The investigation of reaction kinetics is the key to understanding the nature of reaction processes.However,monitoring fast photochemical reactions by mass spectrometry remains challenging.Herein,we developed an optic...The investigation of reaction kinetics is the key to understanding the nature of reaction processes.However,monitoring fast photochemical reactions by mass spectrometry remains challenging.Herein,we developed an optical focusing inductive electrospray(OF-iESI)mass spectrometry platform for real-time and in-situ photoreaction monitoring.Coaxial irradiation from back of nanoelectrospray emitter with a taper section was utilized,so the emitter could act as optical lens to help achieving much larger optical power density at emitter tip compared to other sections,which allowed for in-situ reaction monitoring of photoreactions.Through theoretical calculations,the highest optical power density region volume was ca.45 nL.We also integrated a controller for the laser source(450 nm),enabling the modulation of pulse duration(>1 ms).This facilitates the study of photochemical reaction kinetics.The in-situ capability of this device was proved by capturing the short-lived photogenerated intermediates during the dehydrogenation of tetrahydroquinoline.This device was further used to investigate the kinetics of triplet energy transfer based Paternò-Büchi reaction.The reaction order has hitherto remained undetermined while the result of OF-iESI suggested it followed pseudo-second-order reaction kinetics.The short-lived donor-acceptor collision complex intermediate was also successfully identified by tandem mass spectrometry.展开更多
Chromatographic fingerprinting has been perceived as an essential tool for assessing quality and chemical equivalence of traditional Chinese medicine.However,this pattern-oriented approach still has some weak points i...Chromatographic fingerprinting has been perceived as an essential tool for assessing quality and chemical equivalence of traditional Chinese medicine.However,this pattern-oriented approach still has some weak points in terms of chemical coverage and robustness.In this work,we proposed a multiple reaction monitoring(MRM)-based fingerprinting method in which approximately 100 constituents were simultaneously detected for quality assessment.The derivative MRM approach was employed to rapidly design MRM transitions independent of chemical standards,based on which the large-scale fingerprinting method was efficiently established.This approach was exemplified on QiShenYiQi Pill(QSYQ),a traditional Chinese medicine-derived drug product,and its robustness was systematically evaluated by four indices:clustering analysis by principal component analysis,similarity analysis by the congruence coefficient,the number of separated peaks,and the peak area proportion of separated peaks.Compared with conventional ultraviolet-based fingerprints,the MRM fingerprints provided not only better discriminatory capacity for the tested normal/abnormal QSYQ samples,but also higher robustness under different chromatographic conditions(i.e.,flow rate,apparent pH,column temperature,and column).The result also showed for such large-scale fingerprints including a large number of peaks,the angle cosine measure after min-max normalization was more suitable for setting a decision criterion than the unnormalized algorithm.This proof-of-concept application gives evidence that combining MRM technique with proper similarity analysis metrices can provide a highly sensitive,robust and comprehensive analytical approach for quality assessment of traditional Chinese medicine.展开更多
Objective To briefly introduce the construction and operation of the National Sentinel Alliance for Adverse Drug Reaction(ADR)Monitoring,and provide reference for strengthening the safety monitoring of drugs after lis...Objective To briefly introduce the construction and operation of the National Sentinel Alliance for Adverse Drug Reaction(ADR)Monitoring,and provide reference for strengthening the safety monitoring of drugs after listing in China.Methods The literature research method was used to analyze the establishment and promotion measures of the National Sentinel Alliance for ADR Monitoring,and then some countermeasures and suggestions were put forward to enhance the construction of the alliance.Results and Conclusion The alliance based on Chinese hospital pharmacovigilance system(CHPS)has played an important role in ADR monitoring and reporting.Promoting the construction of the alliance can provide a new method for improving the scientific evaluation system and active supervision system of drug safety after listing.Therefore,the construction of alliances at the national and provincial levels should be strengthened.Besides,relevant laws and regulations must be improved to accelerate the research and development of information systems,which will deepen the active monitoring of the alliance continuously.展开更多
Synaptic dysfunction occurs early in Alzheimer＇s disease （AD） and is acknowledged as a primary pathologic target for treatment. Synaptic degeneration is the pathological feature most strongly correlated with loss o...Synaptic dysfunction occurs early in Alzheimer＇s disease （AD） and is acknowledged as a primary pathologic target for treatment. Synaptic degeneration is the pathological feature most strongly correlated with loss of cognitive function ante mortern （Terry et al., 1991）. Synapses are heavily damaged in hippocampal and neocortical regions of AD brain, whereas motor and occipital cortices are relatively spared （Honer et al., 1992）. Despite extensive work, the molecular mechanisms underlying synaptic degeneration are largely unknown.展开更多
Monitoring adverse drug reactions(ADRs)in primary medical institutions is crucial to ensuring medication safety.Currently,this work faces difficulties such as insufficient professional ability of staff,imperfect monit...Monitoring adverse drug reactions(ADRs)in primary medical institutions is crucial to ensuring medication safety.Currently,this work faces difficulties such as insufficient professional ability of staff,imperfect monitoring systems,and low patient awareness.It is necessary to improve the level of ADR monitoring at the grassroots level and ensure the safety and effectiveness of medication through countermeasures such as strengthening personnel training,optimizing monitoring processes,and raising public awareness.展开更多
Attributing to the rapid demand expansion for the edible medicinal materials in the market,the limited throughput of highperformance liquid chromatography-multiple reaction monitoring(HPLC-MRM)cannot fully address the...Attributing to the rapid demand expansion for the edible medicinal materials in the market,the limited throughput of highperformance liquid chromatography-multiple reaction monitoring(HPLC-MRM)cannot fully address the measurement workload for a huge number of testing samples.Hence,it is urgent to pursue more efficient approaches for the quality evaluation.Because of the greater selectivity of MRM cubed(MRM^(3))over MRM,there might be a chance to omit the time-intensive LC separation.In current study,we attempted to develop a direct infusion(DI)-MRM^(3) program,and the applicability was thereafter assessed through simultaneous determination of four ganoderic acids(GAs)in one of the most famous tonic herbal medicines namely Ganoderma(Chinese name:Lingzhi).Primary parameters such as Q1>Q3>QLIT ion transitions,collision energy(CE),and excitation energy were optimized by programming online energy-resolved mass spectrometry with authentic compounds.A single DI-MRM measurement merely costed four minutes,and in spite of the wide occurrences of isomers,satisfactory selectivity was achieved.Method validation assays demonstrated the method to be sensitive,precise,accurate,and reproducible.The quantitative results from DI-MRM^(3) were also justified by conducting LC-MRM measurements in parallel.Significant differences occurred for the content patterns between the two original sources namely Ganoderma lucidum and G.sinense,and,moreover,either cultivar or harvest time showed dramatical influence on the quantitative features of the four targeted GAs.More importantly,DI-MRM3 is a meaningful analytical option for rapid quantitative analysis of herbal medicines,because of the comparable reliability,nonetheless,less consumptions of both measurement time and solvent,compared with LC-MRM.展开更多
Fatty acids(FAs)are an important class of functional small molecules and participate in a variety of life biological processes.This experiment proposed a liquid chromatography–quadrupole-Qrbitrap mass spectrometry(LC...Fatty acids(FAs)are an important class of functional small molecules and participate in a variety of life biological processes.This experiment proposed a liquid chromatography–quadrupole-Qrbitrap mass spectrometry(LC–Q-Orbitrap MS)method to perform FA profiling under parallel reaction monitoring(PRM)acquisition mode.The FA was derivatized by 2-dimethylaminoethylamine(DMED)to increase the ionization e fficiency and provide the characterized fragment pattern.The mass spectra obtained from full scan,multiple ion monitoring(MIM),and PRM were compared.The results showed that the protonated ion of FA+DMED–H2O was detected and the neutral loss of 45.06 Da was observed in the tandem mass spectrum.The PRM method provided the highest selectivity and sensitivity for FA detection with the help of accurate mass weight and specific neutral loss-based fragments.The method validation was performed using the FA standards and pooled quality control serum sample,which showed that the established method had good repeatability,stability,and linearity.Finally,the developed method was successfully applied to analyze the rat serum and brain tissue samples for the drug e ffi-cacy evaluation of gross saponin of Tribulus terrestris L.fruit(GSTTF)against middle cerebral artery occlusion(MCAO)-induced ischemic stroke.This method has extensive practicability and great potential in the detection of FA,especially for the analysis of samples with complex matrices.展开更多
Online monitoring of chemical reactions by using analytical chemistry tools is a powerful way to maximize control over these processes.In this paper,we demonstrate the use of molecular rotational resonance,an emerging...Online monitoring of chemical reactions by using analytical chemistry tools is a powerful way to maximize control over these processes.In this paper,we demonstrate the use of molecular rotational resonance,an emerging and extraordinarily selective spectroscopic technique,to perform automated reaction monitoring measurements.An interface using a six-port valve with a calibrated sample loop,coupled to a temperature controlled inlet for analyte volatilization,was developed and tested.Two reactions were chosen for initial characterization:an amine-aldehyde condensation reaction to form an imine product and an isotopic exchange reaction of aβ-ketoester with keto-enol tautomerization.The spectrometer was able to provide kinetic information about the reaction and determine reaction completion.In the future,this system can be extended to detect and quantify impurities and characterize reaction selectivity,in addition to the reaction progress.展开更多
Objective:Multiple reaction monitoring(MRM),is a highly sensitive targeted mass spectrometry technique that is used to validate discovery phase mass spectrometry data.Through this simple technique,relative protein exp...Objective:Multiple reaction monitoring(MRM),is a highly sensitive targeted mass spectrometry technique that is used to validate discovery phase mass spectrometry data.Through this simple technique,relative protein expressions can be acquired without using commercially available antibodies.Methods:Our previous work showed Gipie silencing of UM-HACC-2A(adenoid cystic carcinoma)cells resulted in upregulation of a plethora of immune proteins in immune cells in 3D ACC-immune co-culture model.Results:MRM enabled determining relative protein expression of significantly upregulated immune proteins due to silencing of Gipie.Granzyme A,CD48,granzyme B,HLA class I,antigen B,HLA class I,antigen A,galectin 1,vimentin,endoplasmic reticulum chaperone BiP,and dipeptidyl peptidase 1 differential expressions were validated.Whereas coactosin-like protein expressions were found non-significant among control and Gipie silenced ACC.Conclusions:This manuscript presents the validation data of previous discovery phase mass spectrometry and also accentuate the use of MRM in translational or preclinical studies in the field of biomedical sciences.展开更多
Objective: to explore the important role of clinical pharmacists in monitoring adverse drug reactions. Methods: the subjects of this study were 368 ADR reports reported by our department from December 2019 to December...Objective: to explore the important role of clinical pharmacists in monitoring adverse drug reactions. Methods: the subjects of this study were 368 ADR reports reported by our department from December 2019 to December 2020, of which 188 were the observation group;In addition, 180 cases without clinical pharmacist intervention were the control group. The incidence of adverse reactions was checked and the reporting rate of adverse reactions in the two groups was counted. Results: compared with 25 patients with serious adverse reactions such as leukocyte establishment and arrhythmia in the control group, the incidence of adverse reactions in the observation group was only 1.06%, which was significantly better, χ2 = 8.345, P < 0.05. In the observation group, the physician reported 118 (62.77%), the outpatient reported 115 (61.17%), the nursing staff reported 15 (7.98%), the pharmacist reported 43 (22.87%), and the ward reported 84 (44.68%). Compared with the control group, the difference was statistically significant (P < 0.05). Conclusion: clinical pharmacists play an important role in hospital adverse drug reaction monitoring, greatly reducing the incidence of adverse drug reactions and improving the reporting rate of adverse drug reactions.展开更多
A novel high sensihtity, small-volume photothermal intheence detector has beenintroduced for capillap zone electrophoresis separation analysis. The utility of thes sdriulboconstecheque for momtomp chelating reachon of...A novel high sensihtity, small-volume photothermal intheence detector has beenintroduced for capillap zone electrophoresis separation analysis. The utility of thes sdriulboconstecheque for momtomp chelating reachon of light rare earth with tribromoarsenazo has beenreported.展开更多
In this study,the interaction between primary amine and diketones was investigated.Three diketones with a general structure of—(CH2C(O)CH2C(O))-X-R(X is C,O or N and R is H and/or alkyl groups)were selected to react ...In this study,the interaction between primary amine and diketones was investigated.Three diketones with a general structure of—(CH2C(O)CH2C(O))-X-R(X is C,O or N and R is H and/or alkyl groups)were selected to react with primary amine in aqueous solutions.The reaction was in-situ monitored by Raman technique and the reaction products were identified by FTIR,NMR and LC-MS.It is found that the reaction products strongly depend on the structures of diketones.When X is nitrogen,the expected Schiff base or its analog can be obtained.However,Schiff base or its analog is not detected if X is C or O,instead,ion pairs or hydrolysis products are formed accordingly,suggesting critical impacts of acidity of CH2 inβ-diketone on the product formation.This study also shows that in-situ Raman is a powerful technique for reaction monitoring and structure characterization,which is useful for mechanism understanding.展开更多
Proton NMR-spectra of Wang resin bound compounds were obtained using the magic angle spinning 1HNMR technique with standard equipment. It was possible to analyse the spectra to evaluate their utility in solid-phase ch...Proton NMR-spectra of Wang resin bound compounds were obtained using the magic angle spinning 1HNMR technique with standard equipment. It was possible to analyse the spectra to evaluate their utility in solid-phase chernistry. A typical example was presented, which could directly monitor solid-phase reactions展开更多
Rapid analysis of metal ions and organic compounds in strong acidic solutions is of sustainable interest in multiple disciplines.However,complicated and time-consuming pretreatments are always required for MS analysis...Rapid analysis of metal ions and organic compounds in strong acidic solutions is of sustainable interest in multiple disciplines.However,complicated and time-consuming pretreatments are always required for MS analysis of the compounds in strong acidic solutions.Otherwise,it will result in a weak signal and cause serious damage to the mass spectrometer.Herein,a simple method inherited from nano-ESI MS was developed for rapid analysis of strong acidic solutions.Nanoliter(nL)strong acidic solution was first loaded in the nano-ESI emitter,followed by evaporation to remove the H+and leave the analytes on the wall of the nano-ESI emitter.The evaporation process can be completed within 1 min because of the extremely tiny volume(≤1 nL)of the loaded solution.Then,the dried analytes on the wall of the nano-ESI emitter were redissolved by loading a new solvent,followed by nano-ESI MS analysis.By using this method,metal ions and organic compounds in the strong acidic solution can be detected with low sample consumption(1 nL),high speed(<2 min/sample),high sensitivity(limit of detection=0.2µg/L),and high accuracy(>90%).Proof-of-concept applications of the present method have been successfully achieved for the analysis of gastric juice(pH of the sample=1),monitoring reaction catalyzed by strong acid(pH of the system=0),and micro-area analysis of ores(pH of the extraction solvent=0),showing great application potential in multiple fields.展开更多
Ogura cytoplasmic male sterility(Ogura CMS)is extensively applied in hybrid seed production in cruciferous crops.However,the posttranscriptional molecular basis of Ogura CMS in cruciferous crops remains elusive.Here,a...Ogura cytoplasmic male sterility(Ogura CMS)is extensively applied in hybrid seed production in cruciferous crops.However,the posttranscriptional molecular basis of Ogura CMS in cruciferous crops remains elusive.Here,a data-independent acquisition-based proteomic approach coupled with a parallel reaction monitoring-based targeted proteomic assay was used to analyze the proteome dynamics of Ogura CMS cabbage line RM and its maintainer line RF during floral bud development to obtain insights into the mechanism underlying Ogura CMS in cruciferous crops.A total of 9162 proteins corresponding to 61464 peptides were identified in RM and RF floral buds.The proteomic fluctuation of RM was weaker than that of RF.Differences in protein expression between RM and RF gradually enlarged with floral bud development.Fifteen continually up-regulated and eight continually down-regulated proteins were found in RM relative to RF throughout floral bud development.Differentially expressed proteins between RM and RF during floral bud development were implicated in the endoplasmic reticulum(ER)-associated protein processing pathway,in which most of them exhibited down-regulated expression in RM.These data suggest that ER-associated protein processing may be involved in pollen abortion in Ogura CMS cabbage by inhibiting the expression of critical factors.Our findings not only deepen the understanding of the molecular mechanisms of Ogura CMS in cruciferous crops but also provide better guidance for applying Ogura CMS in the hybrid breeding of cruciferous crops.展开更多
Xiaoer-Feire-Kechuan(XFK) is an 11-herb Chinese medicine formula to treat cough and pulmonary inflammation.The complicated composition rendered its chemical analysis and effective-component elucidation.In this study,w...Xiaoer-Feire-Kechuan(XFK) is an 11-herb Chinese medicine formula to treat cough and pulmonary inflammation.The complicated composition rendered its chemical analysis and effective-component elucidation.In this study,we combined quantitative analysis and bioactivity test to reveal the antiinflammatory constituents of XFK.First,UPLC-DAD and UHPLC/Q-Orbitrap-MS methods were established and validated to quantify 35 analytes(covering 9 out of 11 herbs) in different XFK formulations.Parallel reaction monitoring mode built in Q-Orbitrap-MS was used to improve the sensitivity and selectivity.Then,anti-inflammatory activities of the 35 analytes were analyzed using in vitro COX-2 inhibition assay.Finally,major analytes forsythosides H,I,A(8-10),and baicalin(15)(total contents varied from 21.79 to 91.20 mg/dose in different formulations) with significant activities(inhibitory rate ≥ 80%) were proposed as the anti-inflammatory constituents of XFK.The present study provided an effective strategy to discover effective constituents of multi-herb formulas.展开更多
Plant viruses in the families Luteoviridae and Geminiviridae are phloem restricted and are transmitted in a persistent,circulative manner by homopteran insects.Using fluorescence 2-D difference gel electrophoresis to ...Plant viruses in the families Luteoviridae and Geminiviridae are phloem restricted and are transmitted in a persistent,circulative manner by homopteran insects.Using fluorescence 2-D difference gel electrophoresis to compare the proteomes of F2 genotypes of Schizaphis graminum segregating for virus transmission ability,we recently discovered a panel of protein biomarkers that predict vector competency.Here we used aphid and whitefly nucleotide and expressed sequence tag database mining to test whether these biomarkers are conserved in other homopteran insects.S.graminum gene homologs that shared a high degree of predicted amino acid identity were discovered in two other aphid species and in the whitefly Bemisia tabaci.Selected reaction monitoring mass spectrometry was used to validate the expression of these biomarkers proteins in multiple aphid vector species.The conservation of these proteins in multiple insect taxa that transmit plant viruses along the circulative transmission pathway creates the opportunity to use these biomarkers to rapidly identify insect populations that are the most efficient vectors and allow them to be targeted for control prior to the spread of virus within a crop.展开更多
BACKGROUND Colorectal cancer(CRC)is the second leading cause of cancer-related death,with high morbidity worldwide.There is an urgent need to find reliable diagnostic biomarkers of CRC and explore the underlying molec...BACKGROUND Colorectal cancer(CRC)is the second leading cause of cancer-related death,with high morbidity worldwide.There is an urgent need to find reliable diagnostic biomarkers of CRC and explore the underlying molecular mechanisms.Exosomes are involved in intercellular communication and participate in multiple pathological processes,serving as an important part of the tumor microenvironment.AIM To investigate the proteomic characteristics of CRC tumor-derived exosomes and to identify candidate exosomal protein markers for CRC.METHODS In this study,10 patients over 50 years old who were diagnosed with moderately differentiated adenocarcinoma were recruited.We paired CRC tissues and adjacent normal intestinal tissues(>5 cm)to form the experimental and control groups.Purified exosomes were extracted separately from each tissue sample.Data-independent acquisition mass spectrometry was implemented in 8 matched samples of exosomes to explore the proteomic expression profiles,and differentially expressed proteins(DEPs)were screened by bioinformatics analysis.Promising exosomal proteins were verified using parallel reaction monitoring(PRM)analysis in 10 matched exosome samples.RESULTS A total of 1393 proteins were identified in the CRC tissue group,1304 proteins were identified in the adjacent tissue group,and 283 proteins were significantly differentially expressed between them.Enrichment analysis revealed that DEPs were involved in multiple biological processes related to cytoskeleton construction,cell movement and migration,immune response,tumor growth and telomere metabolism,as well as ECM-receptor interaction,focal adhesion and mTOR signaling pathways.Six differentially expressed exosomal proteins(NHP2,OLFM4,TOP1,SAMP,TAGL and TRIM28)were validated by PRM analysis and evaluated by receiver operating characteristic curve(ROC)analysis.The area under the ROC curve was 0.93,0.96,0.97,0.78,0.75,and 0.88(P<0.05)for NHP2,OLFM4,TOP1,SAMP,TAGL,and TRIM28,respectively,indicating their good ability to distinguish CRC tissues from adjacent intestinal tissues.CONCLUSION In our study,comprehensive proteomic profiles were obtained for CRC tissue exosomes.Six exosomal proteins,NHP2,OLFM4,TOP1,SAMP,TAGL and TRIM28,may be promising diagnostic markers and effective therapeutic targets for CRC,but further experimental investigation is needed.展开更多
Research on pollution characteristics and toxicities of emerging polycyclic aromatic sulfur heterocycles(PASHs) in PM_(2.5) has not been reported due to the lack of analytical method with the needed performance.In the...Research on pollution characteristics and toxicities of emerging polycyclic aromatic sulfur heterocycles(PASHs) in PM_(2.5) has not been reported due to the lack of analytical method with the needed performance.In the present study,a novel method for the determination of 14 PASHs in PM_(2.5) was developed using atmospheric pressure gas chro matography-tandem mass spectrometry(APGC-MS/MS).Atmospheric pressure chemical ionization was operated with multiple reaction monitoring in positive ionization mode.High sensitivity(method detection limit <1.673 pg/m^(3)),acceptable re coveries(67.6%-120.8%) and precisions(RSD of 2.2%-15.4%) were obtained.The method was successfully applied for analyzing PASHs in 10 PM_(2.5) samples collected from Taiyuan,a typical industrial city in China,in 2016,The total concentrations were from 929 pg/m^(3) to 14,593 pg/m^(3).The determined levels indicated that further investigations on environmental fate and toxicities of PM_(2.5)-bound PASHs may be needed.展开更多
基金financially supported by the National Natural Science Foundation of China(Nos.22104112 and 22374110)the Fundamental Research Funds for the Central Universities。
文摘The investigation of reaction kinetics is the key to understanding the nature of reaction processes.However,monitoring fast photochemical reactions by mass spectrometry remains challenging.Herein,we developed an optical focusing inductive electrospray(OF-iESI)mass spectrometry platform for real-time and in-situ photoreaction monitoring.Coaxial irradiation from back of nanoelectrospray emitter with a taper section was utilized,so the emitter could act as optical lens to help achieving much larger optical power density at emitter tip compared to other sections,which allowed for in-situ reaction monitoring of photoreactions.Through theoretical calculations,the highest optical power density region volume was ca.45 nL.We also integrated a controller for the laser source(450 nm),enabling the modulation of pulse duration(>1 ms).This facilitates the study of photochemical reaction kinetics.The in-situ capability of this device was proved by capturing the short-lived photogenerated intermediates during the dehydrogenation of tetrahydroquinoline.This device was further used to investigate the kinetics of triplet energy transfer based Paternò-Büchi reaction.The reaction order has hitherto remained undetermined while the result of OF-iESI suggested it followed pseudo-second-order reaction kinetics.The short-lived donor-acceptor collision complex intermediate was also successfully identified by tandem mass spectrometry.
基金financially supported by the National Natural Science Foundation of China(Grant No.81803714)the Fundamental Research Funds for the Central Universities(Grant No.2019QNA7041).
文摘Chromatographic fingerprinting has been perceived as an essential tool for assessing quality and chemical equivalence of traditional Chinese medicine.However,this pattern-oriented approach still has some weak points in terms of chemical coverage and robustness.In this work,we proposed a multiple reaction monitoring(MRM)-based fingerprinting method in which approximately 100 constituents were simultaneously detected for quality assessment.The derivative MRM approach was employed to rapidly design MRM transitions independent of chemical standards,based on which the large-scale fingerprinting method was efficiently established.This approach was exemplified on QiShenYiQi Pill(QSYQ),a traditional Chinese medicine-derived drug product,and its robustness was systematically evaluated by four indices:clustering analysis by principal component analysis,similarity analysis by the congruence coefficient,the number of separated peaks,and the peak area proportion of separated peaks.Compared with conventional ultraviolet-based fingerprints,the MRM fingerprints provided not only better discriminatory capacity for the tested normal/abnormal QSYQ samples,but also higher robustness under different chromatographic conditions(i.e.,flow rate,apparent pH,column temperature,and column).The result also showed for such large-scale fingerprints including a large number of peaks,the angle cosine measure after min-max normalization was more suitable for setting a decision criterion than the unnormalized algorithm.This proof-of-concept application gives evidence that combining MRM technique with proper similarity analysis metrices can provide a highly sensitive,robust and comprehensive analytical approach for quality assessment of traditional Chinese medicine.
文摘Objective To briefly introduce the construction and operation of the National Sentinel Alliance for Adverse Drug Reaction(ADR)Monitoring,and provide reference for strengthening the safety monitoring of drugs after listing in China.Methods The literature research method was used to analyze the establishment and promotion measures of the National Sentinel Alliance for ADR Monitoring,and then some countermeasures and suggestions were put forward to enhance the construction of the alliance.Results and Conclusion The alliance based on Chinese hospital pharmacovigilance system(CHPS)has played an important role in ADR monitoring and reporting.Promoting the construction of the alliance can provide a new method for improving the scientific evaluation system and active supervision system of drug safety after listing.Therefore,the construction of alliances at the national and provincial levels should be strengthened.Besides,relevant laws and regulations must be improved to accelerate the research and development of information systems,which will deepen the active monitoring of the alliance continuously.
基金Financial support was provided by the Alzheimer’s Australia Dementia Research Foundation Scholarship Program(AAR Postgraduate Research Scholarship),Alzheimer’s Association(USA)under grant#RG1-96-005the Judith Jane Mason and Harold Stannett Williams Memorial Foundation+1 种基金The Queensland Brain Bank,part of Australian Brain Bank Networksupported by an NHMRC(Australia)Enabling Grant No.605210
文摘Synaptic dysfunction occurs early in Alzheimer＇s disease （AD） and is acknowledged as a primary pathologic target for treatment. Synaptic degeneration is the pathological feature most strongly correlated with loss of cognitive function ante mortern （Terry et al., 1991）. Synapses are heavily damaged in hippocampal and neocortical regions of AD brain, whereas motor and occipital cortices are relatively spared （Honer et al., 1992）. Despite extensive work, the molecular mechanisms underlying synaptic degeneration are largely unknown.
文摘Monitoring adverse drug reactions(ADRs)in primary medical institutions is crucial to ensuring medication safety.Currently,this work faces difficulties such as insufficient professional ability of staff,imperfect monitoring systems,and low patient awareness.It is necessary to improve the level of ADR monitoring at the grassroots level and ensure the safety and effectiveness of medication through countermeasures such as strengthening personnel training,optimizing monitoring processes,and raising public awareness.
基金financially supported by the National Natural Science Foundation of China(81973444)the Open Research Project Programme of the State Key Laboratory of Quality Research in Chinese Medicine(University of Macao)(SKLQRCM-OP21011).
文摘Attributing to the rapid demand expansion for the edible medicinal materials in the market,the limited throughput of highperformance liquid chromatography-multiple reaction monitoring(HPLC-MRM)cannot fully address the measurement workload for a huge number of testing samples.Hence,it is urgent to pursue more efficient approaches for the quality evaluation.Because of the greater selectivity of MRM cubed(MRM^(3))over MRM,there might be a chance to omit the time-intensive LC separation.In current study,we attempted to develop a direct infusion(DI)-MRM^(3) program,and the applicability was thereafter assessed through simultaneous determination of four ganoderic acids(GAs)in one of the most famous tonic herbal medicines namely Ganoderma(Chinese name:Lingzhi).Primary parameters such as Q1>Q3>QLIT ion transitions,collision energy(CE),and excitation energy were optimized by programming online energy-resolved mass spectrometry with authentic compounds.A single DI-MRM measurement merely costed four minutes,and in spite of the wide occurrences of isomers,satisfactory selectivity was achieved.Method validation assays demonstrated the method to be sensitive,precise,accurate,and reproducible.The quantitative results from DI-MRM^(3) were also justified by conducting LC-MRM measurements in parallel.Significant differences occurred for the content patterns between the two original sources namely Ganoderma lucidum and G.sinense,and,moreover,either cultivar or harvest time showed dramatical influence on the quantitative features of the four targeted GAs.More importantly,DI-MRM3 is a meaningful analytical option for rapid quantitative analysis of herbal medicines,because of the comparable reliability,nonetheless,less consumptions of both measurement time and solvent,compared with LC-MRM.
基金supported by the National Natural Science Foundation of China(82104366)the Department of Science and Technology of Jilin Province(20210101426JC and 20220505047ZP)the Changchun University of Chinese Medicine(202326)。
文摘Fatty acids(FAs)are an important class of functional small molecules and participate in a variety of life biological processes.This experiment proposed a liquid chromatography–quadrupole-Qrbitrap mass spectrometry(LC–Q-Orbitrap MS)method to perform FA profiling under parallel reaction monitoring(PRM)acquisition mode.The FA was derivatized by 2-dimethylaminoethylamine(DMED)to increase the ionization e fficiency and provide the characterized fragment pattern.The mass spectra obtained from full scan,multiple ion monitoring(MIM),and PRM were compared.The results showed that the protonated ion of FA+DMED–H2O was detected and the neutral loss of 45.06 Da was observed in the tandem mass spectrum.The PRM method provided the highest selectivity and sensitivity for FA detection with the help of accurate mass weight and specific neutral loss-based fragments.The method validation was performed using the FA standards and pooled quality control serum sample,which showed that the established method had good repeatability,stability,and linearity.Finally,the developed method was successfully applied to analyze the rat serum and brain tissue samples for the drug e ffi-cacy evaluation of gross saponin of Tribulus terrestris L.fruit(GSTTF)against middle cerebral artery occlusion(MCAO)-induced ischemic stroke.This method has extensive practicability and great potential in the detection of FA,especially for the analysis of samples with complex matrices.
文摘Online monitoring of chemical reactions by using analytical chemistry tools is a powerful way to maximize control over these processes.In this paper,we demonstrate the use of molecular rotational resonance,an emerging and extraordinarily selective spectroscopic technique,to perform automated reaction monitoring measurements.An interface using a six-port valve with a calibrated sample loop,coupled to a temperature controlled inlet for analyte volatilization,was developed and tested.Two reactions were chosen for initial characterization:an amine-aldehyde condensation reaction to form an imine product and an isotopic exchange reaction of aβ-ketoester with keto-enol tautomerization.The spectrometer was able to provide kinetic information about the reaction and determine reaction completion.In the future,this system can be extended to detect and quantify impurities and characterize reaction selectivity,in addition to the reaction progress.
基金supported by Australian and New Zealand Head and Neck Cancer Society Trudi Shine Adenoid Cystic Carcinoma Grant Award 2021.
文摘Objective:Multiple reaction monitoring(MRM),is a highly sensitive targeted mass spectrometry technique that is used to validate discovery phase mass spectrometry data.Through this simple technique,relative protein expressions can be acquired without using commercially available antibodies.Methods:Our previous work showed Gipie silencing of UM-HACC-2A(adenoid cystic carcinoma)cells resulted in upregulation of a plethora of immune proteins in immune cells in 3D ACC-immune co-culture model.Results:MRM enabled determining relative protein expression of significantly upregulated immune proteins due to silencing of Gipie.Granzyme A,CD48,granzyme B,HLA class I,antigen B,HLA class I,antigen A,galectin 1,vimentin,endoplasmic reticulum chaperone BiP,and dipeptidyl peptidase 1 differential expressions were validated.Whereas coactosin-like protein expressions were found non-significant among control and Gipie silenced ACC.Conclusions:This manuscript presents the validation data of previous discovery phase mass spectrometry and also accentuate the use of MRM in translational or preclinical studies in the field of biomedical sciences.
文摘Objective: to explore the important role of clinical pharmacists in monitoring adverse drug reactions. Methods: the subjects of this study were 368 ADR reports reported by our department from December 2019 to December 2020, of which 188 were the observation group;In addition, 180 cases without clinical pharmacist intervention were the control group. The incidence of adverse reactions was checked and the reporting rate of adverse reactions in the two groups was counted. Results: compared with 25 patients with serious adverse reactions such as leukocyte establishment and arrhythmia in the control group, the incidence of adverse reactions in the observation group was only 1.06%, which was significantly better, χ2 = 8.345, P < 0.05. In the observation group, the physician reported 118 (62.77%), the outpatient reported 115 (61.17%), the nursing staff reported 15 (7.98%), the pharmacist reported 43 (22.87%), and the ward reported 84 (44.68%). Compared with the control group, the difference was statistically significant (P < 0.05). Conclusion: clinical pharmacists play an important role in hospital adverse drug reaction monitoring, greatly reducing the incidence of adverse drug reactions and improving the reporting rate of adverse drug reactions.
文摘A novel high sensihtity, small-volume photothermal intheence detector has beenintroduced for capillap zone electrophoresis separation analysis. The utility of thes sdriulboconstecheque for momtomp chelating reachon of light rare earth with tribromoarsenazo has beenreported.
文摘In this study,the interaction between primary amine and diketones was investigated.Three diketones with a general structure of—(CH2C(O)CH2C(O))-X-R(X is C,O or N and R is H and/or alkyl groups)were selected to react with primary amine in aqueous solutions.The reaction was in-situ monitored by Raman technique and the reaction products were identified by FTIR,NMR and LC-MS.It is found that the reaction products strongly depend on the structures of diketones.When X is nitrogen,the expected Schiff base or its analog can be obtained.However,Schiff base or its analog is not detected if X is C or O,instead,ion pairs or hydrolysis products are formed accordingly,suggesting critical impacts of acidity of CH2 inβ-diketone on the product formation.This study also shows that in-situ Raman is a powerful technique for reaction monitoring and structure characterization,which is useful for mechanism understanding.
文摘Proton NMR-spectra of Wang resin bound compounds were obtained using the magic angle spinning 1HNMR technique with standard equipment. It was possible to analyse the spectra to evaluate their utility in solid-phase chernistry. A typical example was presented, which could directly monitor solid-phase reactions
基金supported by the National Natural Science Foundation of China(Nos.21864001,21727812 and 21765001)the Ph.D.Start-up Foundation of East China University of Technology(No.DHBK2020001).
文摘Rapid analysis of metal ions and organic compounds in strong acidic solutions is of sustainable interest in multiple disciplines.However,complicated and time-consuming pretreatments are always required for MS analysis of the compounds in strong acidic solutions.Otherwise,it will result in a weak signal and cause serious damage to the mass spectrometer.Herein,a simple method inherited from nano-ESI MS was developed for rapid analysis of strong acidic solutions.Nanoliter(nL)strong acidic solution was first loaded in the nano-ESI emitter,followed by evaporation to remove the H+and leave the analytes on the wall of the nano-ESI emitter.The evaporation process can be completed within 1 min because of the extremely tiny volume(≤1 nL)of the loaded solution.Then,the dried analytes on the wall of the nano-ESI emitter were redissolved by loading a new solvent,followed by nano-ESI MS analysis.By using this method,metal ions and organic compounds in the strong acidic solution can be detected with low sample consumption(1 nL),high speed(<2 min/sample),high sensitivity(limit of detection=0.2µg/L),and high accuracy(>90%).Proof-of-concept applications of the present method have been successfully achieved for the analysis of gastric juice(pH of the sample=1),monitoring reaction catalyzed by strong acid(pH of the system=0),and micro-area analysis of ores(pH of the extraction solvent=0),showing great application potential in multiple fields.
基金supported by Heilongjiang Provincial Natural Science Foundation of China(Grant No.YQ2022C012)China Postdoctoral Science Foundation(Grant No.2022MD713728)+1 种基金Heilongjiang Provincial Postdoctoral Fund(Grant No.LBHZ21046)the Open Project of Key Laboratory of Biology and Genetic Improvement of Horticultural Crops(Northeast Region),Ministry of Agriculture and Rural Affairs,and National Key Research and Development Program of China(Grant No.2023YFD1201501).
文摘Ogura cytoplasmic male sterility(Ogura CMS)is extensively applied in hybrid seed production in cruciferous crops.However,the posttranscriptional molecular basis of Ogura CMS in cruciferous crops remains elusive.Here,a data-independent acquisition-based proteomic approach coupled with a parallel reaction monitoring-based targeted proteomic assay was used to analyze the proteome dynamics of Ogura CMS cabbage line RM and its maintainer line RF during floral bud development to obtain insights into the mechanism underlying Ogura CMS in cruciferous crops.A total of 9162 proteins corresponding to 61464 peptides were identified in RM and RF floral buds.The proteomic fluctuation of RM was weaker than that of RF.Differences in protein expression between RM and RF gradually enlarged with floral bud development.Fifteen continually up-regulated and eight continually down-regulated proteins were found in RM relative to RF throughout floral bud development.Differentially expressed proteins between RM and RF during floral bud development were implicated in the endoplasmic reticulum(ER)-associated protein processing pathway,in which most of them exhibited down-regulated expression in RM.These data suggest that ER-associated protein processing may be involved in pollen abortion in Ogura CMS cabbage by inhibiting the expression of critical factors.Our findings not only deepen the understanding of the molecular mechanisms of Ogura CMS in cruciferous crops but also provide better guidance for applying Ogura CMS in the hybrid breeding of cruciferous crops.
基金supported by the National Key Research and Development Program of China (Grant No.: 2018YFC1707304, 2018YFC1707301)Beijing Natural Science Foundation (Grant No.: JQ18027)National Natural Science Foundation of China (Grant No.: 81725023)。
文摘Xiaoer-Feire-Kechuan(XFK) is an 11-herb Chinese medicine formula to treat cough and pulmonary inflammation.The complicated composition rendered its chemical analysis and effective-component elucidation.In this study,we combined quantitative analysis and bioactivity test to reveal the antiinflammatory constituents of XFK.First,UPLC-DAD and UHPLC/Q-Orbitrap-MS methods were established and validated to quantify 35 analytes(covering 9 out of 11 herbs) in different XFK formulations.Parallel reaction monitoring mode built in Q-Orbitrap-MS was used to improve the sensitivity and selectivity.Then,anti-inflammatory activities of the 35 analytes were analyzed using in vitro COX-2 inhibition assay.Finally,major analytes forsythosides H,I,A(8-10),and baicalin(15)(total contents varied from 21.79 to 91.20 mg/dose in different formulations) with significant activities(inhibitory rate ≥ 80%) were proposed as the anti-inflammatory constituents of XFK.The present study provided an effective strategy to discover effective constituents of multi-herb formulas.
基金supported by NSF BREAD IOS:1109989,USDA-NRI 2007-04567,NSFDBI-0606596USDA-ARS 764 CRIS projects1907-101-16,1907-21000-024/25-00DNIH/NCRR funded Yeast Resource Center P41RR01182
文摘Plant viruses in the families Luteoviridae and Geminiviridae are phloem restricted and are transmitted in a persistent,circulative manner by homopteran insects.Using fluorescence 2-D difference gel electrophoresis to compare the proteomes of F2 genotypes of Schizaphis graminum segregating for virus transmission ability,we recently discovered a panel of protein biomarkers that predict vector competency.Here we used aphid and whitefly nucleotide and expressed sequence tag database mining to test whether these biomarkers are conserved in other homopteran insects.S.graminum gene homologs that shared a high degree of predicted amino acid identity were discovered in two other aphid species and in the whitefly Bemisia tabaci.Selected reaction monitoring mass spectrometry was used to validate the expression of these biomarkers proteins in multiple aphid vector species.The conservation of these proteins in multiple insect taxa that transmit plant viruses along the circulative transmission pathway creates the opportunity to use these biomarkers to rapidly identify insect populations that are the most efficient vectors and allow them to be targeted for control prior to the spread of virus within a crop.
基金Supported by National Key Development Plan for Precision Medicine Research,No.2017YFC0910002。
文摘BACKGROUND Colorectal cancer(CRC)is the second leading cause of cancer-related death,with high morbidity worldwide.There is an urgent need to find reliable diagnostic biomarkers of CRC and explore the underlying molecular mechanisms.Exosomes are involved in intercellular communication and participate in multiple pathological processes,serving as an important part of the tumor microenvironment.AIM To investigate the proteomic characteristics of CRC tumor-derived exosomes and to identify candidate exosomal protein markers for CRC.METHODS In this study,10 patients over 50 years old who were diagnosed with moderately differentiated adenocarcinoma were recruited.We paired CRC tissues and adjacent normal intestinal tissues(>5 cm)to form the experimental and control groups.Purified exosomes were extracted separately from each tissue sample.Data-independent acquisition mass spectrometry was implemented in 8 matched samples of exosomes to explore the proteomic expression profiles,and differentially expressed proteins(DEPs)were screened by bioinformatics analysis.Promising exosomal proteins were verified using parallel reaction monitoring(PRM)analysis in 10 matched exosome samples.RESULTS A total of 1393 proteins were identified in the CRC tissue group,1304 proteins were identified in the adjacent tissue group,and 283 proteins were significantly differentially expressed between them.Enrichment analysis revealed that DEPs were involved in multiple biological processes related to cytoskeleton construction,cell movement and migration,immune response,tumor growth and telomere metabolism,as well as ECM-receptor interaction,focal adhesion and mTOR signaling pathways.Six differentially expressed exosomal proteins(NHP2,OLFM4,TOP1,SAMP,TAGL and TRIM28)were validated by PRM analysis and evaluated by receiver operating characteristic curve(ROC)analysis.The area under the ROC curve was 0.93,0.96,0.97,0.78,0.75,and 0.88(P<0.05)for NHP2,OLFM4,TOP1,SAMP,TAGL,and TRIM28,respectively,indicating their good ability to distinguish CRC tissues from adjacent intestinal tissues.CONCLUSION In our study,comprehensive proteomic profiles were obtained for CRC tissue exosomes.Six exosomal proteins,NHP2,OLFM4,TOP1,SAMP,TAGL and TRIM28,may be promising diagnostic markers and effective therapeutic targets for CRC,but further experimental investigation is needed.
基金financial support from the National Natural Science Foundation of China (Nos.91843301 and 91543202)National Key Research and Development Program Cooperation on Scientific and Technological Innovation in Hong Kong,Macao and Taiwan (No. 2017YFE0191000)。
文摘Research on pollution characteristics and toxicities of emerging polycyclic aromatic sulfur heterocycles(PASHs) in PM_(2.5) has not been reported due to the lack of analytical method with the needed performance.In the present study,a novel method for the determination of 14 PASHs in PM_(2.5) was developed using atmospheric pressure gas chro matography-tandem mass spectrometry(APGC-MS/MS).Atmospheric pressure chemical ionization was operated with multiple reaction monitoring in positive ionization mode.High sensitivity(method detection limit <1.673 pg/m^(3)),acceptable re coveries(67.6%-120.8%) and precisions(RSD of 2.2%-15.4%) were obtained.The method was successfully applied for analyzing PASHs in 10 PM_(2.5) samples collected from Taiyuan,a typical industrial city in China,in 2016,The total concentrations were from 929 pg/m^(3) to 14,593 pg/m^(3).The determined levels indicated that further investigations on environmental fate and toxicities of PM_(2.5)-bound PASHs may be needed.
