The intermolecular reductive coupling of nitrites with azobenzene induced by SmI2 was studied. Amidine derivatives were prepared in good yields under neutral and mild conditions.
A series of novel amidine derivatives of doxifluridine were synthesized using acid amide as the starting material,and their antitumor activity was evaluated in A549 cells.Compounds 10 and 11 demonstrated were more pot...A series of novel amidine derivatives of doxifluridine were synthesized using acid amide as the starting material,and their antitumor activity was evaluated in A549 cells.Compounds 10 and 11 demonstrated were more potent than 5-Fu,which was used as a positive control.Compound 10,which were found to be the most potent one with IC_(50) of 3.2μmol/L,was 16 times more potent than 5-Fu with IC_(50) of 52μmol/L to the A549 cells.A new route was designed to synthesize 5 -deoxy-5-fluorocytidine.All compounds were c...展开更多
A lipoplex （i.e., pDNA#1/lipid complex and transfection reagent for pDNA delivery） containing galactosylceramide （GalCer） and an amidine-bearing lipid （TRX） was examined whether the bound pDNA was specifically i...A lipoplex （i.e., pDNA#1/lipid complex and transfection reagent for pDNA delivery） containing galactosylceramide （GalCer） and an amidine-bearing lipid （TRX） was examined whether the bound pDNA was specifically ingested by hepatocyte via asialoglycoprotein receptor （ASGPR） and then expressed protein. Gel electrophoresis and small-angle X-ray scattering （SAXS） confirmed that the TRX-GalCer liposome#2 complexed with pDNA and the resultant lipoplex took a hexagonally packed inverted cylinder structure when the GalCer composition was less than 20 wt.% of the total lipid. When the lipoplex carrying pGL3 （luciferase-cording pDNA） was administrated to HepG2, the luciferase activity was increased with increasing the GalCer composition until it reached 3 wt.% and then decreased upon further addition of GalCer. When we added galactose itself as a competitor, the luciferase activity was decreased, while glucose did not show such decrease, suggesting that HepG2 ingested the lipoplex via ASGPR-mediated endocytosis. This paper indicated that the hexagonally packed inverted cylinder structures of lipoplex may not always provide excellent transfection and presented a possibility that the TRX lipoplex#3 can obtain a cellulartargeting ability through the receptors for oligosaccharide.展开更多
Background Salmonella Typhimurium challenge causes a huge detriment to chicken production.N-acyl homoserine lactonase(AHLase),a quorum quenching enzyme,potentially inhibits the growth and virulence of Gram-negative ba...Background Salmonella Typhimurium challenge causes a huge detriment to chicken production.N-acyl homoserine lactonase(AHLase),a quorum quenching enzyme,potentially inhibits the growth and virulence of Gram-negative bacteria.However,it is unknown whether AHLase can protect chickens against S.Typhimurium challenge.This study aimed to evaluate the effects of AHLase on growth performance and intestinal health in broilers challenged by S.Typhimurium.A total of 240 one-day-old female crossbred broilers(817C)were randomly divided into 5 groups(6 replicates/group):negative control(NC),positive control(PC),and PC group supplemented with 5,10 or 20 U/g AHLase.All birds except those in NC were challenged with S.Typhimurium from 7 to 9 days of age.All parameters related to growth and intestinal health were determined on d 10 and 14.Results The reductions(P<0.05)in body weight(BW)and average daily gain(ADG)in challenged birds were alleviated by AHLase addition especially at 10 U/g.Thus,samples from NC,PC and PC plus 10 U/g AHLase group were selected for further analysis.S.Typhimurium challenge impaired(P<0.05)intestinal morphology,elevated(P<0.05)ileal inflammatory cytokines(IL-1βand IL-8)expression,and increased(P<0.05)serum diamine oxidase(DAO)activity on d 10.However,AHLase addition normalized these changes.Gut microbiota analysis on d 10 showed that AHLase reversed the reductions(P<0.05)in several beneficial bacteria(e.g.Bacilli,Bacillales and Lactobacillales),along with increases(P<0.05)in certain harmful bacteria(e.g.Proteobacteria,Gammaproteobacteria,Enterobacteriaceae and Escherichia/Shigel a)in PC group.Furthermore,AHLase-induced increased beneficial bacteria and decreased harmful bacteria were basically negatively correlated(P<0.05)with the reductions of ileal IL-1βand IL-8 expression and serum DAO activity,but positively correlated(P<0.05)with the increased BW and ADG.Functional prediction revealed that AHLase abolished S.Typhimurium-induced upregulations(P<0.05)of certain pathogenicity-related pathways such as lipopolysaccharide biosynthesis,shigellosis,bacterial invasion of epithelial cells and pathogenic Escherichia coli infection of gut microbiota.Conclusions Supplemental AHLase attenuated S.Typhimurium-induced growth retardation and intestinal disruption in broilers,which could be associated with the observed recovery of gut microbiota dysbiosis.展开更多
The reactions of 5-methyl-3-hydroxyisoxazole with 2, 2-dimethyl, 3-substituted cyclopropanecarboxylic chlorides give O-acyl-5-methyl-3-hydroxyisoxazole and N-acyl-5-methylisoxazolin-3-one derivatives. The ratio of O-a...The reactions of 5-methyl-3-hydroxyisoxazole with 2, 2-dimethyl, 3-substituted cyclopropanecarboxylic chlorides give O-acyl-5-methyl-3-hydroxyisoxazole and N-acyl-5-methylisoxazolin-3-one derivatives. The ratio of O-acyl to N-acyl product depends upon the acylation reagents. O-acyl derivatives can be converted to the N-acyl compounds by isomerization under acidic conditions or heating.展开更多
Acylation of 5-methyl-3-hydroxyisoxazole (1) with 3-substituted cyclopropanecarboxylic chlorides (3) in the presence of triethylamine (TEA) in acetonitrile yields predominantly O-acylated products (4).The N-acyl isome...Acylation of 5-methyl-3-hydroxyisoxazole (1) with 3-substituted cyclopropanecarboxylic chlorides (3) in the presence of triethylamine (TEA) in acetonitrile yields predominantly O-acylated products (4).The N-acyl isomers (5) are afforded regiospecifically using trimethylsilyl ether of 3-hydroxyisoxazole (2).展开更多
The aim of this research was to detect the N-acyl homoserine lactones (AHLs) production and QseB/C gene of Aeromonas hydrophila. We analyzed the potentials of these isolates of Aeromonas hydrophila in causing biofilm ...The aim of this research was to detect the N-acyl homoserine lactones (AHLs) production and QseB/C gene of Aeromonas hydrophila. We analyzed the potentials of these isolates of Aeromonas hydrophila in causing biofilm formation, hemolysis, protease, and lipase. The antibiotic susceptibility of the 15 Aeromonas hydrophila isolates was also investigated. The detection of AHLs was carried out using the Chromobacterium violaceum strain CV026 as biosensors. The isolated strains were tested for the reaction of C. violaceum CV026 by cross-streaking on an agar plate. Production of AHLs was determined by the diffusing via the agar plates and the tinge of the biosensor strains. All isolated strains produced AHLs. A polymerase chain reaction (PCR) showed the isolated strains had qseB and qseC genes. Susceptibility tests of A. hydrophila isolates were administered against 25 different antibiotic disks representing 12 classes of antibiotics. The strains were highly resistant to β-Lactam with 96.7% showing resistibility, whereas 97.7% susceptibility was found towards Aminoglycoside class of the antibiotic used. 60% showed intermediate resistant to Polypeptide. 100% of the strains showed no resistant to Aminoglycoside, Polypeptide, Monobactam, and Carbapenems class of antibiotics. Each of the isolates was found to be associated with at least one virulent factor. Our results clearly demonstrated that there is a presence of QseB/C genes in A. hydrophila and also produces AHLs molecule and virulence factors. The investigated isolates showed the pathogenic potential of Aeromonas hydrophila which makes it a serious threat to public health.展开更多
Bacterial cells rely on signaling molecules to communicate with others from the same species and induce certain genes in a process known as quorum sensing (QS). A common molecule is N-acyl homoserine lactone (AHL) whi...Bacterial cells rely on signaling molecules to communicate with others from the same species and induce certain genes in a process known as quorum sensing (QS). A common molecule is N-acyl homoserine lactone (AHL) which is responsible for the expression of virulence and other factors that allow the organisms to compete in a given environment. On the other hand, other bacteria produce certain enzymes such as AHL-lactonase that break down AHL molecules and prevent gene expression of these factors. The aim of this work was to examine the level of degradation of AHL molecules by AHL-lactonase in 62 Bacillus thuringiensis (Bt) strains isolated from Middle Tennessee, Mississippi, and Alabama. N-hexanoyl-homoserine lactone (C<sub>6</sub>-HSL) and N-3-oxo-hexanoyl homoserine lactone (3-oxo-C<sub>6</sub>-HSL), which cause Chromobacterium violaceum (CV026) to produce a purple pigment were tested at different concentrations to view the Bt lactonase activity. In addition, PCR was used to test for the presence of the lactonase gene. The results showed that among the 62 Bt strains, there were 58 that possessed the AHL-lactonase (aiiA) gene and 48 strains were able to degrade C<sub>6</sub>-HSL. At high concentrations of AHL, only 13 strains were able to completely degrade C6-HSL. In addition, degradation of 3-oxo-C<sub>6</sub>-HSL was weak compared to C<sub>6</sub>-HSL. The results also revealed that AHL lactonase was thermostable, and it was concluded that the level of degradation varies in Bt strains. Only 13 of the strains studied have potent inhibitory activity against C<sub>6</sub>-HSL, which may be good to be used in field applications to control agricultural pest.展开更多
文摘The intermolecular reductive coupling of nitrites with azobenzene induced by SmI2 was studied. Amidine derivatives were prepared in good yields under neutral and mild conditions.
文摘A series of novel amidine derivatives of doxifluridine were synthesized using acid amide as the starting material,and their antitumor activity was evaluated in A549 cells.Compounds 10 and 11 demonstrated were more potent than 5-Fu,which was used as a positive control.Compound 10,which were found to be the most potent one with IC_(50) of 3.2μmol/L,was 16 times more potent than 5-Fu with IC_(50) of 52μmol/L to the A549 cells.A new route was designed to synthesize 5 -deoxy-5-fluorocytidine.All compounds were c...
基金SORST of JST and a Grant-in-Aid for Scientific Research(No.16350068 and 16655048)SAXS was performed at SPring-8 BL40B2(No.2006A1510).
文摘A lipoplex （i.e., pDNA#1/lipid complex and transfection reagent for pDNA delivery） containing galactosylceramide （GalCer） and an amidine-bearing lipid （TRX） was examined whether the bound pDNA was specifically ingested by hepatocyte via asialoglycoprotein receptor （ASGPR） and then expressed protein. Gel electrophoresis and small-angle X-ray scattering （SAXS） confirmed that the TRX-GalCer liposome#2 complexed with pDNA and the resultant lipoplex took a hexagonally packed inverted cylinder structure when the GalCer composition was less than 20 wt.% of the total lipid. When the lipoplex carrying pGL3 （luciferase-cording pDNA） was administrated to HepG2, the luciferase activity was increased with increasing the GalCer composition until it reached 3 wt.% and then decreased upon further addition of GalCer. When we added galactose itself as a competitor, the luciferase activity was decreased, while glucose did not show such decrease, suggesting that HepG2 ingested the lipoplex via ASGPR-mediated endocytosis. This paper indicated that the hexagonally packed inverted cylinder structures of lipoplex may not always provide excellent transfection and presented a possibility that the TRX lipoplex#3 can obtain a cellulartargeting ability through the receptors for oligosaccharide.
基金financially supported by the National Natural Science Foundation of China(No.31872390)the Modern Feed Industry Innovation Team Project of Guangdong Province(No.2021KJ115)。
文摘Background Salmonella Typhimurium challenge causes a huge detriment to chicken production.N-acyl homoserine lactonase(AHLase),a quorum quenching enzyme,potentially inhibits the growth and virulence of Gram-negative bacteria.However,it is unknown whether AHLase can protect chickens against S.Typhimurium challenge.This study aimed to evaluate the effects of AHLase on growth performance and intestinal health in broilers challenged by S.Typhimurium.A total of 240 one-day-old female crossbred broilers(817C)were randomly divided into 5 groups(6 replicates/group):negative control(NC),positive control(PC),and PC group supplemented with 5,10 or 20 U/g AHLase.All birds except those in NC were challenged with S.Typhimurium from 7 to 9 days of age.All parameters related to growth and intestinal health were determined on d 10 and 14.Results The reductions(P<0.05)in body weight(BW)and average daily gain(ADG)in challenged birds were alleviated by AHLase addition especially at 10 U/g.Thus,samples from NC,PC and PC plus 10 U/g AHLase group were selected for further analysis.S.Typhimurium challenge impaired(P<0.05)intestinal morphology,elevated(P<0.05)ileal inflammatory cytokines(IL-1βand IL-8)expression,and increased(P<0.05)serum diamine oxidase(DAO)activity on d 10.However,AHLase addition normalized these changes.Gut microbiota analysis on d 10 showed that AHLase reversed the reductions(P<0.05)in several beneficial bacteria(e.g.Bacilli,Bacillales and Lactobacillales),along with increases(P<0.05)in certain harmful bacteria(e.g.Proteobacteria,Gammaproteobacteria,Enterobacteriaceae and Escherichia/Shigel a)in PC group.Furthermore,AHLase-induced increased beneficial bacteria and decreased harmful bacteria were basically negatively correlated(P<0.05)with the reductions of ileal IL-1βand IL-8 expression and serum DAO activity,but positively correlated(P<0.05)with the increased BW and ADG.Functional prediction revealed that AHLase abolished S.Typhimurium-induced upregulations(P<0.05)of certain pathogenicity-related pathways such as lipopolysaccharide biosynthesis,shigellosis,bacterial invasion of epithelial cells and pathogenic Escherichia coli infection of gut microbiota.Conclusions Supplemental AHLase attenuated S.Typhimurium-induced growth retardation and intestinal disruption in broilers,which could be associated with the observed recovery of gut microbiota dysbiosis.
基金Supposed by the National Natural Science Foundation of China
文摘The reactions of 5-methyl-3-hydroxyisoxazole with 2, 2-dimethyl, 3-substituted cyclopropanecarboxylic chlorides give O-acyl-5-methyl-3-hydroxyisoxazole and N-acyl-5-methylisoxazolin-3-one derivatives. The ratio of O-acyl to N-acyl product depends upon the acylation reagents. O-acyl derivatives can be converted to the N-acyl compounds by isomerization under acidic conditions or heating.
文摘Acylation of 5-methyl-3-hydroxyisoxazole (1) with 3-substituted cyclopropanecarboxylic chlorides (3) in the presence of triethylamine (TEA) in acetonitrile yields predominantly O-acylated products (4).The N-acyl isomers (5) are afforded regiospecifically using trimethylsilyl ether of 3-hydroxyisoxazole (2).
文摘The aim of this research was to detect the N-acyl homoserine lactones (AHLs) production and QseB/C gene of Aeromonas hydrophila. We analyzed the potentials of these isolates of Aeromonas hydrophila in causing biofilm formation, hemolysis, protease, and lipase. The antibiotic susceptibility of the 15 Aeromonas hydrophila isolates was also investigated. The detection of AHLs was carried out using the Chromobacterium violaceum strain CV026 as biosensors. The isolated strains were tested for the reaction of C. violaceum CV026 by cross-streaking on an agar plate. Production of AHLs was determined by the diffusing via the agar plates and the tinge of the biosensor strains. All isolated strains produced AHLs. A polymerase chain reaction (PCR) showed the isolated strains had qseB and qseC genes. Susceptibility tests of A. hydrophila isolates were administered against 25 different antibiotic disks representing 12 classes of antibiotics. The strains were highly resistant to β-Lactam with 96.7% showing resistibility, whereas 97.7% susceptibility was found towards Aminoglycoside class of the antibiotic used. 60% showed intermediate resistant to Polypeptide. 100% of the strains showed no resistant to Aminoglycoside, Polypeptide, Monobactam, and Carbapenems class of antibiotics. Each of the isolates was found to be associated with at least one virulent factor. Our results clearly demonstrated that there is a presence of QseB/C genes in A. hydrophila and also produces AHLs molecule and virulence factors. The investigated isolates showed the pathogenic potential of Aeromonas hydrophila which makes it a serious threat to public health.
文摘Bacterial cells rely on signaling molecules to communicate with others from the same species and induce certain genes in a process known as quorum sensing (QS). A common molecule is N-acyl homoserine lactone (AHL) which is responsible for the expression of virulence and other factors that allow the organisms to compete in a given environment. On the other hand, other bacteria produce certain enzymes such as AHL-lactonase that break down AHL molecules and prevent gene expression of these factors. The aim of this work was to examine the level of degradation of AHL molecules by AHL-lactonase in 62 Bacillus thuringiensis (Bt) strains isolated from Middle Tennessee, Mississippi, and Alabama. N-hexanoyl-homoserine lactone (C<sub>6</sub>-HSL) and N-3-oxo-hexanoyl homoserine lactone (3-oxo-C<sub>6</sub>-HSL), which cause Chromobacterium violaceum (CV026) to produce a purple pigment were tested at different concentrations to view the Bt lactonase activity. In addition, PCR was used to test for the presence of the lactonase gene. The results showed that among the 62 Bt strains, there were 58 that possessed the AHL-lactonase (aiiA) gene and 48 strains were able to degrade C<sub>6</sub>-HSL. At high concentrations of AHL, only 13 strains were able to completely degrade C6-HSL. In addition, degradation of 3-oxo-C<sub>6</sub>-HSL was weak compared to C<sub>6</sub>-HSL. The results also revealed that AHL lactonase was thermostable, and it was concluded that the level of degradation varies in Bt strains. Only 13 of the strains studied have potent inhibitory activity against C<sub>6</sub>-HSL, which may be good to be used in field applications to control agricultural pest.
