Formyl peptide receptors (FPRs) were observed to expand in rodents and were recently suggested as candidate vomeronasal chemo-sensory receptors. Since vomeronasal chemosensory receptors usually underwent positive sele...Formyl peptide receptors (FPRs) were observed to expand in rodents and were recently suggested as candidate vomeronasal chemo-sensory receptors. Since vomeronasal chemosensory receptors usually underwent positive selection and evolved concordantly with the vomeronasal organ (VNO) morphology, we surveyed FPRs in primates in which VNO morphology is greatly diverse and thus it would provide us a clearer view of VNO-FPRs evolution. By screening available primate genome sequences, we obtained the FPR repertoires in representative primate species. As a result, we did not find FPR family size expansion in primates. Further analyses showed no evolution-ary force variance between primates with or without VNO structure, which indicated that there was no functional divergence among pri-mates FPRs. Our results suggest that primates lack the VNO-specific FPRs and the FPR expansion is not a common phenomenon in mammals outside rodent lineage, regardless of VNO complexity.展开更多
Objective:Premature rupture of membranes(PROM)is a common pregnancy disorder that is closely associated with structural weakening of fetal membranes.Studies have found that formyl peptide receptor 1(FPR1)activates inf...Objective:Premature rupture of membranes(PROM)is a common pregnancy disorder that is closely associated with structural weakening of fetal membranes.Studies have found that formyl peptide receptor 1(FPR1)activates inflammatory pathways and amniotic epithelial-mesenchymal transition(EMT),stimulates collagen degradation,and leads to membrane weakening and membrane rupture.The purpose of this study was to investigate the anti-inflammatory and EMT inhibitory effects of FPR1 antagonist(BOC-MLF)to provide a basis for clinical prevention of PROM.Methods:The relationship between PROM,FPR1,and EMT was analyzed in human fetal membrane tissue and plasma samples using Western blotting,PCR,Masson staining,and ELISA assays.Lipopolysaccharide(LPS)was used to establish a fetal membrane inflammation model in pregnant rats,and BOC-MLF was used to treat the LPS rat model.We detected interleukin(IL)-6 in blood from the rat hearts to determine whether the inflammatory model was successful and whether the anti-inflammatory treatment was effective.We used electron microscopy to analyze the structure and collagen expression of rat fetal membrane.Results:Western blotting,PCR and Masson staining indicated that the expression of FPR1 was significantly increased,the expression of collagen was decreased,and EMT appeared in PROM.The rat model indicated that LPS caused the collapse of fetal membrane epithelial cells,increased intercellular gaps,and decreased collagen.BOC-MLF promoted an increase in fetal membrane collagen,inhibited EMT,and reduced the weakening of fetal membranes.Conclusion:The expression of FPR1 in the fetal membrane of PROM was significantly increased,and EMT of the amniotic membrane was obvious.BOC-MLF can treat inflammation and inhibit amniotic EMT.展开更多
Carbohydrate metabolism disorders(CMDs),such as diabetes,galactosemia,and mannosidosis,cause ciliopathy-like multiorgan defects.However,the mechanistic link of cilia to CMD complications is still poorly understood.Her...Carbohydrate metabolism disorders(CMDs),such as diabetes,galactosemia,and mannosidosis,cause ciliopathy-like multiorgan defects.However,the mechanistic link of cilia to CMD complications is still poorly understood.Herein,we describe significant cilium disassembly upon treatment of cells with pathologically relevant aldoses rather than the corresponding sugar alcohols.Moreover,environmental aldehydes are able to trigger cilium disassembly by the steric hindrance effect of their formyl groups.Mechanistic studies reveal that aldehydes stimulate extracellular calcium influx across the plasma membrane,which subsequently activates the calmodulin-Aurora A-histone deacetylase 6 pathway to deacetylate axonemal microtubules and triggers cilium disassembly.In vivo experiments further show that Hdac6 knockout mice are resistant to aldehyde-induced disassembly of tracheal cilia and sperm flagella.These findings reveal a previously unrecognized role for formyl group-mediated cilium disassembly in the complications of CMDs.展开更多
BACKGROUND Formyl peptide receptor 2(Fpr2)is an important receptor in host resistance to bacterial infections.In previous studies,we found that the liver of Fpr2-/-mice is the most severely damaged target organ in blo...BACKGROUND Formyl peptide receptor 2(Fpr2)is an important receptor in host resistance to bacterial infections.In previous studies,we found that the liver of Fpr2-/-mice is the most severely damaged target organ in bloodstream infections,although the reason for this is unclear.AIM To investigate the role of Fpr2 in liver homeostasis and host resistance to bacterial infections.METHODS Transcriptome sequencing was performed on the livers of Fpr2-/-and wild-type(WT)mice.Differentially expressed genes(DEGs)were identified in the Fpr2-/-and WT mice,and the biological functions of DEGs were analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Quantitative real time-polymerase chain reaction(qRT-PCR)and western blot(WB)analyses were used to further validate the expression levels of differential genes.Cell counting kit-8 assay was employed to investigate cell survival.The cell cycle detection kit was used to measure the distribution of cell cycles.The Luminex assay was used to analyze cytokine levels in the liver.The serum biochemical indices and the number of neutrophils in the liver were measured,and hepatic histopathological analysis was performed.RESULTS Compared with the WT group,445 DEGs,including 325 upregulated genes and 120 downregulated genes,were identified in the liver of Fpr2-/-mice.The enrichment analysis using GO and KEGG showed that these DEGs were mainly related to cell cycle.The qRT-PCR analysis confirmed that several key genes(CycA,CycB1,Cdc20,Cdc25c,and Cdk1)involved in the cell cycle had significant changes.The WB analysis confirmed a decrease in the expression of CDK1 protein.WRW4(an antagonist of Fpr2)could inhibit the proliferation of HepG2 cells in a concentration dependent manner,with an increase in the number of cells in the G0/G1 phase,and a decrease in the number of cells in the S phase.Serum alanine aminotransferase levels increased in Fpr2-/-mice.The Luminex assay measurements showed that interleukin(IL)-10 and chemokine(C-X-C motif)ligand(CXCL)-1展开更多
Preparation of twelve 1-methyl-2-formyl-5-substituted pyrroles (2a–1), with five of them as new compounds, is described. Their derivatives, i.e., 1-methyl-2-formyl-5-substituted pyrrole phenyl hydrazones (3a–1) and ...Preparation of twelve 1-methyl-2-formyl-5-substituted pyrroles (2a–1), with five of them as new compounds, is described. Their derivatives, i.e., 1-methyl-2-formyl-5-substituted pyrrole phenyl hydrazones (3a–1) and 1-methyl-2-formyl-5-substituted pyrrole (4-nitrophenyl) hydrazones (4a–1) are all new compounds. They have also been prepared and further identified.展开更多
Two metal-organic frameworks [(Zn0.5L)·(H2O)]n (1) and [(Ni0.5L)?(H2O)]n (2) constructed by the 3-formyl-4-(pyridin-4-yl) benzoic acid ligand (HL) were synthesized and characterized by single-cry...Two metal-organic frameworks [(Zn0.5L)·(H2O)]n (1) and [(Ni0.5L)?(H2O)]n (2) constructed by the 3-formyl-4-(pyridin-4-yl) benzoic acid ligand (HL) were synthesized and characterized by single-crystal X-ray diffraction. 1 crystallizes in orthorhombic space group Pnna with a = 16.6152(8), b = 12.6825(6), c = 15.3908(8) A, V = 3243.2(3) ?3, Z = 4, Mr = 511.12, Dc = 1.047 g/cm3, F(000) = 1048, μ = 1.144 mm-1, GOOF = 1.061, the final R = 0.0471 and wR = 0.1262 for 12168 observed reflections with I 〉 2σ(I). 2 is isostructural to 1, which also crystallizes in orthorhombic space group Pnna with a = 16.6152(8), b = 12.6825(6), c = 15.3908(8) ?, V = 3243.2(3) ?3, Z = 4, Mr = 511.12, Dc = 1.047 g/cm3, F(000) = 1048, μ = 1.144 mm-1, GOOF = 1.061, the final R = 0.0471 and wR = 0.1262 for 12168 observed reflections with I 〉 2σ(I). Additionally, thermogravimetric analysis, FT-IR spectroscopy and powder X-ray diffraction were discussed.展开更多
AIM:To solidify the involvement of Saa-related pathway in corneal neovascularization(CorNV).The pathogenesis of inflammatory CorNV is not fully understood yet,and our previous study implicated that serum amyloid A(Saa...AIM:To solidify the involvement of Saa-related pathway in corneal neovascularization(CorNV).The pathogenesis of inflammatory CorNV is not fully understood yet,and our previous study implicated that serum amyloid A(Saa)1(Saa1)and Saa3 were among the genes up-regulated upon CorNV induction in mice.METHODS:Microarray data obtained during our profiling project on CorNV were analyzed for the genes encoding the four SAA family members(Saa1-4),six reported SAA receptors(formyl peptide receptor 2,Tlr2,Tlr4,Cd36,Scarb1,P2rx7)and seven matrix metallopeptidases(Mmp)1a,1b,2,3,9,10,13reportedly to be expressed upon SAA pathway activation.The baseline expression or changes of interested genes were further confirmed in animals with CorNV using molecular or histological methods.CorNV was induced in Balb/c and C57BL/6 mice by placing either three interrupted 10-0 sutures or a 2 mm filter paper soaked with sodium hydroxide in the central area of the cornea.At desired time points,the corneas were harvested for histology examination or for extraction of mRNA and protein.The mRNA levels of Saa1,Saa3,Fpr2,Mmp2and Mmp3 in corneas were detected using quantitative reverse transcription-PCR,and SAA3 protein in tissues detected using immunohistochemistry or western blotting.RESULTS:Microarray data analysis revealed that Saa1,Saa3,Fpr2,Mmp2,Mmp3 messengers were readily detected in normal corneas and significantly upregulated upon CorNV induction.The changes of these five genes were confirmed with real-time PCR assay.Onthe contrary,other SAA members(Saa2,Saa4),other SAA receptors(Tlr2,Tlr4,Cd36,P2rx7,etc),or other Mmps(Mmp1a,Mmp1b,Mmp9,Mmp10,Mmp13)did not show consistent changes.Immunohistochemistry study and western blotting further confirmed the expression of SAA3 products in normal corneas as well as their upregulation in corneas with CorNV.CONCLUSION:SAA-FPR2 pathway composing genes were expressed in normal murine corneas and,upon inflammatory stimuli challenge to the corneas,their expressions were up-regulated,suggesting their roles in 展开更多
In this paper the equilibrium structure of HCO has been optimized by using density functional theory (DFT)/ B3P86 method and CC-PVTZ basis. It has a bent (Cs, X^2A') ground state structure with an angle of 124.40...In this paper the equilibrium structure of HCO has been optimized by using density functional theory (DFT)/ B3P86 method and CC-PVTZ basis. It has a bent (Cs, X^2A') ground state structure with an angle of 124.4095 °. The vibronic frequencies and force constants have also been calculated. Based on the principles of atomic and molecular reaction statics, the possible electronic states and reasonable dissociation limits for the ground state of HCO molecule have been determined. The analytic potential energy function of HCO (X^2A') molecule has been derived by using the many-body expansion theory. The contour lines are constructed, which show the static properties of HCO (X^2A'), such as the equilibrium structure, the lowest energies, etc. The potential energy surface of HCO (X^2A') is reasonable and very satisfactory.展开更多
N-formyl peptide receptors(FPRs)were first identified upon phagocytic leukocytes,but more than four decades of research has unearthed a plethora of non-myeloid roles for this receptor family.FPRs are expressed within ...N-formyl peptide receptors(FPRs)were first identified upon phagocytic leukocytes,but more than four decades of research has unearthed a plethora of non-myeloid roles for this receptor family.FPRs are expressed within neuronal tissues and markedly in the central nervous system,where FPR interactions with endogenous ligands have been implicated in the pathophysiology of several neurodegenerative diseases including Alzheimer's disease and Parkinson's disease,as well as neurological cancers such as neuroblastoma.Whilst the homeostatic function of FPRs in the nervous system is currently undefined,a variety of novel physiological roles for this receptor family in the neuronal context have been posited in both human and animal settings.Rapid developments in recent years have implicated FPRs in the process of neurogenesis and neuronal differentiation which,upon greater characterisation,could represent a novel pharmacological target for neuronal regeneration therapies that may be used in the treatment of brain/spinal cord injury,stroke and neurodegeneration.This review aims to summarize the recent progress made to determine the physiological role of FPRs in a neuronal setting,and to put forward a case for FPRs as a novel pharmacological target for conditions of the nervous system,and for their potential to open the door to novel neuronal regeneration therapies.展开更多
OBJECTIVE To identify the mechanisms by which the formyl peptide receptor 2(FPR2)mediates both inflammatory and anti-inflammatory signaling in an agonist-dependent manner.METHODS Cells expressing FPR2 were incubated w...OBJECTIVE To identify the mechanisms by which the formyl peptide receptor 2(FPR2)mediates both inflammatory and anti-inflammatory signaling in an agonist-dependent manner.METHODS Cells expressing FPR2 were incubated with weak agonists,Aβ42 and Ac2-26,before stimulation with a strong agonist,WKYMVm.Calcium mobilization,c AMP inhibition and MAP kinase activation were measured.Intramolecular FRET were determined using FPR2 constructs with an ECFP attached to the C-terminus and a Fl As H binding motif embedded in the first or third intracellular loop(IL1 or IL3,respectively).RESULTS Aβ42 did not induce significant Ca^(2+) mobilization,but positively modulated WKYMVm-induced Ca^(2+) mobilization and c AMP reduction in a dose-variable manner within a narrow range of ligand concentrations.Treating FPR2-expressing cells with Ac2-26,a peptide with anti-inflammatory activity,negatively modulated WKYMVm-induced Ca^(2+) mobilization and c AMP reduction.Intramolecular FRET assay showed that stimulation of the receptor constructs with Aβ42 brought the C-terminal domain closer to IL1 but away from IL3.An opposite conformational change was induced by Ac2-26.The FPR2 conformation induced by Aβ42 corresponded to enhanced ERK phosphorylation and attenuated p38 MAPK phosphorylation,whereas Ac2-26 induced FPR2 conformational change corresponding to elevated p38 MAPK phosphorylation and reduced ERK phosphorylation.CONCLUSION Aβ42 and Ac2-26 induce different conformational changes in FPR2.These findings provide a structural basis for FPR2 mediation of inflammatory vs anti-inflammatory functions and identify a type of receptor modulation that differs from the classic positive and negative allosteric modulation.展开更多
The bimetallic Ru-M (M=Co,Fe,Ni,Mo, Rh,Cr, Mn) catalysts were prepared from SiO_2-supported bimetallic carbonyl clusters, and it was found that the Ru-Co, Ru-Fe and Ru-Mo bimetallic carbonyl cluster-derived catalysts ...The bimetallic Ru-M (M=Co,Fe,Ni,Mo, Rh,Cr, Mn) catalysts were prepared from SiO_2-supported bimetallic carbonyl clusters, and it was found that the Ru-Co, Ru-Fe and Ru-Mo bimetallic carbonyl cluster-derived catalysts showed higher activity and selectivity for oxygenates such as C_1-C_5 alcohols in CO hydrogenation,in contrast to catalysts prepared from SiO_2-supported homometallic Ru and Co carbonyl clusters. In situ FT-IR studies revealed that the bands at 1584 and 1555 cm^(-1) species were intermediates to produce methanol and higher oxygenates,and at higher temperatures the 1584 cm^(-1) species could react with alkyl to form 1555 cm^(-1) species. By the surface chemical reaction and the IR study of isotopic molecules,it was suggested that 1584 and 1555 cm^(-1) were assigned to surface formyl and acetyl species.展开更多
A series of novel polyphosphonates containing 5-flouro- N1-furanyl-N3- glyceroalkyl-uracil and formyl groups was synthesized by the condensation of 3-(w- (1-furanyl-5-flourouracil-3-yl) alkoxy)-1, 2-dihydroxy propane ...A series of novel polyphosphonates containing 5-flouro- N1-furanyl-N3- glyceroalkyl-uracil and formyl groups was synthesized by the condensation of 3-(w- (1-furanyl-5-flourouracil-3-yl) alkoxy)-1, 2-dihydroxy propane with phosphonyl dichloride. The products were characterized by IR, 1H NMR, 31P NMR, M, and elemental analysis. The results of bioassay show that compound 8a possesses potential anticancer activity.展开更多
Although many aroma components have been identified in green tea leaves, the aroma compounds contributing to green tea's characteristic odor have not yet been reported. The authors recently reported that aroma compon...Although many aroma components have been identified in green tea leaves, the aroma compounds contributing to green tea's characteristic odor have not yet been reported. The authors recently reported that aroma components with a matcha-like odor are present in both green tea and black tea prepared from the Sayamakaori tea cuttivar. This matcha-like odor is similar to the odor of commercial available matcha (high-quality powdered green tea), and is a specific odor feature of green tea leaves. At present, the green-tea odor is thought to arise from the combination of a large number of constituents. Recent reports indicate that a complex interaction between olfactory receptors and odorants is important for the evaluation of the odors. Taking into consideration these findings, the authors investigated the aroma profile of green tea, focusing on the characteristic molecular structures of the constituents that give matcha-like odor. Using a combination of organic synthesis and gas chromatography-mass spectrometry plus gas chromatography-olfactometry, the authors identified aroma components with matcha-like odors in five other tea cultivars. This investigation also revealed that several compounds with a formyl group were important constituents of the aroma of green tea leaves, although the odor of each constituent was not individually similar to the tea's overall aroma. The authors found for the first time a group of key components that have the matcha-like odor.展开更多
A highly sensitive HPLC method for the detection of amino acids and oligopeptides with 9-acridine formyl chloride by pre-column fluorescence derivatization has been developed. Glycine, glycylglycine, histidine, trigly...A highly sensitive HPLC method for the detection of amino acids and oligopeptides with 9-acridine formyl chloride by pre-column fluorescence derivatization has been developed. Glycine, glycylglycine, histidine, triglycine and glutathione were separated on a reversed-phase C-18 column with methanol-water-triethylamine eluent, derivatization and chromatographic conditions were optimized. The five derivatives were eluted in 28 min with a good reproducibility. Linear range of the calibration graph was 0.08-260 nmol/ml(-1). The relative standard deviations(n=6) are < 5%. Detection limits (signal-to-noise ratio=3) for the five derivatives are 20-40 fmol.展开更多
The mechanisms and kinetics of the gas phase reactions that the hydrogen atom in formyl fluoride (FCHO) abstracted by OH in the presence of water, formic acid (FA), or sulfuric acid (SA) are theoretically invest...The mechanisms and kinetics of the gas phase reactions that the hydrogen atom in formyl fluoride (FCHO) abstracted by OH in the presence of water, formic acid (FA), or sulfuric acid (SA) are theoretically investigated at the CCSD(T)/6-311++G(3df, 3pd)//MO6-2X/6- 311++G(3df, 3pd) level of theory. The calculated results show that the barriers of the transition states involving catalysts are lowered to -2.89, -6.25, and -7.76 kcal/mol from 3.64 kcal/mol with respect to the separate reactants, respectively, which reflects that those catalysts play an important role in reducing the barrier of the hydrogen abstraction reaction of FCHO with OH. Additionally, using conventional transition state theory with Eckart tun- neling correction, the kinetic data demonstrate that the entrance channel X…FCHO+OH (X=H2O, FA, or SA) is significantly more favorable than the pathway X…OH+FCHO. More- over, the rate constants of the reactions of FCHO with OH radical with H2O, FA, or SA introduced are computed to be smaller than that of the naked OH+FCHO reaction because the concentration of the formed X…FCHO or X…OH complex is quite low in the atmosphere.展开更多
We compute the thermodynamic and the kinetic properties for the reaction: HCOCN→HCH+CO using the statistical theory and the transition-state theory.The equi- librium constants and the rate coefficients of this reacti...We compute the thermodynamic and the kinetic properties for the reaction: HCOCN→HCH+CO using the statistical theory and the transition-state theory.The equi- librium constants and the rate coefficients of this reaction are also reported here,and the half lives of formyl cyanide at different temperatures are first estimated in this work.展开更多
基金supported by grants from National Natural Science Foundation of China (No. 30900793)a grant from Key Project from National Natural Science Foundation of China (No. 30930015) to P.S.+1 种基金West Light Foundation of the Chinese Academy of Sciences to H.Y.by a start-up fund of "Hundreds Talent Program" from Chinese Academy of Sciences
文摘Formyl peptide receptors (FPRs) were observed to expand in rodents and were recently suggested as candidate vomeronasal chemo-sensory receptors. Since vomeronasal chemosensory receptors usually underwent positive selection and evolved concordantly with the vomeronasal organ (VNO) morphology, we surveyed FPRs in primates in which VNO morphology is greatly diverse and thus it would provide us a clearer view of VNO-FPRs evolution. By screening available primate genome sequences, we obtained the FPR repertoires in representative primate species. As a result, we did not find FPR family size expansion in primates. Further analyses showed no evolution-ary force variance between primates with or without VNO structure, which indicated that there was no functional divergence among pri-mates FPRs. Our results suggest that primates lack the VNO-specific FPRs and the FPR expansion is not a common phenomenon in mammals outside rodent lineage, regardless of VNO complexity.
文摘Objective:Premature rupture of membranes(PROM)is a common pregnancy disorder that is closely associated with structural weakening of fetal membranes.Studies have found that formyl peptide receptor 1(FPR1)activates inflammatory pathways and amniotic epithelial-mesenchymal transition(EMT),stimulates collagen degradation,and leads to membrane weakening and membrane rupture.The purpose of this study was to investigate the anti-inflammatory and EMT inhibitory effects of FPR1 antagonist(BOC-MLF)to provide a basis for clinical prevention of PROM.Methods:The relationship between PROM,FPR1,and EMT was analyzed in human fetal membrane tissue and plasma samples using Western blotting,PCR,Masson staining,and ELISA assays.Lipopolysaccharide(LPS)was used to establish a fetal membrane inflammation model in pregnant rats,and BOC-MLF was used to treat the LPS rat model.We detected interleukin(IL)-6 in blood from the rat hearts to determine whether the inflammatory model was successful and whether the anti-inflammatory treatment was effective.We used electron microscopy to analyze the structure and collagen expression of rat fetal membrane.Results:Western blotting,PCR and Masson staining indicated that the expression of FPR1 was significantly increased,the expression of collagen was decreased,and EMT appeared in PROM.The rat model indicated that LPS caused the collapse of fetal membrane epithelial cells,increased intercellular gaps,and decreased collagen.BOC-MLF promoted an increase in fetal membrane collagen,inhibited EMT,and reduced the weakening of fetal membranes.Conclusion:The expression of FPR1 in the fetal membrane of PROM was significantly increased,and EMT of the amniotic membrane was obvious.BOC-MLF can treat inflammation and inhibit amniotic EMT.
基金supported by grants from the National Natural Science Foundation of China(31991193 and 32230025)the National Key R&D Program of China(2021YFA1101001).
文摘Carbohydrate metabolism disorders(CMDs),such as diabetes,galactosemia,and mannosidosis,cause ciliopathy-like multiorgan defects.However,the mechanistic link of cilia to CMD complications is still poorly understood.Herein,we describe significant cilium disassembly upon treatment of cells with pathologically relevant aldoses rather than the corresponding sugar alcohols.Moreover,environmental aldehydes are able to trigger cilium disassembly by the steric hindrance effect of their formyl groups.Mechanistic studies reveal that aldehydes stimulate extracellular calcium influx across the plasma membrane,which subsequently activates the calmodulin-Aurora A-histone deacetylase 6 pathway to deacetylate axonemal microtubules and triggers cilium disassembly.In vivo experiments further show that Hdac6 knockout mice are resistant to aldehyde-induced disassembly of tracheal cilia and sperm flagella.These findings reveal a previously unrecognized role for formyl group-mediated cilium disassembly in the complications of CMDs.
基金the State Key Laboratory of Pathogen and Biosecurity,No.SKLPBS2119 and SKLPBS2212the Medical Science Research Project of Dalian,No.2112015。
文摘BACKGROUND Formyl peptide receptor 2(Fpr2)is an important receptor in host resistance to bacterial infections.In previous studies,we found that the liver of Fpr2-/-mice is the most severely damaged target organ in bloodstream infections,although the reason for this is unclear.AIM To investigate the role of Fpr2 in liver homeostasis and host resistance to bacterial infections.METHODS Transcriptome sequencing was performed on the livers of Fpr2-/-and wild-type(WT)mice.Differentially expressed genes(DEGs)were identified in the Fpr2-/-and WT mice,and the biological functions of DEGs were analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Quantitative real time-polymerase chain reaction(qRT-PCR)and western blot(WB)analyses were used to further validate the expression levels of differential genes.Cell counting kit-8 assay was employed to investigate cell survival.The cell cycle detection kit was used to measure the distribution of cell cycles.The Luminex assay was used to analyze cytokine levels in the liver.The serum biochemical indices and the number of neutrophils in the liver were measured,and hepatic histopathological analysis was performed.RESULTS Compared with the WT group,445 DEGs,including 325 upregulated genes and 120 downregulated genes,were identified in the liver of Fpr2-/-mice.The enrichment analysis using GO and KEGG showed that these DEGs were mainly related to cell cycle.The qRT-PCR analysis confirmed that several key genes(CycA,CycB1,Cdc20,Cdc25c,and Cdk1)involved in the cell cycle had significant changes.The WB analysis confirmed a decrease in the expression of CDK1 protein.WRW4(an antagonist of Fpr2)could inhibit the proliferation of HepG2 cells in a concentration dependent manner,with an increase in the number of cells in the G0/G1 phase,and a decrease in the number of cells in the S phase.Serum alanine aminotransferase levels increased in Fpr2-/-mice.The Luminex assay measurements showed that interleukin(IL)-10 and chemokine(C-X-C motif)ligand(CXCL)-1
基金Project supported by the National Natural Science Foundation of China (No. 29472075)the Postdoctoral Science Foundation of China
文摘Preparation of twelve 1-methyl-2-formyl-5-substituted pyrroles (2a–1), with five of them as new compounds, is described. Their derivatives, i.e., 1-methyl-2-formyl-5-substituted pyrrole phenyl hydrazones (3a–1) and 1-methyl-2-formyl-5-substituted pyrrole (4-nitrophenyl) hydrazones (4a–1) are all new compounds. They have also been prepared and further identified.
基金supported by the National Natural Science Foundation of China(No.21371119,21431004,21401128,21522104,and 21620102001)the National Key Basic Research Program of China(No.2014CB932102 and 2016YFA0203400)the Shanghai“Eastern Scholar”Program
文摘Two metal-organic frameworks [(Zn0.5L)·(H2O)]n (1) and [(Ni0.5L)?(H2O)]n (2) constructed by the 3-formyl-4-(pyridin-4-yl) benzoic acid ligand (HL) were synthesized and characterized by single-crystal X-ray diffraction. 1 crystallizes in orthorhombic space group Pnna with a = 16.6152(8), b = 12.6825(6), c = 15.3908(8) A, V = 3243.2(3) ?3, Z = 4, Mr = 511.12, Dc = 1.047 g/cm3, F(000) = 1048, μ = 1.144 mm-1, GOOF = 1.061, the final R = 0.0471 and wR = 0.1262 for 12168 observed reflections with I 〉 2σ(I). 2 is isostructural to 1, which also crystallizes in orthorhombic space group Pnna with a = 16.6152(8), b = 12.6825(6), c = 15.3908(8) ?, V = 3243.2(3) ?3, Z = 4, Mr = 511.12, Dc = 1.047 g/cm3, F(000) = 1048, μ = 1.144 mm-1, GOOF = 1.061, the final R = 0.0471 and wR = 0.1262 for 12168 observed reflections with I 〉 2σ(I). Additionally, thermogravimetric analysis, FT-IR spectroscopy and powder X-ray diffraction were discussed.
基金Supported by National Natural Science Foundation of China(No.8120066481271050)
文摘AIM:To solidify the involvement of Saa-related pathway in corneal neovascularization(CorNV).The pathogenesis of inflammatory CorNV is not fully understood yet,and our previous study implicated that serum amyloid A(Saa)1(Saa1)and Saa3 were among the genes up-regulated upon CorNV induction in mice.METHODS:Microarray data obtained during our profiling project on CorNV were analyzed for the genes encoding the four SAA family members(Saa1-4),six reported SAA receptors(formyl peptide receptor 2,Tlr2,Tlr4,Cd36,Scarb1,P2rx7)and seven matrix metallopeptidases(Mmp)1a,1b,2,3,9,10,13reportedly to be expressed upon SAA pathway activation.The baseline expression or changes of interested genes were further confirmed in animals with CorNV using molecular or histological methods.CorNV was induced in Balb/c and C57BL/6 mice by placing either three interrupted 10-0 sutures or a 2 mm filter paper soaked with sodium hydroxide in the central area of the cornea.At desired time points,the corneas were harvested for histology examination or for extraction of mRNA and protein.The mRNA levels of Saa1,Saa3,Fpr2,Mmp2and Mmp3 in corneas were detected using quantitative reverse transcription-PCR,and SAA3 protein in tissues detected using immunohistochemistry or western blotting.RESULTS:Microarray data analysis revealed that Saa1,Saa3,Fpr2,Mmp2,Mmp3 messengers were readily detected in normal corneas and significantly upregulated upon CorNV induction.The changes of these five genes were confirmed with real-time PCR assay.Onthe contrary,other SAA members(Saa2,Saa4),other SAA receptors(Tlr2,Tlr4,Cd36,P2rx7,etc),or other Mmps(Mmp1a,Mmp1b,Mmp9,Mmp10,Mmp13)did not show consistent changes.Immunohistochemistry study and western blotting further confirmed the expression of SAA3 products in normal corneas as well as their upregulation in corneas with CorNV.CONCLUSION:SAA-FPR2 pathway composing genes were expressed in normal murine corneas and,upon inflammatory stimuli challenge to the corneas,their expressions were up-regulated,suggesting their roles in
基金Project supported by the National Natural Science Foundation of China and CAEP (Grant No 10676025), by the scientific project of Jiangxi education departments of China (Grant Nos 2006261 and 2006236), and by the Research Funds of College of Jinggangshan, China (Grant No JZ0616).
文摘In this paper the equilibrium structure of HCO has been optimized by using density functional theory (DFT)/ B3P86 method and CC-PVTZ basis. It has a bent (Cs, X^2A') ground state structure with an angle of 124.4095 °. The vibronic frequencies and force constants have also been calculated. Based on the principles of atomic and molecular reaction statics, the possible electronic states and reasonable dissociation limits for the ground state of HCO molecule have been determined. The analytic potential energy function of HCO (X^2A') molecule has been derived by using the many-body expansion theory. The contour lines are constructed, which show the static properties of HCO (X^2A'), such as the equilibrium structure, the lowest energies, etc. The potential energy surface of HCO (X^2A') is reasonable and very satisfactory.
文摘N-formyl peptide receptors(FPRs)were first identified upon phagocytic leukocytes,but more than four decades of research has unearthed a plethora of non-myeloid roles for this receptor family.FPRs are expressed within neuronal tissues and markedly in the central nervous system,where FPR interactions with endogenous ligands have been implicated in the pathophysiology of several neurodegenerative diseases including Alzheimer's disease and Parkinson's disease,as well as neurological cancers such as neuroblastoma.Whilst the homeostatic function of FPRs in the nervous system is currently undefined,a variety of novel physiological roles for this receptor family in the neuronal context have been posited in both human and animal settings.Rapid developments in recent years have implicated FPRs in the process of neurogenesis and neuronal differentiation which,upon greater characterisation,could represent a novel pharmacological target for neuronal regeneration therapies that may be used in the treatment of brain/spinal cord injury,stroke and neurodegeneration.This review aims to summarize the recent progress made to determine the physiological role of FPRs in a neuronal setting,and to put forward a case for FPRs as a novel pharmacological target for conditions of the nervous system,and for their potential to open the door to novel neuronal regeneration therapies.
基金supported by National Natural Science Foundation of China(31470856 to RDY)the Science and Technology Development Fund of Macao(FDCT 072/2015/A2)the University of Macao(SRG2015-00047-ICMS-QRCM)
文摘OBJECTIVE To identify the mechanisms by which the formyl peptide receptor 2(FPR2)mediates both inflammatory and anti-inflammatory signaling in an agonist-dependent manner.METHODS Cells expressing FPR2 were incubated with weak agonists,Aβ42 and Ac2-26,before stimulation with a strong agonist,WKYMVm.Calcium mobilization,c AMP inhibition and MAP kinase activation were measured.Intramolecular FRET were determined using FPR2 constructs with an ECFP attached to the C-terminus and a Fl As H binding motif embedded in the first or third intracellular loop(IL1 or IL3,respectively).RESULTS Aβ42 did not induce significant Ca^(2+) mobilization,but positively modulated WKYMVm-induced Ca^(2+) mobilization and c AMP reduction in a dose-variable manner within a narrow range of ligand concentrations.Treating FPR2-expressing cells with Ac2-26,a peptide with anti-inflammatory activity,negatively modulated WKYMVm-induced Ca^(2+) mobilization and c AMP reduction.Intramolecular FRET assay showed that stimulation of the receptor constructs with Aβ42 brought the C-terminal domain closer to IL1 but away from IL3.An opposite conformational change was induced by Ac2-26.The FPR2 conformation induced by Aβ42 corresponded to enhanced ERK phosphorylation and attenuated p38 MAPK phosphorylation,whereas Ac2-26 induced FPR2 conformational change corresponding to elevated p38 MAPK phosphorylation and reduced ERK phosphorylation.CONCLUSION Aβ42 and Ac2-26 induce different conformational changes in FPR2.These findings provide a structural basis for FPR2 mediation of inflammatory vs anti-inflammatory functions and identify a type of receptor modulation that differs from the classic positive and negative allosteric modulation.
基金Project supported by the JSPS and NSF Japan-US Cooperative Science Program (1989-1990)the National Natural Science Foundation of China.
文摘The bimetallic Ru-M (M=Co,Fe,Ni,Mo, Rh,Cr, Mn) catalysts were prepared from SiO_2-supported bimetallic carbonyl clusters, and it was found that the Ru-Co, Ru-Fe and Ru-Mo bimetallic carbonyl cluster-derived catalysts showed higher activity and selectivity for oxygenates such as C_1-C_5 alcohols in CO hydrogenation,in contrast to catalysts prepared from SiO_2-supported homometallic Ru and Co carbonyl clusters. In situ FT-IR studies revealed that the bands at 1584 and 1555 cm^(-1) species were intermediates to produce methanol and higher oxygenates,and at higher temperatures the 1584 cm^(-1) species could react with alkyl to form 1555 cm^(-1) species. By the surface chemical reaction and the IR study of isotopic molecules,it was suggested that 1584 and 1555 cm^(-1) were assigned to surface formyl and acetyl species.
基金This project was supported by the National Natural Science Foundation of China.
文摘A series of novel polyphosphonates containing 5-flouro- N1-furanyl-N3- glyceroalkyl-uracil and formyl groups was synthesized by the condensation of 3-(w- (1-furanyl-5-flourouracil-3-yl) alkoxy)-1, 2-dihydroxy propane with phosphonyl dichloride. The products were characterized by IR, 1H NMR, 31P NMR, M, and elemental analysis. The results of bioassay show that compound 8a possesses potential anticancer activity.
文摘Although many aroma components have been identified in green tea leaves, the aroma compounds contributing to green tea's characteristic odor have not yet been reported. The authors recently reported that aroma components with a matcha-like odor are present in both green tea and black tea prepared from the Sayamakaori tea cuttivar. This matcha-like odor is similar to the odor of commercial available matcha (high-quality powdered green tea), and is a specific odor feature of green tea leaves. At present, the green-tea odor is thought to arise from the combination of a large number of constituents. Recent reports indicate that a complex interaction between olfactory receptors and odorants is important for the evaluation of the odors. Taking into consideration these findings, the authors investigated the aroma profile of green tea, focusing on the characteristic molecular structures of the constituents that give matcha-like odor. Using a combination of organic synthesis and gas chromatography-mass spectrometry plus gas chromatography-olfactometry, the authors identified aroma components with matcha-like odors in five other tea cultivars. This investigation also revealed that several compounds with a formyl group were important constituents of the aroma of green tea leaves, although the odor of each constituent was not individually similar to the tea's overall aroma. The authors found for the first time a group of key components that have the matcha-like odor.
文摘A highly sensitive HPLC method for the detection of amino acids and oligopeptides with 9-acridine formyl chloride by pre-column fluorescence derivatization has been developed. Glycine, glycylglycine, histidine, triglycine and glutathione were separated on a reversed-phase C-18 column with methanol-water-triethylamine eluent, derivatization and chromatographic conditions were optimized. The five derivatives were eluted in 28 min with a good reproducibility. Linear range of the calibration graph was 0.08-260 nmol/ml(-1). The relative standard deviations(n=6) are < 5%. Detection limits (signal-to-noise ratio=3) for the five derivatives are 20-40 fmol.
文摘The mechanisms and kinetics of the gas phase reactions that the hydrogen atom in formyl fluoride (FCHO) abstracted by OH in the presence of water, formic acid (FA), or sulfuric acid (SA) are theoretically investigated at the CCSD(T)/6-311++G(3df, 3pd)//MO6-2X/6- 311++G(3df, 3pd) level of theory. The calculated results show that the barriers of the transition states involving catalysts are lowered to -2.89, -6.25, and -7.76 kcal/mol from 3.64 kcal/mol with respect to the separate reactants, respectively, which reflects that those catalysts play an important role in reducing the barrier of the hydrogen abstraction reaction of FCHO with OH. Additionally, using conventional transition state theory with Eckart tun- neling correction, the kinetic data demonstrate that the entrance channel X…FCHO+OH (X=H2O, FA, or SA) is significantly more favorable than the pathway X…OH+FCHO. More- over, the rate constants of the reactions of FCHO with OH radical with H2O, FA, or SA introduced are computed to be smaller than that of the naked OH+FCHO reaction because the concentration of the formed X…FCHO or X…OH complex is quite low in the atmosphere.
文摘We compute the thermodynamic and the kinetic properties for the reaction: HCOCN→HCH+CO using the statistical theory and the transition-state theory.The equi- librium constants and the rate coefficients of this reaction are also reported here,and the half lives of formyl cyanide at different temperatures are first estimated in this work.