Determination of mycotoxin exposure in Germany
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DOI 10.1002/mnfr.201400406R ESEARCH A RTICLE
Determination of mycotoxin exposure in Germany using an LC-MS/MS multibiomarker approach
Johannes Gerding 1,2,Benedikt Cramer 1and Hans-Ulrich Humpf 1,2
1Institute of Food Chemistry,Westf ¨alische Wilhelms-Universit ¨at M ¨unster,M ¨unster,Germany
2
NRW Graduate School of Chemistry,M ¨unster,Germany
Received:June 13,2014
Revised:September 11,2014Accepted:September 15,2014
Scope:In this study,the exposure of a German population (n =101)to mycotoxins was assessed using an LC-MS/MS urinary multibiomarker approach.Food consumption of the participants was documented with a food frequency questionnaire to correlate mycotoxin exposure with individual nutritional habits.
Methods and results:The presence of 23urinary biomarkers including trichothecenes (de-oxynivalenol (DON),DON-3-glucuronide (DON-3-GlcA),T-2toxin,HT-2toxin (HT-2,HT-2-toxin-4-glucuronide (HT-2-GlcA),fumonisins (fumonisin B 1,fumonisin B 2),a?atoxins (a?a-toxin B 1,a?atoxin G 2,a?atoxin B 2,a?atoxin M 1),zearalenone and derivatives (zearalanone,?-zearalenol,?-zearalenol,zearalenone-14-O-glucuronide,zearalanone-14-O-glucuronide,?-zearalenol-14-O-glucuronide/?-zearalenol-14-O-glucuronide),ochratoxin A,ochratoxin al-pha,enniatin B and dihydrocitrinone was evaluated using a validated,sensitive “dilute and shoot”-LC-MS/MS method applying Scheduled MRM TM technology.Six mycotoxins and uri-nary metabolites were detected (DON,DON-3-GlcA,zearalenone-14-O-glucuronide,T-2toxin,enniatin B,and dihydrocitrinone)in 87%of the samples in single-or co-occurence.Only DON and DON-3-GlcA were detectable in quanti?able amounts.A provisional mean daily intake of 0.52?g DON/kg body weight was calculated.No statistical evidence for the correlation of staple food intake and urinary biomarker concentration could be determined.
Conclusion:The results of this study suggest a low everyday exposure of the investigated German population to mycotoxins,but reveal peak exposures above the widely accepted toler-able daily intake to DON in parts of the population.
Keywords:
Exposure assessment /Mass spectrometry /Mycotoxins /Scheduled MRM TM /Urinary biomarker
Additional supporting information may be found in the online version of this article at the publisher’s web-site
Correspondence :Professor Hans-Ulrich Humpf,Institute of
Food Chemistry,Westf ¨alische Wilhelms-Universit ¨at M ¨unster,Corrensstra?e 45,48149M ¨unster,Germany
E-mail :humpf@wwu.de Fax :+49-251-83-8-33396
Abbreviations:AFB 1,a?atoxin B 1;AFB 2,a?atoxin B 2;AFG 1,a?atoxin G 1;AFG 2,a?atoxin G 2;AFM 1,a?atoxin M 1;bw ,body weight;DON ,deoxynivalenol;DON-15-GlcA ,DON-15-O-glucuronide;DON-3-GlcA ,DON-3-O-glucuronide;DH-CIT ,dihy-drocitrinone;EnB ,enniatin B;FFQ ,food frequency questionnaire;FA ,formic acid;FB 1,fumonisin B 1;FB 2,fumonisin B 2;HT-2,HT-2toxin;HT-2-4-GlcA ,HT-2-toxin-4-O-glucuronide;MRM ,mul-tiple reaction monitoring;OTA ,ochratoxin A;OT ?,ochratoxin alpha;PDI ,provisional daily intake;R A ,apparent recovery;
1
Introduction
Mycotoxins are toxic secondary metabolites produced by a
large number of fungal species potentially infesting food-stuffs at all stages of food production,processing and storage [1].Over the past decades,an increased understanding of the acute and chronic toxicity led to the regulation of mycotoxin contamination in various foodstuffs worldwide.In the focus of most of these regulatory attempts are mycotoxins from the
T-2,T-2toxin;TDI ,tolerable daily intake;ZAN ,zearalanone;ZAN-14-GlcA ,zearalanone-14-O-glucuronide;ZEN ,zearalenone;ZEN-14-GlcA ,zearalenone-14-O-glucuronide;?-ZEL ,?-zearalenol;?-ZEL ,?-zearalenol;?-ZEL-14-GlcA ,?-zearalenol-14-O-glucuronide;?-ZEL-14-GlcA ,?-zearalenol-14-O-glucuronide
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group of a?atoxins,trichothecenes,zearalenone(ZEN),fu-monisins,ochratoxin A(OTA),citrinin,and ergot alkaloids [2].The determination of maximum contamination levels for mycotoxins is commonly based on estimations of tolerable daily intakes(TDIs)with reference to comprehensive food consumption databases in single countries or regions.One major drawback of such risk assessments is a potential un-derrepresentation of subgroups with a regional or cultural deviation in their nutritional habits,hence resulting in an al-tered exposition than estimated based on global consumption databases[3].This is of particular interest related to myco-toxins since the presence of mycotoxins is heterogeneously distributed across various types of food[4].Monitoring the presence of mycotoxins and their metabolites in physiolog-ical samples to assess the actual exposure of an individual or a subpopulation has gained increased acceptance in re-cent years and could signi?cantly contribute to improved risk assessments[5].
Modern LC-MS/MS techniques allow urinary multi-biomarker assessments at environmentally relevant concentration levels with measurements of both parent compounds and metabolites such as glucuronides[6].In combination with individual food consumption data,studies using multimycotoxin analytical approaches have produced calculated estimates of exposure in probed populations that often signi?cantly exceed established TDIs[7,8].The majority of these studies focus on the sub-Saharan Africa and are therefore not transferable to the European consumer due to the limited regulation of mycotoxin contamination in these regions and different dietary habits of staple foods[9,10].
A recent study of Solfrizzo et al.revealed human exposure that exceeded TDIs for various mycotoxins in southern Italy[11].Biomarker-assisted exposure data are currently not available for a central European population.This study was designed to strengthen the database on mycotoxin exposure in this population.We analyzed urine samples of 101individuals from Germany applying a“dilute and shoot”-LC-MS/MS multibiomarker approach quantifying a total of 23mycotoxins and their urinary metabolites.Among these compounds are the trichothecenes deoxynivalenol(DON), deoxynivalenol-3-glucuronide(DON-3-GlcA),T-2toxin (T-2),HT-2toxin(HT-2),HT-2-toxin-4-O-glucuronide(HT-2-4-GlcA),fumonisins(fumonisin B1(FB1),fumonisin B2 (FB2)),a?atoxins(a?atoxin B1(AFB1),a?atoxin G2,a?atoxin B2,a?atoxin M1(AFM1)),ZEN,zearalanone(ZAN),their urinary metabolites?-zearalanol(?-ZEL)and?-zearalenol (?-ZEL)and corresponding14-O-glucuronic acid adducts (zearalenone-14-O-glucuronide(ZEN-14-GlcA),zearalanone-14-O-glucuronide,?-ZEL,?-zearalenol-14-O-glucuronide/?-zearalenol-14-O-glucuronide),OTA and ochratoxin alpha (OT?)as well as enniatin B(EnB)and dihydrocitrinone (DH-CIT),the major urinary metabolite of citrinin[12]. HT-2-4-GlcA was incorporated for the?rst time in a biomon-itoring approach since its identi?cation as microsomal HT-2 metabolite[13].Participants of this study?lled out a food frequency questionnaire(FFQ)covering the consumption of23food items on basis of a24h recall and long-term nutrition habits.Correlating the consumption and exposure data,we gained?rst time insights to the nutrition-related exposure to mycotoxins in a central European population.
2Material and methods
2.1Chemicals and reagents
Methanol and ACN were of LC gradient grade purity (VWR,Darmstadt,Germany).Formic acid(FA)was purchased from Merck,Darmstadt,Germany.ZAN,?-ZEL,?-ZEL,AFM1and AFB1/2,AFG1/2were purchased from Sigma-Aldrich(Schnelldorf,Germany).DH-CIT was purchased from AnalytiCon Discovery(Potsdam, Germany).EnB was from Enzo Life Sciences(L¨o rrach, Germany).ZEN,DON,FB1,FB2,OTA,OT?,T-2, HT-2were isolated and puri?ed from fungal cultures [14–20].Glucuronic acid adducts(DON-3-GlcA,ZEN-14-GlcA,zearalanone-14-O-glucuronide,?-zearalenol-14-O-glucuronide,?-zearalenol-14-O-glucuronide,and HT-2-GlcA were synthesized enzymatically using rat and pig liver microsomes according to a recently published procedure [13].Solid analytes were dissolved in ACN or ACN/H2O (DON-3-GlcA,FB1,FB2).Stock solutions were prepared at a concentration of10?g/mL in ACN or ACN/H2O and stored at?20?C.A working solution was prepared at20-fold concentration of the highest calibration point at each day of measurement in ACN/H2O(50:50,v/v).
2.2Sample collection
Urine samples were collected from healthy volunteers in the city of M¨u nster,Germany(n=101;44males,57females). Volunteers were predominantly university students in the range of20–30years of age.All participants were asked to ?ll out an FFQ following the sample donation and age,body weight(bw)and height were registered.All participants were informed about scope and aim of this study and gave written consent about their participation.Samples and FFQs were number encoded to ensure the anonymity of participants. The design of this study was approved by the research ethi-cal committee of the University Hospital M¨u nster,Germany (File reference:2012-378-f-S).
2.3Sample preparation
Some recent studies use?rst morning void urine or24-h urine for analysis.For reasons of simplicity and signi?-cance for everyday’s exposure,donations of urine were dis-tributed randomly throughout the day.Urinary creatinine levels were measured for each sample to normalize biomarker concentrations to nanograms per milligram creatinine.Cre-atinine in urine was measured on an ADVIA1800clinical
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2360J.Gerding et al.Mol.Nutr.Food Res.2014,58,2358–2368
chemistry analyzer using the Jaffe method(Siemens Health-care Diagnostics,Eschborn,Germany)at the central lab-oratory of the University Hospital,M¨u nster,Germany. Samples were aliquoted and stored at?80?C until further analysis.At the day of analysis,samples were allowed to reach room temperature and were centrifuged at14000×g for10min to remove solid residues.Hundred microliters of the supernatant were diluted with900?L H2O/ACN/FA (0.94:0.05:0.01,v/v/v)and subjected to LC-MS/MS analysis. All measurements were performed in duplicate and included the measurement of a blank urine sample for quality control.
2.4Food frequency questionnaire
All participants of this study?lled out an FFQ containing information on their short-and long-term(24-h recall,re-call of past30days)nutritional habits to take the variety in toxicokinetics of the different biomarkers into account.The FFQ was designed to monitor the speci?c aspects concern-ing the exposure of participants to mycotoxins,focusing on the assessment of consumption of cereal and grain-derived products.Other aspects of interest were the consumption of beer,coffee,nuts,and dried fruits.Participants were fur-thermore asked about their preference for organic products and the consumption of meat and dairy products.The FFQ was generated and automatically processed with Evasys V5.1 software.
2.5Statistical analysis
A statistical analysis was carried out to identify signi?cant cor-relations between nutritional habits and biomarker concen-trations found in urine.Samples were grouped in quartiles according to the consumption frequency stated by the par-ticipants for each food group represented in the FFQ.These groups were subjected to an analysis of variances involving biomarker concentration and the consumption frequency of the respective food item of interest.Means of groups were subjected to a post-hoc test(Scheff′e’s method)to further char-acterize differences between the groups.Signi?cant changes were accepted at a p-value of0.05.Statistical analysis was realized with IBM SPPS22.
2.6LC-MS/MS conditions
Analysis was carried out on a Merck-Hitachi/VWR LaChromeUltra UHPLC system coupled to an AB SCIEX QTRAP R 5500mass spectrometer.
2.6.1HPLC setup
Separation of analytes was carried out by RP chromatogra-phy on a NUCLEODUR R C18Pyramid column(3?m,2.0×150mm,MACHEREY-NAGEL,D¨u ren,Germany)equipped with a C18EC guard column(2mm x4mm,MACHEREY-NAGEL).Eluent A was ACN(0.1%FA)and eluent B was water (0.1%FA)at a?ow rate of600?L/min.The total runtime was 13min.Gradient started at5%A for2min and solvent A was increased to40%until7min,subsequently raised to95%A until8min,and kept for1min at95%A.Afterwards percent-age of A was decreased to starting conditions(10min)and was allowed to re-equilibrate until13min.
2.6.2MS/MS setup
Detection of analytes of interest was carried out on an AB SCIEX QTRAP R 5500mass spectrometer with ESI ionization in Scheduled MRM TM detection mode.Application of Sched-uled MRM TM limits the time of detection of characteristic multiple reaction monitoring(MRM)transitions of an ana-lyte to a prede?ned expected window of retention.This results in an increased number of data points per peak.ESI-source parameters were optimized and preset for all measurements as follows:source temperature:500?C,curtain gas30psi,gas 1:45psi,gas2:35psi.Ion spray voltage was set to?4000V in negative ionization mode and5500V in positive ioniza-tion mode.A number of two characteristic MRM transitions per analyte were monitored to ensure accurate identi?cation. MS/MS parameters were optimized for each analyte in posi-tive and negative ionization mode by direct infusion of pure standard solutions.The?nal method was build based on the best S/N ratio in positive or negative ionization mode.Sched-uled MRM TM parameters were set to a window width of15s and a target scan time of0.5s.The software used was Analyst 1.5.2.Detection of analytes in positive and negative ionization mode was done in two separate chromatographic runs since parallel monitoring of two polarities is only available from software version Analyst1.6.Detailed MS parameters can be found in Supporting Information Table1.
2.7Validation of the analytical method
The analytical method was subject to an in-house validation comprising linearity,apparent recovery(R A),reproducibility and accuracy along with the determination of LOD and LOQ. Quantitation was carried out with an external matrix-matched calibration with spiked blank urine samples using a freshly prepared working solution(2.1).Blank urine was pooled out of samples negative for all analytes in a preliminary mea-surement.The calibration curves covered two magnitudes in concentration of each analyte.Coef?cient of determina-tion was de?ned as measure of linearity of the calibration curves.The calibration range was chosen based on the pre-liminary determination of LOD and LOQ of the analytes. LOD was de?ned at an S/N ratio of S/N=3and LOQ at S/N= 6.All validation experiments were executed in triplicate.R A was calculated from the slope of the linear calibration curves of spiked urine samples and neat standard
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T a b l e 1.D e t a i l e d v a l i d a t i o n p a r a m e t e r s o b t a i n e d d u r i n g i n -h o u s e v a l i d a t i o n .S e v e n c a l i b r a t i o n p o i n t s w e r e h o m o g e n e o u s l y d i s t r i b u t e d a c r o s s t h e r e s p e c t i v e c a l i b r a t i o n r a n g e o f e a c h a n a l y t e .L i n e a r i t y w a s c h e c k e d b y d e t e r m i n a t i o n o f t h e c o e f ?c i e n t o f c o r r e l a t i o n (R 2).L i m i t s o f d e t e c t i o n q u a n t i t a t i o n (L O D a n d L O Q )w e r e d e t e r m i n e d a t S /N =3(L O D )a n d S /N =6(L O Q ).L O D (a )a n d L O Q (a )d e s c r i b e t h e m e t h o d p e r f o r m a n c e m e a s u r i n g n e a t s t a n d a r d s o l u t i o n s .L O D (b )a n d L O Q (b )d e s c r i b e t h e m e t h o d p e r f o r m a n c e i n s p i k e d u r i n e s a m p l e s .V a l u e s i n b r a c k e t s t a k e t h e t e n f o l d d i l u t i o n f r o m s a m p l e c l e a n u p i n t o a c c o u n t .A p p a r e n t r e c o v e r y (R A )w a s c a l c u l a t e d f r o m t h e s l o p e o f c a l i b r a t i o n c u r v e s o f n e a t s t a n d a r d s o l u t i o n s a n d m a t r i x -m a t c h e d c a l i b r a t i o n s a m p l e s .I n t r a d a y p r e c i s i o n w a s i n v e s t i g a t e d a t s e c o n d h i g h e s t c a l i b r a t i o n l e v e l b y t e n f o l d i n j e c t i o n o n t h e s a m e d a y o f a n a l y s i s .I n t e r d a y p r e c i s i o n w a s d e t e r m i n e d a t t h r e e d i f f e r e n t d a y s a t s e c o n d h i g h e s t ,m e d i u m ,a n d s e c o n d l o w e s t c a l i b r a t i o n p o i n t
A n a l y t e
C a l i b r a t i o n r a n g e (n g /m L )
R 2L O D a )(n g /m L )L O Q a )(n g /m L )L O D b )(n g /m L )L O Q b )(n g /m L )R A (%)I n t r a d a y c )(%)
I n t e r d a y d )(%)
D O N 0.4–400.999
0.05000.10000.05(0.5)0.2(2)61.412.67.1/10.6/8.9H T -20.8–800.9980.10000.20000.2(2)0.4(4)68.64.461.7/5.5/19.3H T -2-4-G l c A 0.1–100.9990.02500.05000.025(0.25)0.05(0.5)93.48.211.1/1.9/1.0T -20.1–100.9970.01250.02500.025(0.25)0.05(0.5)108.47.931.8/14.1/5.6F B 1
0.005–0.50.9810.00250.00500.005(0.05)0.0125(0.125)121.28.935.1/26.4/14.9F B 2
0.02–20.9990.01000.02000.02(0.2)0.05(0.5)119.93.467.6/2.9/14.2A F B 1
0.01–10.9990.00250.00500.005(0.05)0.01(0.1)116.517.85.9/0.7/0.8A F B 2
0.0029–0.2890.9970.00140.00290.0014(0.014)0.0029(0.029)139.87.769.5/5.7/11.7A F G 2
0.0029–0.2890.9980.00290.00720.00072(0.0072)0.0014(0.014)126.58.575.4/15.7/4.7A F M 1
0.005–0.50.9990.00130.00250.0025(0.025)0.005(0.05)219.613.824.5/5.8./1.4E n B 0.0005–0.050.9920.00050.00130.0005(0.005)0.00125(0.0125)200.87.534.3/2.2/20.5D O N -3-G l c A 0.4–400.9990.10000.20000.2(2)0.4(4)77.73.814.1/2.0/0.8Z A N 0.1–100.9950.01250.10000.05(0.5)0.1(1)124.48.921.8/14.8/11.2Z E N 0.02–200.9970.00250.00500.0025(0.025)0.01(0.1)77.45.429.5/2.3/2.4?-Z E L 0.025–2.50.9980.00310.00630.0125(0.125)0.025(0.25)61.36.63.8/8.4/2.9?-Z E L 0.025–2.50.9990.00310.00630.00625(0.0625)0.0125(0.125)86.17.91.5/3.3/3.7Z E N -14-G l c A 0.15–150.9990.01880.01880.075(0.75)0.15(1.5)91.55.226.2/6.4/1.2Z A N -14-G l c A 0.3–300.9990.03750.15000.3(3)0.75(7.5)89.46.410.5/12.2/0.7?-Z E L -14-G l c A 2.5–2500.9980.31250.31251.25(12.5)2.5(25)78.85.39.3/0.6/0.6?-Z E L -14-G l c A 0.5–500.9960.06250.06250.25(25)0.5(50)40.46.117.5/4.4/1.1O T A 0.01–10.9920.01000.02500.01(0.1)0.025(0.25)151.37.616.6/14.3/14.9O T ?0.01–10.9990.010.010.005(0.05)0.01(0.1)83.16.429.4/2.6/3.8D H -C I T 0.02–2
0.9990.020.050.02(0.2)0.05(0.5)97.35
7.6
14.9/5.3/2.8
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2362J.Gerding et al.Mol.Nutr.Food Res.2014,58,2358–2368
solutions.Reproducibility was investigated at low-,medium-and high-spiking level in blank urine on three different days. Intraday precision was determined by tenfold injection of a spiked urine sample at second highest spiking level.A de-tailed summary with all validation parameters can be found in Table1.
3Results
3.1Method development and validation
The developed method is capable of chromatographic separation of all23biomarkers mentioned above.As a representative example,Fig.1shows the reconstructed ion chromatograms of the RP-HPLC separation of the23 biomarkers in the positive(a)and negative(b)ESI mode.In Table2,the corresponding retention times and the monitored MRM transitions either in the positive or negative mode are shown.Chromatography is robust and highly reproducible with retention time standard deviation of1.73s or lower (Table2),allowing the application of Scheduled MRM TM algo-rithm during MS/MS detection(all detailed MS parameters can be found in Supporting Information Table1).As DON-3-GlcA and DON-15-GlcA could not be chromatographically separated,the resulting signal was subsequently assumed as a sum of DON-3-and DON-15-glucuronide(DON-GlcA) [21].
Validation experiments were carried out as described in detail in Section2with regard to the linearity,R A, and reproducibility of the method.The obtained LODs in urine,ranging from0.005to12.5ng/mL(de?ned at LOD (S/N=3);Table1),are in good agreement with LC-MS/MS multibiomarker approaches described elsewhere and found suitable for the analysis of biomarker concentrations in hu-man urine samples[22,23].All analytes showed linear cal-ibration curves in their respective calibration range with a coef?cient of determination(R2)between0.981and0.999. R A ranged from40.4to151.8%for most compounds.Only EnB showed a higher R A due to the high signal enhance-ment observed for this compound.Repeatability was de-termined by intraday-and interday assays.RSDs ranged from4.5and17.7%in intraday assays and0.60and14.9% during interday assays at medium-and high-spiking level for most analytes.EnB and FB1showed higher RSDs of 20.5and26.5%at medium and high concentration levels. RSDs were determined to be above20%for several tox-ins at low concentration levels.This was accepted since the scope of this study was to get quantitative estimates of myco-toxin concentrations in urine samples close to the instru-ments LOD and LOQ.All compounds that were quanti-tated in naturally contaminated urine samples showed an RSD below15%across the calibration range.A detailed summary with all validation parameters can be found in Table1and Supporting Information Table2.3.2Biomonitoring in human urine samples
The presence of23biomarkers in101human urine sam-ples from the area of M¨u nster,Germany,was monitored. Single and multimycotoxin occurrence was observed in87% of the samples.Table3summarizes the obtained results for each individual mycotoxin.The most abundant mycotoxin urinary metabolite was DON-GlcA,occurring in82%of an-alyzed samples in quanti?able amounts.DON was detected in29%of the samples.The presence of EnB(20%),DH-CIT(12%),Zen-14-GlcA(4%),and T-2(1%)was con?rmed by qualitative means since concentrations ranged below the respective LOQ established for these compounds(Table1). The analysis proved the absence of all other investigated biomarkers.In total,13%of the samples were negative for all monitored mycotoxins and their metabolites.A vast ma-jority of samples showed occurrence of a single biomarker (37%)or co-occurrence of two toxins(40%;see Table4). DON was almost exclusively found in co-occurrence with the urinary metabolite Don-3-GlcA/DON-15-GlcA.Three or four biomarkers were present in11%of the samples.In total,the presence of six urinary biomarkers could be con?rmed with a maximum of four compounds co-occurring in one sample.
Based on these?ndings,we calculated a provisional daily intake(PDI)for DON out of the urinary concentrations of the biomarkers DON and DON-3-GlcA based on the elimination rates proposed by Turner et al.in2010(72.3%)re?ned with excretion rates suggested by Warth et al.in2013[24,25]. Assuming a total excretion rate of68%of ingested DON (15%as DON,14%as DON-3-GlcA,and39%as DON-15-GlcA),PDI was calculated using the following formula: PDI
?g
kg
body weight
=C×V×100
W×E
where C=biomarker concentration(?g/L),V=(mean)daily urine excretion(L),W=(mean)bw(kg),E=excretion rate (%).
DON-3-GlcA and DON-15-GlcA excretion was estimated as sum of glucuronide excretion rate(53%)assuming co-detection of these compounds during LC-MS/MS analy-sis.Glucuronide concentrations were adjusted to equivalent DON concentrations.When concentration of an analyte was below the LOQ or LOD,a concentration half of the respective values was estimated.Participants’individual body weight was used instead of a global value of a mean body weight. Daily mean urine excretion was set to1.8L in all samples. The mean PDI for DON was determined to be0.52?g/kg bw with a lowest determined PDI for one individual of0.07?g/kg bw and an individual peak exposure of5.67?g/kg bw.Based on these data,12%of samples exceeded the established TDI of1?g/kg bw set by the Scienti?c Committee on Food in 2002[26].
Correlation of biomarker occurrence and food consump-tion was subjected to a statistical analysis to identify food intake dependent changes of urinary DON and DON-GlcA
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Figure 1.Reconstructed total ion chromatogram based on MRM transitions for each myco-toxin analyte in positive(A)and negative(B)ionization mode (see Table2and Supporting In-formation Table1for detailed MS parameters).
concentrations.Participants’statements on food consump-tion were grouped in quartiles representing low,medium, increased,and high intake of a speci?c food item.As can be seen from Fig.2,no food group showed signi?cant alter-ations in urinary biomarker concentration at a p value of0.05 applied to both30day and24h recalls.
4Discussion
The novel multibiomarker method was validated and found suitable for the detection of trace levels of mycotoxins and their metabolites in human urine.Sample preparation was kept as simple as possible by diluting the urine samples without any additional time-consuming hydrolysis of glu-curonides.Retention time of analytes was highly reproducible and allowed the application of Scheduled MRM TM detection mode enabling the simultaneous detection of23biomarkers. The Scheduled MRM TM technology furthermore facilitates an effortless increase of the number of accurately detectable an-alytes to support studies with extended biomarker coverage.
It is noteworthy that“dilute and shoot”based multi-biomarker are at the expenses of reduced LODs compared to single toxin methods or methods involving glucuronide hydrolysis and subsequent SPE or immunoaf?nity cleanup. The striking advantage of simple sample preparation has to be compensated by latest MS equipment and emphasizes a high demand for devices with increased sensitivity.
A total of87%of urine samples were positive for one or multiple urinary biomarkers with DON and DON-GlcA being the most abundant compounds.Approximately one-third of the samples(35%)showed occurrence or co-occurrence of other than only DON-derived biomarkers.DH-CIT,EnB, Zen-14-GlcA,and T-2were only detected close or below their respective LOQ.These?ndings are in contrast to the abundant occurrence of urinary mycotoxin biomarkers doc-umented in recent studies covering other geographic areas. Shephard et al.reported co-occurrence of various mycotoxins in human urine in the region of Transkei,South Africa, with mean concentrations of1.52ng/mL in the case of FB1, 11.3ng/mL for DON,0.61ng/mL and0.70ng/mL for?-and ?-ZEL,0.53for ZEN,and0.041ng/mL for OTA in76–100%of the samples[9].Similar contamination levels are documented for Cameroon and Nigeria,although at lower occurrence rates [7,8].High urinary concentrations were also reported for ZEN and metabolites in New Jersey,USA in78%of the analyzed samples with average contamination levels of1.3ng/mL for the sum of ZEN and derivatives and peak concentrations of up to33ng/mL for ZEN without?-glucuronidase treatment. High concentrations were related to maize(popcorn)and beef consumption[27].These concentrations are within the LODs of the present study and support the assumption that there is a lower risk of exposure to mycotoxins in central Europe.
Regarding the European situation,only a limited number of studies have investigated the mycotoxin exposure with urinary(multi)-biomarker approaches and are mostly
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J.Gerding et al.Mol.Nutr.Food Res.2014,58,2358–2368
T able 2.Summarized parameters of the LC-MS/MS method for the quantitation of 23mycotoxin biomarkers.Retention time SD was
determined from multiple injections (n =42)across the whole calibration range.LOD was de?ned at an S/N ratio =3and LOQ at S/N =6
Analyte Retention time (min)±SD (s)Q1mass (m/z )
Q3mass (m/z )a)LOD (ng/mL)b)LOQ (ng/mL)b)
(a)Positive ionization mode
DON 3.85±0.59297[M +H]+249/2030.05(0.5)0.2(2)AFM
1 6.49±1.73329[M +H]+273/2290.0025(0.025)0.005(0.05)FB
1 6.58±1.01722[M +H]+334/3520.005(0.05)0.013(0.13)AFG
2 6.91±0.69331[M +H]+245/2750.00072(0.0072)
0.0014(0.014)FB
27.28±0.54706[M +H]+336/3180.02(0.2)0.05(0.5)AFB
2
7.28±0.58315[M +H]+259/2870.0014(0.014)0.0029(0.029)
HT-2-4-GlcA 7.51±0.31618[M +NH 4]+263/2150.025(0.25)0.05(0.5)AFB
17.63±0.56313[M +H]+241/2850.005(0.05)0.01(0.1)
HT-27.84±0.25442[M +NH 4]+215/2630.2(2)0.4(4)
T-28.28±0.29484[M +NH 4]+215/3050.025(0.25)0.05(0.5)
EnB
8.89±0.31
640[M +H]+
196/214
0.0005(0.005)
0.00125(0.0125)
(b)Negative ionization mode
DON-3-GlcA 4.08±0.83471[M +H]?265/1750.05(0.5)0.1(1)?
-ZEL-14-GlcA 6.64±1.29495[M +H]?319/1750.25(2.5)0.5(5)?
-ZEL-14-GlcA 7.13±0.30495[M +H]?319/175 1.25(12.5) 2.5(25)
ZEN-14-GlcA 7.57±0.30493[M +H]?317/1750.075(0.75)0.15(1.5)
ZAN-14-GlcA 7.56±0.32495[M +H]?319/1750.3(3)0.75(7.5)?
-ZEL 8.10±0.18319[M +H]?160/1740.00625(0.0625)0.0125(0.125)?
-ZEL 8.26±0.20319[M +H]?160/1740.0125(0.125)0.025(0.25)
ZAN 8.39±0.01319[M +H]?275/2050.05(0.5)0.1(1)
OTA 8.39±0.13402[M +H]?358/1670.01(0.1)0.025(0.25)
ZEN 8.41±0.09317[M +H]?175/1310.0125(0.125)0.025(0.25)OT
?8.42±0.26255[M +H]?211/1670.005(0.05)0.01(0.1)
DH-CIT
10.20±0.35
265[M +H]?
177/221
0.02(0.2)
0.05(0.5)
a)Quanti?er/quali?er.
b)Values in brackets represent biomarker concentration in spiked blank urine,taking the tenfold dilution into account.
suffering from small sample cohorts.During a pilot study in Germany,OTA and its metabolite OT ?were detected in all of 13urine samples with mean concentrations of 0.07ng/mL for OTA and 1.14ng/mL for OT ?.The mean concentration of OT ?increased to 2.88ng/mL after enzymatic hydrolysis [28].Coronel et al.reported mean urinary OTA concentrations of 0.24and 0.44ng/mL in 60%of a cohort of 72urine samples from Spain after enzymatic cleavage [29].Data from Croatia are close to these values [30].A study by Duarte et al.documented even lower concentrations for OTA in a Portuguese population with mean values around 0.02ng/mL in urine samples [31].Considering the low concentrations of OTA and OT ?without enzymatic treatment,mean values are close to the LOD (0.1and 0.05ng/mL)of the present
“dilute and shoot”approach and may explain the negative
results in our study.Nevertheless,the method was suitable for the detection of OTA and OT ?at the concentration levels previously reported.For this reason,we assume a similar or even reduced exposure of the assessed German group to OTA compared to the studies mentioned above,which do not consider the resulting exposure as harmful.An analogous picture can be drawn for the exposure of the German population concerning the exposure to ZEN.Rupert et al.did not con?rm the presence of ZEN in a pilot study involving samples of 27persons in Spain at an LOD of 3ng/mL [32].A recent study of Solfrizzo et al.determined mean concentration for ZEN,?-ZEL,and ?-ZEL below 0.1ng/mL after enzymatic hydrolysis in an Italian population [11].This
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https://www.wendangku.net/doc/a014146173.html,
Mol.Nutr.Food Res.2014,58,2358–23682365 T able3.Summary of mycotoxin exposure and calculated provisional daily intakes(PDI).Mean concentrations were calculated from samples with biomarker concentrations>LOD.If biomarker concentration was DON DON-GlcA T-2ZEN-14-GlcA EnB DH-CIT Positive samples%(n)29.41(30)82.35(84)0.98(1) 3.96(4)19.61(20)11.88(12) Quantitated%(n)10.78(11)56.86(58) SD quantitated samples%71.37104.54---- PDI mean(?g/kg body weight)0.52 PDI median(?g/kg body weight)0.20 PDI lowest(?g/kg body weight)0.07b) PDI highest(?g/kg body weight) 5.67 TDI DON(?g/kg body weight)1c) %of samples>TDI11.88 a)Samples with highest/lowest determined concentration are not identical with highest/lowest creatinine normalized samples. b)Sample below LOQ of biomarkers. c)According to Scienti?c Committee for Food(SCF),2002. resulted in an estimated PDI for ZEN of0.015?g/kg bw. Since this value is about ten times lower than the established TDI of0.2?g/kg bw,a low risk for exposure to ZEN was assumed[11].Our method is capable of detecting the ZEN metabolites at these concentration levels,despite ranging close to their respective LOD.We exclusively detected ZEN-14-GlcA in four of the analyzed samples around the LOD of0.75ng/mL.We did not detect any of the other parent compounds nor their glucuronides.This could be due to the fact that the individual determination of glucuronides and parent compounds results in concentrations below their respective LOD and has to be further investigated. Nevertheless,we conclude a similar or reduced exposure of the German subpopulation to ZEN.The absence of ZAN and ZAN-GlcA makes these compounds interesting candidates for quality control or internal standards for the determination of urinary ZEN and ZEN-GlcA concentrations,since they have not been reported as human metabolite so far.None of the monitored a?atoxins,AFB1,AFB2,AFG2,or AFM1, were detected.This is probably due to the low consumption preference of the main contributors to a?atoxin uptake,nuts and maize of the German study population,paired with generally low contamination levels.Although incorporated in several multimycotoxin methods,neither T-2nor HT-2 or its metabolite HT-2-4-GlcA were detected in urine during biomarker-based exposure assessments.With the exception of one sample positive for T-2near the LOD,we con?rm the absence of these biomarkers in the German sample pool, Figure2.Correlation of cereals (A,B)and pasta consumption (C,D)and urinary concentra- tions of DON and DON-GlcA with FFQ information of30days (solid line)and24h recall (dashed line)biomarker concen- tration. C 2014WILEY-VCH Verlag GmbH&Co.KGaA,Weinheim https://www.wendangku.net/doc/a014146173.html, 2366J.Gerding et al.Mol.Nutr.Food Res.2014,58,2358–2368 T able4.Occurrence and co-occurrence of mycotoxins and my-cotoxin metabolites in urine samples(n=101)from Germany Mycotoxins and metabolites%(n) Four toxins0.99(1) DON/DON-GlcA/EnB/ZEN-14-GlcA0.99(1) Three toxins9.90(10) DON/DON-GlcA/EnB 3.98(4) DON/DON-GlcA/ZEN-14-GlcA 1.98(2) DON/DON-GlcA/DHCIT 2.97(3) DON-GlcA/DHCIT/T-20.99(1) T wo toxins39.60(40) DON/DON-GlcA17.82(18) DON-GlcA/EnB14.85(15) DON-GlcA/DHCIT 6.93(7) One toxin36.63(37) DON 1.98(2) DON-GlcA32.70(33) ZEN-14-GlcA0.99(1) DHCIT0.99(1) Negatives12.9(13) Positives87.1(88) including the?rst direct measurements of HT-2-toxin-4-GlcA.Interestingly,we con?rm the presence of EnB and DH-CIT in20and12%of the samples,although at low concentrations.To date,little is known about the urinary excretion of citrinin and human exposure to this nephrotoxic mycotoxin[33].A pilot study of Blaszkewicz et al.reported the presence of CIT and its urinary metabolite DH-CIT in all analyzed samples[12].Even less is known about the urinary excretion of the“emerging”mycotoxin EnB.We detected EnB for the?rst time in human urine.A recent study from Italy determined enniatins in a large portion of grain-derived products[34].In combination with the outcome of our study, this underlines the importance of further research being car-ried out on the occurrence,exposure,and toxicological impact of these poorly investigated toxins.With an occurrence in 85%of samples,DON and DON-GlcA were the biomarkers with the highest prevalence in this study.A PDI of0.52?g/kg bw DON was calculated from the urinary biomarker concen-trations of DON and DON-GlcA.Twelve percent of samples positive for DON or DON-GlcA showed TDI values above 1?g/kg bw revealing a peak exposures of up to5.67?g/kg bw DON.This exceeds the TDI of1?g/kg bw set by the Scienti?c Committee on Food in2002signi?cantly[26].The deter-mined mean values of3.38ng/mL for DON and12.21ng/mL are in line with recent data from Italy and Croatia.Solfrizzo et al.reported the occurrence of DON after enzymatic cleav-age in96%of samples from Italy with a mean concentration of11.9ng/mL and calculated a PDI of1.03?g/kg bw.Sarkanj et al.found DON and DON-GlcA in98%of analyzed samples and conclude a PDI of2.5?g/kg bw in samples from Croatia [30].Together with our results,these data raise some concern about the exposure of the European population to DON. It has to be veri?ed if these?ndings represent the actual exposure situation,or if models for the calculation of PDI values are overestimating the actual exposure.It is also noteworthy that the analysis of24h urines would increase the accuracy of exposure calculations. The estimation of PDI values remains a critical issue in biomarker-assisted mycotoxin exposure assessment since data on the human metabolism and excretion of mycotoxin and especially excretion rates of mycotoxin metabolites are scarce.Calculations in this study are based on the excretion pro?le of DON and DON metabolites in one human volun-teer after consumption of a high concentration DON diet probably leading to an overestimation of DON excretion rates compared to a more realistic intake scenario[24].Results have to be considered a rough estimate rather than an accurate ex-posure assessment. Based on our?ndings,we con?rm a low exposure of the German population to mycotoxins.This re?ects the low oc-currence situation of mycotoxins in grains from Germany documented by the Federal Ministry of Food and Agriculture (BMEL)in the annual German harvest report of2013[35].The BMEL documented a high occurrence rate for DON of99%in raw grains with mean concentrations of61?g/kg(wheat)and 135?g/kg(rye),whereas ZEN,HT-2,and T-2occurred less frequent and in lower concentrations.ZEN was determined in64%in wheat and1%in rye with less than1%of samples exceeding concentration above50?g/kg ZEN in both cases. Occurrence of T-2and HT-2was even less frequent with oc-casional detection in3and23%of samples,respectively.DH-CIT(the main urinary metabolite of citrinin)and EnB were detected in some of the urine samples in this study.It has to be noted that there are no published data on the occurrence of citrinin or the enniatins in grain samples in Germany. Although100%of grain samples were contaminated with DON according to the German grain monitoring,correla-tion of food intake and urinary biomarker concentrations did not show signi?cant changes in biomarker concentrations at high levels of consumption of a certain food item.As cor-relations of DON intake and DON excretion are reported in both humans and animal models[25,36],this aspect has to be further investigated with larger sample libraries.It re?ects as well the balanced diet of German consumers avoiding an ex-clusive consumption of potentially high contaminated staple foods.Mycotoxin biomarker analysis in human urine could be of great use for individual exposure assessments for per-sons with unbalanced diets due to nutritional habit or as a constraint of exhibited adverse food reactions or allergies. 5Summary and conclusions A urinary multimycotoxin biomarker“dilute and shoot”based LC-MS/MS method was developed and successfully https://www.wendangku.net/doc/a014146173.html,ing the Scheduled MRM TM technology and a ro-bust chromatography,this novel approach furthermore qual-i?es for a simple extension with additional analytes. C 2014WILEY-VCH Verlag GmbH&Co.KGaA,Weinheim https://www.wendangku.net/doc/a014146173.html, Mol.Nutr.Food Res.2014,58,2358–23682367 Based on the determination of urinary biomarker concen-trations,this study reports the?rst assessment of mycotoxin exposure in a central European population.We conclude a low exposure of the German consumer to mycotoxins with the exception of DON and its urinary metabolite DON-GlcA, which occurred frequently.Determined urinary concentra-tions of DON and DON-GlcA are resulting in calculated PDI values close to the established TDI of1?g/kg bw and12% of the samples exceeded this value with a maximum PDI of5.67?g/kg bw.Calculations of PDI values also revealed a lack of information concerning the correlation of myco-toxin uptake and urinary excretion rates in humans to qualify multibiomarker approaches for valid exposure assessments. 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C 2014WILEY-VCH Verlag GmbH&Co.KGaA,Weinheim https://www.wendangku.net/doc/a014146173.html, 常见成语解析及成语故事 换骨夺胎 【注音】huàn gǔ duó tāi 【成语故事】换骨夺胎原是道家传说吃了金丹换去凡骨凡胎后成仙。古代文人借用以前古文的意思用自己的语言去表达，黄庭坚认为这是换骨法，深入研究古文的原意进一步加以刻划形容，这叫夺胎法。也有人说不蹈古人一言一句，用夺胎换骨法可以点铁成金。 【出处】然不易其意而造其语，谓之换骨法；窥入其意而形容之，谓之夺胎法。宋·释惠洪《冷斋夜话·换骨夺胎法》 【解释】比喻诗文活用古人之意，推陈出新。 【用法】作谓语、定语；用于诗文等 【相近词】脱胎换骨、夺胎换骨 【成语举例】他临摹古画有换骨夺胎之妙，当然能够乱真。 提名道姓 【拼音】tí míng dào xìng 【成语故事】王夫人、薛宝钗、林黛玉等在贾母房内聊天，有人汇报史湘云来了，众人迎接，大观园内又多了一位金钗。贾宝玉跑来看史湘云，一见十分快乐，亲热的叫她的名字。王夫人要他不要提名道姓，她们在一起又玩个昏天黑地。 【出处】这里老太太才说这一个，他又来提名道姓的了。清·曹雪芹《红楼梦》第31回 【释义】提、道：说。直呼别人姓名，对人不够尊敬。 【用法】作谓语、宾语；指直呼别人姓名 【相近词】指名道姓、习题名道姓 【反义词】含沙射影 【成语例句】 ◎你得喝醉哟，不然哪里敢！既醉，则挑鼻子弄眼，没必要提名道姓，而以散文诗冷嘲，继以热骂：头发烫得像鸡窝，能孵小鸡么？曲线美，直线美又几个钱一斤？老子的钱是容易挣得？哼！诸如此类，无须管层次清楚与否，但求气势畅利。 ◎设若要摆，也不应该提名道姓。 随遇而安 【注音】：suí yùér ān 【释义】：随：顺从；遇：遭遇。指能顺应环境，在任何境遇中都能满足。 【出处】：清·刘献廷《广阳杂记》一：“随寓而安，斯真隐矣。”清·文康《儿女英雄传》第24回：“吾生有涯，浩劫无涯，倒莫如随遇而安。” 【用法】：偏正式；作谓语、宾语、定语、状语；含褒义；指能顺应环境 【示例】：不过能够～——即有船坐船云云——则比起幻想太多的人们来，可以稍为安稳，能够敷衍下去而已。（鲁迅《两地书》六）【近义词】：与世无争、随俗浮沉 五个字的成语故事分享 导读：本文五个字的成语故事分享，仅供参考，如果觉得很不错，欢迎点评和分享。 售胝足之药 【成语故事】从前有人在市场上卖治脚茧药，在门上挂“供御”的招牌，人们讥笑他不诚实。皇帝知道后，派人传唤他，并把他投入监狱。他遇大赦而回家，就又重操旧业，在招牌上面增加“曾经宣唤”4字，以此来招徕顾客。 【出处】昔人有以胝足之药售于市者，辄揭扁于门曰：‘供御。’《厅史》 【解释】胝：手掌或脚掌上的老茧。指卖狗皮膏药骗人。 【用法】作谓语、宾语;指卖狗皮膏药 覆巢无完卵 【成语故事】东汉末年，北海相孔融反对曹操率50万大军征讨刘备与孙权，御史大夫向来与孔融不合，在曹操面前添油加醋，恶意挑拨。曹操大怒，命人逮捕孔融全家，孔融的孩子无动于衷，也不逃跑，说：“大人，岂见覆巢之下复有完卵乎?” 【出处】大人，岂见覆巢之下复有完卵乎?南朝·宋·刘义庆《世说新语·言语》 【解释】复：翻倒。翻倒的鸟窝里不会有完好的卵。比喻灭门大祸，无一幸免。又比喻整体毁灭，个体也不能幸存。 【用法】作定语、分句;比喻整体毁灭，个体不能幸存 【近义词】覆巢破卵 【成语示列】你是知道覆巢无完卵的结局的。 民以食为天 【成语故事】楚汉相争时期，刘邦与项羽在颖阳一带打仗，由于没有后援，刘邦准备放弃敖山粮仓，找谋士郦食其商量。郦食其认为称王要依赖百姓，百姓又依赖粮食。要想赢得战争，必须占据敖仓，才能稳住军心。刘邦赞同并奋勇作战取得了胜利。 【典故】天：比喻赖以生存的最重要的东西。人民以粮食为自己生活所系。指民食的重要。 【释义】天：比喻赖以生存的最重要的东西。人民以粮食为自己生活所系。指民食的重要。 【用法】作宾语、定语;指粮食的重要性 【近义词】国以粮为本 【成语举例】 ◎民以食为天，吃饱肚子是大别山人祖祖辈辈的梦想："谁让我们吃饱饭，就选谁当县长。" ◎解放几十年来农业还没有从根本上过关的历史教训和现实状况都告诉我们：国以民为本、民以食为天。 ◎民以食为天，国以农为本，这是我国的基本国情，要实现跨世纪的宏伟目标，解决好农业问题至关重要. 第二十一课时，成语故事（文言文版）阅读 教学目标： 1，了解成语，学习感悟其中的道理 2，积累文言文实词及虚词的用法。 3，掌握文言文常见语法现象。 课堂笔记： 成语故事（文言文版）阅读 引婴投江 有过于江上者，见人方（）引婴儿而欲投之江中。婴儿啼。人问其故，曰：“此其父善游！” 其父虽善游，其子岂（）遽善游哉？以此任物，亦必悖矣。 刻舟求剑 楚人有涉( )江者，其剑自舟中坠于水。遽( )契其舟，曰：“是( )吾剑之所从坠。”舟止，从其所契者入水求之。 舟已行矣，而剑不行。求剑若此，不亦惑乎！ 叶公好龙 叶公好龙，室中雕文( )尽以为龙。于是天龙闻而下之，窥头于牖( )，拖尾于堂。叶公见之，弃而还走( )，失其魂魄，五神无主。 是( )叶公非好龙也，夫似龙而非龙也。 郑人买履 郑人有且置履( )者，先自度( )而置之其坐，至之市而忘操( )之，已得履，乃曰:“吾忘持度。”反( )归取之。及反，市罢( )，遂不得履。 人曰：“何不试之以足？”曰：“宁信度，无自信也。” 自相矛盾 楚人有卖盾与矛者，誉( )之曰：“吾盾之坚，物莫能陷( )也。”又誉其矛曰：“吾矛之利，于物无不陷也。”或曰：“以子( )之矛，陷子之盾，何如？”其人弗能应也。 夫不可陷之盾与无不陷之矛，不可同世而立。 守株待兔 宋人有耕者。田中有株。兔走（）触株，折颈而死。因释其耒（）而守株，冀（）复得兔。兔不可得得，而身为宋国笑。 拔苗助长 宋人有悯（）其苗之不长而揠（）之者，芒芒然（）归，谓其人曰：“今日病矣！予助苗长矣。”其子趋（）而往视之，苗则槁矣。 天下之不助苗长者（）寡矣。助之长者，揠苗者也。非徒（）无益，而又害之。 滥（）竽充数 齐宣王使人吹竽，必（）三百人。南郭处士请为王吹竽。宣王悦之，廪（）食以数百人。宣王死，湣王立。好一一听之。处士逃。 涸辙之鲋 有关后生可畏成语故事及用法 【解释】后生：青年人，后辈;畏：敬畏，佩服。指青年人势必超过前辈，令人敬畏。 后生可畏成语故事及用法 【读音】hòu shēng kě wèi 【解释】后生：青年人，后辈;畏：敬畏，佩服。指青年人势必超过前辈，令人敬畏。 【出处】《论语·子罕》后生可畏，焉知来者之不如也! 【用法】主谓式;作谓语、宾语、分句;含褒义，称赞年轻人。 【近义词】少年老成、长江后浪推前浪 【反义词】少不更事、乳臭未干 【语法】：主谓式;作谓语、宾语、分句;含褒义，称赞年轻人 故事： 元朝的大臣彻里帖木耳，处理公务精明干练，善于决断。有一年他在浙江任职，正好逢上省城举行科举考试。他目睹了这场考试，从官府到考生都花费了很多钱财，并且免不了有营私舞弊的情况。他暗暗下了决心，待到自己掌握了大权，一定要促使朝廷废除这种制度。后来，他升任相当于副宰相的中书平章政事，便奏告元顺帝，请求废除科举制度。中国科举制度隋唐以来已实行了七百多年，要废除它是一件非常重大的事，在朝中引起了巨大的反响。大师伯颜表示支持，但反对的很多。有位御史坚决反对废除科举制度，他请求顺帝治彻里帖木耳的罪。不料顺帝虽然很昏庸，但对废除科举制度倒是赞成的。所以不但不支持那位御史，反而把他贬到外地去当官。 不久，他命人起草了废除科举制度的诏书，准备颁发下去。书还 未下达，地位略低于平章的参政许有王，又出来反对废除科举制度。 他对伯颜说：“如果废除科举考试制度，世上有才能的人都会怨恨的。”伯颜针锋相对地说：“如果继续实行科举考试制度，世上贪赃 枉法的人还要多。”许有王反驳说：“没有实行科举考试制度的时候，贪赃枉法的人也不是很多吗?”伯颜讽刺他说：“我看中举的人中有用 之材太少，只有你参政一个人能够任用!”许有王不服气，举出很多当 时中举的高官来反驳伯额。伯颜当然不会改变自己的观点，于是两人 争论得非常激烈。第二天，满朝文武被召到祟天门听读皇帝下达的废 除科举制席的诏书，许有王还特地被侮辱性地通知在班首听读。看来，皇帝特意要让这个反对者将诏书听得明白些。许有王心里非常不愿意，但又惧怕得罪皇帝遭到祸害，只好勉强跪在百官前列听读诏书。听读 完诏书后，百官纷纷回府，许有王满脸不高兴地低头走路。 有个名叫普化的御史特地走到他边上，凑着他的耳朵冷嘲热讽他说：“参政，你这下成为过河拆桥的人啦。这话的意思是，你许参政 是靠科举当官的，现在宣读皇上关于废除科举制度诏书，你跪在最前面，似乎是废除科举制度的领头人，就像一个人过了桥后就把桥拆掉 一样。许有王听了又羞又恨，加快步伐离开。之后他借口有病，再也 不上朝了。 成语故事大全.txt当你以为自己一无所有时，你至少还有时间，时间能抚平一切创伤，所以请不要流泪。能满足的期待，才值得期待；能实现的期望，才有价值。保持青春的秘诀，是有一颗不安分的心。不是生活决定何种品位，而是品位决定何种生活。成语故事大全 南柯一梦 隋末唐初的时候，有个叫淳于尊的人，家住在广陵。他家的院中有一棵根深叶茂的大槐树，盛夏之夜，月明星稀，树影婆婆，晚风习习，是一个乘凉的好地方。 淳于尊过生日的那天，亲友都来祝寿，他一时高兴．多贪了几杯。夜晚，亲友散尽，他一个人带着几分酒意坐在槐树下歇凉，醉眼膝俄，不觉沉沉睡去。 梦中，他到了大槐安国，正赶上京城会试，他报名入场，三场结束，诗文写得十分顺手，发榜时，他高中了第一名。紧接着殿试，皇帝着浮于弊生得一表人才，举止惆院，亲笔点为头名状元，并把公主许配给他为妻，状元公成了驸马郎，一时成了京城的美谈。 婚后，夫妻感情十分美满。淳于尊被皇帝派往南河郡任太守，一呆就是20年。淳于尊在太守任内经常巡行各县，使属下各县的县令不敢胡作非为，很受当地百姓的称赞。皇帝几次想把淳于尊调回京城升迁，当地百姓听说淳于太守离任，纷纷拦住马头，进行挽留。淳于尊为百姓的爱戴所感动，只好留下来，并上表向皇帝说明情况。皇帝欣赏淳于尊的政绩，赏给他不少金银珠宝，以示奖励。有一年，敌兵入侵，大槐安国的将军率军迎敌，几次都被敌兵打得溃不成军。败报传到京城，皇帝震动，急忙召集文武群臣商议对策。大臣们听说前线军事屡屡失利，敌兵逼近京城，凶猛异常，一个个吓得面如土色，你看我，我看你，都束手无策。 皇帝看了大臣的样子，非常生气地说：“你们平田养尊处优，享尽荣华，朝中一旦有事，你们都成了没嘴的葫芦，胆小怯阵，一句话都不说，要你们何用？” 宰相立刻向皇帝推荐淳于尊。皇帝立即下令，让淳于尊统率全国精锐与敌军决战。 淳于尊接到圣旨，不敢耽搁，立即统兵出征。可怜他对兵法一无所知，与敌兵刚一接触，立刻一败涂地，手下兵马被杀得丢盔解甲，东逃西散，淳于尊差点被俘。皇帝震怒，把淳于尊撤掉职务，遣送回家。淳于尊气得大叫一声，从梦中惊醒，但见月上枝头，繁星闪烁。此时他才知道，所谓南河郡，不过是槐树最南边的一枝树干而已。 后生可畏 【读音】 hòu shēng kě wai 【解释】后生：青年人，后辈；畏：敬畏，佩服。指青年人势必超过前辈，令人敬畏。【出处】《论语·子罕》后生可畏，焉知来者之不如也! 【用法】主谓式；作谓语、宾语、分句；含褒义，称赞年轻人。 【近义词】少年老成、长江后浪推前浪 【反义词】少不更事、乳臭未干 【语法】：主谓式；作谓语、宾语、分句；含褒义，称赞年轻人 故事： 元朝的大臣彻里帖木耳，处理公务精明干练，善于决断。有一年他在浙江任职，正好逢上省城举行科举考试。他目睹了这场考试，从官府到考生都花费了许多钱财，并且免不了有 300字的成语故事 少数民族地区发生叛乱，他认为是贪官与无赖所为，起义军的力量是星星之火可以燎原，下令惩治贪官悍将，迅速平息了叛乱。 【典故】若火之燎于原，不可向迩。 《尚书·盘庚上》【解释】一点点小火星可以烧掉大片原野。 比喻开始时微小，但有远大发展前途的新事物。 【用法】作宾语、定语、分句;用于新生事物【近义词】星火燎原【示例】你不轻视了。 星星之火，可以燎原，不晓得怎么结局呢!张鸿《续孽海花》第57回【成语造句】◎直到1930年初，毛泽东的《星星之火，可以燎原》的问世，才在实际上解决了这个问题。 ◎是什么力量使他们坚信"星星之火，可以燎原"，革命必然胜利呢?就是因为共产党人心中铭刻着共产主义的丰碑。 300字的成语故事(二)：生公说法，顽石点头【注音】shēng gōng shuō fǎ , wán shí diǎn tóu【成语故事】晋末高僧竺道生15岁就登坛讲法，20岁上庐山讲授佛法，成为江南的佛学大师，他潜心研究刚传入中国的《涅槃经》，参悟到其中的奥妙，得出“人人皆可成佛的理论推断，因此被逐出庐山，他流浪到苏州虎丘山讲法，顽石都为之点头。 【出处】传说晋朝和尚道生法师对着石头讲经，石头都点头了。 比喻精通者亲自来讲解，必能透彻说理而使人感化。 【解释】shēnggōngshuōfǎ，wánshídiǎntóu【用法】作宾语、定语、 分句;用于书面语【相近词】生公说法 武帝在东堂巡游时接见了郤诜，问他自己感觉如何。 郤诜回答说：“臣举贤良对策，为天下第一，犹桂林之一枝，昆山之片玉。 【典故】累迁雍州刺史。 武帝于东堂会送，问诜曰：‘卿自以为何如?’诜对曰：‘臣举贤良对策，为天下第一，犹桂林之一枝，昆山之片玉。 ’《晋书·郤诜传》【解释】昆山：昆冈，古代产玉的地方。 桂花林中的一枝花，昆山中的一块玉。 比喻科举考试中的出类拔萃的佼佼者。 【用法】作宾语、分句;可分开使用【相近词】桂林一枝、昆山片玉300字的成语故事(四)：刻画无盐，唐突西施【拼音】kè huà wú yán , táng tū xī shī【成语故事】东晋初年，很有名望的尚书仆射周顗为人特别谦虚。 人们总喜欢把他与当时同样有名望的尚书令乐广相提并论，说他们两人都是才学过人、德高望重。 周顗谦虚地说：“把我与他相比，是亵渎了他，那是刻画无盐、唐突西施了。 【典故】庚亮尝谓顗曰：‘诸人咸以君方乐广。 ’顗曰：‘何乃刻画无盐，唐突西施也。 ’《晋书·周顗传》【释义】刻画：描绘;无盐：战国时齐国的丑女; 大材小用成语故事 本文是关于大材小用成语故事，感谢您的阅读！ 【成语】： 大材小用 【拼音】： [dàcáixiǎoyòng] 【解释】： 把大的材料用于小的用处，比喻人才使用不当。 【出处】： 晋·石崇《许巢论》：“盖闻圣人在位，则群材必举，官才任能，轻重允宜，大任已备，则不抑大材使居小位;小材已极其分，则不以积久而合处过材之位。” 【举例造句】： ～古所叹，管仲萧何实流业。◎宋·陆游《送辛幼安殿撰造朝》诗 【成语故事】： 周瑜病死后，鲁肃向孙权推荐庞统，孙权不用他。鲁肃就推荐庞统去投奔刘备。刘备见他长相难看，就将他安排到耒阳县当县令，庞统不悦想用才学打动刘备，又见诸葛亮不在，只得辞行。到了那以后，终日借酒浇愁。刘备听闻庞统不理政事，终日把酒取乐，大怒，命张飞去荆南巡视。张飞遂与孙乾一同前往。到时未见庞统出来迎接。庞统的同僚告诉张飞，庞统如何不理政事。张飞大怒，想擒拿庞统。孙 乾劝他见了庞统，治罪不迟。张飞见庞统后，大喝他把县的各种事给废了。而庞统却认为都是小事，结果只用半天的时间，就把这个月的事都处理了，张飞佩服不已，就向刘备推荐了他。后人便演化出了庞统当县令——大材小用的歇后语。 事实上庞统确实去当过县令，也确实当的不是特别好，但没有用半天的时间就解决了一个月的政务。后来(因为当的不好)被免官了，鲁肃便写信告诉刘备，庞统这个人不适合当县令，应该当治中、别驾。而后，庞统的表现也确实很出色。但前面那句歇后语，却绝对不是事实。即使庞统真的有半天就解决一个月的事的本领，这个故事则说明他志向远大，深至天下。而不是大材小用。 感谢您的阅读，本文如对您有帮助，可下载编辑，谢谢 精卫填海 《山海经》记述有一种鸟。它的名字叫精卫。精卫原来是炎帝宠爱的女儿，有一天她去东海玩，可是突然风暴袭来，她死了。女娃变成了鸟，名字就叫作“精卫鸟”。精卫鸟去西山衔来石子儿和树枝，一次又一次投到大海里，想要把东海填平。晋代诗人陶渊明写诗说:“精卫衔微木，将以填沧海”。后来人们常用“精卫填海”这句成语，比喻按既定的目标坚毅不拔地奋斗到底。《精卫填海》也是38集大型古装神话剧的名字。精卫痛恨无情的大海夺去了自己年轻的生命，她要报仇雪恨。因此，她一刻不停地从她住的发鸠山上衔了一粒小石子，展翅高飞，一直飞到东海。她在波涛汹涌的海面上回翔阒，悲鸣着，把石子树枝投下去，想把大海填平。大海奔腾着，咆哮着，嘲笑她:“小鸟儿，算了吧，你这工作就干一百万年，也休想把我填平!”精卫十分执著，在高空答复大海:“哪怕是干上一千万年，一亿年，干到宇宙的尽头，世界的末日，我终将把你填平的!”轮到大海不解了:“你为什么这么恨我呢”“因为你夺去了我年轻的生命，你将来还会夺去许多年轻无辜的生命。我要永无休止地干下去，总有一天会把你填成平地。”精卫锲而不舍的精神，善良的愿望，宏伟的志向，受到人们的尊敬。晋代诗人陶潜在诗中写道:“精卫衔微木，将以填沧海”，热烈赞扬精卫小鸟敢于向大海抗争的悲壮战斗精神。后世人们也常常以“精卫填海”比喻志士仁人所从事的艰巨卓越的事业。 愚公移山 很久以前，有一位老先生，他的名字叫作愚公。愚公家的门口有两座好高好高的山，一座山叫太行，另一座山叫王屋。两座山正好挡在愚公家的门口，让愚公每天进出家里都要绕好远好远的路！ 有一天吃饭的时候，愚公突然对家人说：”我们全家一起合作，把挡在门口的两座大山移开，让门口的路可以直通到外面的大路上，你们看好不好呢”儿子和孙子一听，都点头赞成说：”好呀！好呀！”。可是愚公的妻子却摇摇头说：”不可能的，你连搬一个土丘的力气都没有，还想搬移大山！就算你搬得动，那些挖出来的泥土石块，你要扔到什么地方去呢”愚公和孩子们听了，都哈哈大笑起来：”那有什么困难的！我们可以丢到海里面去呀！” 第二天开始，愚公和他的儿子、孙子，三个人一起扛着锄头，挑着扁担，到山边开始挖。愚公的邻居京城氏和她的小儿子，也兴致勃勃地帮愚公一起做着移山的工作。这时候，有一个叫作智叟的老先生，忍不住嘲笑他们说：”愚公呀！你实在太糊涂了。你这么老了，还要去移什么山就算让你搬到你死掉的那一天，也不可能把大山移开来的！” 愚公听了他的话，笑笑说：”智叟，你才糊涂呢！我虽然很老，我还有儿子可以继续去做呀；儿子还会生孙子，孙子还会再生儿子，我们的子子孙孙可以一直搬下去，只要我们搬掉山的一层，就少一层，总有一天我们会把这两座山搬走，天底下哪儿有不能克服的困难呢”智叟没有话好说，只好走开了。 后来，山神和海神知道愚公要移山的事情，害怕愚公一家人永不停止的搬下去，会把山搬光，把海填满，就跑去告诉天神，天神一听：”嗯！这个愚公真是有恒心呀！我来帮帮他吧！”天神就派了两个神仙去把王屋山与太行山背走，放到别的地方去，不再挡在愚公家门口了。 从此以后，只要有人做事情不怕困难一直做，我们就说他有“愚公移山”的精神，一定会成功的！ 含辛茹苦 传说宋朝时期，人们修养佛性往往一开始就进驻山林，踏着荆棘与蛇虫，在霜雪中裸体行走，甚至更有人割下自己的肉烹烧去喂老虎以及其他的小动物，这些人茹苦含辛以为就能成佛，人们感慨“佛之道难成”。 任劳任怨 抱头鼠窜的成语故事和知识点 成语解释窜：逃跑；乱跑。抱着头像老鼠一样迅速逃跑。多用来形容受到沉 重打击狼狈逃跑的样子。 成语出处宋 苏轼《代侯公说项羽辞》：“夫陆贾，天下之辩士，吾前日遣 之，智穷辞屈，抱头鼠窜，颠狈而归，仅以身免。” 成语繁体抱頭鼠竄 成语简拼 BTSC 成语注音ㄅㄠˋ ㄊㄡˊ ㄕㄨˇ ㄘㄨˋ 常用程度常用成语 成语字数四字成语 感情色彩贬义成语 成语用法抱头鼠窜连动式；含贬义，形容敌人的狼狈相。 成语结构连动式成语 成语年代古代成语 成语正音窜，不能读作“chuàn”。 成语辨形鼠；上边是“臼”不能写作“白”。 成语辨析抱头鼠窜和“逃之夭夭”；都含贬义；都形容逃跑。但抱头鼠窜是 比喻性的；“逃之夭夭”是诙谐说法；有时用作中性。 近义词逃之夭夭、捧头鼠窜 反义词大摇大摆、得胜班师 成语例子夫陆贾天下之辨士， 吾前日遣之， 智穷辞屈， 抱头鼠窜， 颠狈而归。 （宋 苏轼《拟侯公说项羽辞》） 英语翻译 cover one's face and creep away 日语翻译頭をかかえほうほうの体(い)で逃げる 俄语翻译 в п áн и к е е ж áт ь <о р а т и т ь с я > 其他翻译<法>fuir comme un rat la tête dans les mains 成语谜语捂着脑袋赶耗子 成语歇后语抱(捂)着脑袋赶老鼠 成语故事楚汉相争时期，在萧何的极力推荐下，刘邦任用韩信为大将，抄了 项羽的后路，破赵取齐，占据黄河下游地区，被封为齐王。蒯通积极鼓动韩信与 刘邦、 项羽三分天下， 举出当年常山王张耳抱头鼠窜归降了汉王并出兵消灭了生 死与共的好友陈余 天下无难事只怕有心人 【注音】tiān xiàwúnán shì, zhǐpàyǒu xīn r?n 【出处】天下无难事，只怕有心人。明·王骥德《韩夫人题红记·花阴私祝》 【解释】指只要有志向，有毅力，没有什么办不到的事情。 【用法】作宾语、分句；用于劝诫人 【结构】复句式 【相近词】天下无难事 【同韵词】鹤立鸡群、纬武经文、敬老怜贫、卖俏倚门、咂嘴舔唇、黯然销魂、扬幡招魂、裂石流云、以郄视文、尔雅温文、...... 【英文】[idiom] it's dogged as does it. 【德语】Werwillensstarkist,demistinderWeltnichtsschwer. 【成语故事】香菱因薛蟠不在家，就向林黛玉学习作诗。黛玉教他作诗的基本常识，香菱就想出很多好诗来问黛玉，黛玉与宝钗、李纨等姐妹纷纷鼓励她，夸奖她说：“天下无难事，只怕有心人”，香菱从此学诗作诗的劲头更加大了 【成语示列】这首不但好，而且新巧有意趣。可知俗语说：‘天下无难事，只怕有心人。’清·曹雪芹《红楼梦》第四十九回 【其它使用】 ◎真是天下无难事，只怕有心人，一来二去，朱桂梅居然又能在小车床上镟活儿了。 词类符号：名词；时间名词；方位名词；处所名词；人名；姓氏；名字；地名；机构名；其他专有名词；动词；联系动词；能愿动词；趋向动词；形容词；区别词；数词；量词；副词；代词；介词；连词；助词；叹词；拟声词；习用语；缩略语；前接成分；后接成分；语素字；非语素字； 运筹帷幄之中，决胜千里之外 【注音】yùn ch?u w?i w?, ju?shang qiān lǐ 【出处】夫运筹帷幄之中，决胜千里之外，吾不如子房。《史记·高祖本纪》 【解释】筹：计谋、谋划；帷幄：古代军中帐幕。拟定作战策略，获取战斗的胜利。 【用法】作宾语、定语；用于处事 【结构】复句式 【近义词】运筹帷幄之中，决胜千里之外 【同韵词】徇国忘己、威福自己、今非昔比、腾空而起、间不容瞚、转嗔为喜、为仁由己、生花妙笔、皆大欢喜、庆父不死，鲁难未已、...... 【年代】古代 【英语】to map out or devise strategy in the command tent 【成语故事】西汉时期，刘邦当皇帝后在都城洛阳南宫摆酒宴，招待文武百官。他问百官他与项羽的区别，百官纷纷夸赞他大仁大义。刘邦说运筹帷幄不如张良，安抚百姓不如萧何，率军打仗不如韩信，但他能合理地使用他们三位俊杰，所以能得天下 【成语举例】如单二哥、王伯当，都是将之才；若说运筹帷幄，决胜千里，恐还未能。清·褚人获《隋唐演义》第37回 避其锐气击其惰归 【注音】bìqíruìqì, jīqídu?guī 【典故】故善用兵者，避其锐气，击其惰归，此治气者也。春秋·齐·孙武《孙子·军争》 大材小用的成语故事 诗：“大材小用古所叹，管仲、萧何实流亚。 释义比喻对人材的使用不当。 故事南宋著名爱国词人辛弃疾，父亲在他童年就去世，由祖父抚养成人。辛弃疾曾拜当时著名的田园诗人刘瞻为师，并和党怀英两人是刘瞻最得意的学生。有一次，刘瞻问他们两人道：“孔子曾经要学生谈各人的志向，我也问问你们将来准备干什么?”党怀英回答说：“读书为了做官，为了取得功名，光宗耀祖。我一定要到朝廷里去做大官;如果做不了官，就回家隐居，学老师的样子写田园诗。” 刘瞻听了很高兴，连连称好，认为他的志向很高洁。辛弃疾却回答说：“我不想做官，我要用词写尽天下的贼，用剑杀尽天下的贼!”刘瞻听了大吃一惊，要辛弃疾今后不要再说这样荒唐的话。此后，辛、党两人的生活道路截然不同：辛弃疾英勇地投身到抗金的民族战场上去，以爱国词人著称于世;而党怀英则混迹于金人统治集团，为金人 作了一些帮闲乃至帮凶的工作。 金人南侵后，辛弃疾组织了两千多人的队伍在故乡起义。后来，又率领队伍投奔济南府农民耿京组织的起义军。不久，起义军接受朝廷任命，与朝廷的军队配合作战，打击南侵的金军。但由于投降派的排挤和打击，辛弃疾后来曾长期闲居在江西上饶一带。1203年春，才被任命为绍兴府知府兼浙江东路安抚使。这一年，辛弃疾已经六十四岁了。 绍兴西郊有一处地方叫三山，当时著名的爱国诗人陆游就在那里闲居。陆游比辛弃疾大十五岁，当时快八十岁了，他的爱国诗句早已为辛弃疾所景仰，因此辛弃疾到任不久，就去拜访了这位前辈，两人一起议论国家大事，相见恨晚。陆游听了辛弃疾对形势的分析和统一、全国的设想，觉得他是一个很有才能的人，希望他在事业上取得成功。 次年春天，宋宁宗降下圣旨，要辛弃疾到京城临安去，征询他对北伐金国的意见。”辛弃疾把这件事告诉陆游，陆游觉得这是辛弃疾施展自己才能的好机会，为他感到高兴。 高考经典成语故事汇总 2020高考就要到了，为了帮助大家更好地学习语文知识，接下来是小编为大家整理的高考经典成语故事汇总，希望大家喜欢! 高考经典成语故事汇总一 江郎才尽 【出处】《南史·江淹传》：尝宿守冶亭，梦一丈夫，自称郭璞谓淹曰：“吾有笔 在卿处多年。可以见还。”淹乃探怀中，得玉色彩笔以授之;尔后为诗，绝无美句，时人谓之才尽。 四字成语“江郎才尽”描述的哲理是什么：江郎：指南朝江淹。原指江淹少有文名，晚年诗文无佳句。比喻人的文采思情衰退。“江郎才尽”这一带贬意的成语，一千五百 多年来就一直陪伴着江淹。他自幼勤奋好学，六岁能诗，十八岁己熟背“五经”，所作《恨赋》、《别赋》，更显其才华横溢，被誉为千古奇文。只可惜，中年的江淹突然 罢笔，落了个“江郎才尽”的名声。也许人们并不清楚，聪明的江淹正是用“江郎才尽”的 把戏，把后人给涮了一把。 梁上君子 东汉灵帝时小官吏陈寔心地善良，做事公正无私。有天晚上一个小偷溜进他的屋 里躲在屋梁上，他发现后并没有下令捉拿，而是把儿子、孙子叫到身边，给他们讲如 何做人，不要学梁上的那位君子。小偷深受感动就下地求饶。 四字成语“梁上君子”描述的哲理是什么：比喻小偷，现在有时也指脱离实际、脱 离群众的人。梁指的是房梁，四字成语“梁上君子”躲在梁上的君子 鞭长不及 春秋时期，楚庄王仗着势力强大不征得宋国同意派大夫申舟经宋国出使齐国，宋 国杀了申舟。楚庄王派兵攻打宋国。宋国向晋国求援，大夫伯宗向晋景公建议不要出兵，说“虽鞭之长，不及马腹”，没有理由为了宋国而得罪楚国。 四字成语“鞭长莫及”描述的哲理是什么：很多事情并非你的能力强就能办到，力 所不能及的事情非常多 高考经典成语故事汇总二 改弦更张 【注音】gǎi xián gēng zhāng 成语典故 1，草木皆兵 解释：把山上的草木都当做敌兵。形容人在惊慌时疑神疑鬼。 故事：东晋时，前秦皇帝符坚率大军入侵东晋，后大败，回国途中他感到极度恐惧，觉得山上的树木都是东晋的追兵，故有“草木皆兵” 的说法 2，背水一战 故事：楚汉相争时，韩信率兵攻打韩国，他故意将军营安扎在河边，背水为阵，意在断绝退路，逼迫军队拼死进攻，最后大获全胜，故有“背水一战”的说法 3，四面楚歌 故事：楚汉相争时，韩信在垓下布下十面埋伏，围困楚霸王项羽，韩信让军队在夜间吟唱项羽故乡的楚歌，涣散项羽的军心，大收其效。 4.揭杆而起 故事：秦末时，民怨四起，陈胜吴广不堪忍受，终于在大泽乡起义，起义时没有旗帜，就用竹竿代替，就有了“揭竿而起”的说法 5.破釜沉舟 故事：秦末，项羽进攻汉中，过河后，项羽下令凿沉渡船，砸碎锅灶，表示不留退路，果然一战成功 6.明修栈道，暗渡陈仓 故事：楚汉相争时，刘邦讨伐项羽，明地里派兵修整入栈道，暗里却将大部队调遣到废弃以久的陈仓道，偷袭项羽 7.退避三舍 春秋时，晋国公子重耳落难，逃亡楚国，应承楚王说：“我若为晋国国君，若与楚国敌对，必退避三舍（一舍是三十里）。”后楚晋果然发生战争，重耳信守诺言，果然退兵九十里 8.纸上谈兵 战国时赵国名将赵奢有一子名赵括，幼读兵书，谈起用兵之道，如数家珍，但他没有任何实战经验，在长平之战中导致赵国惨败，留下了纸上谈兵的说法。在纸面上谈论打仗。比喻空谈理论,不能解决实际问题。也比喻空谈不能成为现实。 9.卧薪尝胆：薪：柴草。睡觉睡在柴草上，吃饭睡觉都尝一尝苦胆。形容人刻苦自励，发奋图强。 春秋时期，吴越相争，越王勾践大败，几乎亡国，但勾践并不死心，终日以柴草不床，每天吃饭时都要舔一下苦胆，激励自己不忘国耻10.一鸣惊人：一声鸣叫使人震惊。比喻平时没有突出的表现，一下子做出惊人的成绩。 楚庄公继位后三年不上朝，终日饮乐，大臣终于看不下去了，冒死进谏，庄公说：“有一大鸟，羽色艳丽，三年不鸣，一鸣惊人，三年不飞，一飞冲天。”果然，不久庄公就重临朝庭，把这三年中他暗中观察发现的弊病全部修正。 11．孟母三迁：【解释】孟轲的母亲为选择良好的环境教育孩子，三次迁居。形容家长教子有方。 100个成语典故及其历史人物故事（一） 成语故事 中国文化源远流长，博大精深，成语即是我国文化遗产中的一颗璀璨的明珠。其中许多成语来源于历史典故，你对以下100个成语典故及其历史人物故事了解多少呢？ 1、一鼓作气 [释义] 一鼓：第一次击鼓；作：振作；气：士气。作战时第一次敲鼓可以鼓起战士的锐气。比喻趁劲足时一下子把事情完成。 [语出] 《左传庄公十年》：“夫战；勇气也；一鼓作气；再而衰；三而竭。” [正音] 一；不能读作“yì”。 [辨形] 作；不能写作“做”。 [近义] 一气呵成趁热打铁 [反义] 一败如水一败涂地偃旗息鼓 [用法] 含褒义。一般作谓语、定语。 [结构] 紧缩式。 [成语故事] 春秋时，齐国发兵攻打鲁国（两国都在今山东省境）。当时齐国强大，鲁国弱小，双方实力悬殊。可是结果鲁国却以弱胜强，把齐军打得大败。据《左传》载，这次鲁国的胜利，与曹刿的精明策划有很大关系。 曹刿既非武将，也非文臣，但深通兵法。他得悉齐国发兵来犯，鲁庄公准备抵抗，便主动要求面见庄公。他的亲友邻人劝他：“国家大事，自有那些天天吃肉的大官管着，你何必瞎操心？”曹刿说：“那些大官目光短浅，不会有深谋远见。” 曹刿见了庄公，首先提出：取信于民，是战前重要的政治准备，也是获胜的保证。并要求作战时允许他一起去，于是庄公便叫他同车出发。在长勺的地方，齐、鲁两军相遇。双方列成阵势，战斗即将开始。只见齐军大擂战鼓，准备进兵。庄公也准备擂鼓迎击。曹刿阻止道：“等一等。”齐军见鲁军没有反应，又擂了一通鼓。这样齐军擂鼓三通，鲁军总是按兵不动。直到齐军三通鼓罢，曹刿才说：“现在可以进兵了！”鲁军战鼓一响，下令冲杀，士兵们一声呐喊，直扑敌阵，猛不可当。齐军大败，狼狈而逃。 庄公正想下令追击，曹刿却又阻止，并下车细看地面齐军兵车轮迹，又攀上车前横木，注意暸望敌军退走的情形，然后说：“现在可以追击了！”庄公当即下令追击。鲁军乘胜前进，把齐军全部赶出国境。 关于随遇而安的儿童成语故事及用法【注音】：suí yù ér ān 【释义】：随：顺从;遇：遭遇。指能顺应环境，在任何境遇中都能满足。 【出处】：清·刘献廷《广阳杂记》一：“随寓而安，斯真隐矣。” 清·文康《儿女英雄传》第24回：“吾生有涯，浩劫无涯，倒莫如随遇而安。” 【用法】：偏正式;作谓语、宾语、定语、状语;含褒义 ;指能顺应环境 【示例】：不过能够～——即有船坐船云云——则比起幻想太多的人们来，能够稍为安稳，能够敷衍下去而已。(鲁迅《两地书》六) 【近义词】：与世无争、随俗浮沉 【反义词】：愤世嫉俗、愤愤不平 【灯谜】：旅行家 【英文】：feel at home wherever one is 【成语故事】 俗话说“不如意之事十有八九”，在每个人的一生当中，根本就不可能永远都是风平浪静。人生遭际不是个人力量所能左右的。而在诡谲多变、不如意事常存的环境中，能使我们不觉其拂逆而使得心情轻松的办法，那就是要做到使自己“随遇而安”。 “橘生淮南则为橘，橘生淮北则为枳”，是何缘故成了如此?水土不同是也。想一想，人如果像此橘，应该如何应对呢?当今这个社会，千变万化，每个人一生当中所处的环境不会一成不变，我们怎么去面对呢?有大智慧的人都认为，坚持自己的信念，随遇而安吧。 在很久以前，有一个寺院，里面住着一老一小两位和尚。 有一天老和尚给小和尚一些花种，让他种在自己的院子里，小和 尚拿着花种正往院子里走去，突然被门槛绊了一下，摔了一跤。手中 的花种洒了满地。这时方丈在屋中说道“随遇”。小和尚看到花种洒了，连忙要去扫。等他把扫帚拿来正要扫的时候，突然天空中刮起了 一阵大风，把散在地上的花种吹得满院都是，方丈这个时候又说了一 句“随缘”。 小和尚一看这下可怎么办呢?师傅交代的事情，因为自己不小心给 耽搁了，连忙努力地去扫院子里的花种，这时天上下起了瓢泼大雨， 小和尚连忙跑回了屋内，哭着说，自己的不小心把花种全撒了，不过 老方丈微笑着说道“随安”。冬去春来，一天清晨，小和尚突然发现 院子里开满了各种各样的鲜花，他蹦蹦跳跳地告诉师傅，老方丈这时 说道“随喜”。 对于随遇、随缘、随安、随喜这四个随，能够说就是我们人生的 缩影，在遇到不同事情、不同情况的时候，我们最需要具有心态就是“随遇而安”。而且，一个人如能不管际遇如何，都保持快乐的心境，那真比有百万家产还有福气! 大文学家苏东坡以前多次被流放，不过，他说，要想心情愉快， 只需要看到松柏与明月也就行了。何处无明月，何处无松柏?仅仅很少 人有他那般的闲情与心情罢了。如果大家都能够做到随遇而安，即时 挖掘出身边的趣闻乐事，甚至于去找寻苍穹中的闪耀星星，这样，就 是环境没有任何改变，你的心境从此也会大不一样了。 环境往往会有不如人意的时候，问题在个人怎么面对拂逆和不顺。知道人力不能改变的时候，就不如面对现实，随遇而安。与其怨天尤人，徒增苦恼，就不如因势利导，适合环境，从既有的条件中，尽自 己的力量和智慧去发掘乐趣。从容地由不如意中去发掘新的前进道路，才是求得快乐与安静的办法。 儿童成语故事卡 一、儿童成语故事100个选择 按照字母顺序选择100个故事性、趣味性比较强的四字成语。 二、画面安排 插画在正面，故事在背面，这样看起来讲起来都比较方便。 四字成语加拼音，故事生动、浅显易懂，字数控制在300以内，最后点名成语的用法，语句形式为“爱不释手用来形容………………” 三、初选成语如下（93个） （红色已写黄色可更换） A 暗箭伤人 B 班门弄斧半途而废病入膏肓别开生面杯水车薪拔苗助长不寒而栗 C 草木皆兵出人头地草船借箭 D对牛弹琴道听途说大材小用对症下药打草惊蛇 F 负荆请罪分道扬镳 G 过河拆桥刮目相看孤注一掷 H 狐假虎威画蛇添足后生可畏画龙点睛华而不实画地为牢囫囵吞枣 J 嗟来之食惊弓之鸟井底之蛙鸡犬不宁举棋不定江郎才尽 K 刻舟求剑 L 滥竽充数老生常谈老马识途力不从心来之不易 M 买椟还珠毛遂自荐名落孙山 N 南柯一梦南辕北辙 O 呕心沥血 P 破釜沉舟匹夫之勇 Q 杞人忧天起死回生千变万化请君入瓮歧路亡羊巧取豪夺 R 入木三分孺子可教如坐针毡 S 守株待兔双管齐下三顾茅庐塞翁失马三令五申水滴石穿熟能生巧T 天衣无缝天下无双退避三舍 W 亡羊补牢闻鸡起舞完璧归赵望梅止渴望洋兴叹卧薪尝胆 X 洗耳恭听悬梁刺股胸有成竹小心翼翼 Y 掩耳盗铃一鸣惊人以卵击石约法三章一字千金以貌取人夜郎自大一诺千金一毛不拔鸦雀无声一叶障目有恃无恐一箭双雕庸人自扰Z 朝三暮四指鹿为马争先恐后捉襟见肘凿壁偷光专心致志郑人买履自惭形秽纸上谈兵 四、资料搜集网站 https://www.wendangku.net/doc/a014146173.html,/cygs.html 五、进度安排 1、每天6个成语故事 2、下午4：30之前提交审核。 笨鸟先飞的成语故事 东汉时，乐羊子的妻子是一位贤德的女子。一次，乐羊子拾到了一块金子，高兴地拿回来交给妻子。妻子说：“有志气的人会严格要求自己，把捡来的东西拿回家是败坏自己的名声。乐羊子深感惭愧，就把金子放回原处，然后说：“你很笨要笨鸟先飞，要出外求学去。”所以乐羊子就出外求学去了。 但一年后，乐羊子因为思念妻子返回家中。妻子把他领到织机旁说：“这布是一寸寸、一尺尺织出来的，日积月累才能成丈、成匹。如果我把它剪断，就前功尽弃了。求学也和织布一样，不能在学到一半的时候放弃。”乐羊子深受感动，又回去求学了，七年没有回家。 笨鸟先飞的成语故事【注音】bèn niǎo xiān fēi 【解释】元·关汉卿《陈母教子》第一折：“二哥;你得了官也。我和你有个比喻：我似那灵禽在后;你这等坌(笨)鸟先飞。” 【用法】作谓语、定语;比喻能力差的人加倍努力 【近义词】钝学累功跛鳖千里 笨鸟先飞的成语故事很笨要笨鸟先飞，要出外求学去。羊子的妻子就是这么鼓励乐羊子外出求学的，既然天子不够聪颖，那么就要好好的努力，行动笨拙的鸟要先飞。比喻能力差的人怕落后，做事比别人先动手。 东汉时，乐羊子的妻子是一位贤德的女子。一次，乐羊子拾到了一块金子，高兴地拿回来交给妻子。妻子说：“有志气的人会严格要求自己，把捡来的东西拿回家是败坏自己的名声。乐羊子深感惭愧，就把金子放回原处，然后说：“你很笨要笨鸟先飞，要出外求学去。”所以乐羊子就出外求学去了。 但一年后，乐羊子因为思念妻子返回家中。妻子把他领到织机旁说：“这布是一寸寸、一尺尺织出来的，日积月累才能成丈、成匹。如果我把它剪断，就前功尽弃了。求学也和织布一样，不能在学到一半的时候放弃。”乐羊子深受感动，又回去求学了，七年没有回家。 2013年10月28日至11月成语故事 1、自相矛盾：比喻自己说话做事前后抵触。 造句：（1）你早上说昨晚去朋友家了，下午又说昨晚去看电影了，你这不是自相矛盾吗，你到底去干嘛了？ （2）小明刚才说花盆是她打破的，现在又说是小丽打破的，简直是自相矛盾。 2、鹬蚌相争：“鹬蚌相争，渔翁得利”的省语。比喻双方相持不下，而使第三者从中得利。 造句：（1）如果我们自己内部不团结，就会发生鹬蚌相争，渔翁得利的事情。 （２）兄弟间为了一点点恩怨、矛盾而互相争斗,必定会做出鹬蚌相争的蠢事来。 （３）这对夫妇刚下火车，就为乘公共汽车还是打的回家争吵起来。等到他们的“内战”结束时，才发现随身携带的行李不见了，真是鹬蚌相争，渔翁得利。 3、螳螂捕蝉：螳螂捕蝉，黄雀在后。螳螂正想要捕捉蝉，却不知道黄雀在它后面正要吃它。今指人只顾追求眼前的利益，而不顾身后隐藏的祸患。 造句：（１）公交车一停，小张就从车窗把自己的包扔进车里占座，等到他从门口上车后，发现包不见了，真是螳螂捕蝉，黄雀在后。 （２）小偷只顾着偷东西，没想到警察就盯着他，当场被抓了个现行，真是螳螂捕蝉黄雀在后。 4、无价之宝：无法估价的宝物。指极珍贵的东西。 （１）老师的这些教导，对我来说，将会是我人生中的无价之宝。 （２）这些知识，这些经验，都是日积月累来的，是买不来的财富，是他一生的无价之宝。 （３）伴随着他成长的这些友情，这些亲情，是多么可贵的无价之宝啊，是那么的温暖人心。 5、庖丁解牛：庖丁：厨工；解：肢解分割。比喻经过反复实践，掌握了事物的客观规律，做事得心应手，运用自如。 造句：（1）平时多注意作文素材的积累，这样写作文自然就会像庖丁解牛一般游刃有余（做事熟练，解决问题轻松利落）（他经验丰富，办起事情总是能够游刃有余）了。 （2）我的老师板书清雅挺秀,朗诵范文抑扬顿挫,讲解文章有如庖丁解牛,条分缕析（有条有理的细细分析）,透辟独到。 （3）我深深体会到,学习英语,要想达到庖丁解牛那样的驾驭能力,并非一朝一夕所能至，是要付出辛勤汗水的。 50字的成语故事 吕后听从张良的主意，让太子刘盈请出商山四位贤士。 刘邦看到太子有商山四贤辅佐，羽翼已成，对戚夫人唱道：“鸿鹄高飞，一举千里。 羽挧已就，横绝四海。 【典故】鸿鹄高飞，一举千里。 西汉·司马迁《史记·留侯世家》【释义】鸿鹄：天鹅。 天鹅高高飞翔，一飞千里。 指人有雄才大略。 【用法】作宾语、分句;指人有雄才大略50字的成语故事(二)：同病相怜，同忧相救【拼音】tóng bìng xiāng lián , tóng yōu xiāng jiù【成语故事】春秋时期，楚国奸臣费无极杀害郤宛全家。 郤宛的亲戚伯暿听到消息，连夜逃到吴国，向吴王及伍子胥汇报此事。 伍子胥说：“咱们一样有冤仇，你是否听过《河上歌》?这歌真让人有同病相怜、同忧相救之感。 【出处】子不闻河上之歌乎?同病相怜，同忧相救。 汉·赵晔《吴越春秋·阖闾内传》【解释】比喻因有同样的遭遇或痛苦而互相同情、援助。 【用法】作定语、宾语;用于人的处境【近义词】同病相怜 晚上一头兽头人身的怪物来舔食剩菜剩饭。 徐秀才吓得拼命狂叫吓跑了那怪物，后来再也没发现了，人们感叹：“黄狸黑狸，得鼠者雄。 【出处】异史氏曰：‘黄狸黑狸，得鼠者雄。 ’此非空言也。 清·蒲松龄《聊斋志异·驱怪》【释义】狸：野猫，山猫;雄：威武，借喻杰出的人物或国家。 比喻不论是什么办法，只要能取得好的或预期的效果，就是好办法。 【用法】作宾语、定语、分句;指取得好效果的方法【成语举例】黄狸黑狸，得鼠者雄演化为现代的白猫黑猫论。 50字的成语故事(四)：两虎相斗，必有一伤【拼音】liǎng hǔ xiāng dòu , bì yǒu yī shāng【成语故事】战国时期，韩国和魏国打了一年多还不分胜负，秦惠王想出兵干涉，楚国使者陈轸给秦惠王讲卞庄子利用两虎相争必有一伤的道理，得到它们两败俱伤时一举打死两只老虎，劝秦惠王采取坐山观虎斗的计策，等待时机再消灭这两国。 【出处】虎者，戾虫;人者，甘饵。 今两虎争人而斗，小者必死，大者必伤。 西汉·刘向《战国策·秦策二》【释义】斗：争斗。 比喻两个强者互相搏斗，必然有一方要遭严重损害。 【用法】作宾语、定语、分句;用于处事【相近词】两虎相争，必有一伤【成语示列】两虎相斗，必有一伤，陛下但默观动静。 中国古代的成语故事 在学习汉语的过程中,成语是不可缺失的一堂课程，成语故事可以帮助我们更好地去了解成语的意思。下面是分享的中国古代的成语故事，一起来看一下吧。 （1）【对症下药】 东汉末年，有一个杰出的医学家叫华佗，他的医术非常高明。有两个病人，一个叫李延，一个叫倪寻，都得了头痛发热病，找过很多医生也没治好，于是来找华佗。华佗经过细心诊断，给他们各开了一个药方。给李延开的药方是发散药，给倪寻开的药方是泻药。他们俩一看，心里就嘀咕起来：都是一样的病，怎么用药完全不同呀？便问华佗这是什么道理。 华佗说：“吃药要看具体情况，你们症状相同，可是得病的原因却不同。倪寻的病是从内部伤食引起的，李延却是从外部受寒造成的。病因不同，当然用药就不能相同了。” 两人听了，便放心服药，病果然很快好了。由这个故事产生了成语“对症下药”。“症”指病症。现在这成语的用法广泛得多。不光形容治病，凡是针对具体情况，具体问题，采取恰当措施和方法的，都可以用这个成语来比喻。相近的成语还有“有的放矢”。“的”是靶子；“矢”是箭。意思是要有目标地射箭。“对症下药”强调的是要根据客观 情况采取有效方法；“有的放矢”强调的是办事要有目的性、针对性。 （2）【拔山举鼎】 “拔山举鼎”这则成语的字面意思是移动大山，举起巨鼎。引申之义为形容力强气壮。亦作“拔山扛鼎”。 项羽，名籍，少年时代，项羽不喜欢读书写字，改学击剑，也不肯好好学。叔父项梁很生气，项羽说：“学写字只要能记记姓名就够了。击剑是对付个把人的，也不值得学，我要学习抵敌万人的本领。”项梁于是教他兵法，他很高兴，但也只求略知大意，不肯认真钻研。据说，项羽二十二、三岁时，身体魁梧，体力强壮，能把几百斤重的鼎举起来。 后来，项羽起兵反秦，接着又同刘邦争夺天下，从24岁开始，奋战了8年，最后被刘邦等包围在垓下，终于自刎于乌江。自刎前，在四面楚歌的那天晚上，项羽在营帐中对着爱妾虞姬和叫骓的名马，慷慨高唱道：力拔山兮气盖世，时不利兮骓不逝！骓不逝兮可奈何？虞兮虞兮奈若何！ （3）【程门立雪】 “程门立雪”这则成语的意思是比喻尊敬老师，诚恳求学。 这个成语来源于《宋史。杨时传》，一日见颐，颐偶瞑坐，时与游酢侍立不去。颐既觉，则门外雪深一尺矣。常见成语解析及成语故事
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