Methylparaben(MeP)is an emerging aquatic pollutant that is found to impact neural functions.However,it still lacks a comprehensive understanding about its neurotoxicology.The present study exposed adult zebrafish to e...Methylparaben(MeP)is an emerging aquatic pollutant that is found to impact neural functions.However,it still lacks a comprehensive understanding about its neurotoxicology.The present study exposed adult zebrafish to environmentally realistic concentrations(0,1,3,and 10μg/L)of MeP for 28 days,with objectives to elucidate the neurotoxic effects andmechanisms.Proteomic profiling found that MeP pollutant induced distinct mechanism of neurotoxicity as a function of sex.MeP pollutant appeared to preferentially target the neurotransmission cascade via synapse junctions.In male brain,glutamatergic neural signaling was enhanced by 10μg/L of MeP in characteristics of higher glutamate neurotransmitter content(by 61.9%)and up-regulated glutamate receptor expression by 2.6-fold relative to the control.In MeP-exposed female brain,biomarker proteins of synapse formation and regeneration had significantly lower abundance,accounting for the blockage of synaptic neurotransmission.Furthermore,under the stress of MeP pollutant,both male and female zebrafish initiated a negative feedback mechanism along stress neuroendocrine axis by down-regulating the transcriptions of corticotropin-releasing hormone and its binding protein,which subsequently decreased blood cortisol concentrations.MeP subchronic exposure also disturbed innate immune function.In particular,significant increases in lipopolysaccharide(LPS)content by 15.6%were caused by MeP exposure in male brain,thereby inducing the synthesis of pro-inflammatory cytokines.In contrast,female brain was able to adaptively up-regulate the protein expression of blood brain barrier to inhibit the infiltration of LPS endotoxin into brain.Overall,the present findings pinpoint the potent neurotoxicity of MeP pollutant even at environmentally realistic concentrations.展开更多
Stability indicating RP-UPLC technique was developed for the simultaneous quantification of glycopyrrolate, methylparaben, and propylparaben in glycopyrrolate oral solution. The method was established by using gradien...Stability indicating RP-UPLC technique was developed for the simultaneous quantification of glycopyrrolate, methylparaben, and propylparaben in glycopyrrolate oral solution. The method was established by using gradient UPLC and a Waters Acquity UPLC BEH C18, 100 mm 2.1 mm, i.d 1.7 μm particle size column with a gradient program of mobile phase A and mobile phase B with a flow rate of 0.25 mL/minute, UV wavelength detection at 222 nm, column temperature of 40°C, injection volume of 2 μL, mobile phase A contains 0.05% trifluoro acetic acid in water and Acetonitrile (90:10) v/v and mobile phase-B contains 0.05% trifluoro acetic acid in water and Acetonitrile (10:90) v/v. The current research describes a single UPLC method for developing an assay method for Glycopyrrolate Oral solution that includes Glycopyrrolate (Active), Methylparaben (Preservative), and Propylparaben (Preservative). The assay method was validated in accordance with ICH guidelines. The retention times of glycopyrrolate, methyl paraben and propylparaben were 6.051 min, 3.458 min and 8.095 min, respectively. Linearity range of glycopyrrolate, methyl paraben and propylparaben were in the range of 4 - 32 μg per mL, 35 - 290 μg per mL and 4 - 32 μg per mL, respectively. Recovery of glycopyrrolate, methylparaben and propylparaben ranged from 100.1% to 98.9%, 100.2% - 100.8%, and 100.2% - 100.8%. Validation of analytical method demonstrated that the method is suitable, specific, linear, accurate, precise, rugged and stability indicating for estimating three components in the pharmaceutical dosage form.展开更多
Polydichlorophosphazene(PDCP)was synthesized from PCl5 and NH4Cl via a one-pot approach,and then further reacted with glycine ethyl ester and methylparaben via a two-step nucleophilic substitution approach to give pol...Polydichlorophosphazene(PDCP)was synthesized from PCl5 and NH4Cl via a one-pot approach,and then further reacted with glycine ethyl ester and methylparaben via a two-step nucleophilic substitution approach to give poly(methylparaben/glycine ethyl ester)phosphazene(PMGP),which was a kind of mix-substituted biodegradable polymer.NMR and FT-IR were used to characterize its structure.A series of experiments were conducted to study the effects of the ratio of methylparaben to glycine ethyl ester and the experimental conditions to the degradability of PMGP samples.The degradability of PMGP can be adjusted by altering the ratio of methylparaben to glycine ethyl ester easily.展开更多
基金supported by the National Natural Science Foundation of China(No.31971236)the Natural Science Foundation of Hubei Province,China(No.2021CFA086)the Innovative Team Program of Natural Science Foundation of Hubei Province,China(No.2021CFA032).
文摘Methylparaben(MeP)is an emerging aquatic pollutant that is found to impact neural functions.However,it still lacks a comprehensive understanding about its neurotoxicology.The present study exposed adult zebrafish to environmentally realistic concentrations(0,1,3,and 10μg/L)of MeP for 28 days,with objectives to elucidate the neurotoxic effects andmechanisms.Proteomic profiling found that MeP pollutant induced distinct mechanism of neurotoxicity as a function of sex.MeP pollutant appeared to preferentially target the neurotransmission cascade via synapse junctions.In male brain,glutamatergic neural signaling was enhanced by 10μg/L of MeP in characteristics of higher glutamate neurotransmitter content(by 61.9%)and up-regulated glutamate receptor expression by 2.6-fold relative to the control.In MeP-exposed female brain,biomarker proteins of synapse formation and regeneration had significantly lower abundance,accounting for the blockage of synaptic neurotransmission.Furthermore,under the stress of MeP pollutant,both male and female zebrafish initiated a negative feedback mechanism along stress neuroendocrine axis by down-regulating the transcriptions of corticotropin-releasing hormone and its binding protein,which subsequently decreased blood cortisol concentrations.MeP subchronic exposure also disturbed innate immune function.In particular,significant increases in lipopolysaccharide(LPS)content by 15.6%were caused by MeP exposure in male brain,thereby inducing the synthesis of pro-inflammatory cytokines.In contrast,female brain was able to adaptively up-regulate the protein expression of blood brain barrier to inhibit the infiltration of LPS endotoxin into brain.Overall,the present findings pinpoint the potent neurotoxicity of MeP pollutant even at environmentally realistic concentrations.
文摘Stability indicating RP-UPLC technique was developed for the simultaneous quantification of glycopyrrolate, methylparaben, and propylparaben in glycopyrrolate oral solution. The method was established by using gradient UPLC and a Waters Acquity UPLC BEH C18, 100 mm 2.1 mm, i.d 1.7 μm particle size column with a gradient program of mobile phase A and mobile phase B with a flow rate of 0.25 mL/minute, UV wavelength detection at 222 nm, column temperature of 40°C, injection volume of 2 μL, mobile phase A contains 0.05% trifluoro acetic acid in water and Acetonitrile (90:10) v/v and mobile phase-B contains 0.05% trifluoro acetic acid in water and Acetonitrile (10:90) v/v. The current research describes a single UPLC method for developing an assay method for Glycopyrrolate Oral solution that includes Glycopyrrolate (Active), Methylparaben (Preservative), and Propylparaben (Preservative). The assay method was validated in accordance with ICH guidelines. The retention times of glycopyrrolate, methyl paraben and propylparaben were 6.051 min, 3.458 min and 8.095 min, respectively. Linearity range of glycopyrrolate, methyl paraben and propylparaben were in the range of 4 - 32 μg per mL, 35 - 290 μg per mL and 4 - 32 μg per mL, respectively. Recovery of glycopyrrolate, methylparaben and propylparaben ranged from 100.1% to 98.9%, 100.2% - 100.8%, and 100.2% - 100.8%. Validation of analytical method demonstrated that the method is suitable, specific, linear, accurate, precise, rugged and stability indicating for estimating three components in the pharmaceutical dosage form.
文摘Polydichlorophosphazene(PDCP)was synthesized from PCl5 and NH4Cl via a one-pot approach,and then further reacted with glycine ethyl ester and methylparaben via a two-step nucleophilic substitution approach to give poly(methylparaben/glycine ethyl ester)phosphazene(PMGP),which was a kind of mix-substituted biodegradable polymer.NMR and FT-IR were used to characterize its structure.A series of experiments were conducted to study the effects of the ratio of methylparaben to glycine ethyl ester and the experimental conditions to the degradability of PMGP samples.The degradability of PMGP can be adjusted by altering the ratio of methylparaben to glycine ethyl ester easily.
