Transcriptomic and metabolomic insights into the role of the flgK gene in the pathogenicity of Pseudomonas plecoglossicida to orange-spotted grouper(Epinephelus coioides)

Pseudomonas plecoglossicida is the pathogen responsible for visceral white spot disease in large yellow croaker(Larimichthys crocea)and orangespotted grouper(Epinephelus coioides).Previously,RNA sequencing showed that P.plecoglossicida flgK gene expression was significantly up-regulated in orange-spotted grouper spleens during infection.To explore the role of flgK in P.plecoglossicida pathogenicity,RNA interference(RNAi)was performed to silence the P.plecoglossicida flgK gene,and the mutant(flgK-RNAi strain)with the best silencing efficiency(89.40%)was chosen for further study.Results showed that flgK gene silencing significantly attenuated P.plecoglossicida motility,adhesion,and biofilm formation.Compared to those fish infected with the wild-type strain of P.plecoglossicida,orange-spotted grouper infected with the flgK-RNAi strain showed a 55%increase in the survival rate and a one-day delay in time of first death,with fewer pathogens in the spleen and fewer white spots on the spleen surface.RNAi of flgK significantly affected the transcriptome and metabolome of the spleen in infected orange-spotted grouper.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis showed that the C-type lectin receptor signaling pathway was the most significantly changed immune-related pathway and the mitogen-activated protein kinase(MAPK)signaling pathway was related to multiple immunerelated pathways.Furthermore,arginine biosynthesis and glycerophospholipid metabolism were the most significantly changed metabolism-related pathways.These findings suggest that flgK is a virulence gene of P.plecoglossicida.Furthermore,flgK appears to be involved in the regulation of motility,adhesion,and biofilm formation in P.plecoglossicida,as well as in the regulation of inflammatory and immune responses of orange-spotted grouper to P.plecoglossicida infection.

The active ingredients of Huanglian Jiedu Decoction in treating COVID- 19 based on network pharmacology, molecular docking and molecular dynamics simulation

Objective:To explore the active ingredients of Huanglian Jiedu Decoction(HLJD)for the treatment of COVID-19 and to further verify the combination mode.Methods:The TCMSP database was used to search for HLJD active ingredients and targets.COVID-19 targets were collected from GeneCards,DisGeNET and OMIM databases.Material-active-ingredients-targets(gene)network and targets protein-protein interaction network were constructed using Cytoscape 3.8.0 and the STRING database.GO functional enrichment analysis and KEGG pathway enrichment analysis of core targets were performed using R software.Cytoscape 3.8.0 was used to build“compound-targets-pathways”to predict HLJD mechanisms,and active ingredients were used as ligands to molecularly dock with SARS-CoV-23CL hydrolase,Spike glycoprotein and ACE2.The binding energy was calculated by molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area method,and intermolecular interactions and the contribution of each residue to the binding free energy were analyzed.Results:Four medicinal materials,66 compounds and 219 targets were identified.It is found that the Protein-Protein Interaction core network contained 35 HLJD key targets proteins for COVID-19 treatment.705 GO functional enrichment entries(P<0.05)were produced;while KEGG pathway enrichment analysis identified 142 pathways(P<0.05)involving the Tumor Necrosis Factor signaling pathway and Interleukin-17 signaling pathway,etc.The binding energies of Kihadanin A,Palmidin A,Obacunone and Hispidone are much smaller than those of the currently reported clinical drugs with anti-SARS-CoV-2 drugs.The results of the binding energy indicate that van der Waals force is the main driving force for enzyme-substrate combination,whereas the electrostatic interaction and non-polar solvents contribute less.Conclusion:The“multi-component-multi-targets-multi-pathway”synergy of HLJD,which binds to SARSCoV-23CL hydrolase,Spike glycoprotein and ACE2,can act on targets Heat Shock Protein 90 Alpha Family Class A Member 1,Adrenoceptor Beta 2,Checkpoint Kinase 1,Peroxisome Proliferator-Activated Receptor Gamma and Mitogen-activated protein kinase 14 to regulate multiple signal pathways,and it may have a therapeutic effect on COVID-19.

The immunoreactivity of Cra a 4 decreased after Maillard reaction with xylose and glucose

Cra a 4 is a heat stable allergen in oyster,the effect of Maillard reaction on the immunoreactivity and structure of Cra a 4 was investigated.Firstly,Cra a 4 was cloned,expressed and identified.The purified Cra a 4 was incubated with xylose at 100℃,pH 8.5 for 30 min or with glucose for 60 min.After Maillard reaction,the IgE-binding activity of Cra a 4 and in vitro digested samples was reduced by about 50%.The unfoldα-helix and higher surface hydrophobicity of glycated Cra a 4 were identified as the reason for hypo-immunoreactivity.The higher frequency of lysine(13%)in the primary structure and exposure on the surface of the spatial structure was attributed to the hypo-immunoreactivity of Cra a 4 after Maillard reaction.It comprehensively evaluated the effects of Maillard reaction on Cra a 4 and provids new methods for the industrial production of hypoallergenic oyster.The modified Cra a 4 by Maillard reaction could be a hypoallergenic therapeutic agent for allergy to oyster.

Cesium lead halide perovskite nanocrystals for ultraviolet and blue light blocking

Using cesium lead halide perovskite nanocrystals, CsPb(Cl/Br)3, as a light absorber, we report a highly effective UV and blue light blocking film. The CsPb(Cl/Br)3 nanocrystals are well dispersed in the ethyl cellulose(EC) matrix to compose a UV and blue light shielding film, and the absorption edge of the film is tunable by adjusting Cl to Br ratio using anion exchange. The CsPbCl2 Br-EC film exhibits a transmittance of 5% at 459 nm, 90% at 478 nm and 95% in the range of 500–800 nm, which makes it excellent for UV and blue light shielding. In addition, the as-prepared EC-CsPb(Cl/Br)3 film shows excellent photostability under UV irradiation. Results demonstrate that this EC-CsPb(Cl/Br)3 based materials with sharp absorbance edges, tunable blocking wavelength, and high photostability can be useful for the applications in UV and blue light blocking and optical filters.

Study of the effect of chemical composition on the surface wettability of three-dimensional graphene foams

The chemical composition obviously affects the surface wettability of a three-dimensional(3D)graphene material apart from its surface energy and microstructure.In the hydrothermal preparation,the heteroatom doping changes the chemical composition and wettability of the 3D graphene material.To realize the controllable surface wettability of graphene materials,aminobenzene sulfonic acid(ABSA)was selected as a typical doping agent for the preparation of nitrogen and sulfur co-doped 3D graphene foam(SNGF)using a hydrothermal method.Different from using o-ABSA or p-ABSA as the dopant,SNGF with tunable surface wettability is obtained only when m-ABSA is used.This result indicates that the substituent position of-SO3H group in the benzene ring of ABSA is rather important for the tunable wettability.This work provides some theo retical foundations for dopant selection and some new insights in manipulating the properties of 3D graphene foams by adjusting the configuration of dopants.

Construction of diaminobenzoquinone imines via ferrocene-initiated radical reaction of benzoquinone with amines

A ferrocene-initiated radical reaction of benzoquinone with amines has been successfully developed for the direct access to diaminobenzoquinone imines in high yields,in which the comme rcially available and cheap ferrocene was employed as a radical initiator and TBHP was used as an oxidant.Moreover,this reaction could be achieved with low loading of ferrocene(0.5 mol%).This protocol is highly efficient with good substrate tolera nce and provides a new approach for the construction of benzoquinone imines with potential pharmaceutical interest.

Ir-catalyzed regiospecific mono-sulfamidation of arylquinazolinones

An Ir-catalyzed selective mono-sulfamidation of 2-arylquinazolinones has been achieved with a low catalyst loading under mild conditions.A series of regioselective mono-sulfamided 2-arylquinazolinones were obtained in up to 90%yields.Compared with our previous work of constructing di-sulfamidated 2-arylquinazolinones,the mono-sulfamided products could be obtained selectively by changing the ratio of substrates,the loading of catalyst,acid additive,and reaction time.