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1.
Glutathione (GSH) content and GSH S-transferase activity are consistently increased in corn roots on 24-hr exposure of corn seedlings to part per million levels of N,N-diallyl-2,2-dichloroacetamide (R-25788) and related antidotes for thiocarbamate herbicide injury in susceptible corn varieties. This combined enhancement of enzyme activity and cofactor level leads to rapid detoxification of thiocarbamate sulfoxides, which are proposed to be the active herbicidal compounds formed on metabolic sulfoxidation. S-(N,N-Dipropylcarbamyl)-GSH is formed by this enzyme-catalyzed detoxification of EPTC sulfoxide. This hypothesis on antidote mode of action is supported by studies on 32 dichloroacetamides and related compounds and on the concentration- and time-dependent relationships of R-25788 action. The liver GSH content is normal in mice injected with high doses of R-25788, but the content is reduced when EPTC or EPTC sulfoxide is administered. EPTC sulfoxide also carbamoylates the thiol group of coenzyme A in neutral aqueous medium.  相似文献   

2.
Metribuzin [4-amino-6-tert-butyl-3-(methylthio)-1,2,4-triazin-5(4H)-one] metabolism was studied in tomato (Lycopersicon esculentum Mill. “Sheyenne”). Pulse-treatment studies with seedlings and excised leaves showed that [5-14C]metribuzin was rapidly absorbed, translocated (acropetal), and metabolized to more polar products. Foliar tissues of 19-day-old seedlings metabolized 96% of the root-absorbed [14C]metribuzin in 120 hr. Excised mature leaves metabolized 85–90% of the petiole-absorbed [14C]metrubuzin in 48 hr. Polar metabolites were isolated by solvent partitioning, and purified by adsorption, thin-layer, and high-performance liquid chromatography. A minor intermediate metabolite (I) was identified as the polar β-d-(N-glucoside) conjugate of metribuzin. The biosynthesis of (I) was demonstrated with a partially purified UDP-glucose: metribuzin N-glucosyltransferase from tomato leaves. A possible correlation between foliar UDP-glucose: metribuzin N-glucosyltransferase activity levels and differences in the tolerance of selected tomato seedling cultivars to metribuzin was suggested. The major polar metabolite (II) was identified as the malonyl β-d-(N-glucoside) conjugate of metribuzin.  相似文献   

3.
The microsome-NADPH system of mouse liver oxidizes each of benthiocarb, butylate, cycloate, EPTC, molinate, pebulate, and vernolate herbicide chemicals to the corresponding thiocarbamate sulfoxide which is then cleaved by the liver soluble-glutathione system. These sulfoxides are also detected as transient metabolites in the liver of mice injected with EPTC, molinate, pebulate, and vernolate but not with the other three thiocarbamates. Thiocarbamate sulfones are not detected as metabolites of the thiocarbamates. Studies in vivo and in vitro with [14C]EPTC and -pebulate or their corresponding sulfoxides and/or sulfones further indicate that sulfoxidation is the initial metabolic step in cleavage of the thiocarbamate ester group. Sulfoxidation appears to be a detoxification mechanism for thiocarbamate herbicides in mammals.  相似文献   

4.
The average endogenous GSH content of eight lines of inbred corn was almost twofold greater than ten varieties of hybrid corn. When inbred and hybrid corn lines were treated with R-25788, the average GSH content increased by 56 and 95%, respectively. R-25788 protected two special inbred corn lines, GT 112 (atrazine susceptible) and GT 112 RfRf (atrazine resistant) from EPTC injury by increasing the GSH content and GSH S-transferase activity in roots. Most of the radiolabel from [14C]R-25788-treated plants remained in the root tissues whereas the radiolabel in [14C]EPTC-treated plants was evenly distributed between foliar and root tissues. From radiolabel experiments, hybrid corn seedlings were found to absorb more R-25788 from soil than EPTC. There was no difference between inbred and hybrid corn in the amounts of R-25788 or EPTC taken up or in the enhancement of GSH S-transferase activity caused by R-25788.  相似文献   

5.
The deamination of metribuzin was studied in vitro in peroxisomes isolated from the leaves of soybean cultivars which were either metribuzin tolerant, intermediate, or sensitive. The deamination rate observed with peroxisomes from tolerant leaves was about twice the rate observed with peroxisomes from sensitive leaves. The intermediate group was also intermediate with respect to the in-vitro deamination rate. Tolerant and sensitive intact soybean plants were pulse-labeled with [14C]metribuzin via the roots for 5 h. The extractable radioactivity in roots, stems and leaves was measured and separated into metabolites after the 5 h pulse and after an additional 24 h growth in water. The level of DA (deaminated metribuzin) was always significantly higher in the stems and leaves of tolerant soybean plants (4.8–10.0% of the extracted radioactivity) than in sensitive stems and leaves (1.8–2.9%). Conjugates were rapidly formed in tolerant as well as in sensitive soybean tissues. More conjugates were found in the tolerant cultivars, especially after the 5 + 24 h incubation time. Labeled [14C]DA fed to soybean plants via the roots was conjugated two to four times faster than [14C]metribuzin. Tolerant soybean tissue conjugated [14C] DA two to three times faster than sensitive tissue. The results are interpreted as showing that, in tolerant soybean plants, metribuzin is metabolized via deamination and subsequent conjugation, in addition to the well-known direct conjugation of metribuzin parent compound.  相似文献   

6.
Protection of tomato (Lycopersicon esculentum Mill., cv. UC 134) against metribuzin was increased by placing a small quantity of activated carbon near each seed position before pre-emergent application of the herbicide. The most protective location of the carbon was the surface of the soil, immediately above the seed. In this location, 0.10 g of activated carbon protected tomatoes from the phytotoxic effects of 0.700 kg metribuzin ha?1 whereas, without the activated carbon, 0.175 kg metribuzin ha?1 killed both tomato and blackberry nightshade (Solanum nigrum L.). Placing plastic discs in this location did not reduce the phytotoxicity; however, a barrier that prevented lateral invasion by the herbicide, of the zone of soil through which the plumule emerged, partially protected the plains from 0.350 kg metribuzin ha?1, showing that metribuzin entered the plants in substantial quantities via the plumule as well as the roots. This result suggests that activated carbon maintained a lower metribuzin concentration in the plumule/root zone than the bulk concentration. It also explains way the soil surface was the most protective carbon location. These findings provide the basis for extending the use of preemergent herbicides to situations in which previously they could not be used safely or economically.  相似文献   

7.
A 140-day laboratory incubation, using surface soil from a long-term soybean tillage study, evaluated tillage influence on [14C]metribuzin degradation. Higher plant residue conditions in no-tillage (NT) soil inhibited metribuzin mineralization to [14C]carbon dioxide as compared to metribuzin degradation patterns observed in conventional tillage (CT) soil. At 140 days, relative abundance of extractable 14C components in NT included polar metabolites > metribuzin = deaminated metribuzin (DA) = deaminated diketometribuzin (DADK), while in CT, components included metribuzin > polar metabolites > DADK?DA. Conditions in NT apparently inhibited polar 14C degradation, and resulted in its accumulation, while in CT polar 14C degradation proceeded relatively rapidly. For both NT and CT, more 14 C was measured in an unextractable fraction than in any other fraction. A greater portion of the unextractable fraction in NT was associated with decomposed plant residue than in CT. Surface accumulation of crop residue, such as occurs under NT, provided a soil environment which altered metribuzin degradation patterns.  相似文献   

8.
Organophosphorus insecticides (OPIs) may induce oxidative stress leading to generation of free radicals and alteration in antioxidant system of animals. Many studies reported that enzymatic and non-enzymatic antioxidant may play protective role against OPIs induced toxicity in human and rats. The aim of present study was to investigate the possible protective role of vitamin E on ethion-induced hepatotoxicity in rats using qualitative, quantitative and biochemical approaches. Adult male albino rats of Wistar strain were randomly divided into four groups; each group consists of six animals. Animals were treated for a period of 28 days. Group I (control group received corn oil); Group II [ethion treated (2.7 mg/kg bw/day)]; Group III (vitamin E treated (50 mg/kg of bw/day)]; Group IV (ethion + vitamin E treated). Animals were sacrificed after 7, 14, 21 and 28 days by decapitation and liver tissue was used for the measurement of proteins, lipid peroxidation (LPO), reduced glutathione (GSH) content and activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) glutathione reductase (GR) and glutathione-S-transferase (GST). Erythrocytes were analyzed for acetyl cholinesterase activity. The result of this study shows that in vivo administration of ethion caused a significant induction of oxidative damage in liver tissue as evidenced by increased level of LPO and decreased GSH content. Ethion toxicity also led to a significant increase in the activities of SOD, CAT, GPx and GST in liver tissue. In addition, decrease in GR activity was observed in ethion administered rats compared to control. Histopathological findings revealed that exposure to ethion caused damage in liver tissue. However, simultaneous supplementation with vitamin E restored these parameters partially. In conclusion, the results of the current study revealed that ethion-induced toxicity caused lipid peroxidation, alterations in the antioxidant enzymes and histopathological changes in liver. Supplementation of vitamin E exhibited protective effect by inhibiting ethion-induced toxicity in liver and erythrocytes.  相似文献   

9.
Plant residue and soil depth effects on metribuzin degradation were investigated. Dundee silt loam soil collected at depth increments of 0–10 cm (SUR) and 10–35 cm (SUB) was treated with labeled [5?14 C]metribuzin. Samples were assayed at several time points up to 140 days after treatment. Soybean residue was added to half of the SUR samples (RES), with remaining SUR unamended (NORES). None of the SUB samples were amended with soybean residue. Metribuzin mineralization to 14CO2 proceeded more slowly in RES and SUB than in NORES and SUR, respectively. Extractable components in SUR samples included polar metabolites, plus deaminated metribuzin (DA) in the RES, and parent metribuzin in the NORES. Deaminated diketometribuzin (DADK) and metribuzin comprised major 14C components extracted from SUB, while in SUR, faster degradation of metabolites resulted in metrizubin as the primary identifiable compound. Unextractable 14C increased until day 35 for both RES and NORES, after which it remained constant for NORES. but declined for RES. A corresponding rise in RES polar 14C suggested that as soybean residue decomposed, 14C bound in the residue was released as extractable polar material. Soil with soybean residue accumulation may alter metabolite degradation patterns, but does not impede initial metribuzin degradation. Depth differences in metribuzin degradation were attributed to reductions in microbial activity with increasing soil depth.  相似文献   

10.
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11.
Metribuzin [4-amino-6-tert-butyl-3(methylthio)-1,2,4-triazin-5(4H)-one] metabolism was studied in soybean [Glycine max (L.) Merr. Tracy]. Pulse treatment studies with seedlings and excised mature leaves showed that [5-14C]metribuzin was absorbed rapidly and translocated acropetally. In seedlings, >97% of the root-absorbed 14C was present in foliar tissues after 24 hr. In excised leaves, 50–60% of the absorbed 14C remained as metribuzin 48 hr after pulse treatment, 12–20% was present as polar metabolites, and 20–30% was present as an insoluble residue. Metabolites were isolated by solvent partitioning, and were purified by adsorption, ion-exchange, thin-layer, and high-performance liquid chromatography. The major metabolite (I) was identified as a homoglutathione conjugate, 4-amino-6-tert-butyl-3-S-(γ-glutamyl-cysteinyl-β-alanine)-1,2,4-triazin-5(4H)-one. Metabolite identification was confirmed by qualitative analysis of amino acid hydrolysis products, fast atom bombardment (FAB), and chemical ionization (CI) mass spectrometry, and by comparison with a reference glutathione conjugate synthesized in vitro with a hepatic microsomal oxidase system from rat. Minor metabolites were identified as an intermediate N-glucoside conjugate (II), a malonyl N-glucoside conjugate (III), and 4-malonylamido-6-tert-butyl-1,2,4-triazin-3,5(2H,4H)-dione (N-malonyl DK, IV) by CI and FAB mass spectrometry. Alternative pathways of metribuzin metabolism are proposed.  相似文献   

12.
The mechanism and sequence of reaction of chlorothalonil in cells of Saccharomyces pastorianus was investigated by the use of either 14C-labeled fungicide or Na235SO4-labeled cells. The initial uptake of fungicide resulted in rapid formation of substituted chlorothalonil-reduced glutathione (GSH) derivatives. Chlorothalonil reacted with proteins during derivative formation but decreased cell viability did not occur until all the GSH was reacted and inhibition of specific NAD thiol-dependent glycolytic and respiratory enzymes occurred. It is postulated that enzyme activity and cell viability are controlled either directly or indirectly by the concentration of GSH. The loss of GSH through derivative formation with chlorothalonil and the lack of regeneration of the reduced thiol could be an important feature in the sequence of toxicity of the fungicide. The general mechanism of action of chlorothalonil resembles the trichloromethyl sulfenyl fungicides in that treated cells accumulate large concentrations of fungicide; reactions involve both low and high molecular-weight thiols, with the formation of glutathione-fungicide derivatives; and toxicity resides ultimately with the inhibition of thiol-dependent enzymes.  相似文献   

13.
The effects of the herbicide antidotes CGA-92194 (α-[(1,3-dioxolan-2-yl-methoxy)-imino]benzeneacetonitrile), flurazole [phenylmethyl 2-chloro-4-(trifluoromethyl)-5-thiazolecarboxylate], dichlormid (2,2-dichloro-N,N-di-2-propenylacetamide), and naphthalic anhydride (1H,3H-naphtho(1,8-cd)-pyran-1,3-dione) on nonprotein thiol content, glutathione content, and glutathione S-transferase (GST) activity in etiolated sorghum (Sorghum bicolor L.) Moench) shoots were examined. CGA-92194 and naphthalic anhydride had no effect on nonprotein thiol or reduced glutathione (GSH) content of sorghum shoots. In contrast, dichlormid and flurazole increased nonprotein thiol content of sorghum shoots by 24 and 48%, respectively. These increases were largely attributable to an increase in GSH. The antidotes increased GST activity less than twofold when using CDNB (1-chloro-2,4-dinitrobenzene) as a substrate. In contrast, when using metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide] as a substrate, the increase in GST activity in response to antidote treatment was much greater: flurazole (30-fold), CGA-92194 (20-fold), naphthalic anhydride (17-fold), dichlormid (5-fold). The degree of protection from metolachlor injury conferred by a particular antidote was strongly correlated (R2 = 0.95) with its ability to enhance GST activity, as evaluated with metolachlor as substrate. A comparison of GST activity in untreated and CGA-92194-treated seedlings, over a range of metolachlor concentrations (0.5–500 μM), indicated that the relative enhancement of enzyme activity by CGA-92194 was greater at lower metolachlor concentrations. The rate of nonenzymatic conjugation of metolachlor and GSH in vitro was much less (on a gram fresh weight equivalent basis) than the enzymatic rate. These results are consistent with the hypothesis that the above antidotes protect sorghum by enhancing GST activity which results in accelerated detoxification of metolachlor via GSH conjugation.  相似文献   

14.
Metribuzin belongs to the triazine group of herbicides, which are frequently used in agriculture. The aim of this study was to assess the impact of metribuzin on growth and development of early life stages of fish. Subchronic toxic effects of metribuzin at concentrations of 0.9, 4, 14, and 32 mg/L on embryos and larvae of common carp (Cyprinus carpio) were investigated during a 30 day toxicity test under experimental conditions. Exposure to metribuzin at 32 mg/L was associated with increased mortality. Negative effects on total body length, weight, and inhibition of specific growth rate were induced by all experimental concentrations. Length and weight parameters were the most sensitive. The negative impact of metribuzin was observed in the highest tested concentration beginning on day 6 of exposure. Retardation of early ontogeny was associated with concentrations ?4 mg/L. Histological examination revealed changes in liver and caudal kidney after 30 days exposure to 32 mg/L. Based on growth parameters, development, and histological examination, the Lowest Observed Effect Concentration (LOEC) value was 0.9 mg/L.  相似文献   

15.
为明确小麦Triticum aestivum田新型除草剂砜吡草唑与嗪草酮复配应用于大豆Glycine max-玉米Zea mays带状复合种植田的可行性,在温室内采用Gowing法测定砜吡草唑与嗪草酮复配的联合作用类型,并通过盆栽法测定两者复配制剂80%砜吡·嗪草酮水分散粒剂（water dispersiblegranule,WDG）的杂草防除谱以及对大豆和玉米的安全性。结果显示,砜吡草唑与嗪草酮复配防除禾本科杂草马唐Digitaria sanguinalis和稗Echinochloa oryzicola的联合作用类型属于增效作用;对阔叶杂草苘麻Abutilon theophrasti和龙葵Solanum nigrum的联合作用类型属于加成作用。80%砜吡·嗪草酮WDG对6种禾本科杂草马唐、稗、牛筋草Eleusine indica、狗尾草Setaira viridis、虎尾草Chloris virgata、大狗尾草Setaira faberii和4种阔叶杂草马齿苋Portulaca oleracea、青葙Celosia argentea、铁苋菜Acalypha australis、反枝苋Amaranthus retroflexus的防除效果均很好,其GR50在6.1~21.6 g (a.i.)/hm2之间,GR90在16.3~50.5 g (a.i.)/hm2之间,对苘麻和龙葵的防除效果略差,其GR50分别为53.3 g (a.i.)/hm2和25.4 g (a.i.)/hm2,GR90分别为282.1 g (a.i.)/hm2和96.7 g (a.i.)/hm2,低于其田间推荐剂量300~360 g (a.i.)/hm2,且该药剂对玉米和大豆的安全性都很高,在玉米与马唐、稗、牛筋草、马齿苋、青葙及铁苋菜这6种杂草之间的选择性指数均大于13.6,在大豆与这6种杂草之间的选择性指数均远大于28.5。表明砜吡草唑完全可与嗪草酮复配应用于大豆-玉米带状复合种植田的杂草防除。  相似文献   

16.
Daily 75 mg/kg phenobarbital ip injections for 3 days or 25 ppm dieldrin in the diet of mice for 14 days caused an increase in liver cytochrome P-450 and blood B-esterase. Liver A-esterase was not significantly increased. Under in vitro conditions, phenobarbital and dieldrin induced the oxidative as well as hydrolytic metabolism of dicrotophos, dimethoate, and phosphamidon by liver homogenates or combined microsomes plus 105,000g supernatant fractions. The concentration of dimethoxon was increased more than fourfold by the pretreatments after incubation for 4 hr at 37.5°C with NADPH added. The organophosphorus insecticides used in this study were not metabolized as well by the liver microsomes alone or 105,000g supernatant alone, as by the combination of microsomes and 105,000g supernatant. Under in vivo conditions in mice, phenobarbital and dieldrin treatments increased the urinary recovery of metabolites in the initial 6 hr after [14C]carbonyl-dimethoate or [14C]N-ethyl-phosphamidon administration. Analysis of urine showed that the inducers caused a more than sixfold increase in dimethoxon recovered and twofold increase in water-soluble nontoxic metabolites within 6 hr after dimethoate administration. With phosphamidon both inducers increased the rate of metabolism, and the total recovery in aqueous and chloroform fractions was decreased. These results suggest that increased dimethoate toxicity after phenobarbital and dieldrin treatments in whole animals results from stimulation of the activation of dimethoate to dimethoxon, while the increase in hydrolytic products after both pretreatments results in decreased toxicity of the direct acetylcholinesterase inhibitors, dicrotophos and phosphamidon.  相似文献   

17.
Thirteen methylenedioxyphenyl (MDP) compounds, including commercial insecticide synergists and juvenile hormone analogs, were compared in their effect on detoxifying enzymes in the housefly (Musca domestica). Flies were fed a diet containing 1% of the compounds for 3 days. Enzymes were then assayed in vitro for their activity using aldrin and DDT as substrates. Piperonyl butoxide (PB), sesamex, propyl isome, sulfoxide, safrole, isosafrole, 6,7-epoxy-3,7-diethyl-1-[3-4(methylenedioxy) phenoxy]-2-octene (MDP-JH I) and 6,7-epoxy-3-methyl-7-ethyl-1-[3,4-(methylenedioxy) phenoxy]-2-octene (MDP-JH II) all caused a bimodal effect, inhibiting microsomal epoxidase and inducing DDT-dehydrochlorinase in the resistant Isolan-B strain. Two of these, PB and MDP-JH I, gave similar results with the susceptible strain, stw;w5 and two resistant strains, Fc-B and Orlando-DDT. However, o-safrole, piperonylic acid, piperonal, 3,4-methylenedioxybenzyl acetate and methyl-(3,4-methylenedioxy) benzoate had little or no effect on the enzyme systems studied. The standard susceptible strain (WHO-SRS) responded to these compounds very differently. Among those tested, piperonyl butoxide, sesamex, safrole, and isosafrole were inducers of microsomal epoxidase, a 4-fold increase occurring after treatment with sesamex. Only MDP-JH II showed a marked inhibition of the epoxidase. These treatments did not effect DDT-dehydrochlorinase activity in this strain.The enhancement of DDT-dehydrochlorinase activity by the MDP compounds is associated with an increased rate of DDT dehydrochlorination in vivo. The stimulatory effect could be blocked by treatment with actinomycin D or cycloheximide.  相似文献   

18.
The rapid effects of the thiocarbamate herbicide S-ethyl dipropyl thiocarbamate (EPTC) and the herbicide protectant N,N-diallyl-2,2-dichloroacetamide (DDCA) on macromolecular syntheses and glutathione (GSH) levels in maize cell cultures were studied to determine whether stimulation of GSH could be the primary mechanism of action of DDCA. EPTC (0.5 and 1 mM) reduced incorporation of radioactive precursors within 1 hr after treatment, and affected incorporation of [3H]acetate into lipids more than incorporation of [3H]adenosine into acid-precipitable nucleic acids, or [14C]protein hydrolysate into protein. [14C]EPTC was rapidly biotransformed within 8 hr by maize cell suspensions. Measureable decreases in GSH levels following treatment with 1 mM EPTC occurred after 15 hr. DDCA stimulated incorporation of [3H]acetate into lipids within 4 hr but did not affect incorporation of [14C]protein hydrolysate into protein or [3H]adenosine incorporation into nucleic acids. Measureable increases in GSH following DDCA treatment began after 12 hr. Treatment with EPTC and DDCA in combination inhibited incorporation of [3H]acetate into lipids less than EPTC given alone. Increases in GSH levels could be observed following pretreatments with glutathione precursors, but no protectant activity could be detected, in contrast to treatments with DDCA. It is suggested that DDCA has an initial rapid effect on lipid metabolism followed by a slower effect involving increases in cellular GSH.  相似文献   

19.
Herbicide degradation in soils is highly temperature‐dependent. Laboratory incubations and field experiments are usually conducted with soils from the temperate climatic zone. Few data are available for cold conditions and the validation of approaches to correct the degradation rate at low temperatures representative of Nordic environments is scarce. Laboratory incubation studies were conducted at 5, 15 and 28°C to compare the influence of temperature on the dissipation of metribuzin in silt/sandy loam soils in southern and northern Norway and in a sandy loam soil under temperate climate in France. Using 14C‐labelled metribuzin, sorption and biodegradation were studied over an incubation period of 49 days. Metribuzin mineralisation and total soil organic carbon mineralisation rates showed a positive temperature response in all soils. Metribuzin mineralisation was low, but metabolites were formed and their abundance depended on temperature conditions. The rate of dissipation of 14C‐metribuzin from soil pore water was strongly dependent on temperature. In Nordic soils with low organic content, metribuzin sorption is rather weak and biodegradation is the most important process controlling its mobility and persistence.  相似文献   

20.
Development and phenobarbital (PB) induction of microsomal cytochrome P-450, cytochrome P-450 reductase, two epoxidation, and two O-demethylation activities were examined in chronologically timed populations of insecticide-susceptible (NAIDM) and -resistant (Rutgers) house flies. Measurements of these enzymes started with the pharate adult stage and ended 5 days following eclosion. Untreated insects of both strains had comparable reductase levels, whereas cytochrome P-450 and associated monooxygenase activities were 1.5-fold or more higher in Rutgers. Maximum induction, as well as toxicity, occurred at a lower PB concentration in NAIDM than Rutgers. The drug caused consistently higher increases in enzymes and activities within 12 hr of starting treatment in both strains. When PB was withdrawn from treated flies (both strains) 48 hr after treatment began, specific activities (product min?1 mg protein?1) in all enzymes returned to control values in 24 hr while metabolic capacity (product min?1 insect?1) achieved control values within 48 hr. The changes in turnover numbers (pmol product min?1 pmol P-450?1), in conjunction with the differences in the monooxygenation of the four substrates, suggest that PB treatment induced both a quantitative and qualitative change in NAIDM monooxygenation but only a quantitative change in Rutgers monooxygenation.  相似文献   

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