A combined approach of target,suspected target and non-target screening using liquid chromatography-high-resolution mass spectrometry(LC-HRMS)was used to develop a new concept for water monitoring.With the current LC-...A combined approach of target,suspected target and non-target screening using liquid chromatography-high-resolution mass spectrometry(LC-HRMS)was used to develop a new concept for water monitoring.With the current LC-MS/MS target approach for water monitoring,all targets can be quantified,but no additional information about the sample is collected.With the new concept,it is possible to detect 97%of the target compounds with a simplified quantification method without losing accuracy.Furthermore,a suspect target screening can be performed to get broader qualitative information about the water samples.In addition,the non-target screening offers the possibility to identify unknown micropollutants.All three evaluation steps depend on the same analytical measurement so that a lot of measurement and quality assurance effort can be saved.This concept could change water monitoring and assessment,and make it much more efficiently without losing information.There is a chance to measure less but learn more about the water bodies.展开更多
The article evaluated the degradation of the captopril in aqueous solution after ozonation and chlorination. The process was continuously monitored focusing on the identification, mass spectrometry and elucidation of ...The article evaluated the degradation of the captopril in aqueous solution after ozonation and chlorination. The process was continuously monitored focusing on the identification, mass spectrometry and elucidation of its by-products by applying direct infusion and high performance liquid chromatography, electrospray ionization high resolution mass spectrometry, in the negative ion mode. The cytotoxicity of its by-products solutions were evaluated with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. It was observed through that after 30 min of ozonation and chlorination, there was complete oxidation of captopril, i.e., 100% removal efficiency. At these conditions, the rate of mineralization, by total organic carbon, was only 7.63% for ozonation and 6.40% for chlorination, evidencing the formation of degradation by-products. Ten captopril by-products were identified and their respective chemical structures elucidations are proposed. The treated samples and their by-products were nontoxic to HepG2 cells by MTT assay.展开更多
Steam flooding is a widely used technique to enhance oil recovery of heavy oil.Thermal viscosity reduction and distillation effect are considered as two main displacement mechanisms in steam flooding process.However,t...Steam flooding is a widely used technique to enhance oil recovery of heavy oil.Thermal viscosity reduction and distillation effect are considered as two main displacement mechanisms in steam flooding process.However,the molecular composition understanding and contribution for oil production are still unclear.In this study,the composition analysis of the heavy oil was investigated in the core scale steam flooding process with the temperature from 120 to 280℃.The crude oil,produced oils and residual oils were characterized comprehensively by gas chromatography and high-resolution mass spectrometry.It is found that steam flooding preferentially extracts aromatics and remains more resins in the residual oil.Viscosity reduction is the dominant mechanism when steam is injected at a low temperature.Large molecular heteroatoms with high carbon number and high double bond equivalent(DBE)are eluted into the produced oil,while compounds with low carbon number and low DBE are remained in the residual oil.As the steam temperature rises,the increased distillation effect results in the extraction of light hydrocarbons from the residual oil to the produced oil.More small heteroatoms with low carbon number and low DBE enter into the produced oil,especially in the none water cut stage.The compositional difference of produced oils is characterized in DBE versus carbon number distribution of the N and O containing compound classes.This work uses a variety of composition analysis methods to clarify the steam flooding mechanism and provides a novel understanding of steam flooding mechanisms with various temperatures and production stages from the molecular perspective.展开更多
Improving analytical throughput is the focus of many quantitative workflows being developed for early drug discovery.For drug candidate screening,it is common practice to use ultra-high performance liquid chromatograp...Improving analytical throughput is the focus of many quantitative workflows being developed for early drug discovery.For drug candidate screening,it is common practice to use ultra-high performance liquid chromatography(U-HPLC)coupled with triple quadrupole mass spectrometry.This approach certainly results in short analytical run time;however,in assessing the true throughput,all aspects of the workflow needs to be considered,including instrument optimization and the necessity to re-run samples when information is missed.Here we describe a high-throughput metabolic stability assay with a simplified instrument set-up which significantly improves the overall assay efficiency.In addition,as the data is acquired in a non-biased manner,high information content of both the parent compound and metabolites is gathered at the same time to facilitate the decision of which compounds to proceed through the drug discovery pipeline.展开更多
Ensuring the health and safety of drinking water is crucial for both nations and their citizens.Since the 20th century,the disinfection of drinking water,effectively controlling pathogens in water sources,has become o...Ensuring the health and safety of drinking water is crucial for both nations and their citizens.Since the 20th century,the disinfection of drinking water,effectively controlling pathogens in water sources,has become one of the significant advances in public health.However,the disinfectants used in the process,such as chlorine and chlorine dioxide,react with natural organic matter in the water to produce disinfection by-products(DBPs).Most of these DBPs contain chlorine,and if the source water contains bromine or iodine,brominated or iodinated DBPs,collectively referred to as Halogenated disinfection byproducts(X-DBPs),are formed.Numerous studies have found that X-DBPs pose potential risks to human health and the environment,leading to widespread concern.Mass spectrometry has become an important means of discovering new types of X-DBPs.This paper focuses on the study of methods for analyzing X-DBPs in drinking water using mass spectrometry.展开更多
Ambient air pollution,containing numerous known and hitherto unknown compounds,is a major risk factor for public health.The discovery of harmful components is the prerequisite for pollution control;however,this raises...Ambient air pollution,containing numerous known and hitherto unknown compounds,is a major risk factor for public health.The discovery of harmful components is the prerequisite for pollution control;however,this raises a great challenge on recognizing previously unknown species.Here we systematically review the analytical techniques on air pollution in the framework of an omics approach,with a brief introduction on sample preparation and analysis,and in more detail,compounds prioritization and identification.Through high-resolution mass spectrometry(HRMS,typically coupled with chromatography),the complicated environmental matrix can be digitalized into“fullcomponent”data.A key step to discover emerging compounds is the prioritization of compounds from massive data.Chemical fingerprints,suspect lists and biological effects are the most vital untargeted strategies for comprehensively screening critical and hazardous substances.Afterward,compressed data of compounds can be identified at various confidence levels according to exact mass and the derived molecular formula,MS libraries,and authentic standards.Such an omics approach on full-component data provides a paradigm for discovering emerging air pollutants;nonetheless,new technological advancements of instruments and databases are warranted for further tracking the environmental behaviors,hence to evaluate the health risk of key pollutants.展开更多
Parkinson’s disease(PD)is a complex neurological disorder that typically worsens with age.A wide range of pathologies makes PD a very heterogeneous condition,and there are currently no reliable diagnostic tests for t...Parkinson’s disease(PD)is a complex neurological disorder that typically worsens with age.A wide range of pathologies makes PD a very heterogeneous condition,and there are currently no reliable diagnostic tests for this disease.The application of metabolomics to the study of PD has the potential to identify disease biomarkers through the systematic evaluation of metabolites.In this study,urine metabolic profiles of 215 urine samples from 104 PD patients and 111 healthy individuals were assessed based on liquid chromatography-mass spectrometry.The urine metabolic profile was first evaluated with partial leastsquares discriminant analysis,and then we integrated the metabolomic data with ensemble machine learning techniques using the voting strategy to achieve better predictive performance.A combination of 8-metabolite predictive panel performed well with an accuracy of over 90.7%.Compared to control subjects,PD patients had higher levels of 3-methoxytyramine,N-acetyl-l-tyrosine,orotic acid,uric acid,vanillic acid,and xanthine,and lower levels of 3,3-dimethylglutaric acid and imidazolelactic acid in their urine.The multi-metabolite prediction model developed in this study can serve as an initial point for future clinical studies.展开更多
Chemical profiles of non-invasive biological material,such as feces,have great potential to study elusive animals or those with low population densities.Here,we use a metabolomic approach to evaluate Neotropical mustel...Chemical profiles of non-invasive biological material,such as feces,have great potential to study elusive animals or those with low population densities.Here,we use a metabolomic approach to evaluate Neotropical mustelids as a biological model to describe the diversity of the metabolites present in fecal samples,as well as to evaluate the potential of chemical profiles for taxonomic discrimination.We collected fecal samples from captive individuals of 5 species of mustelids occurring in Brazil and analyzed them by liquid chromatography coupled to high-resolution mass spectrometry.Over 200 compounds have been annotated;“bile acids,alcohols and derivatives”was the most expressive class in the metabolome of all the species.We successfully discriminated 3 taxonomic groups:1—tayra(Eira barbara);2—otters(Lontra longicaudis and Pteronura brasiliensis;1);and 3—grisons(Galictis vittata and Galictis cuja).Several compounds seemed to be associated with food intake and the digestive process,while others were found for thefirst time in Neotropical mustelids.We concluded that mustelids show high metabolome diversity and that species-specific identification through metabolomic profiles is possible,thus contributing to the development and implementation of additional non-invasive approaches in the study of mustelids.展开更多
Soil salinity is among the abiotic stressors that threaten agriculture the most,and purslane(Portulaca oleracea L.)is a dicot species adapted to inland salt desert and saline habitats that hyper accumulates salt and h...Soil salinity is among the abiotic stressors that threaten agriculture the most,and purslane(Portulaca oleracea L.)is a dicot species adapted to inland salt desert and saline habitats that hyper accumulates salt and has high phytoremediation potential.Many researchers consider purslane a suitable model species to study the mechanisms of plant tolerance to drought and salt stresses.Here,a robust salinity stress protocol was developed and used to characterize the morphophysiological responses of young purslane plants to salinity stress;then,leaf tissue underwent characterization by distinct omics platforms to gain further insights into its response to very high salinity stress.The salinity stress protocol did generate different levels of stress by gradients of electrical conductivity at field capacity and water potential in the saturation extract of the substrate,and the morphological parameters indicated three distinct stress levels.As expected from a halophyte species,these plants remained alive under very high levels of salinity stress,showing salt crystal-like structures constituted mainly by Na^(+),Cl^(−),and K^(+)on and around closed stomata.A comprehensive and large-scale metabolome and transcriptome single and integrated analyses were then employed using leaf samples.The multi-omics integration(MOI)system analysis led to a data-set of 51 metabolic pathways with at least one enzyme and one metabolite differentially expressed due to salinity stress.These data sets(of genes and metabolites)are valuable for future studies aimed to deepen our knowledge on the mechanisms behind the high tolerance of this species to salinity stress.In conclusion,besides showing that this species applies salt exclusion already in young plants to support very high levels of salinity stress,the initial analysis of metabolites and transcripts data sets already give some insights into other salt tolerance mechanisms used by this species to support high levels of salinity stress.展开更多
Qing-Fei-Pai-Du decoction(QFPDD)is a Chinese medicine compound formula recommended for combating corona virus disease 2019(COVID-19)by National Health Commission of the People's Republic of China.The latest clinic...Qing-Fei-Pai-Du decoction(QFPDD)is a Chinese medicine compound formula recommended for combating corona virus disease 2019(COVID-19)by National Health Commission of the People's Republic of China.The latest clinical study showed that early treatment with QFPDD was associated with favorable outcomes for patient recovery,viral shedding,hospital stay,and course of the disease.However,the effective constituents of QFPDD remain unclear.In this study,an UHPLC-Q-Orbitrap HRMS based method was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD.A total of 405 chemicals,including 40 kinds of alkaloids,162 kinds of flavonoids,44 kinds of organic acids,71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature.With the help of the standards and in vitro metabolites,195 chemical components(including 104 prototypes and 91 metabolites)were identified in mice serum after oral administration of QFPDD.In addition,165,177,112,120,44,53 constituents were identified in the lung,liver,heart,kidney,brain,and spleen of QFPDD-treated mice,respectively.These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.展开更多
Pharmaceutical and personal care products(PPCPs)and corresponding transformation products have caused widespread concern due to their persistent emissions and potential toxicity.They have wide octanol-water partition ...Pharmaceutical and personal care products(PPCPs)and corresponding transformation products have caused widespread concern due to their persistent emissions and potential toxicity.They have wide octanol-water partition coefficients(K_(ow))and different ionization constants(pK_(a))resulting in a poor analysis accuracy and efficiency.A suitable analytical method is the first prerequisite for further research on their environmental behavior to prioritize the substances.This study reviewed a full-scale analytical protocol for environmental samples in the recent ten years:from sampling to instrumental methods.Passive sampling techniques were compared and recommended for long-term continuous and scientific observation.A quick and effective sample extraction and clean-up method are highly required.Chromatographic methods coupled to mass spectrometry for determining PPCPs with a wide range of logK_(ow)(-7.53 to 10.80)were summed up.High-resolution mass spectrometry was confirmed to be a promising strategy for screening unknown transformation products,which would provide a nanogram level of detection limits and more accurate mass resolution.Screening strategies and mass change principles were summarized in detail.The recovery rate was important in multiple contaminants analysis identification and factors affecting the recovery rate of PPCPs were also discussed in this review,including sample matrix,target compounds characteristics,extraction method and solid-phase adsorbent.This review provides useful information for the selection of appropriate analytical methods and future development directions.展开更多
Gestational diabetes mellitus(GDM),a frequently-occurring disease during pregnancy,may cause some adverse healthy outcome of both mother and offspring.However,the knowledge about metabolite alterations during the path...Gestational diabetes mellitus(GDM),a frequently-occurring disease during pregnancy,may cause some adverse healthy outcome of both mother and offspring.However,the knowledge about metabolite alterations during the pathogenesis and development process is limited.Here,a large longitudinal nontargeted metabolomics study of 195 pregnant women(64 women with subsequently developed GDM and131 healthy controls)was conducted.Each participant provided urine samples at three timepoints during early,middle and late pregnancy,respectively.The metabolic profiles of 585 urine samples(195×3)were measured by using ultra-high performance liquid chromatography coupled with Orbitrap high-resolution mass spectrometry.Among the 56 identified metabolites,the levels of eight metabolites increased and three ones decreased in the first trimester,the concentration of one metabolite increased and those of 20 decreased in the second trimester,as well as the levels of five metabolites increased and two decreased in the third trimester.After false discovery rate correction,the levels of valine and 5-acetamidovalerate in GDM group significantly increased in the first trimester,the levels of 1-methylguanine and 1,3-dihydro-(2 H)-indol-2-one significantly decreased in the second trimester and three metabolites(threonine,OH-octanedioyl-carnitine and pimelylcarnitine)increased and N-acetyltryptophan decreased in the third trimester,respectively.Six metabolites,such as pantothenic acid and threonine,had significant interaction effects between gestational stage(different trimester)and group(GDM or control).The differential metabolites were involved in“tryptophan metabolism”,“purine metabolism”,“valine,leucine and isoleucine degradation”and other pathways.The findings may provide insights into further pathogenesis study of GDM.展开更多
Despite the widespread occurrence of phenols in anthropogenic and natural compounds, their fate in reactions with hypochlorous acid(HOCl), one of the most common water treatment disinfectants, remains incompletely und...Despite the widespread occurrence of phenols in anthropogenic and natural compounds, their fate in reactions with hypochlorous acid(HOCl), one of the most common water treatment disinfectants, remains incompletely understood. To close this knowledge gap, this study investigated the formation of disinfection by-products(DBPs) in the reaction of free chlorine with seven para-substituted phenols. Based on the chemical structures of the DBPs and the reaction mechanisms leading to their formation, the DBPs were categorized into four groups: chlorophenols, coupling products, substituent reaction products, and ring cleavage products. In contrast to previous studies that investigated the formation of earlystage chlorophenols, the primary focus of this study was on the elucidation of novel ring cleavage products, in particular α, β-unsaturated C-dialdehydes, and C-dicarboxylic acids, which, for the first time, were identified and quantified in this study. The molar yields of 2-butene-1,4-dial(BDA), one of the identified α, β-unsaturated C-dialdehydes, varied among the different phenolic compounds, reaching a maximum value of 10.4% for bisphenol S. Molar yields of 2-chloromaleic acid(Cl-MA), one of the identified C-dicarboxylic acids, reached a maximum value of 30.5% for 4-hydroxy-phenylacetic acid under given conditions. 2,4,6-trichlorophenol(TCP) was shown to be an important intermediate of the parent phenols and the C-ring cleavage products. Based on the temporal trends of α, β-unsaturated C-dialdehydes and C-dicarboxylic acids, their formation is likely attributable to two separate ring cleavage pathways. Based on the obtained results, an overall transformation pathway for the reaction of para-substituted phenols with free chlorine leading to the formation of novel Cring cleavage products was proposed.展开更多
Exposure to environmental cadmium increases the health risk of residents.Early urine metabolic detection using high-resolution mass spectrometry and machine learning algorithms would be advantageous to predict the adv...Exposure to environmental cadmium increases the health risk of residents.Early urine metabolic detection using high-resolution mass spectrometry and machine learning algorithms would be advantageous to predict the adverse health effects.Here,we conducted machine learning approaches to screen potential biomarkers under cadmium exposure in 403 urine samples.In positive and negative ionization mode,4207 and 3558 features were extracted,respectively.We compared seven machine learning algorithms and found that the extreme gradient boosting(XGBoost)and random forest(RF)classifiers showed better accuracy and predictive performance than others.Following 5-fold cross-validation,the value of area under curve(AUC)was both 0.93 for positive and negative ionization modes in XGBoost classifier.In the RF classifier,AUC were 0.80 and 0.84 for positive and negative ionization modes,respectively.We then identified a biomarker panel based on XGBoost and RF classifiers.The incorporation of machine learning models into urine analysis using high-resolution mass spectrometry could allow a convenient assessment of cadmium exposure.展开更多
Allergy to sesame seeds is a food allergy of high relevance due to its high abundance and the potential to elicit allergenic reactions,possibly resulting in anaphylaxis.The major sesame allergen Ses i 1 is a 2S albumi...Allergy to sesame seeds is a food allergy of high relevance due to its high abundance and the potential to elicit allergenic reactions,possibly resulting in anaphylaxis.The major sesame allergen Ses i 1 is a 2S albumin belonging to the family of seed storage proteins and despite its high allergenicity,comprehensive knowledge about Ses i 1 variants is still lacking.We,therefore,performed a detailed sequence analysis and characterized the C-and N-terminal ragged clipping of the small and large subunit of Ses i 1 using high-resolution mass spectrometry and the combination of bottom–up,middle–down,and top–down proteomic approaches.We detected extensive clipping at the C-terminus of the large(3–9 aa)and the small subunit(0–7 aa).In addition,the N-terminal conversion from glutamine to pyroglutamate and limited N-terminal clipping was confirmed for both subunits.Furthermore,we observed a sequence conflict at position 147 of Ses i 1 as well as a sequence shift of the large subunit compared to the reference sequence of the precursor.展开更多
Brominated disinfection by-products(Br-DBPs)can form during the chlorination of drinking water in treatment plants(DWTP).Regulations exist for a small subset of Br-DBPs;however,hundreds of unregulated Br-DBPs have bee...Brominated disinfection by-products(Br-DBPs)can form during the chlorination of drinking water in treatment plants(DWTP).Regulations exist for a small subset of Br-DBPs;however,hundreds of unregulated Br-DBPs have been detected,and limited information exists on their occurrence,concentrations,and seasonal trends.Here,a data-independent precursor isolation and characteristic fragment(DIPIC-Frag)method were optimized to screen chlorinated waters for Br-DBPs.There were 553 Br-DBPs detected with m/z values ranging from 170.884 to 497.0278 and chromatographic retention times from 2.4 to 26.2 min.With MS2 information,structures for 40 of the 54 most abundant Br-DBPs were predicted.The method was then applied to a year-long study in which raw,clear well,and finished water were analyzed monthly.The 54 most abundant unregulated Br-DBPs were subjected to trend analysis.Br-DBPs with higher oxygen-to-carbon(O/C)and bromine-to-carbon(Br/C)ratios increased as water moved from the clear well to the finished stage,which indicated the dynamic formation of Br-DBPs.Monthly trends of unregulated Br-DBPs were compared to raw water parameters,such as natural organic matter,temperature,and total bromine,but no correlations were observed.It was found that total concentrations of bromine(TBr)in finished water(0.04–0.12 mg/L)were consistently and significantly greater than in raw water(0.013–0.038 mg/L,P<0.001),suggesting the introduction of bromine during the disinfection process.Concentrations of TBr in treatment units,rather than raw water,were significantly correlated to 34 of the Br-DBPs atα?0.05.This study provides the first evidence that monthly trends of unregulated Br-DBPs can be associated with the concentration of TBr in treated waters.展开更多
Traditional Chinese medicine(TCM)belongs to the most elaborate and extensive systems of plant-based healing.The herb Northern Ban Lan(Isatis tinctoria)is famous for its antiviral and anti-inflammatory activity.Althoug...Traditional Chinese medicine(TCM)belongs to the most elaborate and extensive systems of plant-based healing.The herb Northern Ban Lan(Isatis tinctoria)is famous for its antiviral and anti-inflammatory activity.Although numerous components isolated from I.tinctoria have been characterized so far,their modes of action have remained unclear.Here,we show that extracts from I.tinctoria exert antimicrotubular activity.Using time-lapse microscopy in living tobacco BY-2(Nicotiana tabacum L.cvBrightYellow2)cellsexpressing greenfluorescentprotein-tubulin,weuse activity-guided fractionation to screen out the biologically active compounds of I.tinctoria.Among 54 fractions obtained from either leaves or roots of I.tinctoria by methanol(MeOH/H_(2)O 8:2),or ethyl acetate extraction,one specific methanolic root fraction was selected,because it efficiently and rapidly eliminated microtubules.By combination of further purification with ultrahigh-performance liquid chromatography and high-resolution tandem mass spectrometry most of the bioactivity could be assigned to the glucosinolate compound glucobrassicin.Glucobrassicin can also affect microtubules and induce apoptosis in HeLa cells.In the light of these findings,the antiviral activity of Northern Ban Lan is discussed in the context of microtubules being hijacked by many viral pathogens for cell-to-cell spread.展开更多
文摘A combined approach of target,suspected target and non-target screening using liquid chromatography-high-resolution mass spectrometry(LC-HRMS)was used to develop a new concept for water monitoring.With the current LC-MS/MS target approach for water monitoring,all targets can be quantified,but no additional information about the sample is collected.With the new concept,it is possible to detect 97%of the target compounds with a simplified quantification method without losing accuracy.Furthermore,a suspect target screening can be performed to get broader qualitative information about the water samples.In addition,the non-target screening offers the possibility to identify unknown micropollutants.All three evaluation steps depend on the same analytical measurement so that a lot of measurement and quality assurance effort can be saved.This concept could change water monitoring and assessment,and make it much more efficiently without losing information.There is a chance to measure less but learn more about the water bodies.
基金the Minas Gerais State Science Foundation(FAPEMIG)-process APQ-00918-13the Brazilian National Research Council(CNPq)-process 473893-2013-1 for their financial support and the granting of research fellowships.
文摘The article evaluated the degradation of the captopril in aqueous solution after ozonation and chlorination. The process was continuously monitored focusing on the identification, mass spectrometry and elucidation of its by-products by applying direct infusion and high performance liquid chromatography, electrospray ionization high resolution mass spectrometry, in the negative ion mode. The cytotoxicity of its by-products solutions were evaluated with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. It was observed through that after 30 min of ozonation and chlorination, there was complete oxidation of captopril, i.e., 100% removal efficiency. At these conditions, the rate of mineralization, by total organic carbon, was only 7.63% for ozonation and 6.40% for chlorination, evidencing the formation of degradation by-products. Ten captopril by-products were identified and their respective chemical structures elucidations are proposed. The treated samples and their by-products were nontoxic to HepG2 cells by MTT assay.
文摘Steam flooding is a widely used technique to enhance oil recovery of heavy oil.Thermal viscosity reduction and distillation effect are considered as two main displacement mechanisms in steam flooding process.However,the molecular composition understanding and contribution for oil production are still unclear.In this study,the composition analysis of the heavy oil was investigated in the core scale steam flooding process with the temperature from 120 to 280℃.The crude oil,produced oils and residual oils were characterized comprehensively by gas chromatography and high-resolution mass spectrometry.It is found that steam flooding preferentially extracts aromatics and remains more resins in the residual oil.Viscosity reduction is the dominant mechanism when steam is injected at a low temperature.Large molecular heteroatoms with high carbon number and high double bond equivalent(DBE)are eluted into the produced oil,while compounds with low carbon number and low DBE are remained in the residual oil.As the steam temperature rises,the increased distillation effect results in the extraction of light hydrocarbons from the residual oil to the produced oil.More small heteroatoms with low carbon number and low DBE enter into the produced oil,especially in the none water cut stage.The compositional difference of produced oils is characterized in DBE versus carbon number distribution of the N and O containing compound classes.This work uses a variety of composition analysis methods to clarify the steam flooding mechanism and provides a novel understanding of steam flooding mechanisms with various temperatures and production stages from the molecular perspective.
文摘Improving analytical throughput is the focus of many quantitative workflows being developed for early drug discovery.For drug candidate screening,it is common practice to use ultra-high performance liquid chromatography(U-HPLC)coupled with triple quadrupole mass spectrometry.This approach certainly results in short analytical run time;however,in assessing the true throughput,all aspects of the workflow needs to be considered,including instrument optimization and the necessity to re-run samples when information is missed.Here we describe a high-throughput metabolic stability assay with a simplified instrument set-up which significantly improves the overall assay efficiency.In addition,as the data is acquired in a non-biased manner,high information content of both the parent compound and metabolites is gathered at the same time to facilitate the decision of which compounds to proceed through the drug discovery pipeline.
文摘Ensuring the health and safety of drinking water is crucial for both nations and their citizens.Since the 20th century,the disinfection of drinking water,effectively controlling pathogens in water sources,has become one of the significant advances in public health.However,the disinfectants used in the process,such as chlorine and chlorine dioxide,react with natural organic matter in the water to produce disinfection by-products(DBPs).Most of these DBPs contain chlorine,and if the source water contains bromine or iodine,brominated or iodinated DBPs,collectively referred to as Halogenated disinfection byproducts(X-DBPs),are formed.Numerous studies have found that X-DBPs pose potential risks to human health and the environment,leading to widespread concern.Mass spectrometry has become an important means of discovering new types of X-DBPs.This paper focuses on the study of methods for analyzing X-DBPs in drinking water using mass spectrometry.
基金This research was supported by the National Natural Science Foundation of China(Nos.41961134034 and 21876002)the 111 Project of Urban Air Pollution and Health Effects(China)(B20009)the International Joint Laboratory for Regional Pollution Control,Ministry of Education(China)。
文摘Ambient air pollution,containing numerous known and hitherto unknown compounds,is a major risk factor for public health.The discovery of harmful components is the prerequisite for pollution control;however,this raises a great challenge on recognizing previously unknown species.Here we systematically review the analytical techniques on air pollution in the framework of an omics approach,with a brief introduction on sample preparation and analysis,and in more detail,compounds prioritization and identification.Through high-resolution mass spectrometry(HRMS,typically coupled with chromatography),the complicated environmental matrix can be digitalized into“fullcomponent”data.A key step to discover emerging compounds is the prioritization of compounds from massive data.Chemical fingerprints,suspect lists and biological effects are the most vital untargeted strategies for comprehensively screening critical and hazardous substances.Afterward,compressed data of compounds can be identified at various confidence levels according to exact mass and the derived molecular formula,MS libraries,and authentic standards.Such an omics approach on full-component data provides a paradigm for discovering emerging air pollutants;nonetheless,new technological advancements of instruments and databases are warranted for further tracking the environmental behaviors,hence to evaluate the health risk of key pollutants.
基金support from the Collaborative Research Fund(No.C2011–21GF)from Guangdong Province Basic and Applied Basic Research Foundation(No.2021B1515120051).
文摘Parkinson’s disease(PD)is a complex neurological disorder that typically worsens with age.A wide range of pathologies makes PD a very heterogeneous condition,and there are currently no reliable diagnostic tests for this disease.The application of metabolomics to the study of PD has the potential to identify disease biomarkers through the systematic evaluation of metabolites.In this study,urine metabolic profiles of 215 urine samples from 104 PD patients and 111 healthy individuals were assessed based on liquid chromatography-mass spectrometry.The urine metabolic profile was first evaluated with partial leastsquares discriminant analysis,and then we integrated the metabolomic data with ensemble machine learning techniques using the voting strategy to achieve better predictive performance.A combination of 8-metabolite predictive panel performed well with an accuracy of over 90.7%.Compared to control subjects,PD patients had higher levels of 3-methoxytyramine,N-acetyl-l-tyrosine,orotic acid,uric acid,vanillic acid,and xanthine,and lower levels of 3,3-dimethylglutaric acid and imidazolelactic acid in their urine.The multi-metabolite prediction model developed in this study can serve as an initial point for future clinical studies.
基金Lana Resende de Almeida received CAPES(Coordination for the Improvement of Higher Education Personnel from Brazil)Ph.D.scholarships:88882.439375/2019-01Rufford Foundation Small Grant(25871-1)Maria João Ramos Pereira was supported by a CNPq(National Council for Scientific and Technological Development)Productivity Grant(311297/2018-8)。
文摘Chemical profiles of non-invasive biological material,such as feces,have great potential to study elusive animals or those with low population densities.Here,we use a metabolomic approach to evaluate Neotropical mustelids as a biological model to describe the diversity of the metabolites present in fecal samples,as well as to evaluate the potential of chemical profiles for taxonomic discrimination.We collected fecal samples from captive individuals of 5 species of mustelids occurring in Brazil and analyzed them by liquid chromatography coupled to high-resolution mass spectrometry.Over 200 compounds have been annotated;“bile acids,alcohols and derivatives”was the most expressive class in the metabolome of all the species.We successfully discriminated 3 taxonomic groups:1—tayra(Eira barbara);2—otters(Lontra longicaudis and Pteronura brasiliensis;1);and 3—grisons(Galictis vittata and Galictis cuja).Several compounds seemed to be associated with food intake and the digestive process,while others were found for thefirst time in Neotropical mustelids.We concluded that mustelids show high metabolome diversity and that species-specific identification through metabolomic profiles is possible,thus contributing to the development and implementation of additional non-invasive approaches in the study of mustelids.
基金Funding The authors disclose receipt of the following financial support for the research,authorship,and/or publication of this article:the grant(01.13.0315.00-DendePalm Project)for this study was awarded by the Brazilian Research and Innovation Agency(FINEP).
文摘Soil salinity is among the abiotic stressors that threaten agriculture the most,and purslane(Portulaca oleracea L.)is a dicot species adapted to inland salt desert and saline habitats that hyper accumulates salt and has high phytoremediation potential.Many researchers consider purslane a suitable model species to study the mechanisms of plant tolerance to drought and salt stresses.Here,a robust salinity stress protocol was developed and used to characterize the morphophysiological responses of young purslane plants to salinity stress;then,leaf tissue underwent characterization by distinct omics platforms to gain further insights into its response to very high salinity stress.The salinity stress protocol did generate different levels of stress by gradients of electrical conductivity at field capacity and water potential in the saturation extract of the substrate,and the morphological parameters indicated three distinct stress levels.As expected from a halophyte species,these plants remained alive under very high levels of salinity stress,showing salt crystal-like structures constituted mainly by Na^(+),Cl^(−),and K^(+)on and around closed stomata.A comprehensive and large-scale metabolome and transcriptome single and integrated analyses were then employed using leaf samples.The multi-omics integration(MOI)system analysis led to a data-set of 51 metabolic pathways with at least one enzyme and one metabolite differentially expressed due to salinity stress.These data sets(of genes and metabolites)are valuable for future studies aimed to deepen our knowledge on the mechanisms behind the high tolerance of this species to salinity stress.In conclusion,besides showing that this species applies salt exclusion already in young plants to support very high levels of salinity stress,the initial analysis of metabolites and transcripts data sets already give some insights into other salt tolerance mechanisms used by this species to support high levels of salinity stress.
基金the National Key Research and Development Program of China(2020YFC0845400)the NSF of China(81922070)+3 种基金Shanghai Science and Technology Innovation Action Plans(20S2190150020S21900900)supported by Shanghai Science and Technology Committeethe Three-year Action Plan of Shanghai TCM Development(ZY-(2018-2020)-CCCX-5001)Program of Shanghai Academic/Technology Research Leader(18XD1403600)。
文摘Qing-Fei-Pai-Du decoction(QFPDD)is a Chinese medicine compound formula recommended for combating corona virus disease 2019(COVID-19)by National Health Commission of the People's Republic of China.The latest clinical study showed that early treatment with QFPDD was associated with favorable outcomes for patient recovery,viral shedding,hospital stay,and course of the disease.However,the effective constituents of QFPDD remain unclear.In this study,an UHPLC-Q-Orbitrap HRMS based method was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD.A total of 405 chemicals,including 40 kinds of alkaloids,162 kinds of flavonoids,44 kinds of organic acids,71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature.With the help of the standards and in vitro metabolites,195 chemical components(including 104 prototypes and 91 metabolites)were identified in mice serum after oral administration of QFPDD.In addition,165,177,112,120,44,53 constituents were identified in the lung,liver,heart,kidney,brain,and spleen of QFPDD-treated mice,respectively.These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.
基金supported by the National Natural Science Foundation of China(No.41977142)the Major Science and Technology Program for Water Pollution Control and Treatment(No.2018ZX07111003)+1 种基金the Key Technologies Research and Development Program(No.2019YFC1806104)the Fundamental Research Funds for the Central Universities(No.JD2006)。
文摘Pharmaceutical and personal care products(PPCPs)and corresponding transformation products have caused widespread concern due to their persistent emissions and potential toxicity.They have wide octanol-water partition coefficients(K_(ow))and different ionization constants(pK_(a))resulting in a poor analysis accuracy and efficiency.A suitable analytical method is the first prerequisite for further research on their environmental behavior to prioritize the substances.This study reviewed a full-scale analytical protocol for environmental samples in the recent ten years:from sampling to instrumental methods.Passive sampling techniques were compared and recommended for long-term continuous and scientific observation.A quick and effective sample extraction and clean-up method are highly required.Chromatographic methods coupled to mass spectrometry for determining PPCPs with a wide range of logK_(ow)(-7.53 to 10.80)were summed up.High-resolution mass spectrometry was confirmed to be a promising strategy for screening unknown transformation products,which would provide a nanogram level of detection limits and more accurate mass resolution.Screening strategies and mass change principles were summarized in detail.The recovery rate was important in multiple contaminants analysis identification and factors affecting the recovery rate of PPCPs were also discussed in this review,including sample matrix,target compounds characteristics,extraction method and solid-phase adsorbent.This review provides useful information for the selection of appropriate analytical methods and future development directions.
基金National Natural Science Foundation of China(Nos.42177412 and 21437002)National Key Research and Development Program of China(Nos.2017YFC1600500 and 2019YFC1804602)。
文摘Gestational diabetes mellitus(GDM),a frequently-occurring disease during pregnancy,may cause some adverse healthy outcome of both mother and offspring.However,the knowledge about metabolite alterations during the pathogenesis and development process is limited.Here,a large longitudinal nontargeted metabolomics study of 195 pregnant women(64 women with subsequently developed GDM and131 healthy controls)was conducted.Each participant provided urine samples at three timepoints during early,middle and late pregnancy,respectively.The metabolic profiles of 585 urine samples(195×3)were measured by using ultra-high performance liquid chromatography coupled with Orbitrap high-resolution mass spectrometry.Among the 56 identified metabolites,the levels of eight metabolites increased and three ones decreased in the first trimester,the concentration of one metabolite increased and those of 20 decreased in the second trimester,as well as the levels of five metabolites increased and two decreased in the third trimester.After false discovery rate correction,the levels of valine and 5-acetamidovalerate in GDM group significantly increased in the first trimester,the levels of 1-methylguanine and 1,3-dihydro-(2 H)-indol-2-one significantly decreased in the second trimester and three metabolites(threonine,OH-octanedioyl-carnitine and pimelylcarnitine)increased and N-acetyltryptophan decreased in the third trimester,respectively.Six metabolites,such as pantothenic acid and threonine,had significant interaction effects between gestational stage(different trimester)and group(GDM or control).The differential metabolites were involved in“tryptophan metabolism”,“purine metabolism”,“valine,leucine and isoleucine degradation”and other pathways.The findings may provide insights into further pathogenesis study of GDM.
基金supported by internal funding from Johns Hopkins University。
文摘Despite the widespread occurrence of phenols in anthropogenic and natural compounds, their fate in reactions with hypochlorous acid(HOCl), one of the most common water treatment disinfectants, remains incompletely understood. To close this knowledge gap, this study investigated the formation of disinfection by-products(DBPs) in the reaction of free chlorine with seven para-substituted phenols. Based on the chemical structures of the DBPs and the reaction mechanisms leading to their formation, the DBPs were categorized into four groups: chlorophenols, coupling products, substituent reaction products, and ring cleavage products. In contrast to previous studies that investigated the formation of earlystage chlorophenols, the primary focus of this study was on the elucidation of novel ring cleavage products, in particular α, β-unsaturated C-dialdehydes, and C-dicarboxylic acids, which, for the first time, were identified and quantified in this study. The molar yields of 2-butene-1,4-dial(BDA), one of the identified α, β-unsaturated C-dialdehydes, varied among the different phenolic compounds, reaching a maximum value of 10.4% for bisphenol S. Molar yields of 2-chloromaleic acid(Cl-MA), one of the identified C-dicarboxylic acids, reached a maximum value of 30.5% for 4-hydroxy-phenylacetic acid under given conditions. 2,4,6-trichlorophenol(TCP) was shown to be an important intermediate of the parent phenols and the C-ring cleavage products. Based on the temporal trends of α, β-unsaturated C-dialdehydes and C-dicarboxylic acids, their formation is likely attributable to two separate ring cleavage pathways. Based on the obtained results, an overall transformation pathway for the reaction of para-substituted phenols with free chlorine leading to the formation of novel Cring cleavage products was proposed.
基金supported by the National Key Research and Development Program of China(No.2017YFC1600500)。
文摘Exposure to environmental cadmium increases the health risk of residents.Early urine metabolic detection using high-resolution mass spectrometry and machine learning algorithms would be advantageous to predict the adverse health effects.Here,we conducted machine learning approaches to screen potential biomarkers under cadmium exposure in 403 urine samples.In positive and negative ionization mode,4207 and 3558 features were extracted,respectively.We compared seven machine learning algorithms and found that the extreme gradient boosting(XGBoost)and random forest(RF)classifiers showed better accuracy and predictive performance than others.Following 5-fold cross-validation,the value of area under curve(AUC)was both 0.93 for positive and negative ionization modes in XGBoost classifier.In the RF classifier,AUC were 0.80 and 0.84 for positive and negative ionization modes,respectively.We then identified a biomarker panel based on XGBoost and RF classifiers.The incorporation of machine learning models into urine analysis using high-resolution mass spectrometry could allow a convenient assessment of cadmium exposure.
文摘Allergy to sesame seeds is a food allergy of high relevance due to its high abundance and the potential to elicit allergenic reactions,possibly resulting in anaphylaxis.The major sesame allergen Ses i 1 is a 2S albumin belonging to the family of seed storage proteins and despite its high allergenicity,comprehensive knowledge about Ses i 1 variants is still lacking.We,therefore,performed a detailed sequence analysis and characterized the C-and N-terminal ragged clipping of the small and large subunit of Ses i 1 using high-resolution mass spectrometry and the combination of bottom–up,middle–down,and top–down proteomic approaches.We detected extensive clipping at the C-terminus of the large(3–9 aa)and the small subunit(0–7 aa).In addition,the N-terminal conversion from glutamine to pyroglutamate and limited N-terminal clipping was confirmed for both subunits.Furthermore,we observed a sequence conflict at position 147 of Ses i 1 as well as a sequence shift of the large subunit compared to the reference sequence of the precursor.
基金supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada of Canada(Project#326415-07)and a grant from the Western Economic Diversification Canada(Projects#6578,6807,and 000012711).Prof.Giesy was supported by the Canada Research Chair program,and the 2014“High Level Foreign Experts”(#GDT20143200016)program funded by the State Administration of Foreign Experts Affairs,the P.R.China to Nanjing University,the Einstein Professor Program of the Chinese Academy of Sciences,and a Distinguished Visiting Professorship in the School of Biological Sciences of the University of Hong Kong.Prof.Peng was supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada of Canada(Project#RGPIN-2018-06511)and University of Toronto Start-up Funds.
文摘Brominated disinfection by-products(Br-DBPs)can form during the chlorination of drinking water in treatment plants(DWTP).Regulations exist for a small subset of Br-DBPs;however,hundreds of unregulated Br-DBPs have been detected,and limited information exists on their occurrence,concentrations,and seasonal trends.Here,a data-independent precursor isolation and characteristic fragment(DIPIC-Frag)method were optimized to screen chlorinated waters for Br-DBPs.There were 553 Br-DBPs detected with m/z values ranging from 170.884 to 497.0278 and chromatographic retention times from 2.4 to 26.2 min.With MS2 information,structures for 40 of the 54 most abundant Br-DBPs were predicted.The method was then applied to a year-long study in which raw,clear well,and finished water were analyzed monthly.The 54 most abundant unregulated Br-DBPs were subjected to trend analysis.Br-DBPs with higher oxygen-to-carbon(O/C)and bromine-to-carbon(Br/C)ratios increased as water moved from the clear well to the finished stage,which indicated the dynamic formation of Br-DBPs.Monthly trends of unregulated Br-DBPs were compared to raw water parameters,such as natural organic matter,temperature,and total bromine,but no correlations were observed.It was found that total concentrations of bromine(TBr)in finished water(0.04–0.12 mg/L)were consistently and significantly greater than in raw water(0.013–0.038 mg/L,P<0.001),suggesting the introduction of bromine during the disinfection process.Concentrations of TBr in treatment units,rather than raw water,were significantly correlated to 34 of the Br-DBPs atα?0.05.This study provides the first evidence that monthly trends of unregulated Br-DBPs can be associated with the concentration of TBr in treated waters.
基金supported by fellowships from the China Scholarship Council。
文摘Traditional Chinese medicine(TCM)belongs to the most elaborate and extensive systems of plant-based healing.The herb Northern Ban Lan(Isatis tinctoria)is famous for its antiviral and anti-inflammatory activity.Although numerous components isolated from I.tinctoria have been characterized so far,their modes of action have remained unclear.Here,we show that extracts from I.tinctoria exert antimicrotubular activity.Using time-lapse microscopy in living tobacco BY-2(Nicotiana tabacum L.cvBrightYellow2)cellsexpressing greenfluorescentprotein-tubulin,weuse activity-guided fractionation to screen out the biologically active compounds of I.tinctoria.Among 54 fractions obtained from either leaves or roots of I.tinctoria by methanol(MeOH/H_(2)O 8:2),or ethyl acetate extraction,one specific methanolic root fraction was selected,because it efficiently and rapidly eliminated microtubules.By combination of further purification with ultrahigh-performance liquid chromatography and high-resolution tandem mass spectrometry most of the bioactivity could be assigned to the glucosinolate compound glucobrassicin.Glucobrassicin can also affect microtubules and induce apoptosis in HeLa cells.In the light of these findings,the antiviral activity of Northern Ban Lan is discussed in the context of microtubules being hijacked by many viral pathogens for cell-to-cell spread.
