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1.
In this work, only N-substituted chitosan derivatives (water-soluble N-carboxymethylchitosan derivatives: N-CMC) with different degrees of substitution were obtained by reaction of a fully deacetylated chitosan (derived from deacetylation of chitosan using decrystallized method) with monochloroacetic acid at pH 8 and temperature of 90 °C. The structure of N-carboxymethylchitosan and chitosan was characterized by IR, 1H, 13C and 1H–13C NMR-HSQC spectra. In the IR spectrum of the N-carboxymethylchitosan, the appearance of peak at 1742 cm?1 was assigned for CO group of NHCH2COOH of substituted chitosan. In the 1H NMR spectra, the peaks at about 3.81÷4.06 ppm, assigned for CH2 groups of NHCH2 and N(CH2)2, were the major feature, while in the 1H–13C NMR-HSQC spectra, signals of CH2 confirmed the presence of these two different substituted CH2 groups. The degree of substitution (DS) of N-monosubstitution (DSN-mono) decreased from 0.47 to 0.03 meanwhile that of N,N-disubstitution (DSN,N-di) increased from 0.52 to 0.96 since the mass ratio of chitosan/monochloroacetic acid changing from 1/1 to 1/4. The N-carboxymethylchitosan derivatives have been used for adsorption Cu(II) ion from aqueous solution. The results shown that the optimum conditions for adsorption Cu(II) ion in nitrate solution were pH 6.5, temperature of 30 °C, for 60–90 min and the substituted chitosan derivative having DSN-mono of 0.16 and DSN,N-di of 0.81 had maximum adsorption capacity of 192 mg Cu(II) per gram of N-CMC.  相似文献   

2.
2-Indolcarbohydrazones 128 were synthesized and evaluated for their α-glucosidase inhibitory potential. A varying degree of inhibitory potential with IC50 values in the range of 2.3 ± 0.11–226.4 ± 6.8 μM was observed while comparing these outcomes with the standard acarbose (IC50 = 906.0 ± 6.3 μM). The stereochemistry of ten (10) randomly selected compounds (1, 3, 6, 8, 12, 18, 19, 23, 25 and 28) was predicted by Density Functional Theory (DFT). The stability of E isomer was deduced by comparing the calculated and experimental vibration modes of νCO, νNC and νCH (CH in NCH-R). It was observed that except compound 18, all other compounds were deduced to have E configuration while molecular modeling studies revealed the key interactions between enzyme and synthesized compounds.  相似文献   

3.
Sulfur particles, which could cause diseases, were the main powder of smog. And activated carbon had the very adsorption characteristics. Therefore, five sulfur particles were adsorbed by activated carbon and were analyzed by FT-IR. The optimal adsorption time were 120 min of Na2SO3, 120 min of Na2S2O8, 120 min of Na2SO4, 120 min of Fe2(SO4)3 and 120 min of S. FT-IR spectra showed that activated carbon had the eight characteristic absorption of SS stretch, H2O stretch, OH stretch, CH stretch, conjugated CO stretch or CC stretch, CH2 bend, CO stretch and acetylenic CH bend vibrations at 3850 cm–1, 3740 cm–1, 3430 cm–1, 2920 cm–1, 1630 cm–1, 1390 cm–1, 1110 cm–1 and 600 cm–1, respectively. For Na2SO3, the peaks at 2920 cm–1, 1630 cm–1, 1390 cm–1 and 1110 cm–1 achieved the maximum at 20 min. For Na2S2O8, the peaks at 3850 cm–1, 3740 cm–1 and 2920 cm–1 achieved the maximum at 60 min. The peaks at 1390 cm–1, 1110 cm–1 and 600 cm–1 achieved the maximum at 40 min. For Na2SO4, the peaks at 3430 cm–1, 2920 cm–1, 1630 cm–1, 1390 cm–1, 1110 cm–1 and 600 cm–1 achieved the maximum at 60 min. For Fe2(SO4)3, the peaks at 1390 cm–1, 1110 cm–1 and 600 cm–1 achieved the maximum at 20 min. For S, the peaks at 1630 cm–1, 1390 cm–1 and 600 cm–1 achieved the maximum at 120 min. It provided that activated carbon could remove sulfur particles from smog air to restrain many anaphylactic diseases.  相似文献   

4.
Hydroxyl radical (OH) is a radical species highly destructive for lignin during solid-state fermentation (SSF) of straw with Phanerochaete chrysosporium (Pc). The production of OH at different initial Pb2+ concentrations during SSF of straw with Pc was investigated. The results showed that a modest amount (under 200 mg kg−1) of Pb2+ could enhance the production of OH, while a higher Pb2+ concentration resulted in inhibition. The content of OH reached the peak value at day 12 in the whole tested samples, and the maximal content of OH was obtained at initial Pb2+ concentration of 100 mg kg−1. It was also found that the production of OH was connected to enzymatic activity and oxalate content in some degree, in particular, a significant positive correlation was found between oxalate concentration and production of OH.We found that low concentration of Pb2+ can promote the degradation of lignin, and the higher initial Pb2+ concentration (400 mg kg−1) resulted in inhibition. In addition, it appeared that there was no significant correlation between lignin degradation rate and the production of OH when Pb2+ concentration was taken into account.  相似文献   

5.
A series of 2-arylbenzimidazole derivatives (3a3p and 4a4i) were synthesized and evaluated as potential antioxidant and antimicrobial agents. Their antioxidant properties were evaluated by various in vitro assays including hydroxyl radical (HO) scavenging, superoxide radical anion (O2?) scavenging, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, and ferric reducing antioxidant power. Results demonstrated that compounds with hydroxyl group at the 5-position of benzimidazole ring had a comparable or better antioxidant activity in comparison to standard antioxidant tert-butylhydroquinone (TBHQ). Markedly, compound 4h that showed the highest HO scavenging activity (EC50 = 46 μM) in vitro had a significant reduction of 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced intracellular oxidative stress and H2O2-induced cell death. In addition, these compounds showed moderate to good inhibitory activity against Staphylococcus aureus selectively at noncytotoxic concentrations.  相似文献   

6.
In this study, 45 bisindolylmethanes having sulfonamide moiety had been synthesized through 3 steps. In vitro assay for inhibition of carbonic anhydrase showed that some of the compounds having sulfonamide moiety are capable of inhibiting carbonic anhydrase II. Bisindoles having halogens at fifth position showed better inhibitory activity as compared to unsubstituted bisindoles. The results obtained from in vitro inhibitory activity were subjected through 3D QSAR and docking studies to identify important features contributing to the activity and further improve the structure. Pharmacophore studies suggest that bisindolylmethane moiety is contributing significantly towards the inhibition activity. Docking studies showed that compounds having nitro substituent (5g and 5i) were found to be able interact with Zn2+ ion, Thr199, His94, His96, and His119, which interferes with the ZnOHThr199Glu106 hydrogen bond network. Bulky nitro substituent at ortho position for compound 5g prevents the compound from interacting with other residues like Thr199 and Thr200. Methyl substituent at ortho position for Compound 5i induces less steric hindrance effect, thus allowing second oxygen atom of sulfonamide to interact with Thr199 (2.51 Å). Hydrogen bonding between NH on indole ring with Glu69 might have increased stability of ligand-receptor complex.  相似文献   

7.
The human cholesteryl ester transfer protein (CETP) transfers cholesteryl ester from high-density lipoprotein (HDL) to other lipoproteins and has been established as an attractive target for reducing the risk of atherosclerosis. Here, an amphipathic α-helix peptide, namely SBH-peptide (465EHLLVDFLQSLS476), was derived from the C-terminal tail of CETP. The peptide exhibits self-binding capability towards the CETP. Crystal structure analysis, molecular dynamics (MD) simulations and ab initio electron correlation characterizations of CETP–SBH-peptide complex system revealed that the Phe471 residue plays a key role in SBH-peptide binding, which can form a π-π stacking with the Phe197 residue of CETP. In addition, substitution of the hydrogen atom H4 of Phe471 with halogen atoms, in particular the bromine atom Br4, can constitute a geometrically satisfactory halogen bonding with the oxygen atom O of CETP Ile193 residue. Fluorescence polarization assays substantiated that (i) mutation of the aromatic Phe471 to small Ala residue would impair the SBH-peptide affinity with Kd change from 10.5 to 26.4 μM, indicating that the π-π stacking should exist in Phe471⋯Phe197 adduct, and (ii) substitution with Br4 can considerably improve SBH-peptide affinity by ∼3-fold, but the SBH-peptide binding does not change essentially upon substitution with Br3 (a negative control that is theoretically unable to form the halogen bonding), indicating that the rationally designed halogen bonding should form between the Phe471(Br4) residue of SBH-peptide and the Ile193 residue of CETP protein.  相似文献   

8.
The objectives of this study were to determine phenolic content and antioxidant activities of chloroform, acetone, methanol and hot water extracts of Bauhinia vahlii leaves. The hot water extract afforded the highest yield (6.3%) while the lowest yield was obtained from the chloroform extract (2.1%). The methanol extract contains higher levels of total phenolics (48.7 ± 0.7 g GAE/100 g extract), tannins (21.7 ± 0.7 g GAE/100 g extract) and flavonoids (10.3 ± 0.2 RE/100 g extract). The extracts were subjected to assess their antioxidant potential using various in vitro systems such as DPPH, ABTS+, FRAP, OH, β-carotene linoleic acid bleaching system, phosphomolybdenum reduction and Fe2+ chelation. It is concluded that the methanolic extract of B. vahlii leaves have strong antioxidant potential. Further study is necessary for isolation and characterization of the active antioxidants, which may serve as a potential source of natural antioxidants.  相似文献   

9.
《Inorganica chimica acta》2006,359(9):2771-2779
Addition of o-Ph2PC6H4CHN-2,6-iPr2C6H3 (1) to [RhCl(coe)2]2 (coe = cis-cycloctene) gave several new iminophosphino rhodium(I) complexes including [Rh(κ2-o-Ph2PC6H4CHN-2,6-iPr2C6H3)(μ-Cl)]2 (2). Addition of 1 to Rh(acac)(coe)2 (acac = acetylacetonato) gave [Rh(acac)(κ2-o-Ph2PC6H4CHN-2,6-iPr2C6H3)] (3) in yields of up to 75%. Complex 3 has been examined for its ability to catalyze the hydroboration of a series of vinyl arenes. Reactions using catecholborane and pinacolborane seem to proceed largely through a dehydrogenative borylation mechanism to give a number of boronated products.  相似文献   

10.
Evidence for Zn protection against Cd-induced reactive oxygen species in the free-floating hydrophyte Ceratophyllum demersum L. is presented in this paper. Metal treatments of 10 μmol/L Cd, 10 Cd μmol/L supplemented with Zn (10, 50, 100 and 200 μmol/L) and Zn-alone treatments of the same concentrations were used. Using 5,5 dimethyl pyrroline-N-oxide as the spin-probe, electron spin resonance spectra indicated a drastic increase in hydroxyl radicals (OH) in Cd-10 μmol/L treatments, which was closely correlating with the enhanced formation of hydrogen peroxide (H2O2) and generation of superoxide radical (O2?) triggered by the oxidation of NADPH. The supplementation of adding Zn (10–200 μmol/L) to the Cd-10 μmol/L treatments significantly decreased the production of free radicals especially by eliminating the precursors of OH through inhibition of NADPH oxidation. Cd-enhanced ROS production which substantially increased the oxidative products of proteins measured as carbonyls was effectively inhibited by Zn supplementation.  相似文献   

11.
Wei Liu  Shiyong Wu 《Nitric oxide》2010,22(3):199-205
Ultraviolet B light (UVB) activates nitric oxide synthase(s) (NOSs) and nitric oxide (NO) production, which plays a role in regulation of apoptosis. However, the role of NO in UVB-induced apoptosis remains controversial. In this study, we analyzed expression and activation of constitutive NOSs (cNOSs) and their roles in UV-induced apoptosis of HaCaT keratinocytes. Our data showed that the expression of neuronal NOS (nNOS) was increased while endothelial NOS (eNOS) was uncoupled in the early phase (0–6 h) post-UVB. The expression of both cNOSs peaked at 12 h post-UVB and NO was transiently elevated with 30 min and then steadily rose from 6 to 18 h post-UVB. The expression of iNOS was detected at 6 h post-UVB and then sturdily increased. Inhibition of cNOSs with l-NAME reduced the inducibility of NO in the early and late phases of irradiation. Along with the eNOS uncoupling, an increased level of peroxynitrite (ONOO?) was detected in the early phase, but not in the late phase post-UVB. Inhibition of cNOSs reduced the production of ONOO? in the early time, but led to an increase of ONOO? in the late time after UVB-irradiation. The results indicate that cNOSs regulate NO/ONOO? imbalance after UVB-irradiation. Our data suggested that the activation of cNOSs in the early phase post-UVB leads to NO/ONOO? imbalance and promotes apoptosis via a caspase 3-independent pathway. The elevation of NO in the late phase of UVB-irradiation is mainly produced by inducible NOS (iNOS). However, cNOSs also contribute to the NO production and to maintain a higher NO/ONOO? ratio, which reduces caspase 3 activity and protects cells from UVB-induced apoptosis.  相似文献   

12.
A novel class of indomethacin analogs were synthesized wherein a N-difluoromethyl-1,2-dihydropyrid-2-one moiety (5-LOX pharmacophore) was attached at its C-4 or C-5 position via either a CO (14ab) or CH2 (19ab) linker to the indole N1-position. In this regard, replacement of the 4-chlorobenzoyl group present in indomethacin by N-difluoromethyl-1,2-dihydropyrid-2-one-4-(or 5-)carbonyl and N-difluoromethyl-1,2-dihydropyrid-2-one-4-yl(or 5-yl)methylene moieties furnished compounds showing no inhibitory activities against the COX-2/5-LOX enzymes (except for the weak but selective COX-2 inhibitor 19a, COX-2 IC50 = 31 μM), and moderate in vivo anti-inflammatory activities (except for the methylene compound 19a that was inactive). These structure–activity data indicate replacement of the 4-chlorobenzoyl group present in indomethacin by a N-difluoromethyl-1,2-dihydropyrid-2-one ring system connected by a CO or CH2 linker is not a suitable approach for the design of dual COX-2/5-LOX inhibitory analogs of indomethacin.  相似文献   

13.
Reductions of (Z)-C6H5CHCXC(O)CH3 (X = Cl, Br) mediated by Saccharomyces cerevisiae, Candida albicans, Rhodotorula glutinis, Geotrichum candidum and Micrococcus luteus gave the corresponding halohydrins through consecutive reduction reactions of CC and CO bonds. In general, the reactions performed in the biphasic system water/[(bmim)PF6] gave better diastereoselectivity and enantioselectivity than in pure water.  相似文献   

14.
The 1-(secondary amino) diazen-1-ium-1,2-diolates (NONOates) are the most commonly utilized nitric oxide (NO, nitrogen monoxide) donor because of the ability of different NONOates to spontaneously break down liberating NO at different rates, which can be utilized to control NO fluxes. However, the parameters that determine these fluxes of NO generation, half-lives and stoichiometry of NO per donor, can vary significantly with specific experimental conditions in addition to the donor chosen. Here we report straightforward methods that can be used to determine these parameters. For donors of intermediate half-life (10–80 min) a real-time oxymyoglobin (oxyMb) assay can be analyzed to simultaneously determine both the half-life and the total amount of NO liberated, from which the NO flux can be obtained for any given donor concentration. The half-lives obtained by oxyMb assay are very similar to those obtained by following NONOate decomposition kinetics spectrophotometrically, and a survey of several NONOates from different commercial sources show consistent results. These data provide validation for the methodologies employed. In addition, procedures are described for calibration of donors with shorter (<10 min) and longer (>80 min) half-lives. These procedures can be used to reproducibly and routinely calibrate NO fluxes for a variety of donors under any specific condition.  相似文献   

15.
Sorption potential of Citrus sinensis biomass for reactive yellow 42 and reactive red 45 was investigated with variation of pH, biosorbent dose and dye concentration. Biosorbent was treated by organic and inorganic reagents of which acetic acid and acetonitrile enhanced the sorption capacities for reactive yellow 42 and reactive red 45, respectively. Sorption equilibrium was established within 60 min using free and chemically treated biosorbent, while prolonged to 120 min using immobilized biosorbent. Freundlich isotherm and pseudo-second-order rate law described best the sorption mechanism. FT-IR analysis of biosorbent revealed the presence of CO, CO, NH and OH groups on the surface of biosorbent. Desorption experiments were performed to regenerate the sorbent, making the process more economical and environment friendly.  相似文献   

16.
《Inorganica chimica acta》2006,359(9):2812-2818
Alkynylgold(I) complexes incorporating a chiral binaphthyl group have been prepared. Bis(alkyne) reagents [rac-1,1′-C20H12-2,2′-(OCH2CCH)2] (1) and [rac-1,1′-C20H12-2,2′-(OC(O)CH2CCH)2] (2), react with [AuCl(SMe2)] and base to give insoluble oligomeric alkynylgold(I) complexes [rac-1,1′-C20H12-2,2′-(OCH2CCAu)2]n (3) and [rac-1,1′-C20H12-2,2′-(OC(O)CH2CCAu)2]n (4), which react with phosphine or diphosphine ligands to give soluble complexes [rac-1,1′-C20H12-2,2′-(OCH2CCAuPR3)2] (5), R = Ph or Cy, [rac-1,1′-C20H12-2,2′-(OCH2CCAu)2(Ph2P(CH2)nPPh2)] (6), or [rac-1,1′-C20H12-2,2′-(OC(O)CH2CCAu)2(Ph2P(CH2)nPPh2)] (7), with n = 3–5. Several of the complexes 6 and 7 are shown to exist as mixtures of isomeric forms in solution.  相似文献   

17.
The reactions of NO2 with both oxidized and reduced cytochrome c at pH 7.2 and 7.4, respectively, and with N-acetyltyrosine amide and N-acetyltryptophan amide at pH 7.3 were studied by pulse radiolysis at 23 °C. NO2 oxidizes N-acetyltyrosine amide and N-acetyltryptophan amide with rate constants of (3.1±0.3)×105 and (1.1±0.1)×106 M−1 s−1, respectively. With iron(III)cytochrome c, the reaction involves only its amino acids, because no changes in the visible spectrum of cytochrome c are observed. The second-order rate constant is (5.8±0.7)×106 M−1 s−1 at pH 7.2. NO2 oxidizes iron(II)cytochrome c with a second-order rate constant of (6.6±0.5)×107 M−1 s−1 at pH 7.4; formation of iron(III)cytochrome c is quantitative. Based on these rate constants, we propose that the reaction with iron(II)cytochrome c proceeds via a mechanism in which 90% of NO2 oxidizes the iron center directly—most probably via reaction at the solvent-accessible heme edge—whereas 10% oxidizes the amino acid residues to the corresponding radicals, which, in turn, oxidize iron(II). Iron(II)cytochrome c is also oxidized by peroxynitrite in the presence of CO2 to iron(III)cytochrome c, with a yield of ~60% relative to peroxynitrite. Our results indicate that, in vivo, NO2 will attack preferentially the reduced form of cytochrome c; protein damage is expected to be marginal, the consequence of formation of amino acid radicals on iron(III)cytochrome c.  相似文献   

18.
Alcohol intake is associated with myocardial contractile dysfunction and apoptosis although the precise mechanism is unclear. This study was designed to examine the effect of the cytochrome P450 enzyme CYP2E1 inhibition on ethanol-induced cardiac dysfunction. Adult male mice were fed a 4% ethanol liquid or pair-fed control diet for 6 weeks. Following 2 weeks of diet feeding, a cohort of mice started to receive the CYP2E1 inhibitor diallyl sulfide (100 mg/kg/d, i.p.) for the remaining feeding duration. Cardiac function was assessed using echocardiographic and IonOptix systems. Western blot analysis was used to evaluate CYP2E1, heme oxygenase-1 (HO-1), iNOS, the intracellular Ca2 + regulatory proteins sarco(endo)plasmic reticulum Ca2 +-ATPase, Na+Ca2 + exchanger and phospholamban, pro-apoptotic protein cleaved caspase-3, Bax, c-Jun-NH2-terminal kinase (JNK) and apoptosis signal-regulating kinase (ASK-1). Ethanol led to elevated levels of CYP2E1, iNOS and phospholamban, decreased levels of HO-1 and Na+Ca2 + exchanger, cardiac contractile and intracellular Ca2 + defects, cardiac fibrosis, overt O2? production, and apoptosis accompanied with increased phosphorylation of JNK and ASK-1, the effects were significantly attenuated or ablated by diallyl sulfide. Inhibitors of JNK and ASK-1 but not HO-1 inducer or iNOS inhibitor obliterated ethanol-induced cardiomyocyte contractile dysfunction, substantiating a role for JNK and ASK-1 signaling in ethanol-induced myocardial injury. Taken together, these findings suggest that ethanol metabolism through CYP2E1 may contribute to the pathogenesis of alcoholic cardiomyopathy including myocardial contractile dysfunction, oxidative stress and apoptosis, possibly through activation of JNK and ASK-1 signaling.  相似文献   

19.
An efficient domino protocol has been developed for the synthesis of new pyrimidine scaffolds, through a one-pot four-component cascade transformation via [Bmim]HSO4 ionic liquid mediated reaction, using an equimolar mixture of thiochroman-4-one, benzaldehyde, thiourea and 3-bromo-1-phenylpropan-1-one leading to the formation of a double electrophilic pyrimidine-2(5H)-thione intermediate. The intermediate regioselectively undergoes cyclization through intramolecular NH bond activation followed by CS bond formation leading to highly functionalized thiazolo[3,2-a]thiochromeno[4,3-d]pyrimidines. The ionic liquid operates efficiently under mild conditions. The recyclability and scope for recovery of the ionic liquid makes this protocol environmentally benign. Further, the compounds 5d, 5g and 5k showed promising antimicrobial activity against the tested Gram-positive bacterial strains. Among them, the compound 5d was identified as a lead molecule exhibiting promising anti-biofilm activity towards Staphylococcus aureus MTCC 96, Bacillus subtilis MTCC 121, Staphylococcus aureus MLS16 MTCC 2940 and Micrococcus luteus MTCC 2470 with IC50 values of 2.1, 1.9, 2.4 and 5.3 μg/mL, respectively. Further, the compound 5d showed increased levels of intracellular ROS accumulation in Staphylococcus aureus MTCC 96 suggesting that oxidative stress resulted in bacterial cell lysis and death.  相似文献   

20.
Sulfur and ammonia nitrogen are rich nutrient pollutants, after entering water can cause algal blooms, cause eutrophication of water body, the spread of them will not only pollute the environment, destroy the ecological balance, but also harm human health through food chain channels, especially drinking-water toxicosis. Acticarbon can adsorb harmful substances, it was beneficial for people’s health. In order to figure out the optimal adsorption condition and the intrinsic change of acticarbon, five chemicals were adsorbed by acticarbon and analyzed by FT-IR. The optimal adsorption condition of Fe2(SO4)3, Na2SO4, Na2S2O8, S and Na2SO3 was 9 g/1000 g at 80 min, 21 g/1000 g at 20 min, 15g/1000 g at 20 min, 21 g/1000 g at 60 min and 21 g/1000 g at 100 min, respectively. FT-IR spectra showed that acticarbon had eight characteristic peaks, such as S-S stretch, H2O stretch, OH stretch, CH stretch, CO or CC stretch, CH2 bend, CH were at 3850 cm−1, 3740 cm−1, 3435 cm−1, 2925 cm−1, 1630 cm−1, 1390 cm−1, 1115 cm−1, 600 cm−1, respectively. For FT-IR spectra of Fe2(SO4)3, the peaks at 3850 cm−1, 3740 cm−1, 2925 cm−1 achieved the maximum with 9 g/1000 g at 20 min. For Na2SO4, the peaks at 2925 cm−1, 1630 cm−1, 1390 cm−1, 1115 cm−1, 600 cm−1 achieved the maximum with 21 g/1000 g at 120 min. For ones of Na2S2O8, the peaks at 3850 cm−1, 3740 cm−1, 1390 cm−1, 1115 cm−1, 600 cm−1, achieved the maximum with 2 g/1000 g at 80 min. For ones of S, the peaks at 3850 cm−1, 3740 cm−1, 2925 cm−1 achieved the maximum with 19 g/1000 g at 100 min, the peaks at 1390 cm−1, 1115 cm−1, 600 cm−1 achieved the maximum with 19 g/1000 g at 20 min. For FT-IR spectra of Na2SO3, the peaks at 1630 cm−1, 1390 cm−1, 1115 cm−1, 600 cm−1 achieved the maximum with 2 g/1000 g at 100 min. It provided that acticarbon could adsorb and desulphurize from sulfur solution against drinking-water toxicosis.  相似文献   

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