Verticillium wilt(VW),induced by the soil-borne fungus Verticillium dahliae(Vd),poses a substantial threat to a diverse array of plant species.Employing molecular breeding technology for the development of cotton vari...Verticillium wilt(VW),induced by the soil-borne fungus Verticillium dahliae(Vd),poses a substantial threat to a diverse array of plant species.Employing molecular breeding technology for the development of cotton varieties with heightened resistance to VW stands out as one of the most efficacious protective measures.In this study,we successfully generated two stable transgenic lines of cotton(Gossypium hirsutum L.),VdThitRNAi-1 and VdThit-RNAi-2,using host-induced gene silencing(HIGS)technology to introduce double-stranded RNA(dsRNA)targeting the thiamine transporter protein gene(VdThit).Southern blot analysis confirmed the presence of a single-copy insertion in each line.Microscopic examination showed marked reductions in the colonization and spread of Vd-mCherry in the roots of VdThit-RNAi cotton compared to wild type(WT).The corresponding disease index and fungal biomass of VdThit-RNAi-1/2 also exhibited significant reductions.Real-time quantitative PCR(qRT-PCR)analysis demonstrated a substantial inhibition of VdThit expression following prolonged inoculation of VdThit-RNAi cotton.Small RNA sequencing(sRNA-Seq)analysis revealed the generation of a substantial number of VdThit-specific siRNAs in the VdThit-RNAi transgenic lines.Additionally,the silencing of VdThit by the siVdThit produced by VdThit-RNAi-1/2 resulted in the elevated expression of multiple genes involved in the thiamine biosynthesis pathway in Vd.Under field conditions,VdThit-RNAi transgenic cotton exhibited significantly enhanced disease resistance and yield compared with WT.In summary,our findings underscore the efficacy of HIGS targeting VdThit in restraining the infection and spread of Vd in cotton,thereby potentially enabling the development of cotton breeding as a promising strategy for managing VW.展开更多
Bordetella bronchiseptica(Bb)is recognized as a leading cause of respiratory diseases in dogs and cats.However,epidemiological data on Bb in dogs and cats in China are still limited,and there is no commercially availa...Bordetella bronchiseptica(Bb)is recognized as a leading cause of respiratory diseases in dogs and cats.However,epidemiological data on Bb in dogs and cats in China are still limited,and there is no commercially available vaccine.Live vaccines containing Bb that are widely used abroad are generally efective but can establish latency and potentially reactivate to cause illness in some immunodefcient vaccinated recipients,raising safety concerns.In this study,34 canine-derived and two feline-derived Bb strains were isolated from 1809 canine and 113 feline nasopharyngeal swab samples collected from eight provinces in China from 2021 to 2023.The PCR results showed that the percentage of positive Bb was 22.94%(441/1922),and more than 90%of the Bb isolates had four virulence factor-encoding genes(VFGs),namely,fhaB,prn,betA and dnt.All the isolated strains displayed a multidrug-resistant phenotype.The virulence of 10 Bb strains isolated from dogs with respiratory symptoms was tested in mice,and we found that eight isolates were highly virulent.Furthermore,the eight Bb isolates with high virulence were inactivated and intramuscularly injected into mice,and three Bb strains(WH1218,WH1203 and WH1224)with the best protective efcacy were selected.Dogs immunized with these three strains exhibited strong protection against challenge with the Bb feld strain WH1218.Ultimately,the WH1218 strain with the greatest protection in dogs was selected as the vaccine candidate.Dogs and cats that received a vaccine containing 109 CFU of the inactivated WH1218 strain showed complete protection against challenge with the Bb feld strain WH1218.This study revealed that Bb is an important pathogen that causes respiratory diseases in domestic dogs and cats in China,and all the isolates exhibited multidrug resistance.The present work contributes to the current understanding of the prevalence,antimicrobial resistance,and virulence genes of Bb in domestic dogs and cats.Additionally,our results suggest that the WH1218 strain is a promising candidate safe and efcacious inactivated Bb vaccine.展开更多
Brucellosis remains one of the most common zoonoses spread worldwide,inducing enormous economic losses to the livestock industry and posing serious health threats to humans.Brucellosis re-emerged in China in the mid-1...Brucellosis remains one of the most common zoonoses spread worldwide,inducing enormous economic losses to the livestock industry and posing serious health threats to humans.Brucellosis re-emerged in China in the mid-1990s and reached a historically high level in 2015.The National Brucellosis Prevention and Control Plan(NBPCP)was initiated from 2016 to 2020.However,the present epidemiological status in livestock has not been elucidated,and whether Brucella variation occurred remains unclear.This study performed an extensive serological investigation in ruminant livestock from 2019 to 2021 in central Gansu Province,China.In total,11,296 samples from 337 farms were collected to detect the specific antibodies of Brucella.The yearly average serological prevalence of Brucella at the flock level and individual level declined from 11.32%to 8.26%and 1.17%to 0.57%,respectively.The apparent individuallevel seroprevalence of small and large ruminants was 0.89%and 0.52%,respectively.The brucellosis distribution has shifted from pastoral areas to agro-pastoral areas.Flock size and gender may be major risks of Brucella infection.Then,the B.melitensis TZ strain was isolated from female Tibetan sheep blood cell lysates.Phonotypical characterization demonstrated that it belongs to B.melitensis.biovar 3,and multilocus sequencing typing results indicated that it belongs to ST8.The whole genome and subsequent phylogenetic analysis demonstrated that the B.melitensis TZ strain is genetically more closely related to the B.melitensis QH61 strain.The B.melitensis TZ strain has similar growth characteristics to the B.melitensis 16 M strain.Overall,our study suggests that after strengthening control and prevention measures based on the NBPCP,there is a very low prevalence or absence of B.melitensis in the central Gansu Province of China,and the genotype of an epidemic strain of Brucella in Northwest China is relatively stable.展开更多
Feline panleukopenia virus(FPV)is a single-stranded DNA virus that can infect cats and cause feline panleukopenia,which is a highly contagious and fatal disease in felines.The sequence of FPV is highly variable,and mu...Feline panleukopenia virus(FPV)is a single-stranded DNA virus that can infect cats and cause feline panleukopenia,which is a highly contagious and fatal disease in felines.The sequence of FPV is highly variable,and mutations in the amino acids of its capsid protein play crucial roles in altering viral virulence,immunogenicity,host selection,and other abilities.In this study,the epidemiology of FPV was studied using 746 gastrointestinal swab samples derived from cats that presented gastrointestinal symptoms specifcally,diarrhea or vomiting during the period spanning from 2018 to 2022.The overall prevalence of FPV-positive patients among these samples was determined to be 45.4%.Capsid(virion)protein 2(VP2)gene of each FPV-positive sample was sequenced and amplifed,yielding 65 VP2 sequences.Among them,six VP2 gene sequences were detected in the majority of the samples test positive for FPV,and these positive samples originated from a diverse range of geographical locations.These isolates were named FPV-6,FPV-10,FPV-15,FPV-251,FPV-271 and FPV-S2.Additionally,the substitution of Ala300Pro(A300P)in VP2 was detected for the frst time in feline-derived FPV(FPV-251).FPV-251 isolate,with this substitution in VP2 protein,exhibited stable proliferative capacity in Madin-Darby canine kidney(MDCK)cells and A72 cells.FPV-271 was selected as the FPV control isolate due to its single amino acid diference from VP2 protein of FPV-251 at position 300(FPV-271 has alanine,while FPV-251 has proline).After oral infection,both FPV-251 and FPV-271 isolates caused feline panleukopenia,which is characterized by clinical signs of enterocolitis.However,FPV-251 can infect dogs through the oral route and cause gastrointestinal(GI)symptoms with lesions in the intestine and mesenteric lymph nodes(MLNs)of infected dogs.This is the frst report on the presence of an A300P substitution in VP2 protein of feline-derived FPV.Additionally,FPV isolate with a substitution of A300P at VP2 protein demonstrated efcient replication capabilities in canine cell lines and the ability to infect dogs.展开更多
Despite the initial successes of the Bacillus Calmette-Guerin(BCG)vaccine in children,its efficacy against tuberculosis is highly variable.There is a lack of understanding about how mental conditions influence BCG vac...Despite the initial successes of the Bacillus Calmette-Guerin(BCG)vaccine in children,its efficacy against tuberculosis is highly variable.There is a lack of understanding about how mental conditions influence BCG vaccination.Here,we used the chronic social defeat stress(CSDS)model to explore the effects of depression on BCG vaccination efficacy.We observed higher lung and spleen bacterial loads and a lower organ index in depressed compared to BCG mice.Meanwhile,a relatively lower T cell protective efficacy was observed in both compared to control and BCG mice via a mycobacterium growth inhibition assay(MGIA).Cytokine expression of IL-12p40,IL-1β,IL-17,TNF-αand IFN-γwas reduced,whereas the expression of IL-10 and IL-5 was increased in the spleen of both compared to BCG mice.Moreover,the proportions of CD4^(+)IFN-γ^(+),CD8^(+)IFN-γ^(+)T lymphocytes and CD4^(+)effector/central memory T cells were reduced in the splenocytes of the depressed BCG mice.Depression promotes CD4^(+)regulatory T cells(Treg)and myeloid-derived suppressor cell(MDSC)generation in depressed mice,contributing to the reduced pro-inflammatory immune response upon BCG vaccination.This study provides insight into the decreased protective immunity by BCG vaccination attributable to depression in mice.展开更多
A simple, fast and reliable method was developed for the analysis of jinggangmycin A （validamycin A） in commercial formulations. The running buffer used was acetate buffer （100 mmol/L, pH 4.7） with 15 kV as the ap...A simple, fast and reliable method was developed for the analysis of jinggangmycin A （validamycin A） in commercial formulations. The running buffer used was acetate buffer （100 mmol/L, pH 4.7） with 15 kV as the applied voltage. The detection was achieved by using direct UV mode at 200 nm and the detection limit was 0.2 μg/mL. Linearity in the concentration range of 5-500 μg/mL was excellent （RE 〉 0.999）. The run-to-run repeatability （n = 3）, as expressed by the relative standard deviation （RSD） for migration times and peak areas were less than 0.5% and 3.0% respectively. The mean recovery ranged from 97.2% to 101.4%.展开更多
This study presents the cloning and expression of gene encoding transferrin-binding protein A from Actinobacillus pleuropneurnoniae in Escherichia coli expression system and the development of an indirect TbpA-ELISA. ...This study presents the cloning and expression of gene encoding transferrin-binding protein A from Actinobacillus pleuropneurnoniae in Escherichia coli expression system and the development of an indirect TbpA-ELISA. The gene coding TbpA was amplified from the A. pleuropneumoniae serotype 2 genome using polymerase chain reaction and cloned to pET-28b expression vector under the control of strong, inducible T7 promoter. The recombinant plasmid was expressed in E. coli BL21 （DE3）. The expressed fusion protein was analyzed using SDS-PAGE and Western blotting. The diagnostic potential of recombinant TbpA （rTbpA） was evaluated through an antibody-detection indirect ELISA based on the purified rTbpA. The TbpA antibodies were detectable in mice on day 7 after vaccination with purified rTbpA protein or infection with A. pleuropneumoniae serotype 10 with the TbpA-based ELISA. In addition, the TbpA-ELISA was able to detect 12 serotyping rabbit antisera postinoculation （PI） with A. pleuropneumoniae 12 serotypes experimentally. The comparable result was obtained by detecting the 117 clinical serum samples using, respectively, the TbpA-ELISA and indirect hemagglutination test （IHA） based on multiplex antigen. The result indicates that the TbpA-ELISA was the more sensitive method compared with the Mix-IHA method because of its consistent presence in A. pleuropneumoniae serotypes. In conclusion, the conserved TbpA of A. pleuropneumoniae can be used for the development of a cross-serotype diagnostic method for the detection of antibodies against A. pleuropneurnoniae.展开更多
[Objective] To develop a new method for serodiagnosis of swine toxoplasmosis. [Method] With the purified recombinant microneme protein 3 （rMIC3） as coating antigens, an indirect ELISA was developed for detection of ...[Objective] To develop a new method for serodiagnosis of swine toxoplasmosis. [Method] With the purified recombinant microneme protein 3 （rMIC3） as coating antigens, an indirect ELISA was developed for detection of antibodies against Toxoplasma gondii. [ Result] The optimal working concentration of rMIC3 was 3. 40 ug/ml, and the optimal degree of dilution of sera was 1：160. Cross-reaction was not observed between the Toxoplasma gondii-positive sera and the positive sera against classical swine fever virus or some other pathogens. The developed ELISA had 92.56% coincidence rate with latex agglutination test. [ Conclusion] The developed ELISA is sensitive, rapid, specific and reproducible, and thus it can be applied in serodiagnosis and seroprevalence investigation of swine toxoplasmosis.展开更多
Herbicide-based weeds control impacts wheat crops as well.SynComs of Pseudomonas strains reduce the need for high-dose herbicides.100%Axial provides less weed control compared to 75%Axial with C4 SynCom.Axial 75%with ...Herbicide-based weeds control impacts wheat crops as well.SynComs of Pseudomonas strains reduce the need for high-dose herbicides.100%Axial provides less weed control compared to 75%Axial with C4 SynCom.Axial 75%with C4 SynCom promotes wheat growth than the 75%Axial alone.展开更多
Aeriscardovia aeriphila,also known as Bifidobacterium aerophilum,was first isolated from the caecal contents of pigs and the faeces of cotton-top tamarin.Bifidobacterium species play important roles in preventing inte...Aeriscardovia aeriphila,also known as Bifidobacterium aerophilum,was first isolated from the caecal contents of pigs and the faeces of cotton-top tamarin.Bifidobacterium species play important roles in preventing intestinal infections,decreasing cholesterol levels,and stimulating the immune system.In this study,we isolated a strain of bacteria from the duodenal contents of broiler chickens,which was identified as A.aeriphila,and then evaluated the effects of A.aeriphila on growth performance,antioxidant functions,immune functions,and gut microbiota in commercial broiler chickens.Chickens were orally gavaged with A.aeriphila(1×109 CFU/mL)for 21 d.The results showed that A.aeriphila treatment significantly increased the average daily gain and reduced the feed conversion ratio(P<0.001).The levels of serum growth hormone(GH)and insulin-like growth factor 1(IGF-1)were significantly increased following A.aeriphila treatment(P<0.05).Blood urea nitrogen and aspartate aminotransferase levels were decreased,whereas glucose and creatinine levels increased as a result of A.aeriphila treatment.Furthermore,the levels of serum antioxidant enzymes,including catalase(P<0.01),superoxide dismutase(P<0.001),and glutathione peroxidase(P<0.05),and total antioxidant capacity(P<0.05)were enhanced following A.aeriphila treatment.A.aeriphila treatment significantly increased the levels of serum immunoglobulin A(IgA)(P<0.05),IgG(P<0.01),IgM(P<0.05),interleukin-1(IL-1)(P<0.05),IL-4(P<0.05),and IL-10(P<0.05).The broiler chickens in the A.aeriphila group had higher secretory IgA(SIgA)levels in the duodenum(P<0.01),jejunum(P<0.001),and cecum(P<0.001)than those in the control group.The messenger RNA(mRNA)relative expression levels of IL-10(P<0.05)and IL-4(P<0.001)in the intestinal mucosa of chickens were increased,while nuclear factor-κB(NF-κB)(P<0.001)expression was decreased in the A.aeriphila group compared to the control group.Phylum-level analysis revealed Firmicutes as the main phylum,followed by Bacteroidetes,in both groups.The data also found that Phascolarctobacterium and Barnesiella were increased in A.aeriphila-treated group.In conclusion,oral administration of A.aeriphila could improve the growth performance,serum antioxidant capacity,immune modulation,and gut health of broilers.Our findings may provide important information for the application of A.aeriphila in poultry production.展开更多
Probiotics are the treasure of the microbiology fields.They have been widely used in the food industry,clinical treatment,and other fields.The equivocal health-promoting effects and the unknown action mechanism were t...Probiotics are the treasure of the microbiology fields.They have been widely used in the food industry,clinical treatment,and other fields.The equivocal health-promoting effects and the unknown action mechanism were the largest obstacles for further probiotic’s developed applications.In recent years,various genome editing techniques have been developed and applied to explore the mechanisms and functional modifications of probiotics.As important genome editing tools,CRISPR-Cas systems that have opened new improvements in genome editing dedicated to probiotics.The high efficiency,flexibility,and specificity are the advantages of using CRISPR-Cas systems.Here,we summarize the classification and distribution of CRISPR-Cas systems in probiotics,as well as the editing tools developed on the basis of them.Then,we discuss the genome editing of probiotics based on CRISPR-Cas systems and the applications of the engineered probiotics through CRISPR-Cas systems.Finally,we proposed a design route for CRISPR systems that related to the genetically engineered probiotics.展开更多
Background:West Nile virus is a severe zoonotic pathogen that can cause severe central nervous system symptoms in humans and horses,and is fatal for birds,chickens and other poultry.With no specific drugs or vaccines ...Background:West Nile virus is a severe zoonotic pathogen that can cause severe central nervous system symptoms in humans and horses,and is fatal for birds,chickens and other poultry.With no specific drugs or vaccines available,antibody-based therapy is a promising treatment.This study aims to develop neutralizing antibodies against West Nile virus and assess their cross-protective potential against Japanese encephalitis virus.Methods:Monoclonal antibodies against WNV and JEV were isolated by hybridoma technology.The therapeutic efficacy of these antibodies was evaluated using a mouse model,and a humanized version of the monoclonal antibody was generated for potential human application.Results:In this study,we generated eight monoclonal antibodies that exhibit neutralizing activity against WNV.Their therapeutic effects against WNV were validated both in vivo and in vitro.Among these antibodies,C9-G11-F3 also exhibited cross-protective activity against JEV.We also humanized the antibody to ensure that it could be used for WNV infection treatment in humans.Conclusion:This study highlights the importance of neutralizing antibodies as a promising approach for pro-tection against West Nile virus infection and suggests their potential utility in the development of therapeutic interventions.展开更多
Ferroptosis is a newly discovered prototype of programmed cell death (PCD) driven by iron-dependent phospholipid peroxidation accumulation, and it has been linked to numerous organ injuries and degenerative pathologie...Ferroptosis is a newly discovered prototype of programmed cell death (PCD) driven by iron-dependent phospholipid peroxidation accumulation, and it has been linked to numerous organ injuries and degenerative pathologies. Although studies have shown that a variety of cell death processes contribute to JEV-induced neuroinflammation and neuronal injury, there is currently limited research on the specific involvement of ferroptosis. In this study, we explored the neuronal ferroptosis induced by JEV infection in vitro and in vivo. Our results indicated that JEV infection induces neuronal ferroptosis through inhibiting the function of the antioxidant system mediated by glutathione (GSH)/glutathione peroxidase 4 (GPX4), as well as by promoting lipid peroxidation mediated by yes-associated protein 1 (YAP1)/long-chain acyl-CoA synthetase 4 (ACSL4). Further analyses revealed that JEV E and prM proteins function as agonists, inducing ferroptosis. Moreover, we found that treatment with a ferroptosis inhibitor in JEV-infected mice reduces the viral titers and inflammation in the mouse brains, ultimately improving the survival rate of infected mice. In conclusion, our study unveils a critical role of ferroptosis in the pathogenesis of JEV, providing new ideas for the prevention and treatment of viral encephalitis.展开更多
Background Japanese encephalitis virus(JEV)is a leading cause of viral encephalitis worldwide.JEV exhibits significant neuroinvasiveness and neurotoxicity,resulting in considerable damage to the nervous system.Japanes...Background Japanese encephalitis virus(JEV)is a leading cause of viral encephalitis worldwide.JEV exhibits significant neuroinvasiveness and neurotoxicity,resulting in considerable damage to the nervous system.Japanese encephalitis is associated with high morbidity and mortality rate,seriously harming both human health and livestock production.The current lack of specific antiviral drugs means that the development of new therapeutic agents for JEV has become urgent.Methods Anti-JEV drugs were screened from 111 inhibitors of neurotransmitter receptor-related molecules by high content technology.The antiviral effects of clomipramine HCl were evaluated through plaque assay,real-time quantitative PCR,immunofluorescence assay and western blotting assay.Bioinformatic tools were utilized to cluster the altered signaling pathway members after clomipramine HCl treatment.Finally,the anti-JEV mechanism was deeply resolved in vivo via such molecular biology and virological detection techniques.Results In this study,we screened nine compounds with significant anti-JEV activity,of which clomipramine HCl demonstrated the most potent antiviral effect and exhibited dose-dependent activity.Mechanistically,clomipramine HCl may activate endoplasmic reticulum stress and modulate the unfolded protein response,thus inhibiting the assembly stage of JEV infection.Conclusion This study highlights the importance of clomipramine HCl as a promising approach for JEV infection protection,which may lead to new host-directed antiviral approaches to such mosquito-borne viruses.展开更多
Biofilm formation has been implicated to be tightly regulated in bacteria. Mycobacterial species possess a unique cell-wall structure; however, the underlying regulation mechanism for their biofilm formation remains l...Biofilm formation has been implicated to be tightly regulated in bacteria. Mycobacterial species possess a unique cell-wall structure; however, the underlying regulation mechanism for their biofilm formation remains largely unclear. In this study, we characterized a hypothetical mannitol metabolism and transportation gene cluster（Ms5571-Ms5576）, designated as mmt operon, whose expression significantly contributes to the biofilm formation in Mycobacterium smegmatis. We showed that in the operon the Ms5575 gene encodes a GntR-like transcriptional repressor and the Ms5576 gene encodes a mannitol2-dehydrogenase which can produce D-mannitol from D-mannose. Strikingly, the D-mannitol molecule can derepress the negative regulation of Ms5575 on the mmt operon to stimulate the operon＇s expression. Consistently, addition of D-mannitol into the medium can obviously induce mycobacterial biofilm formation. Furthermore, we found that Ms0179 positively regulates the mmt operon through its downstream regulator Ms0180. Ms0180 directly binds the mmt operon to positively regulate its expression. Both Ms0179 and Ms0180 significantly affect the mycobacterial biofilm formation. Taken together, we explored a regulatory pathway for the mannitol metabolism and its coordination with the biofilm formation in M. smegmatis. This finding provides novel insights into the unique mechanism of biofilm formation regulation in mycobacteria.展开更多
A growing body of evidence has linked the gut microbiota to liver metabolism.The manipulation of intestinal microflora has been considered as a promising avenue to promote liver health.However,the effects of Lactobaci...A growing body of evidence has linked the gut microbiota to liver metabolism.The manipulation of intestinal microflora has been considered as a promising avenue to promote liver health.However,the effects of Lactobacillus gasseri LA39,a potential probiotic,on liver metabolism remain unclear.Accumulating studies have investigated the proteomic profile for mining the host biological events affected by microbes,and used the germ-free(GF)mouse model to evaluate host-microbe interaction.Here,we explored the effects of L.gasseri LA39 gavage on the protein expression profiles of the liver of GF mice.Our results showed that a total of 128 proteins were upregulated,whereas a total of 123 proteins were downregulated by treatment with L.gasseri LA39.Further bioinformatics analyses suggested that the primary bile acid(BA)biosynthesis pathway in the liver was activated by L.gasseri LA39.Three differentially expressed proteins(cytochrome P450 family 27 subfamily A member 1(CYP27A1),cytochrome P450 family 7 subfamily B member 1(CYP7B1),and cytochrome P450 family 8 subfamily B member 1(CYP8B1))involved in the primary BA biosynthesis pathway were further validated by western blot assay.In addition,targeted metabolomic analyses demonstrated that serum and fecalβ-muricholic acid(a primary BA),dehydrolithocholic acid(a secondary BA),and glycolithocholic acid-3-sulfate(a secondary BA)were significantly increased by L.gasseri LA39.Thus,our data revealed that L.gasseri LA39 activates the hepatic primary BA biosynthesis and promotes the intestinal secondary BA biotransformation.Based on these findings,we suggest that L.gasseri LA39 confers an important function in the gut‒liver axis through regulating BA metabolism.展开更多
Plant diseases cause enormous economic losses in agriculture and threaten global food security,and application of agrochemicals is an important method of crop disease control.Exploration of disease-resis-tance mechani...Plant diseases cause enormous economic losses in agriculture and threaten global food security,and application of agrochemicals is an important method of crop disease control.Exploration of disease-resis-tance mechanisms and synthesis of highly bioactive agrochemicals are thus important research objectives.Here,we show that propranolol,a phosphatidate phosphatase(Pah)inhibitor,effectively suppresses fungal growth,sporulation,sexual reproduction,and infection of diverse plants.The MoPah1 enzyme activity of the rice blast fungus Magnaporthe oryzae is inhibited by propranolol.Alterations in lipid metabolism are associated with inhibited hyphal growth and appressorium formation caused by propranolol in M.oryzae.Propranolol inhibits a broad spectrum of 12 plant pathogens,effectively inhibiting infection of barley,wheat,maize,tomato,and pear.To improve antifungal capacity,we synthesized a series of propranolol derivatives,one of which shows a 16-fold increase in antifungal ability and binds directly to MoPah1.Propranolol and its derivatives can also reduce the severity of rice blast and Fusarium head blight of wheat in thefield.Taken together,our results demonstrate that propranolol suppresses fungal development and infection through mechanisms involved in lipid metabolism.Propranolol and its derivatives may therefore be promising candidates for fungicide development.展开更多
Mycobacterium tuberculosis possesses unique cellular envelope components that contribute to bacterial escape from host immune surveillance.Phosphatidylinositol mannosides(PIMs)and their higher derivatives are importan...Mycobacterium tuberculosis possesses unique cellular envelope components that contribute to bacterial escape from host immune surveillance.Phosphatidylinositol mannosides(PIMs)and their higher derivatives are important molecules implicated in host-pathogen interactions in the course of tuberculosis.However,the biosynthetic regulation of these specific lipids and its effect on the bacterial fate in the infected host remain unclear.Here,we show that a hypothetical M.tuberculosis transcriptional factor designated as MpbR negatively regulates two transporter genes and affects mycobacterial PIM biosynthesis and biofilm formation.MpbR inhibits the accumulation of acylated PIM lipids and triggers the mycobacterium to reduce the production of reactive oxygen species and NO during infection,which enhances the survival of M.tuberculosis in macrophages.MpbR deletion reduces M.tuberculosis lung burdens and inflammation of infected mice.These findings provide new insights into the regulation of mycobacterial lipid metabolism and its correlation with pathogenesis of M.tuberculosis.展开更多
基金supported by the National Key Research and Development Program of China(2022YFD1200300)the National Natural Science Foundation of China(32072376 and 32372515)+3 种基金Winall Hi-tech Seed Co.,Ltd.,China(GMLM2023)the Nanfan Special Project of Chinese Academy of Agricultural Sciences(CAAS)(ZDXM2303 and YBXM2415)the Natural Science Foundation of Hebei Province,China(C2022204205)the Agricultural Science and Technology Innovation Program of CAAS。
文摘Verticillium wilt(VW),induced by the soil-borne fungus Verticillium dahliae(Vd),poses a substantial threat to a diverse array of plant species.Employing molecular breeding technology for the development of cotton varieties with heightened resistance to VW stands out as one of the most efficacious protective measures.In this study,we successfully generated two stable transgenic lines of cotton(Gossypium hirsutum L.),VdThitRNAi-1 and VdThit-RNAi-2,using host-induced gene silencing(HIGS)technology to introduce double-stranded RNA(dsRNA)targeting the thiamine transporter protein gene(VdThit).Southern blot analysis confirmed the presence of a single-copy insertion in each line.Microscopic examination showed marked reductions in the colonization and spread of Vd-mCherry in the roots of VdThit-RNAi cotton compared to wild type(WT).The corresponding disease index and fungal biomass of VdThit-RNAi-1/2 also exhibited significant reductions.Real-time quantitative PCR(qRT-PCR)analysis demonstrated a substantial inhibition of VdThit expression following prolonged inoculation of VdThit-RNAi cotton.Small RNA sequencing(sRNA-Seq)analysis revealed the generation of a substantial number of VdThit-specific siRNAs in the VdThit-RNAi transgenic lines.Additionally,the silencing of VdThit by the siVdThit produced by VdThit-RNAi-1/2 resulted in the elevated expression of multiple genes involved in the thiamine biosynthesis pathway in Vd.Under field conditions,VdThit-RNAi transgenic cotton exhibited significantly enhanced disease resistance and yield compared with WT.In summary,our findings underscore the efficacy of HIGS targeting VdThit in restraining the infection and spread of Vd in cotton,thereby potentially enabling the development of cotton breeding as a promising strategy for managing VW.
基金the Guangdong Major Project of Basic and Applied Basic Research(2020B0301030007).
文摘Bordetella bronchiseptica(Bb)is recognized as a leading cause of respiratory diseases in dogs and cats.However,epidemiological data on Bb in dogs and cats in China are still limited,and there is no commercially available vaccine.Live vaccines containing Bb that are widely used abroad are generally efective but can establish latency and potentially reactivate to cause illness in some immunodefcient vaccinated recipients,raising safety concerns.In this study,34 canine-derived and two feline-derived Bb strains were isolated from 1809 canine and 113 feline nasopharyngeal swab samples collected from eight provinces in China from 2021 to 2023.The PCR results showed that the percentage of positive Bb was 22.94%(441/1922),and more than 90%of the Bb isolates had four virulence factor-encoding genes(VFGs),namely,fhaB,prn,betA and dnt.All the isolated strains displayed a multidrug-resistant phenotype.The virulence of 10 Bb strains isolated from dogs with respiratory symptoms was tested in mice,and we found that eight isolates were highly virulent.Furthermore,the eight Bb isolates with high virulence were inactivated and intramuscularly injected into mice,and three Bb strains(WH1218,WH1203 and WH1224)with the best protective efcacy were selected.Dogs immunized with these three strains exhibited strong protection against challenge with the Bb feld strain WH1218.Ultimately,the WH1218 strain with the greatest protection in dogs was selected as the vaccine candidate.Dogs and cats that received a vaccine containing 109 CFU of the inactivated WH1218 strain showed complete protection against challenge with the Bb feld strain WH1218.This study revealed that Bb is an important pathogen that causes respiratory diseases in domestic dogs and cats in China,and all the isolates exhibited multidrug resistance.The present work contributes to the current understanding of the prevalence,antimicrobial resistance,and virulence genes of Bb in domestic dogs and cats.Additionally,our results suggest that the WH1218 strain is a promising candidate safe and efcacious inactivated Bb vaccine.
基金the National Key Research and Development Program(2021YFC2600204 and 2021YFD1800403)the Science and Technology Program of Gansu,China(20YF8NH153).
文摘Brucellosis remains one of the most common zoonoses spread worldwide,inducing enormous economic losses to the livestock industry and posing serious health threats to humans.Brucellosis re-emerged in China in the mid-1990s and reached a historically high level in 2015.The National Brucellosis Prevention and Control Plan(NBPCP)was initiated from 2016 to 2020.However,the present epidemiological status in livestock has not been elucidated,and whether Brucella variation occurred remains unclear.This study performed an extensive serological investigation in ruminant livestock from 2019 to 2021 in central Gansu Province,China.In total,11,296 samples from 337 farms were collected to detect the specific antibodies of Brucella.The yearly average serological prevalence of Brucella at the flock level and individual level declined from 11.32%to 8.26%and 1.17%to 0.57%,respectively.The apparent individuallevel seroprevalence of small and large ruminants was 0.89%and 0.52%,respectively.The brucellosis distribution has shifted from pastoral areas to agro-pastoral areas.Flock size and gender may be major risks of Brucella infection.Then,the B.melitensis TZ strain was isolated from female Tibetan sheep blood cell lysates.Phonotypical characterization demonstrated that it belongs to B.melitensis.biovar 3,and multilocus sequencing typing results indicated that it belongs to ST8.The whole genome and subsequent phylogenetic analysis demonstrated that the B.melitensis TZ strain is genetically more closely related to the B.melitensis QH61 strain.The B.melitensis TZ strain has similar growth characteristics to the B.melitensis 16 M strain.Overall,our study suggests that after strengthening control and prevention measures based on the NBPCP,there is a very low prevalence or absence of B.melitensis in the central Gansu Province of China,and the genotype of an epidemic strain of Brucella in Northwest China is relatively stable.
基金the Experimental Animal Research Project of Hubei Province(Grant No.2023CFA005).
文摘Feline panleukopenia virus(FPV)is a single-stranded DNA virus that can infect cats and cause feline panleukopenia,which is a highly contagious and fatal disease in felines.The sequence of FPV is highly variable,and mutations in the amino acids of its capsid protein play crucial roles in altering viral virulence,immunogenicity,host selection,and other abilities.In this study,the epidemiology of FPV was studied using 746 gastrointestinal swab samples derived from cats that presented gastrointestinal symptoms specifcally,diarrhea or vomiting during the period spanning from 2018 to 2022.The overall prevalence of FPV-positive patients among these samples was determined to be 45.4%.Capsid(virion)protein 2(VP2)gene of each FPV-positive sample was sequenced and amplifed,yielding 65 VP2 sequences.Among them,six VP2 gene sequences were detected in the majority of the samples test positive for FPV,and these positive samples originated from a diverse range of geographical locations.These isolates were named FPV-6,FPV-10,FPV-15,FPV-251,FPV-271 and FPV-S2.Additionally,the substitution of Ala300Pro(A300P)in VP2 was detected for the frst time in feline-derived FPV(FPV-251).FPV-251 isolate,with this substitution in VP2 protein,exhibited stable proliferative capacity in Madin-Darby canine kidney(MDCK)cells and A72 cells.FPV-271 was selected as the FPV control isolate due to its single amino acid diference from VP2 protein of FPV-251 at position 300(FPV-271 has alanine,while FPV-251 has proline).After oral infection,both FPV-251 and FPV-271 isolates caused feline panleukopenia,which is characterized by clinical signs of enterocolitis.However,FPV-251 can infect dogs through the oral route and cause gastrointestinal(GI)symptoms with lesions in the intestine and mesenteric lymph nodes(MLNs)of infected dogs.This is the frst report on the presence of an A300P substitution in VP2 protein of feline-derived FPV.Additionally,FPV isolate with a substitution of A300P at VP2 protein demonstrated efcient replication capabilities in canine cell lines and the ability to infect dogs.
基金funded by the National Natural Science Foundation of China(Grant No.U21A20259,31602061,31872470)the National Key Research and Development Program of China(Grant No.2021YFD1800401).
文摘Despite the initial successes of the Bacillus Calmette-Guerin(BCG)vaccine in children,its efficacy against tuberculosis is highly variable.There is a lack of understanding about how mental conditions influence BCG vaccination.Here,we used the chronic social defeat stress(CSDS)model to explore the effects of depression on BCG vaccination efficacy.We observed higher lung and spleen bacterial loads and a lower organ index in depressed compared to BCG mice.Meanwhile,a relatively lower T cell protective efficacy was observed in both compared to control and BCG mice via a mycobacterium growth inhibition assay(MGIA).Cytokine expression of IL-12p40,IL-1β,IL-17,TNF-αand IFN-γwas reduced,whereas the expression of IL-10 and IL-5 was increased in the spleen of both compared to BCG mice.Moreover,the proportions of CD4^(+)IFN-γ^(+),CD8^(+)IFN-γ^(+)T lymphocytes and CD4^(+)effector/central memory T cells were reduced in the splenocytes of the depressed BCG mice.Depression promotes CD4^(+)regulatory T cells(Treg)and myeloid-derived suppressor cell(MDSC)generation in depressed mice,contributing to the reduced pro-inflammatory immune response upon BCG vaccination.This study provides insight into the decreased protective immunity by BCG vaccination attributable to depression in mice.
文摘A simple, fast and reliable method was developed for the analysis of jinggangmycin A （validamycin A） in commercial formulations. The running buffer used was acetate buffer （100 mmol/L, pH 4.7） with 15 kV as the applied voltage. The detection was achieved by using direct UV mode at 200 nm and the detection limit was 0.2 μg/mL. Linearity in the concentration range of 5-500 μg/mL was excellent （RE 〉 0.999）. The run-to-run repeatability （n = 3）, as expressed by the relative standard deviation （RSD） for migration times and peak areas were less than 0.5% and 3.0% respectively. The mean recovery ranged from 97.2% to 101.4%.
基金the National Key Technol- ogy R & D Program during the 11th Five-Year Plan period (2006BAD06A12, 2006BAD06A18)the National Natural Science Foundation of China (30200011)
文摘This study presents the cloning and expression of gene encoding transferrin-binding protein A from Actinobacillus pleuropneurnoniae in Escherichia coli expression system and the development of an indirect TbpA-ELISA. The gene coding TbpA was amplified from the A. pleuropneumoniae serotype 2 genome using polymerase chain reaction and cloned to pET-28b expression vector under the control of strong, inducible T7 promoter. The recombinant plasmid was expressed in E. coli BL21 （DE3）. The expressed fusion protein was analyzed using SDS-PAGE and Western blotting. The diagnostic potential of recombinant TbpA （rTbpA） was evaluated through an antibody-detection indirect ELISA based on the purified rTbpA. The TbpA antibodies were detectable in mice on day 7 after vaccination with purified rTbpA protein or infection with A. pleuropneumoniae serotype 10 with the TbpA-based ELISA. In addition, the TbpA-ELISA was able to detect 12 serotyping rabbit antisera postinoculation （PI） with A. pleuropneumoniae 12 serotypes experimentally. The comparable result was obtained by detecting the 117 clinical serum samples using, respectively, the TbpA-ELISA and indirect hemagglutination test （IHA） based on multiplex antigen. The result indicates that the TbpA-ELISA was the more sensitive method compared with the Mix-IHA method because of its consistent presence in A. pleuropneumoniae serotypes. In conclusion, the conserved TbpA of A. pleuropneumoniae can be used for the development of a cross-serotype diagnostic method for the detection of antibodies against A. pleuropneurnoniae.
基金supported by the Key Research Project of the Ministry of Education (105120)Educational Commission of Hubei Province of China (B20091203)
文摘[Objective] To develop a new method for serodiagnosis of swine toxoplasmosis. [Method] With the purified recombinant microneme protein 3 （rMIC3） as coating antigens, an indirect ELISA was developed for detection of antibodies against Toxoplasma gondii. [ Result] The optimal working concentration of rMIC3 was 3. 40 ug/ml, and the optimal degree of dilution of sera was 1：160. Cross-reaction was not observed between the Toxoplasma gondii-positive sera and the positive sera against classical swine fever virus or some other pathogens. The developed ELISA had 92.56% coincidence rate with latex agglutination test. [ Conclusion] The developed ELISA is sensitive, rapid, specific and reproducible, and thus it can be applied in serodiagnosis and seroprevalence investigation of swine toxoplasmosis.
基金supported by Higher Education Commission,Pakistan in a project(TDF-11)under Technology Development Fund Program,the National Natural Science Foundation of China(32100090)Fundamental Research Funds for the Central Universities of China(2662022ZHQD001)Great gratitude goes to linguistics Prof.Ping Liu from Huazhong Agriculture University,Wuhan,China for her work at English editing and language polishing.
文摘Herbicide-based weeds control impacts wheat crops as well.SynComs of Pseudomonas strains reduce the need for high-dose herbicides.100%Axial provides less weed control compared to 75%Axial with C4 SynCom.Axial 75%with C4 SynCom promotes wheat growth than the 75%Axial alone.
基金supported by the National Natural Science Foundation of China (No.31925037).
文摘Aeriscardovia aeriphila,also known as Bifidobacterium aerophilum,was first isolated from the caecal contents of pigs and the faeces of cotton-top tamarin.Bifidobacterium species play important roles in preventing intestinal infections,decreasing cholesterol levels,and stimulating the immune system.In this study,we isolated a strain of bacteria from the duodenal contents of broiler chickens,which was identified as A.aeriphila,and then evaluated the effects of A.aeriphila on growth performance,antioxidant functions,immune functions,and gut microbiota in commercial broiler chickens.Chickens were orally gavaged with A.aeriphila(1×109 CFU/mL)for 21 d.The results showed that A.aeriphila treatment significantly increased the average daily gain and reduced the feed conversion ratio(P<0.001).The levels of serum growth hormone(GH)and insulin-like growth factor 1(IGF-1)were significantly increased following A.aeriphila treatment(P<0.05).Blood urea nitrogen and aspartate aminotransferase levels were decreased,whereas glucose and creatinine levels increased as a result of A.aeriphila treatment.Furthermore,the levels of serum antioxidant enzymes,including catalase(P<0.01),superoxide dismutase(P<0.001),and glutathione peroxidase(P<0.05),and total antioxidant capacity(P<0.05)were enhanced following A.aeriphila treatment.A.aeriphila treatment significantly increased the levels of serum immunoglobulin A(IgA)(P<0.05),IgG(P<0.01),IgM(P<0.05),interleukin-1(IL-1)(P<0.05),IL-4(P<0.05),and IL-10(P<0.05).The broiler chickens in the A.aeriphila group had higher secretory IgA(SIgA)levels in the duodenum(P<0.01),jejunum(P<0.001),and cecum(P<0.001)than those in the control group.The messenger RNA(mRNA)relative expression levels of IL-10(P<0.05)and IL-4(P<0.001)in the intestinal mucosa of chickens were increased,while nuclear factor-κB(NF-κB)(P<0.001)expression was decreased in the A.aeriphila group compared to the control group.Phylum-level analysis revealed Firmicutes as the main phylum,followed by Bacteroidetes,in both groups.The data also found that Phascolarctobacterium and Barnesiella were increased in A.aeriphila-treated group.In conclusion,oral administration of A.aeriphila could improve the growth performance,serum antioxidant capacity,immune modulation,and gut health of broilers.Our findings may provide important information for the application of A.aeriphila in poultry production.
基金the National Key Research and Development Program of China under grant number 2022YFA0912201the National Natural Science Foundation of China under grant number 32270090+1 种基金the Foundation of Hubei Hongshan Laboratory under grant numbers 2021hszd013 and 2021hszd022the LongYun Program for College of Life Science and Technology,Huazhong Agricultural University.
文摘Probiotics are the treasure of the microbiology fields.They have been widely used in the food industry,clinical treatment,and other fields.The equivocal health-promoting effects and the unknown action mechanism were the largest obstacles for further probiotic’s developed applications.In recent years,various genome editing techniques have been developed and applied to explore the mechanisms and functional modifications of probiotics.As important genome editing tools,CRISPR-Cas systems that have opened new improvements in genome editing dedicated to probiotics.The high efficiency,flexibility,and specificity are the advantages of using CRISPR-Cas systems.Here,we summarize the classification and distribution of CRISPR-Cas systems in probiotics,as well as the editing tools developed on the basis of them.Then,we discuss the genome editing of probiotics based on CRISPR-Cas systems and the applications of the engineered probiotics through CRISPR-Cas systems.Finally,we proposed a design route for CRISPR systems that related to the genetically engineered probiotics.
基金supported by the National Key R&D Program of China (2021YFD1801300)the Fundamental Research Funds for the Central Universities (2662023DKPY004)+1 种基金the Key Technological Innovation Program of Hubei Province (2019ABA089)Natural Science Foundation of Hubei Province (2019CFA010 and 2021CFA056).
文摘Background:West Nile virus is a severe zoonotic pathogen that can cause severe central nervous system symptoms in humans and horses,and is fatal for birds,chickens and other poultry.With no specific drugs or vaccines available,antibody-based therapy is a promising treatment.This study aims to develop neutralizing antibodies against West Nile virus and assess their cross-protective potential against Japanese encephalitis virus.Methods:Monoclonal antibodies against WNV and JEV were isolated by hybridoma technology.The therapeutic efficacy of these antibodies was evaluated using a mouse model,and a humanized version of the monoclonal antibody was generated for potential human application.Results:In this study,we generated eight monoclonal antibodies that exhibit neutralizing activity against WNV.Their therapeutic effects against WNV were validated both in vivo and in vitro.Among these antibodies,C9-G11-F3 also exhibited cross-protective activity against JEV.We also humanized the antibody to ensure that it could be used for WNV infection treatment in humans.Conclusion:This study highlights the importance of neutralizing antibodies as a promising approach for pro-tection against West Nile virus infection and suggests their potential utility in the development of therapeutic interventions.
基金supported by National Natural Science Foundation of China(32022082,31972721)National Key Research and Development Program of China(2022YFD1801500,2022YFD1800105)+1 种基金Natural Science Foundation of Hubei Province(2021CFA056)Fundamental Research Funds for the Central Universities(2662023PY005).
文摘Ferroptosis is a newly discovered prototype of programmed cell death (PCD) driven by iron-dependent phospholipid peroxidation accumulation, and it has been linked to numerous organ injuries and degenerative pathologies. Although studies have shown that a variety of cell death processes contribute to JEV-induced neuroinflammation and neuronal injury, there is currently limited research on the specific involvement of ferroptosis. In this study, we explored the neuronal ferroptosis induced by JEV infection in vitro and in vivo. Our results indicated that JEV infection induces neuronal ferroptosis through inhibiting the function of the antioxidant system mediated by glutathione (GSH)/glutathione peroxidase 4 (GPX4), as well as by promoting lipid peroxidation mediated by yes-associated protein 1 (YAP1)/long-chain acyl-CoA synthetase 4 (ACSL4). Further analyses revealed that JEV E and prM proteins function as agonists, inducing ferroptosis. Moreover, we found that treatment with a ferroptosis inhibitor in JEV-infected mice reduces the viral titers and inflammation in the mouse brains, ultimately improving the survival rate of infected mice. In conclusion, our study unveils a critical role of ferroptosis in the pathogenesis of JEV, providing new ideas for the prevention and treatment of viral encephalitis.
基金National Key Research and Development Program of China(2022YFD1801500,2022YFD1800105,2021YFC2600204)National Natural Science Foundation of China(32022082,31825025,32030107).
文摘Background Japanese encephalitis virus(JEV)is a leading cause of viral encephalitis worldwide.JEV exhibits significant neuroinvasiveness and neurotoxicity,resulting in considerable damage to the nervous system.Japanese encephalitis is associated with high morbidity and mortality rate,seriously harming both human health and livestock production.The current lack of specific antiviral drugs means that the development of new therapeutic agents for JEV has become urgent.Methods Anti-JEV drugs were screened from 111 inhibitors of neurotransmitter receptor-related molecules by high content technology.The antiviral effects of clomipramine HCl were evaluated through plaque assay,real-time quantitative PCR,immunofluorescence assay and western blotting assay.Bioinformatic tools were utilized to cluster the altered signaling pathway members after clomipramine HCl treatment.Finally,the anti-JEV mechanism was deeply resolved in vivo via such molecular biology and virological detection techniques.Results In this study,we screened nine compounds with significant anti-JEV activity,of which clomipramine HCl demonstrated the most potent antiviral effect and exhibited dose-dependent activity.Mechanistically,clomipramine HCl may activate endoplasmic reticulum stress and modulate the unfolded protein response,thus inhibiting the assembly stage of JEV infection.Conclusion This study highlights the importance of clomipramine HCl as a promising approach for JEV infection protection,which may lead to new host-directed antiviral approaches to such mosquito-borne viruses.
基金supported by the National Key R&D Program of China (2017YFD0500300)the National Natural Science Foundation of China (Nos.31730005,31401108,and 31670075)+1 种基金the Fundamental Research Funds for the Central Universities (2662016PY090)Chang Jiang Scholars Program (to Z.-G. He)
文摘Biofilm formation has been implicated to be tightly regulated in bacteria. Mycobacterial species possess a unique cell-wall structure; however, the underlying regulation mechanism for their biofilm formation remains largely unclear. In this study, we characterized a hypothetical mannitol metabolism and transportation gene cluster（Ms5571-Ms5576）, designated as mmt operon, whose expression significantly contributes to the biofilm formation in Mycobacterium smegmatis. We showed that in the operon the Ms5575 gene encodes a GntR-like transcriptional repressor and the Ms5576 gene encodes a mannitol2-dehydrogenase which can produce D-mannitol from D-mannose. Strikingly, the D-mannitol molecule can derepress the negative regulation of Ms5575 on the mmt operon to stimulate the operon＇s expression. Consistently, addition of D-mannitol into the medium can obviously induce mycobacterial biofilm formation. Furthermore, we found that Ms0179 positively regulates the mmt operon through its downstream regulator Ms0180. Ms0180 directly binds the mmt operon to positively regulate its expression. Both Ms0179 and Ms0180 significantly affect the mycobacterial biofilm formation. Taken together, we explored a regulatory pathway for the mannitol metabolism and its coordination with the biofilm formation in M. smegmatis. This finding provides novel insights into the unique mechanism of biofilm formation regulation in mycobacteria.
基金supported by the National Key Research and Development Program of China(2021YFD1901205)the National Natural Science Foundation of China(42177022 and 32071595)+3 种基金the Fundamental Research Funds for the Central Universities(2662023PY010)the Spanish Ministry of Science and Innovation(PID2020-115813RA-I00)the Fondo Europeo de Desarrollo Regional(FEDER)the Consejería de Transformación Económica,Industria,Conocimiento y Universidades of the Junta de Andalucía(FEDER Andalucía 2014–2020 Objetivo temático“01-Refuerzo de la investigación,el desarrollo tecnológico y la innovación”)(P20_00879(ANDABIOMA))。
基金supported by the National Natural Science Foundation of China(Nos.31925037,31730090,and 32102499)the National Postdoctoral Program for Innovative Talents of China(No.BX20190133)+1 种基金the Postdoctoral Science Foundation of China(No.2019M662671)the Natural Science Foundation of Hubei Province(Nos.2022CFB358 and 2021CFA018).
文摘A growing body of evidence has linked the gut microbiota to liver metabolism.The manipulation of intestinal microflora has been considered as a promising avenue to promote liver health.However,the effects of Lactobacillus gasseri LA39,a potential probiotic,on liver metabolism remain unclear.Accumulating studies have investigated the proteomic profile for mining the host biological events affected by microbes,and used the germ-free(GF)mouse model to evaluate host-microbe interaction.Here,we explored the effects of L.gasseri LA39 gavage on the protein expression profiles of the liver of GF mice.Our results showed that a total of 128 proteins were upregulated,whereas a total of 123 proteins were downregulated by treatment with L.gasseri LA39.Further bioinformatics analyses suggested that the primary bile acid(BA)biosynthesis pathway in the liver was activated by L.gasseri LA39.Three differentially expressed proteins(cytochrome P450 family 27 subfamily A member 1(CYP27A1),cytochrome P450 family 7 subfamily B member 1(CYP7B1),and cytochrome P450 family 8 subfamily B member 1(CYP8B1))involved in the primary BA biosynthesis pathway were further validated by western blot assay.In addition,targeted metabolomic analyses demonstrated that serum and fecalβ-muricholic acid(a primary BA),dehydrolithocholic acid(a secondary BA),and glycolithocholic acid-3-sulfate(a secondary BA)were significantly increased by L.gasseri LA39.Thus,our data revealed that L.gasseri LA39 activates the hepatic primary BA biosynthesis and promotes the intestinal secondary BA biotransformation.Based on these findings,we suggest that L.gasseri LA39 confers an important function in the gut‒liver axis through regulating BA metabolism.
基金supported by the National Key R&D Program of China (2022YFA1304402)the National Natural Science Foundation of China (31801723,32172373)+1 种基金the Fundamental Research Funds for the Central Universities to G.L. (2023ZKPY002,2662023PY006,AML2023A)Q.L.(2662020ZKPY005).
文摘Plant diseases cause enormous economic losses in agriculture and threaten global food security,and application of agrochemicals is an important method of crop disease control.Exploration of disease-resis-tance mechanisms and synthesis of highly bioactive agrochemicals are thus important research objectives.Here,we show that propranolol,a phosphatidate phosphatase(Pah)inhibitor,effectively suppresses fungal growth,sporulation,sexual reproduction,and infection of diverse plants.The MoPah1 enzyme activity of the rice blast fungus Magnaporthe oryzae is inhibited by propranolol.Alterations in lipid metabolism are associated with inhibited hyphal growth and appressorium formation caused by propranolol in M.oryzae.Propranolol inhibits a broad spectrum of 12 plant pathogens,effectively inhibiting infection of barley,wheat,maize,tomato,and pear.To improve antifungal capacity,we synthesized a series of propranolol derivatives,one of which shows a 16-fold increase in antifungal ability and binds directly to MoPah1.Propranolol and its derivatives can also reduce the severity of rice blast and Fusarium head blight of wheat in thefield.Taken together,our results demonstrate that propranolol suppresses fungal development and infection through mechanisms involved in lipid metabolism.Propranolol and its derivatives may therefore be promising candidates for fungicide development.
基金supported by the National Key R&D Program of China(2017YFD0500300)the National Natural Science Foundation of China(31730005,31670075 and 31870036)the Ba-Gui Scholar Program of Guangxi(to Z.G.H.).
文摘Mycobacterium tuberculosis possesses unique cellular envelope components that contribute to bacterial escape from host immune surveillance.Phosphatidylinositol mannosides(PIMs)and their higher derivatives are important molecules implicated in host-pathogen interactions in the course of tuberculosis.However,the biosynthetic regulation of these specific lipids and its effect on the bacterial fate in the infected host remain unclear.Here,we show that a hypothetical M.tuberculosis transcriptional factor designated as MpbR negatively regulates two transporter genes and affects mycobacterial PIM biosynthesis and biofilm formation.MpbR inhibits the accumulation of acylated PIM lipids and triggers the mycobacterium to reduce the production of reactive oxygen species and NO during infection,which enhances the survival of M.tuberculosis in macrophages.MpbR deletion reduces M.tuberculosis lung burdens and inflammation of infected mice.These findings provide new insights into the regulation of mycobacterial lipid metabolism and its correlation with pathogenesis of M.tuberculosis.
