxygen content (O>7) indicate that aqueous-phase reactions played a crucial role in multigenerational oxidation of OrgS. This study highlights the important effects of RH on the formation of OrgS, particularly for organosulfates derived from monoterpenes and long-chain alkanes.

Supramolecular biosolvent extraction of antioxidants from orange peel residues from the tea industry

The growing interest in natural antioxidants across various industries has spurred the development and use of alternative green methods for valorizing plant biomass. Supramolecular solvents (bioSUPRAS), composed of self-assembled amphiphilic aggregates, have shown significant potential for the recovery of high-value compounds from plant biomass for industrial applications while adhering to numerous green chemistry principles. In this study, we evaluated various bioSUPRAS (sponge bioSUPRAS of 1,2-octanediol and cubosomic bioSUPRAS of 1,2-hexanediol) and different extraction conditions for the recovery of antioxidants from orange peel waste generated by the tea industry. Sponge bioSUPRAS were selected as optimal and the best conditions for formation consisted of a medium of 15 % v/v of 1,3-propanediol as co-solvent and 85 % v/v of water (acidified with 1 % v/v acetic acid). The most suitable extraction conditions were 1:12 mL:g bioSUPRAS-to-solid ratio at room temperature for 30 min, resulting in a maximum yield of 12.9 ± 1.4 mg GAE/g. Using liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-QTOF), we screened and quantified the natural compounds of interest, identifying the flavonoid hesperidin as the dominant antioxidant at 2.6 ± 0.06 mg/g. This research presents a promising method for valorizing underutilized orange peel waste and highlights the potential of these extracts as ingredients in new value-added formulations.

Bioactive Constituents and the Molecular Mechanism of Melastoma dodecandrum Lour. in the Treatment of Inflammation Based on Network Pharmacology and Molecular Docking

Background: Melastoma dodecandrum Lour. (MD) is a component used in traditional Chinese medicine that is widely distributed in southern China. MD has long been used clinically to treat various diseases, such as inflammation. However, the potential anti-inflammatory mechanism of MD remains to be elucidated. Objective: In this study, network pharmacology and experimental validation have been used to explore the underlying mechanism of MD in inflammation. Methods: The chemical composition of MD was determined using ultra-high performance liquid chromatography-electrospray ionization-high resolution mass spectrometry (UHPLC-ESI-HRMS). The effects of MD on pro-inflammatory cytokines, such as NO, i-NOS, IL-1β, and TNF-α, in RAW264.7 cells stimulated by lipopolysaccharide (LPS) were determined by ELISA and QRT-PCR. Through the analysis of multiple databases, targets for the treatment of inflammation with MD were identified. Other extensive analyses included PPI, GO, and KEGG pathway enrichment, which were completed through the use of the STRING database, Cytoscape software, and the DAVID database. Key targets and key components have been selected for molecular docking. Results: A total of 33 active components were identified in MD, and 134 common targets were obtained and used to construct the networks. Of these, 10 core components and 10 core targets of MD in the treatment of inflammation were identified. The GO and KEGG enrichment analyses revealed that the common targets were involved in multiple signaling pathways, including the PI3K-Akt signaling pathway, NOD-like receptor signaling pathway, chemokine signaling pathway, and IL-17 signaling pathway. The molecular docking methods confirmed the high affinity between bioactive molecules of MD and their targets in inflammation. Two core targets (PIK3CA and AKT) and three core components (asiatic acid, apigenin, and kaempferol) were found to be closely related to MD in the treatment of inflammation. In vitro, MD exerted a significant effect on LPS-stimulated NO, IL- 1β, and TNF-α secretion, and iNOS, IL-1β, and TNF-α expressions in macrophages. Conclusion: This study has demonstrated the bioactive constituents and mechanisms of MD in inhibiting the secretion of inflammatory factors and the multicomponent, multitarget, and multipathway treatment characteristics involved in inflammation, but this still needs further in vivo/in vitro experiments.

Chemical Migration from Reusable Plastic Bottles: Silicone, Polyethylene, and Polypropylene show Highest Hazard Potential in LC-HRMS Analysis

Estimating the chemical hazards of drinking water stored in reusable plastic bottles is challenging due to the numerous intentionally and unintentionally added chemicals. To address this, we developed a broad screening strategy using evaporation enrichment and liquid chromatography high-resolution mass spectrometry (LC-HRMS) to evaluate migration of non-volatile chemicals from various reusable plastic bottles. The study analyzed a wide range of materials, revealing significant variability in chemical profiles across different bottle types. Over 70% of nearly 1,000 unknown compounds were unique to specific bottles. Silicone, HDPE, LDPE, and PP bottles showed the highest migration rates, with silicone releasing the most unknowns, but also phthalates and plasticizers. PP bottles exhibited concerning migration of clarifying agents and bisphenol A derivatives. In contrast, PS, PET, PETG, and PCTG had minimal migration, indicating lower health risks. These findings highlight the need for comprehensive assessments of plastic materials to improve consumer safety.

Platelet storage failure—Metformin as causative agent

AbstractBackgroundPathogen reduction technology (PRT)‐treated apheresis platelets (APs) were returned without platelet swirl and with pH22°C &lt; 6.2. The platelet donor was taking prescription levothyroxine and metformin plus over‐the‐counter medications and supplements. We hypothesized that either PRT or medication was causative.Study Design and MethodsOne AP from a double AP collection from this donor was PRT‐treated, the other unit untreated. Units were assessed over 7‐day storage with a standard panel of platelet assays and metabolomics using high resolution mass spectrometry. The dose effect of metformin on platelets over storage was evaluated in vitro using APs obtained from non‐medicated donors.ResultsThis donor's PRT‐ and non‐PRT treated paired units had pH values &lt;6.2 by the end of day 2. Lactate generation rates in the PRT‐ and non‐PRT units were very high compared to previously reported values and approached that reported for anaerobic storage. Metabolomic analysis revealed impairments in a number of energy metabolic pathways between PRT‐ and non‐PRT platelets; however, this did not support a major causative role of PRT in the significant upregulation of lactic acid production. Metformin caused a dose‐dependent upregulation of glycolysis, resulting in pH decline.DiscussionWe conclude that metformin is the most likely cause for this donor's stored platelet pH failures. Metformin is commonly used to treat type 2 diabetes and is not a donor deferral medication. Further investigation is indicated into the potential impact of metformin on platelet storage characteristics, the potential implications for medication deferral, and the need for additional screening tools in the laboratory.

Enhanced industrial wastewater monitoring: method development for non-target screening of highly polar substances using ZIC-HILIC-HRMS.

Non-target screening (NTS) plays a major role in the monitoring and management of water bodies. While the NTS of moderate to non-polar substances is well-established, the screening of highly polar chemicals remains challenging. In this study, a robust separation method for highly polar substances using zwitterionic hydrophilic interaction liquid chromatography coupled with high-resolution mass spectrometry (ZIC-HILIC-HRMS) was developed. This method was specifically designed for the NTS of industrial wastewater, with the objective of capturing a wide range of polar contaminants in each acquisition run. Method validation included assessing key parameters such as repeatability, reproducibility, linearity, and limit of detection (LOD). For repeatability and reproducibility, the average %RSD of intensity and retention time across all substances in different matrices-solvent, influent, and effluent-remained below 6% and 1%, respectively (n = 10). The method demonstrated good linearity (R2 > 0.99) for 75% of the substances, while LODs varied between 0.1 and 40µg/L depending on the compound tested. The method was then applied for NTS analysis of untreated wastewater at various locations within a chemical industrial park. Additionally, the overall influent and effluent of an industrial wastewater treatment plant (WWTP) were monitored over a 10-day period. Principal component analysis (PCA) was performed to interpret the data, identifying irregularities in the wastewater content. Moreover, the method demonstrated the WWTP's ability to achieve an average removal efficiency of approximately 90% for this category of substances in this period, while also detecting their degradation products in the effluent. Finally, the method was successfully integrated into the daily monitoring routine of the WWTP, ensuring continuous surveillance and improved management of wastewater treatment processes.

Characterization of poly(A) and poly(T) tail lengths in plasmid DNA by liquid chromatography high-resolution mass spectrometry.

Rapid advances in messenger RNA (mRNA) technology necessitate effective analytical methods. This study describes the development of a novel in vitro method using ion-pair reversed-phase liquid chromatography coupled to high-resolution mass spectrometry (IP-RP-LC-HRMS) for assessing the poly(A) and complementary poly(T) tail lengths directly into the DNA template used to manufacture mRNA. Briefly, after the validation of poly(A) tail length in the plasmid by Sanger sequencing, double-stranded DNA fragments containing these tails in the plasmid of interest were amplified by thepolymerase chain reaction (PCR), purified on silica column, and digested with restriction enzymes ClaI and HindIII. Gel or capillary electrophoresis confirmed sample quality and enzymatic digestion efficiency. Subsequently, poly(A) and complementary poly(T) tails were extracted and analyzed by LC-MS to determine their length and heterogeneity at a single-nucleotide resolution. Three DNA templates containing poly(A) tail lengths of 60A-G, 95A, or 108A were studied. LC-MS results correlated well with Sanger sequencing, identifying major populations of 60A-G, 95A, or 108A. Surprisingly, unlike Sanger sequencing, LC-MS analysis revealed minor poly(A) populations with lengths longer or shorter than the theoretically encoded poly(A) tail length. This finding could be explained by (i) the slippage of bacterial DNA polymerase I during plasmid replication in bacterial culture, which occurs on repeat mononucleotide sequences, or (ii) the slippage of Q5® High-Fidelity DNA Polymerase during PCR amplification. In conclusion, the method is easy, rapid, and accurate and could replace Sanger sequencing to assess the poly(A) and complementary poly(T) tail lengths in plasmid DNA.

Pregnancy influences on the rumen environment of Angus heifers differing in feed efficiency

With an expected increase in population by 2050, the demand for high-quality protein for human consumption will increase. To improve the sustainability of US cattle production, producers and researchers have historically focused on improving the feed efficiency of steers through improvements in genetics, nutrition, and microbiome management, producing a more marketable beef product. However, without a successful pregnancy, there would be no marketable animal to feed. The objective of this study was to examine the impact of pregnancy on the rumen environment, microbial communities, and the correlation to feed efficiency status in Angus heifers. Utilizing 17 cannulated Angus heifers, feed efficiency status was determined using the GrowSafe 8000 feed intake monitoring system to monitor feed intake for a 70d trial period to calculate residual feed intake. Following the trial, heifers were bred and 40mL rumen fluid and content samples were collected every two weeks during gestation. Metagenomic DNA was extracted from the rumen samples, sequencing libraries were prepared targeting the bacterial V4 region of the 16S rRNA gene, and resultant libraries were sequenced on an Illumina MiSeq. All microbial analyses were conducted in the R environment v2.6.2 where alpha diversity, beta diversity, and differential abundances were determined. Metabolites were identified using ultra high-performance liquid chromatography high resolution mass spectrometry, and Metabolomic Analysis and Visualization Engine was used to select metabolite peaks. Differential abundance analyses using “ANCOMBC” indicated 10 amplicon sequence variants (ASVs), assigned to seven Prevotella and three Succiniclasticum, significantly varied among weeks of gestation (P&amp;lt;0.05). Based on a one-way ANOVA, 90 metabolites were determined significant throughout pregnancy (P&amp;lt;0.05). The 10 metabolites with the highest variable importance of projection scores from a partial least squares discriminant analysis were used to calculate correlations between. Of the 10 ASVs and 10 metabolites, significant correlations with feed efficiency status were found at various time points (P&amp;lt;0.05). The rumen microbiome and its fermentative profile were different at various time points during pregnancy with several correlations to feed efficiency status. Identifying pregnancy-related microbial and metabolite changes may aid producers to anticipate nutritional or management adjustments, ultimately contributing to the sustainability of beef production.

Integration of high-resolution mass spectrometry technology with molecular network analysis and systems biology techniques to elucidate the active ingredients and mechanisms of Shiduqing capsules.

Shiduqing Capsules, a well-known Chinese patent medicine, are widely used clinically for the treatment of pruritus. However, to date, there is a lack of research on its pharmacological substances and mechanisms of action. In the current study, the chemical components of Shiduqing Capsules were identified using UHPLC-QE-Orbitrap-MS technology. Molecular network analysis was employed to identify structurally similar compounds to the known chemical components. The potential molecular targets of the active ingredients were predicted using the SwissTargetPrediction website. The identified targets were further analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis through the DAVID database. Molecular docking was used to validate the network pharmacology results. Ultimately, A total of 51 chemical components of Shiduqing Capsules were identified. Molecular network analysis identified 21 flavonoids and 13 terpenoids. The core targets of these ingredients include TP53, AKT1, and STAT3. GO and KEGG enrichment analysis revealed 1,371 different biological functions and 177 signaling pathways. Molecular docking confirmed the high affinity between multiple core active ingredients of Shiduqing Capsules and pruritus targets. In conclusion, the effective ingredients of Shiduqing Capsules exert a multifaceted therapeutic effect on pruritus through multiple targets and pathways.

Enhanced removal of trace-level per- and polyfluoroalkyl substances (PFAS) from drinking water using granular activated carbon (GAC): the role of ozonation.

Granular activated carbon (GAC) is a promising approach for removing per- and polyfluoroalkyl substances (PFAS) from drinking water. However, GAC filters usually suffer early PFAS breakthroughs due to the competition between PFAS and natural organic matter (NOM) during sorption. The present study investigated the possibility of using ozonation to enhance the GAC performance for PFAS removal. Rapid-small-scale-column tests were performed for three GACs using filtered or filtered and ozonated water. NOM was fractionated using liquid chromatography-organic carbon detection (LC-OCD), and 76 ambient PFAS were quantified using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). Although ozonation did not remove either NOM or PFAS, it altered their composition in water. Ozonation reduced the hydrophobicity and the molecular size of natural organic matter (NOM). On the other hand, ozonation oxidized some PFAS precursors, leading to a higher total detected PFAS concentration in the filtered and ozonated water than in filtered water (10.2 ± 0.7 ng/L vs. 9.5 ± 0.7 ng/L). The impact of ozonation on GAC performance for NOM and PFAS removal mainly depended on GAC properties. GAC with a lower micropore volume showed an improvement in NOM and PFAS removal when ozonation was applied, approaching the performance of GACs with higher micropore volumes.

Synthesis and Antifungal Activity Evaluation of Novel L-Carvone-Based 1,3,4-Thiadiazole-amide Derivatives as a Potential Succinate Dehydrogenase Inhibitor.

In an effort to explore new-type high-efficiency antifungal agents, 25 novel L-carvone-based 1,3,4-thiadiazole-amide derivatives were designed, synthesized, and structurally characterized by IR, 1H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS) analyses. The antifungal activity of the target compounds was preliminarily assayed at a concentration of 50 μg/mL, and boscalid, a commercialized fungicide identified as a succinate dehydrogenase inhibitor (SDHI), was employed as the positive control. It was found that all of the target compounds showed moderate to potent antifungal activity against the tested fungi compared to boscalid. Surprisingly, compound 4b exhibited broad-spectrum and significant inhibition activity against the growth of eight phytopathogenic strains with inhibitory rates of 67-89%. Further, the results of the EC50 value test suggested that the EC50 values of compound 4b against Physalospora piricola and Colletotrichum orbiculare were 16.33 and 18.06 μg/mL, respectively, and both of them were better than those of boscalid (16.64 and >50). Therefore, compound 4b deserves further study as a lead compound for novel fungicides. In addition, the inhibitory activity of compound 4b against succinate dehydrogenase (SDH) was evaluated as well to prove that compound 4b (IC50 = 3.38 μM) displayed higher SDH-inhibition activity than boscalid (IC50 = 7.02 μM). The binding mode of compound 4b and SDH was simulated by molecular docking and found to be similar to that of boscalid. The structure-activity relationships (SARs) of the target compounds were analyzed by establishing a 3D-QSAR model. Besides, a 4b-loaded complex 4b/CSTA on a reported L-carvone-based nanochitosan carrier CSTA containing the 1,3,4-thiadiazole-amide group was constructed, and its sustained release performance was investigated in the EtOH-H2O system (1:9, v/v). The complex 4b/CSTA exhibited preferred sustained release performance, indicating its potential for developing environmentally friendly nanofungicides.

Advantages of Metabolomics-Based Multivariate Machine Learning to Predict Disease Severity: Example of COVID

The COVID-19 outbreak caused saturations of hospitals, highlighting the importance of early patient triage to optimize resource prioritization. Herein, our objective was to test if high definition metabolomics, combined with ML, can improve prognostication and triage performance over standard clinical parameters using COVID infection as an example. Using high resolution mass spectrometry, we obtained metabolomics profiles of patients and combined them with clinical parameters to design machine learning (ML) algorithms predicting severity (herein determined as the need for mechanical ventilation during patient care). A total of 64 PCR-positive COVID patients at the Poitiers CHU were recruited. Clinical and metabolomics investigations were conducted 8 days after the onset of symptoms. We show that standard clinical parameters could predict severity with good performance (AUC of the ROC curve: 0.85), using SpO2, first respiratory rate, Horowitz quotient and age as the most important variables. However, the performance of the prediction was substantially improved by the use of metabolomics (AUC = 0.92). Our small-scale study demonstrates that metabolomics can improve the performance of diagnosis and prognosis algorithms, and thus be a key player in the future discovery of new biological signals. This technique is easily deployable in the clinic, and combined with machine learning, it can help design the mathematical models needed to advance towards personalized medicine.

Investigation of the mechanism of [M-H]+ ion formation in photoionized N-alkyl-substituted thieno[3,4-c]-pyrrole-4,6-dione derivatives during higher order MSn high-resolution mass spectrometry.

The mechanism underlying dopant-assisted atmospheric pressure photoionization's (APPI) formation of ions is unclear and still under debate for many chemical classes. In this study, we reexamined the gas-phase reaction mechanisms responsible for the generation of [M-H]+ precursor ions, resulting from the loss of a single hydrogen atom, in a series of N-alkyl-substituted thieno[3,4-c]-pyrrole-4,6-dione (TPD) derivatives. Atmospheric pressure photoionization combined with higher order MS/MSn using high-resolution mass spectrometry (APPI-HR-CID-MSn) and electronic structure calculations using density functional theory were used to determine the chemical structure of observed [M-H]+ ions. As a result, the higher order MSn (n = 3) experiments revealed a reversed Diels-Alder fragmentation mechanism, leading to a common fragment ion at m/z 322 from the studied [M1-5-H]+ ion species. In addition, the calculation for two chemical structure models (N-alkyl-TPD1 and N-alkyl-TPD5) showed that the fragment structure, resulting from the removal of the hydrogen atom connected to the third carbon atom of the N-alkyl side chain, has a more stable cyclic form compared with the linear one. The proposed chemical structure of the N-alkyl TPD ion species, following the loss of a single hydrogen atom, was revealed during APPI-HR-CID-MSn (n= 3) experiments on the [M-H]+ species. Hydrogen radical (H•) abstraction from the alkyl side chain (e.g., hexyl, heptyl, octyl, 2-ethylhexyl, and nonyl) triggered a rearrangement in the radical cation structure of the N-alkyl-TPD derivatives, initiating cyclization and forming a six-membered ring that connects the oxygen atom to the third carbon atom in the alkyl chain. In addition, theoretical calculations supported the APPI-HR-CID-MSn (n = 3) experiments by demonstrating that the proposed chemical structure, resulting from the intramolecular cyclization of the N-alkyl-TPD ion species, was stable in the presence of chlorobenzene. These findings will aid the structural determination and elucidation of molecules with similar core structures.

Skeletal Editing of Energetic Materials: Acid-Catalyzed One-Step Synthesis of Bridged Triazoles as High-Energy-Density Materials via the Nef Reaction.

Thermally stable insensitive energetic materials have captivated significant attention from the global research community due to their potential impact. In this study, a series of symmetric and asymmetric nitromethyl-bridged triazole compounds were synthesized from pyrimidine moieties via a skeletal editing approach. Additionally, carbonyl-bridged compounds were synthesized in a single step by using acid-catalyzed Nef reactions from their nitromethyl precursors. Peripheral modifications of pyrimidine resulted in fused energetic moieties. All synthesized compounds were fully characterized by using infrared spectroscopy, high-resolution mass spectrometry, multinuclear magnetic resonance spectroscopy, elemental analysis, and differential scanning calorimetry. Single-crystal X-ray diffraction analysis confirmed the structures of compounds 4 and 10. The newly synthesized moieties exhibit densities ranging from 1.75 to 1.86 g cm-3, detonation velocities between 8044 and 8608 m s-1, and detonation pressures between 23.10 and 30.31 GPa. Notably, compounds 9 and 10 demonstrate exceptional heat resistance, with decomposition temperatures of 315 and 335 °C, respectively. Computational studies, including density functional theory, quantum theory of atoms in molecules, noncovalent interactions, and electrostatic surface potential analysis, account for hydrogen-bonding and noncovalent interactions. This work highlights the potential of skeletal editing in the development of high-performing, thermally stable energetic materials.