FPR1 Antagonist (BOC-MLF) Inhibits Amniotic Epithelial-mesenchymal Transition

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.

Transcriptome sequencing and experiments reveal the effect of formyl peptide receptor 2 on liver homeostasis

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 levels were significantly reduced in the liver of Fpr2-/-mice.There was no difference in the number of neutrophils,serum C-reactive protein levels,and liver pathology between WT and Fpr2-/-mice.CONCLUSION Fpr2 participates in the regulation of cell cycle and cell proliferation,and affects the expression of IL-10 and CXCL-1,thus playing an important protective role in maintaining liver homeostasis.

Synthesis of Novel Bis-enaminones by KHSO4-assisted Facile Michael Addition-elimination Reaction of 3-(dimethylamino)-1-phenylprop-2-en-1-ones with Diamines in Water

3-(Dimethylamino)-1-phenylprop-2-en-1-ones (formylated acetophenones) 1 reacted with aliphatic diamines in water assisted by KHSO4 to give bis-enaminones 2a-h in good yields. Compound 1 also reacted with o-phenylenediamine under similar conditions to produce bis-enaminones 3 instead of benzodiazepines 4 in excellent yields.

Theoretical Study on Gas Phase Reactions of OH Hydrogen-Abstraction from Formyl Fluoride with Different Catalysts

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.

Amine formylation with CO2 and H2 catalyzed by heterogeneous Pd/PAL catalyst

For the first time, Pd supported on natural palygorskite was developed for amine formylation with CO2 and H2. Both secondary and primary amines with diverse structures could be converted into the desired formamides at < 100 °C, and good to excellent yields were obtained.

Zinc phthalocyanine as an efficient catalyst for halogen-free synthesis of formamides from amines via carbon dioxide hydrosilylation under mild conditions

The combination of a zinc phthalocyanine(ZnPc)catalyst and a stoichiometric amount of dimethyl formamide(DMF)provided a simple route to formamide derivatives from amines,CO2,and hydrosilanes under mild conditions.We deduced that formation of an active zinc‐hydrogen(Zn‐H)species promoted hydride transfer from the hydrosilane to CO2.The cooperative activation of the Lewis acidic ZnPc by strongly polar DMF,led to formation of activated amines and hydrosilanes,which promoted the chemical reduction of CO2.Consequently,the binary ZnPc/DMF catalytic system showed excellent yields and superior chemoselectivity,representing a simple and sustainable pathway for the reductive transformation of CO2into valuable chemicals as an alternative to conventional halogen‐containing process.

无溶剂中性条件下分子I_2或Fe(NO_3)_3·9H_2O/NaI原位生成的I_2催化醇与甲酸甲酰化反应(英文)

Different alcohols were formylated by formic acid under solvent-free conditions in the presence of iodine as the catalyst with good-to-high yields at room temperature.I2 generated in situ from Fe(NO3)3·9H2O/NaI also catalyzed the formylation of the alcohols under solvent-free conditions.This gives a green and efficient reaction at room temperature,in which the use of toxic and corrosive molecular I2 is avoided.

Serum amyloid A and pairing formyl peptide receptor 2 are expressed in corneas and involved in inflammation-mediated neovascularization

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 pathogenesis of CorNV.The potential usefulness of SAA-FPR2 targets in future management of CorNVrelated diseases deserves investigation.

Syntheses and Structures of Two Metal-organic Frameworks Constructed from Zn/Ni and 3-Formyl-4-(pyridin-4-yl)Benzoic Acid Ligand

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.

The molecular structure and analytical potential energy function of HCO （X^2A＇）

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.

Rational design and precise manipulation of nano‐catalysts

Nano‐catalysis plays a vital role in the chemical transformations and significantly impacts the booming modern chemical industry.The rapid technological enhancements have resulted in serious energy and environmental issues,which are currently spurring the exploration of the novel nano‐catalysts in diverse fields.In order to develop the efficient nano‐catalysts,it is essential to understand their fundamental physicochemical properties,including the coordination structures of the active centers and substrate‐adsorbate interactions.Subsequently,the nano‐catalyst design with precise manipulation at the atomic level can be attained.In this account,we have summarized our extensive investigation of the factors impacting nano‐catalysis,along with the synthetic strategies developed to prepare the nano‐catalysts for applications in electrocatalysis,photocatalysis and thermocatalysis.Finally,a brief conclusion and future research directions on nano‐catalysis have also been presented.

Investigation of the Aroma Profile of Green Tea Leaves Using Organic Synthesis and Conventional Analytical Techniques

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.

The N-formyl peptide receptors: contemporary roles in neuronal function and dysfunction

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.

Formylation of N-arylpyrazole containing active amino group using Vilsmeier-Haack reaction

Two species of N-arylpyrazoles containing active amino group were synthesized.And formylations of N-arylpyazoles containing amino in different position of pyrazole rings using Vilsmeier-Haack reaction gave a series of useful pyrazole intermediates.The important features of this protocol were cheap materials,easy process,mild reaction conditions and good yield of products.

Synthesis of Polyphosphonates Containing 5-Flouro-N^1-furanyl-N^3-glyceroalkyl-uracil and Formyl Groups

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.

Synthesis and Crystal Structure of 5,17-Diformyl-11,23-di(tert-butyl)25,26,27,28-tetrapropoxy-calix[4]arene

The title compound 5,17-diformyl-11,23-di（tert-butyl）-25,26,27,28-tetrapropoxycalix[4]arene has been synthesized by selective formylation of 5,11,17,23-tetra（tert-butyl）25,26,27,28-tetrahydroxycalix[4]arene in three steps and characterized by1H NMR and X-ray single-crystal diffraction.The crystal belongs to the monoclinic system,space group C2/c with a = 25.760（3）,b = 10.9952（10）,c = 18.630（2）,β = 119.985（4）°,V = 4570.4（9）3,Z = 4,Dc = 1.106 g/cm3,Mr = 761.01,F（000） = 1648,μ = 0.071 mm-1,MoKa radiation（λ = 0.71073）,R = 0.0710 and wR = 0.2411 for 3234 observed reflections with I 2σ（I）.X-ray analysis reveals that the title compound adopts a pinched cone conformation which leads to an open cavity.Intermolecular C–H O weak interactions link the molecules along the bc plane,which are effective in the stabilization of the crystal structure.

A THEORETICAL STUDY OF THE THERMODYNAMIC AND KINETIC PROPERTIES FOR THE REACTION OF FORMYL CYANIDE DECOMPOSITION

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.

Theoretically Catalytic Synthesis of 5-Nitro-1,2,4-Triazol-3-One in Inert Gas Clustered System (X₆, X = He, Ne)

Inert gas-clustered systems (Xn, X = He, Ne, Ar and n = 2 - 20) were established in this study and their stability as a result of interparticulate interaction was examined. Ferric chloride and ferrous oxides were used as catalysts to promote reaction, and 5-nitro-1,2,4-triazol-3-one (NTO) was theoretically synthesized under an inert gas (X6)-clustered environment in this study. The raw material, urea, initially underwent chlorination using chlorine as the reagent, followed by amination, formylation and nitration. Reaction routes closely related to the experimental processes were successfully constructed, and the corresponding energy barriers were estimated for each elementary reaction. The findings revealed that the average errors in the B3LYP/6-31G(d, p)-calculated geometry and vibrational frequency of NTO in an Ne6 system relative to the observed values were 0.83% and 1.84%, respectively. The neon gas-clustered system achieved greater stabilization, which results from the difference in self-consistent field energy (ESCF), than the corresponding stabilization acquired in a helium- or argon-based system. Ferric chloride serves as a good catalyst to reduce the energy barrier of the chlorination reaction, and ferrous oxide is suitable for catalyzing the amination, formylation and nitration reactions, although nitric acid is the better agent for nitration. The catalytic Ne6-clustered reaction system is suggested to be a more feasible pathway for the synthesis of NTO.

Functionally diverse ligands modulate different activation states of the formyl peptide receptor 2,a G protein-coupled receptor

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.

Preparation of Single Substituted Phenyl Porphyrins Form <i>Meso</i>-Tetraphenyl Porphyrin-Synthetic Example from Symmetric Porphyrin into Asymmetric Porphyrins

Two asymmetric porphyrins, 5-(4-chloromethylphenyl)-10, 15, 20-triphenyl porphyrin and 5-(4-formylphenyl)-10, 15, 20-triphenyl porphyrin, were successfully prepared by the symmetric meso-tetraphenyl porphyrin and relative molecular configurations and properties were characterized by spectral determinations. This work presented an example for synthesis of asymmetric porphyrin derivatives from the symmetric porphyrin. Both asymmetric porphyrins are reactive in molecular assembly, the concerned reactions including alkylation with Grignard reagents, etherification with alcohols, aldol condensation and Mannich reaction for modification and enhancing their functionality. In this work, the reaction conditions were improved, synthetic strategy and route were confirmed.