Polyhalogenated carbazoles(PHCZs)have been widely accepted as emerging pollutants,whereas their ecological and health risks remain uncertain.Herein,female and male Sprague-Dawley(SD)mice were treated with four typical...Polyhalogenated carbazoles(PHCZs)have been widely accepted as emerging pollutants,whereas their ecological and health risks remain uncertain.Herein,female and male Sprague-Dawley(SD)mice were treated with four typical PHCZs to investigate their negative consequences,along with alternations in gutmicrobiota to indicate underlyingmechanisms.In female mice,the relative liver weight ratio increased after four PHCZs exposure;2-bromocarbazole(2-BCZ)increased urine glucose level;3-bromocarbazole(3-BCZ)decreased the glucose and total cholesterol levels;3,6-dichlorocarbazole(3,6-DCCZ)decreased glucose level.The only disturbed biochemical index in male mice was the promoted alkaline phosphatase(ALP)level by 3,6-DCCZ.We also found that the differential blood biochemical indices were correlated with gut microbiota.3-BCZ and 3,6-DCCZ altered Bacteroidetes and Proteobacteria phyla in female and male mice,which were correlated with metabolic disorders.Our findings demonstrated the correlation between PHCZs induced potential hepatotoxicity andmetabolic disordersmay be due to their dioxin-like potentials and endocrine disrupting activities,and the gender differences might result from their estrogenic activities.Overall,data presented here can help to evaluate the ecological and health risks of PHCZs and reveal the underlying mechanisms.展开更多
Cypermethrin(CYP), a prototypical synthetic pyrethroid, reportedly causes metabolic disruption, while its stereoselective impact remains elusive. This study initially revealed that only α-CYP caused significant weigh...Cypermethrin(CYP), a prototypical synthetic pyrethroid, reportedly causes metabolic disruption, while its stereoselective impact remains elusive. This study initially revealed that only α-CYP caused significant weight loss at 8.5 mg/(kg·day) in rats. All three CYP isomers caused the accumulation of hepatic glycogen, and hyperlipemia phenotype as the increment of total triglyceride. Rats treated with α-CYP had markedly high blood glucose levels and homeostasis model assessment of insulin resistance index. The systematic inflammation of θ-CYP group rats was evidenced by high lipopolysaccharide-binding protein levels and abnormalities of leukocytes indices. By examining the gut microbiome, we found thatα-CYP-treated rats had low contents of Firmicutes and high levels of Verrucomicrobia while Elusimicrobia was enriched in the β-CYP group. The increasing alpha diversity in the θ-CYP group may be due to the dominance of pathogenic bacteria and the increase of probiotics to counteract adverse effects. Exclusively, the α-CYP group enriched total short-chain fatty acids(SCFAs), whereas most SCFAs depleted in the θ-CYP group. The correlation analysis further found Firmicutes, an energy storage modulator, was positive to body weight(BW),while SCFAs exerted the opposite, confirming the low BW in α-CYP. Blood glucose that correlated well with SCFAs and Verrucomicrobia can be accounted for the discrepancy betweenα-CYP and θ-CYP. Overall, the three isomers exerted stereoselective glycolipid disruption in rats, and gut homeostasis acted as vital indicators.展开更多
V79-8 is an abnormal cell line which does not have detectable G1 and G2 phases in its cell cycle.This cell line is derived from V79 cell line which has G1 phase but lacks G2 phase. By using an anti-sense approach, CDK...V79-8 is an abnormal cell line which does not have detectable G1 and G2 phases in its cell cycle.This cell line is derived from V79 cell line which has G1 phase but lacks G2 phase. By using an anti-sense approach, CDK4 gene expression was partially inhibited to find whether CDK4 might contribute to the lack of G1 phase in V79-8 cells. Anti-CDK4 anti-sense plasmid was constructed and used to transfect V79-8 cells. Clones of transfected cells (V79-8-asCDK4) were examined, in comparison with V79-8 cells, to determine its growth curve, cell doubling-time (GT), the level of CDK4 gene expression and the levels of expression of some other growth related genes. V79-8-asCDK4 cells showed a slower growth rate with a doubling time 2.5-h longer than that of V79-8 cells. A flow cytometry (FCM) analysis demonstrated that the 2.5 h increase of the doubling time of V79-8-asCDK4 cells was mainly due to the appearance of G1 phase because its G2+M phase was not significantly different from that of V79-8 cells. The展开更多
基金supported by Joint Innovation Fund for Regional Development of National Natural Science Foundation of China(No.U20A20134)Leading Talent of Technological Innovation of Ten-Thousands Talents Program of Zhejiang Province(No.2020R52012).
文摘Polyhalogenated carbazoles(PHCZs)have been widely accepted as emerging pollutants,whereas their ecological and health risks remain uncertain.Herein,female and male Sprague-Dawley(SD)mice were treated with four typical PHCZs to investigate their negative consequences,along with alternations in gutmicrobiota to indicate underlyingmechanisms.In female mice,the relative liver weight ratio increased after four PHCZs exposure;2-bromocarbazole(2-BCZ)increased urine glucose level;3-bromocarbazole(3-BCZ)decreased the glucose and total cholesterol levels;3,6-dichlorocarbazole(3,6-DCCZ)decreased glucose level.The only disturbed biochemical index in male mice was the promoted alkaline phosphatase(ALP)level by 3,6-DCCZ.We also found that the differential blood biochemical indices were correlated with gut microbiota.3-BCZ and 3,6-DCCZ altered Bacteroidetes and Proteobacteria phyla in female and male mice,which were correlated with metabolic disorders.Our findings demonstrated the correlation between PHCZs induced potential hepatotoxicity andmetabolic disordersmay be due to their dioxin-like potentials and endocrine disrupting activities,and the gender differences might result from their estrogenic activities.Overall,data presented here can help to evaluate the ecological and health risks of PHCZs and reveal the underlying mechanisms.
基金supported by the National Natural Science Foundation of China (No. 21777147)。
文摘Cypermethrin(CYP), a prototypical synthetic pyrethroid, reportedly causes metabolic disruption, while its stereoselective impact remains elusive. This study initially revealed that only α-CYP caused significant weight loss at 8.5 mg/(kg·day) in rats. All three CYP isomers caused the accumulation of hepatic glycogen, and hyperlipemia phenotype as the increment of total triglyceride. Rats treated with α-CYP had markedly high blood glucose levels and homeostasis model assessment of insulin resistance index. The systematic inflammation of θ-CYP group rats was evidenced by high lipopolysaccharide-binding protein levels and abnormalities of leukocytes indices. By examining the gut microbiome, we found thatα-CYP-treated rats had low contents of Firmicutes and high levels of Verrucomicrobia while Elusimicrobia was enriched in the β-CYP group. The increasing alpha diversity in the θ-CYP group may be due to the dominance of pathogenic bacteria and the increase of probiotics to counteract adverse effects. Exclusively, the α-CYP group enriched total short-chain fatty acids(SCFAs), whereas most SCFAs depleted in the θ-CYP group. The correlation analysis further found Firmicutes, an energy storage modulator, was positive to body weight(BW),while SCFAs exerted the opposite, confirming the low BW in α-CYP. Blood glucose that correlated well with SCFAs and Verrucomicrobia can be accounted for the discrepancy betweenα-CYP and θ-CYP. Overall, the three isomers exerted stereoselective glycolipid disruption in rats, and gut homeostasis acted as vital indicators.
文摘V79-8 is an abnormal cell line which does not have detectable G1 and G2 phases in its cell cycle.This cell line is derived from V79 cell line which has G1 phase but lacks G2 phase. By using an anti-sense approach, CDK4 gene expression was partially inhibited to find whether CDK4 might contribute to the lack of G1 phase in V79-8 cells. Anti-CDK4 anti-sense plasmid was constructed and used to transfect V79-8 cells. Clones of transfected cells (V79-8-asCDK4) were examined, in comparison with V79-8 cells, to determine its growth curve, cell doubling-time (GT), the level of CDK4 gene expression and the levels of expression of some other growth related genes. V79-8-asCDK4 cells showed a slower growth rate with a doubling time 2.5-h longer than that of V79-8 cells. A flow cytometry (FCM) analysis demonstrated that the 2.5 h increase of the doubling time of V79-8-asCDK4 cells was mainly due to the appearance of G1 phase because its G2+M phase was not significantly different from that of V79-8 cells. The
