Plant bacterial diseases have infiicted substantial economic losses in global crop,fruit,and vegetable production.The conventional methods for managing these diseases typically rely on the application of antibiotics.H...Plant bacterial diseases have infiicted substantial economic losses in global crop,fruit,and vegetable production.The conventional methods for managing these diseases typically rely on the application of antibiotics.However,these antibiotics often target the growth factors of the pathogenic bacteria,leading to the accumulation and emergence of drug-resistant strains,which exacerbates antibiotic resistance.Innovative methods are urgently needed to treat and prevent the toxicity caused by these pathogenic bacteria.Targeting virulence mechanisms in pathogens is a globally recognized and effective strategy for mitigating bacterial resistance.TypeⅢsecretion system(T3SS)serves as a crucial virulence determinant in Gram-negative pathogens,and its non-essentials for pathogen growth renders it an ideal target.Targeting the T3SS holds significant potential to alleviate selective pressure for resistance mutations in pathogens.Therefore,targeting T3SS in pathogenic bacteria,while preserving their growth,has emerged as a novel avenue for the development of antimicrobial drugs.In recent years,a multitude of small molecular inhibitors targeting T3SS have been identified.This article offers a comprehensive review of T3SS inhibitors in plant pathogens,while also presenting the latest research advancements in this research direction.展开更多
Secretion systems, macromolecules to pass which can mediate the across cellular membranes, are essential for virulent and genetic material exchange among bacterial species[1]. Type IV secretion system （T4SS） is one ...Secretion systems, macromolecules to pass which can mediate the across cellular membranes, are essential for virulent and genetic material exchange among bacterial species[1]. Type IV secretion system （T4SS） is one of the secretion systems and it usually consists of 12 genes： VirB1, VirB2 ...VirB11, and VirD4[2]. The structure and molecular mechanisms of these genes have been well analyzed in Gram-negative strains[3] and Gram-positive strains were once believed to be lack of T4SS. However, some recent studies revealed that one or more virB/D genes also exist in some kinds of Gram-positive bacteria and play similar role, and form a T4SS-like system[3]. The VirBl-like, VirB4, VirB6, and VirD4 genes were identified in the chromosome of Gram-positive bacterium Streptococcus suis in our previous studies and their role as important mobile elements for horizontal transfer to recipients in an 89 K pathogenicity island （PAl） was demonstrated[45]. However, their structure and molecular mechanisms in other strains, especially in Gram-positive strains, are remained unclear.展开更多
In order to enrich the research about type III secretion system （T3SS） injectisome of Vibrio alginolyticus, vscX gene was cloned from E algianlyticus strain HY9901 for bioinformatics analysis and expression analysis...In order to enrich the research about type III secretion system （T3SS） injectisome of Vibrio alginolyticus, vscX gene was cloned from E algianlyticus strain HY9901 for bioinformatics analysis and expression analysis. Specific primers were designed according to the full-length geanme sequence of V. alginolyticus in GenBank. vscX gene （C, enBank accession number： FR780679） contained a 378 bp open reading frame （ORF）, encoding a putative protein of 125 amino acids. The theoretical molecular weight was 14.209 2 kD and theoretical pI was 5.75. By using Signal 4.1 Server and TMHMM Server 2.0, it was predicted that VscX protein had no transmembrane domain or signal peptide. The results of prediction using SoftBerry-Psite software showed that VscX protein contained three casein ki- nase lI phosphorylation sites, one N-myristoylation site and three C-terminal targeting signal sites. Subcellular localization revealed that VscX might be located in cytoplasm with the possibility of 56.5%. According to SMART prediction, VscX had one Pfam （ 1 - 125 aa） domain. Phylogenetic analysis revealed that VscX from V. alginolyticus and VscX from E parahemolyticus were clustered into the same group. Network interaction analysis showed that vscX was adjacent to vseY, vopB and sycN. By real-time fluorescent quantitative PCR technique and 2-△△△ method, the differences in expression levels of VscX mRNA in V. alginolyticus strain HY9901, T3SS deletion strain AvscO and complementary strain C-vscO at different growth stages were analyzed. The results showed that the expression levels of VscX mRNA in V. algianlyticus strain HY9901 and C-vscO were significantly up-regulated at stable growth stage （ P 〈0.01 ） ; the expression levels of VscX mRNA in deletion strain △vscO were significantly up-regulated at late growth stage （ P 〈0.01 ）. This study provided the basis for revealing the transport mechanism of T3SS injectisome of E alginolyticus.展开更多
BACKGROUND Human milk oligosaccharides(HMOs)are bioactive components of breast milk with diverse health benefits,including shaping the gut microbiota,modulating the immune system,and protecting against infections.HMOs...BACKGROUND Human milk oligosaccharides(HMOs)are bioactive components of breast milk with diverse health benefits,including shaping the gut microbiota,modulating the immune system,and protecting against infections.HMOs exhibit dynamic secretion patterns during lactation,influenced by maternal genetics and environ-mental factors.Their direct and indirect antimicrobial properties have garnered significant research interest.However,a comprehensive understanding of the secretion dynamics of HMOs and their correlation with antimicrobial efficacy remains underexplored.AIM To synthesize current evidence on the secretion dynamics of HMOs during lactation and evaluate their antimicrobial roles against bacterial,viral,and protozoal pathogens.METHODS A systematic search of PubMed,Scopus,Web of Science,and Cochrane Library focused on studies investigating natural and synthetic HMOs,their secretion dynamics,and antimicrobial properties.Studies involving human,animal,and in vitro models were included.Data on HMO composition,temporal secretion patterns,and mechanisms of antimicrobial action were extracted.Quality assess-ment was performed using validated tools appropriate for study design.RESULTS A total of 44 studies were included,encompassing human,animal,and in vitro research.HMOs exhibited dynamic secretion patterns,with 2′-fucosyllactose(2′-FL)and lacto-N-tetraose peaking in early lactation and declining over time,while 3-fucosyllactose(3-FL)increased during later stages.HMOs demonstrated significant antimicrobial properties through pathogen adhesion inhibition,biofilm disruption,and enzymatic activity impairment.Synthetic HMOs,including bioengineered 2′-FL and 3-FL,were structurally and functionally comparable to natural HMOs,effectively inhibiting pathogens such as Pseudomonas aeruginosa,Escherichia coli,and Campylobacter jejuni.Additionally,HMOs exhibited synergistic effects with antibiotics,enhancing their efficacy against resistant pathogens.CONCLUSION HMOs are vital in antimicrobial defense,supporting infant health by targeting various pathogens.Both natural and synthetic HMOs hold significant potential for therapeutic applications,particularly in infant nutrition and as adjuncts to antibiotics.Further research,including clinical trials,is essential to address gaps in knowledge,validate findings,and explore the broader applicability of HMOs in improving maternal and neonatal health.展开更多
The exponential growth of antibiotic-resistant bacteria and antibiotic-resistant genes(ARGs)in soil-crop systems in recent years has posed a great challenge to ecological security and human health.While many studies h...The exponential growth of antibiotic-resistant bacteria and antibiotic-resistant genes(ARGs)in soil-crop systems in recent years has posed a great challenge to ecological security and human health.While many studies have documented the residues of ARGs in soils and crops,but little is known about who drives the proliferation of ARGs in farming systems and what their underlying mechanisms are.Herein,we explored the occurrence and proliferating behavior of ARGs in soil-crop environments in terms of root secretions and plant volatiles.This review highlighted that plant root secretions and volatile organic compounds(VOCs)served as key substances mediating the development of antibiotic resistance in the soil-crop system.Still,there is controversy here as to plant root secretions promote the ARGs proliferation or inhibit.Some studies indicated that root secretions can suppress the colonization of ARGs,mainly attributed by the production of bluntedmetabolic enzymes and blocking of cellular exocytosis systems.Whereas the others have evidenced that root secretions can promote ARGs proliferation,primarily by altering the structure of microbial communities to influence species interactions and thus indirectly affect the proliferation of ARGs.Also,VOCs can act as molecular signals to convey antibiotic resistance information to their neighbors,which in turn drive the up-regulation of ARGs expression.Even so,the mechanism by which VOC-driven antibiotic resistance acquisition and proliferation need to be further probed.Overall,this review contributed to the development of products and technologies to impede the ARGs proliferation in agricultural environment.展开更多
Objective To review the research progress on Type Ⅳ secretion system （T4SS） in HelicobacterpylorL Data sources The data used in this review were identified by searching of PUBMED （1995-2007） online resources usin...Objective To review the research progress on Type Ⅳ secretion system （T4SS） in HelicobacterpylorL Data sources The data used in this review were identified by searching of PUBMED （1995-2007） online resources using the key terms ＇Type Ⅳ secretion system＇ and ＇Helicobacter pylon. Study selection Mainly original articles and critical reviews written by major pioneer investigators of this field were selected. Results The research progress on T4SS in Helicobacter pylori was summarized. The structure and function was discussed. Conclusions T4SS is not only involved in toxin secretion and injection of virulence factors into eukaryotic host target cells, but also involved in horizontal DNA transfer to other bacteria and eukaryotic cells, through DNA uptake from or release into the extracellular milieu. It provides a new insight into the pathogenicity of Helicobacter pylori and a novel target for antimicrobials development. However, many challenges remain for us in understanding the biological role of T4SS in Helicobacter pylori.展开更多
TypeⅥSecretion System(T6SS)plays significant roles in microbial activities via injecting effectors into adjacent cells or environments.T6SS increasingly gained attention due to its important influence on pathogenesis...TypeⅥSecretion System(T6SS)plays significant roles in microbial activities via injecting effectors into adjacent cells or environments.T6SS increasingly gained attention due to its important influence on pathogenesis,microbial competition,etc.T6SS-associated research is explosively expanding on numerous grounds that call for an efficient resource.The SecReT6 version3 provides comprehensive information on T6SS and the interactions between T6SS and T6SS-related proteins such as T6SS regulators and T6SS effectors.To assist T6SS researches like microbial competition and regulatory mechanisms,SecReT6 v3developed online tools for detection and analysis of T6SS and T6SS-related proteins and estimation of T6SS-dependent killing risk.We have identified a novel T6SS regulator and T6SS-dependent killing capacity in Acinetobacter baumannii clinical isolates with the aid of SecReT6 v3.17,212 T6SSs and plentiful T6SS-related proteins in 26,573 bacterial complete genomes were also detected,analyzed and incorporated into the database.The database is freely available at https://bioinfo-mml.sjtu.edu.cn/SecReT6/.展开更多
Bacteria inhabit diverse and dynamic environments,where nutrients may be limited and toxic chemicals can be prevalent.To adapt to these stressful conditions,bacteria have evolved specialized protein secretion systems,...Bacteria inhabit diverse and dynamic environments,where nutrients may be limited and toxic chemicals can be prevalent.To adapt to these stressful conditions,bacteria have evolved specialized protein secretion systems,such as the type VI secretion system(T6SS)to facilitate their survival.As a molecular syringe,the T6SS expels various effectors into neighboring bacterial cells,eukaryotic cells,or the extracellular environment.These effectors improve the competitive fitness and environmental adaption of bacterial cells.Although primarily recognized as antibacterial weapons,recent studies have demonstrated that T6SSs have functions beyond interspecies competition.Here,we summarize recent research on the role of T6SSs in microbiome modulation,pathogenesis,and stress resistance.展开更多
Mycosin-1 protease(MycP1)is a serine protease anchored to the inner membrane of Mycobacterium tuberculosis,and is essential in virulence factor secretion through the ESX-1 type VII secretion system(T7SS).Bacterial phy...Mycosin-1 protease(MycP1)is a serine protease anchored to the inner membrane of Mycobacterium tuberculosis,and is essential in virulence factor secretion through the ESX-1 type VII secretion system(T7SS).Bacterial physiology studies demonstrated that MycP1 plays a dual role in the regulation of ESX-1 secretion and virulence,primarily through cleavage of its secretion substrate EspB.MycP1 contains a putative N-terminal inhibitory propeptide and a catalytic triad of Asp-His-Ser,classic hallmarks of a sub-tilase family serine protease.The MycP1 propeptide was previously reported to be initially inactive and activated after prolonged incubation.In this study,we have deter-mined crystal structures of MycP1 with(MycP124-422)and without(MycP1^(63-422))the propeptide,and conducted EspB cleavage assays using the two proteins.Very high struc-tural similarity was observed in the two crystal structures.Interestingly,protease assays demonstrated positive EspB cleavage for both proteins,indicating that the putative propeptide does not inhibit protease activity.Molecu-lar dynamic simulations showed higher rigidity in regions guarding the entrance to the catalytic site in MycP124-422 than in MycP1^(63-422),suggesting that the putative propeptide might contribute to the conformational stability of the active site cleft and surrounding regions.展开更多
The type Ⅵ secretion system(T6SS)is a widespread protein secretion apparatus deployed by many Gram-negative bacterial species to interact with competitor bacteria,host organisms,and the environment.Yersinia pseudotub...The type Ⅵ secretion system(T6SS)is a widespread protein secretion apparatus deployed by many Gram-negative bacterial species to interact with competitor bacteria,host organisms,and the environment.Yersinia pseudotuber-culosis T6SS4 was recently reported to be involved in manganese acquisition;however,the underlying regulatory mechanism still remains unclear.In this study,we discovered that T6SS4 is regulated by ferric uptake regulator(Fur)in response to manganese ions(Mn^(2+)),and this negative regulation of Fur was proceeded by specifically recogniz-ing the promoter region of T6SS4 in Y.pseudotuberculosis.Furthermore,T6SS4 is induced by low Mn^(2+)and oxidative stress conditions via Fur,acting as a Mn^(2+)-responsive transcriptional regulator to maintain intracellular manganese homeostasis,which plays important role in the transport of Mn^(2+)for survival under oxidative stress.Our results pro-vide evidence that T6SS4 can enhance the oxidative stress resistance and virulence for Y.pseudotuberculosis.This study provides new insights into the regulation of T6SS4 via the Mn^(2+)-dependent transcriptional regulator Fur,and expands our knowledge of the regulatory mechanisms and functions of T6SS from Y.pseudotuberculosis.展开更多
Many bacterial pathogens utilize specialized secretion systems to deliver virulence factors into the extracellular milieu. These exported effectors act to manipulate various processes of targeted cells in order to cre...Many bacterial pathogens utilize specialized secretion systems to deliver virulence factors into the extracellular milieu. These exported effectors act to manipulate various processes of targeted cells in order to create a suitable niche for bacterial growth. Currently, seven different types of secretion system have been described, of which Type I - VI are mainly present in Gram-negative bacteria and the newly discovered Type VII system seems exclusive to Gram-positive species. This review summaries our current understanding on the architecture and transport mechanisms of each secretion apparatus. We also discuss recent studies revealing the roles that these secretion systems and their substrates play in microbial pathogenesis.展开更多
The type VI secretion system(T6SS)is a powerful bacterial molecular weapon that can inject effector proteins into prokaryotic or eukaryotic cells,thereby participating in the competition between bacteria and improving...The type VI secretion system(T6SS)is a powerful bacterial molecular weapon that can inject effector proteins into prokaryotic or eukaryotic cells,thereby participating in the competition between bacteria and improving bacterial environmental adaptability.Although most current studies of the T6SS have focused on animal bacteria,this system is also significant for the adaptation of plant-associated bacteria.This paper briefly introduces the structure and biological functions of the T6SS.We summarize the role of plant-associated bacterial T6SS in adaptability to host plants and the external environment,including resistance to biotic stresses such as host defenses and competition from other bacteria.We review the role of the T6SS in response to abiotic factors such as acid stress,oxidation stress,and osmotic stress.This review provides an important reference for exploring the functions of the T6SS in plantassociated bacteria.In addition,characterizing these anti-stress functions of the T6SS may provide new pathways toward eliminating plant pathogens and controlling agricultural losses.展开更多
Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization o...Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization of numerous TA systems in various bacteria,the investigation of these systems within Streptococcus suis is still limited.Here,we systematically analyzed the type Ⅱ TA systems of 95 S.suis genomes available in the GenBank database using TAfinder.A total of 612 putative type Ⅱ TA systems were retrieved and classified into 10 categories by phylogenetic analysis.Notably,an elevated occurrence of these TA systems was observed among the important prevalent serotypes 2,4,5,9,14,Chz,NCL1,and NCL3 strains.The following study identified the activities of TA systems using 2 strategies and confirmed the regulatory effect of HigBA on the type Ⅶ secretion system in S.suis by measuringβ-galactosidase activity and transcriptional changes.Moreover,we unveiled a hitherto uncharacterized,highly prevalent novel TA system,with the composition of antitoxin–toxin–antitoxin(SS-ATA),which regulates the downstream two-component signaling system.Altogether,this study systematically analyzed the type Ⅱ TA systems within S.suis,highlighting the widespread distribution of Hig BA and SS-ATA as important regulatory elements in S.suis.展开更多
Type VII secretion systems(T7SSs)are found in many disease related bacteria including Mycobacterium tuberculosis(Mtb).ESX-1[early secreted antigen 6 kilodaltons(ESAT-6)system 1]is one of the five subtypes(ESX-1?5)of T...Type VII secretion systems(T7SSs)are found in many disease related bacteria including Mycobacterium tuberculosis(Mtb).ESX-1[early secreted antigen 6 kilodaltons(ESAT-6)system 1]is one of the five subtypes(ESX-1?5)of T7SSs in Mfb,where it delivers virulence factors into host macrophages during infection.However,little is known about the molecular details as to how this occurs.Here,we provide high-resolution crystal structures of the C-terminal ATPase3 domains of EccC subunits from four different Mtb T7SS subtypes.These structures adopt a classic RecA-like a/p fold with a conserved Mg-ATP binding site.The structure of EccCbl in complex with the C-terminal peptide of EsxB identifies the location of substrate recognition site and shows how the specific signaling module XxxxMxF"for Mtb ESX-1 binds to this site resulting in a translation of the bulge loop.A comparison of all the ATPase3 structures shows there are significant differences in the shape and composition of the signal recognition pockets across the family,suggesting that distinct signaling sequences of substrates are required to be specifically recognized by different T7SSs.A hexameric model of the EccC-ATPase3 is proposed and shows the recognition pocket is located near the central substrate translocation channel.The diameter of the channel is?25-A,with a size that would allow helix-bundle shaped substrate proteins to bind and pass through.Thus,our work provides new molecular insights into substrate recognition for Mtb T7SS subtypes and also a possible transportation mechanism for substrate and/or virulence factor secretion.展开更多
The type VI secretion system(T6SS)is a double-tubular nanomachine widely found in gram-negative bacteria.Its spear-like Hcp tube is capable of penetrating a neighboring cell for cytosol-to-cytosol protein delivery.How...The type VI secretion system(T6SS)is a double-tubular nanomachine widely found in gram-negative bacteria.Its spear-like Hcp tube is capable of penetrating a neighboring cell for cytosol-to-cytosol protein delivery.However,gram-positive bacteria have been considered impenetrable to such T6SS action.Here we report that the T6SS of a plant pathogen,Acidovorax citrulli(AC),could deliver an Rhsfamily nuclease effector RhsB to kill not only gram-negative but also gram-positive bacteria.Using bioinformatic,biochemical,and genetic assays,we systematically identified T6SS-secreted effectors and determined that RhsB is a crucial antibacterial effector.RhsB contains an N-terminal PAAR domain,a middle Rhs domain,and an unknown C-terminal domain.RhsB is subject to self-cleavage at both its N-and C-terminal domains and its secretion requires the upstream-encoded chaperone EagT2 and VgrG3.The toxic Cterminus of RhsB exhibits DNase activities and such toxicity is neutralized by either of the two downstream immunity proteins,RimB1 and RimB2.Deletion of rhsB significantly impairs the ability of killing Bacillus subtilis while ectopic expression of immunity proteins RimB1 or RimB2 confers protection.We demonstrate that the AC T6SS not only can effectively outcompete Escherichia coli and B.subtilis in planta but also is highly potent in killing other bacterial and fungal species.Collectively,these findings highlight the greatly expanded capabilities of T6SS in modulating microbiome compositions in complex environments.展开更多
A pressure controlled mechanical ventilator with an automatic secretion clearance function can improve secretion clearance safely and efficiently.Studies on secretion clearance by pressure controlled systems show that...A pressure controlled mechanical ventilator with an automatic secretion clearance function can improve secretion clearance safely and efficiently.Studies on secretion clearance by pressure controlled systems show that these are suited for clinical applications.However,these studies are based on a single lung electric model and neglect the coupling between the two lungs.The research methods applied are too complex for the analysis of a multi-parameter system.In order to understand the functioning of the human respiratory system,this paper develops a dimensionless mathematical model of doublelung mechanical ventilation system with a secretion clearance function.An experiment is designed to verify the mathematical model through comparison of dimensionless experimental data and dimensionless simulation data.Finally,the coupling between the two lungs is studied,and an orthogonal experiment designed to identify the impact of each parameter on the system.展开更多
Tannic acid (TA) and TA containing beverage have been proved to inhibit Ca2+-activated Cl- channel located apical membrane of the secretory cells. However, their effect on salivary fluid secretion is not well investig...Tannic acid (TA) and TA containing beverage have been proved to inhibit Ca2+-activated Cl- channel located apical membrane of the secretory cells. However, their effect on salivary fluid secretion is not well investigated. We used mouse ex Vivo submandibular gland perfusion technique to identify the general effect of TA and related beverage samples on muscarinic agonist carbachol induced fluid secretion. Green tea inhibited fluid secretion by 64% from the control, where oolong tea was by 53%, and red wine by 43% which was linked with their TA concentration. On the other hand, though TA was contained at 4.7 μM in white wine sample and 33 μM in coffee extract, no adverse effect was observed. In addition, coffee induced salivation in the absence of carbachol. TA had a negative effect on fluid secretion with a concentration dependent manner. The effects of TA on carbachol induced calcium increase showed identical as fluid secretion, which was initially no effect, and then gradually decreased over the time. These results demonstrate that TA directly inhibits the salivary fluid secretion and it affects not only Ca2+-activated Cl- channel but also intracellular Ca2+ increasing mechanisms.展开更多
Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction d...Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction during type 2 diabetes mellitus(T2DM)progression.Methods:T2DM rat model was established using a high-fat diet and streptozotocin injection.JTP,BBR,and Metformin were intragastrically administered for 35 days.The analyzed indices included blood glucose,blood lipids,islet hormones,and proteins related to 5-HT synthesis,secretion,and transport.Additionally,an in vitro model of glucose injury in islet cells was established to study the effects of JTP and BBR on islet hormone secretion following tryptophan hydroxylase 1(TPH1)inhibition.Results:JTP and BBR significantly improved blood glucose and lipid levels and islet morphology in T2DM rats.Both models exhibited reduced islet 5-HT levels and impaired islet hormone secretion.However,the administration of JTP and BBR reversed these effects.Furthermore,JTP and BBR upregulated the expression of TPH1(P=.0194,P=.0413)transglutaminase 2(TGase2;P=.0492,P=.0349),serotonin transporter(SERT,P=.0090),and 5-hydroxytryptamine 1F receptor(5-HT1FR)in the islet 5-HT pathway(P=.0194).In the cell model,the regulatory effects of JTP and BBR on islet hormone levels were significantly weakened after TPH1 inhibition(P=.001),suggesting that JTP and BBR influence islet hormone secretion through the pancreatic 5-HT system.Conclusion:The islet 5-HT system is correlated with islet hormone secretion dysfunction in T2DM.JTP and BBR can improve islet hormone secretion by activating the TPH1/TGase2/SERT/5-HT1FR pathway in the islet 5-HT system in T2DM rats.展开更多
BACKGROUND Autonomous cortisol secretion(ACS)is linked to a higher prevalence of metabolic abnormalities and an increased risk of major adverse cardiovascular events.AIM To evaluate glucose and bone metabolism in pati...BACKGROUND Autonomous cortisol secretion(ACS)is linked to a higher prevalence of metabolic abnormalities and an increased risk of major adverse cardiovascular events.AIM To evaluate glucose and bone metabolism in patients with ACS using a continuous glucose monitoring system(CGMS)and dual-energy X-ray absorptiometry(DXA).METHODS Patients diagnosed with ACS,including Cushing syndrome,mild ACS(MACS),and nonfunctional adrenal incidentaloma(NFAI),were recruited for this study.Glucose variability and glycemic status were assessed using CGMS.Regional bone mineral content(BMC),bone mineral density(BMD),and bone area(BA)were evaluated using DXA.CGMS-and DXA-derived parameters were compared across the subgroups of ACS.Correlation analysis was performed to examine relationships between varying degrees of cortisol secretion,measured by cortisol after 1 mg overnight dexamethasone suppression test(DST)or 24-hour urine free cortisol(24h UFC),and CGMS-or DXA-derived parameters.RESULTS A total of 64 patients with ACS were included in this study:19 with Cushing syndrome,11 with MACS,and 34 with NFAI.Glucose variability,time above range(TAR),and time in range(TIR)along with specific areal BMC,BMD,and BA,differed significantly between groups of Cushing syndrome and NFAI.A significant positive correlation was observed between glucose variability or TAR and cortisol after 1 mg overnight DST or 24h UFC.By contrast,TIR,along with regional BMC,BMD,and BA,were negatively correlated with varying degrees of cortisol secretion.CONCLUSION Glucose and bone metabolism impairments are on a continuum alteration from NFAI to MACS and Cushing syndrome.Prompt attention should be given to these patients with ACS,especially those with mild hormone secretion.Parameters of glucose variability and glycemic status along with bone condition in regions rich in cancellous bone will provide valuable information.展开更多
Recent studies have shown that mucilage secretion from aerial roots is an essential feature of modern maize inbred lines,with some retaining the nitrogen-fixing capabilities of ancient landraces.To explore the genetic...Recent studies have shown that mucilage secretion from aerial roots is an essential feature of modern maize inbred lines,with some retaining the nitrogen-fixing capabilities of ancient landraces.To explore the genetic basis of nitrogen fixation in mucilage and its evolution from teosinte(Zea mays ssp.mexicana)to modern maize,we developed a recombinant inbred line(RIL)population from teosinte and cultivated it under low-nitrogen conditions.Large-scale,multi-year,and multi-environment analyses of RIL-Teo,Doubled Haploid-A(DH-A),Doubled Haploid-B(DH-B),and association populations led to the identification of 15 quantitative trait loci(QTL),68 quantitative trait nucleotides(QTN),and 59 candidate genes linked to mucilage secretion from aerial roots.Functional verification of the candidate gene ZmAco3,which is associated with mucilage secretion in aerial roots,demonstrated that deletion of this gene resulted in a reduction in mucilage secretion in aerial roots.In addition,most maize inbred lines exhibited stronger mucilage secretion from aerial roots under low-nitrogen conditions than under normal-nitrogen conditions.We categorized mucilage secretion into constitutive and low-nitrogen-inducible types.Through genotype-by-environment interaction studies,8 QTL,16 QTN,and 19 candidate genes were identified,revealing the genetic mechanisms underlying mucilage secretion under low-nitrogen conditions.These findings provide a comprehensive genetic analysis of the mucilage-secreting ability of maize aerial roots,contributing to our understanding of nitrogen fixation and offering potential avenues for enhancing nitrogen fixation in modern maize lines.This research advances knowledge of plant nutrient acquisition strategies and has implications for sustainable agricultural practices.展开更多
基金the financial support from the National Key Research and Development Program of China(No.2023YFD1701100)the National Natural Science Foundation of China(No.32072450)+2 种基金the National Science Fund for Distinguished Young Scholars of Guangdong Province(No.2021B1515020107)the Opening Foundation of Hubei Key Laboratory of Novel Reactor and Green Chemical Technology(No.NRG202306)the Opening Foundation of Guangdong Province Key Laboratory of Microbial Signals and Disease Control(No.MSDC2023-19)。
文摘Plant bacterial diseases have infiicted substantial economic losses in global crop,fruit,and vegetable production.The conventional methods for managing these diseases typically rely on the application of antibiotics.However,these antibiotics often target the growth factors of the pathogenic bacteria,leading to the accumulation and emergence of drug-resistant strains,which exacerbates antibiotic resistance.Innovative methods are urgently needed to treat and prevent the toxicity caused by these pathogenic bacteria.Targeting virulence mechanisms in pathogens is a globally recognized and effective strategy for mitigating bacterial resistance.TypeⅢsecretion system(T3SS)serves as a crucial virulence determinant in Gram-negative pathogens,and its non-essentials for pathogen growth renders it an ideal target.Targeting the T3SS holds significant potential to alleviate selective pressure for resistance mutations in pathogens.Therefore,targeting T3SS in pathogenic bacteria,while preserving their growth,has emerged as a novel avenue for the development of antimicrobial drugs.In recent years,a multitude of small molecular inhibitors targeting T3SS have been identified.This article offers a comprehensive review of T3SS inhibitors in plant pathogens,while also presenting the latest research advancements in this research direction.
基金supported by the National Natural Science Foundation of China (No. 81201322)the Priority Project on Infectious Disease Control and Prevention 2011ZX10004-001 and 2013ZX10003006-002 by the Chinese Ministry of Science and Technology and the Chinese Ministry of Healththe Foundation of State Key Laboratory for Infectious Disease Prevention and Control (Grand No. 2011SKLID303)
文摘Secretion systems, macromolecules to pass which can mediate the across cellular membranes, are essential for virulent and genetic material exchange among bacterial species[1]. Type IV secretion system （T4SS） is one of the secretion systems and it usually consists of 12 genes： VirB1, VirB2 ...VirB11, and VirD4[2]. The structure and molecular mechanisms of these genes have been well analyzed in Gram-negative strains[3] and Gram-positive strains were once believed to be lack of T4SS. However, some recent studies revealed that one or more virB/D genes also exist in some kinds of Gram-positive bacteria and play similar role, and form a T4SS-like system[3]. The VirBl-like, VirB4, VirB6, and VirD4 genes were identified in the chromosome of Gram-positive bacterium Streptococcus suis in our previous studies and their role as important mobile elements for horizontal transfer to recipients in an 89 K pathogenicity island （PAl） was demonstrated[45]. However, their structure and molecular mechanisms in other strains, especially in Gram-positive strains, are remained unclear.
基金Supported by National Natural Science Foundation of China(31402344,31572656)Major Program of Natural Science Foundation of Guangdong Province(2015A030308020)
文摘In order to enrich the research about type III secretion system （T3SS） injectisome of Vibrio alginolyticus, vscX gene was cloned from E algianlyticus strain HY9901 for bioinformatics analysis and expression analysis. Specific primers were designed according to the full-length geanme sequence of V. alginolyticus in GenBank. vscX gene （C, enBank accession number： FR780679） contained a 378 bp open reading frame （ORF）, encoding a putative protein of 125 amino acids. The theoretical molecular weight was 14.209 2 kD and theoretical pI was 5.75. By using Signal 4.1 Server and TMHMM Server 2.0, it was predicted that VscX protein had no transmembrane domain or signal peptide. The results of prediction using SoftBerry-Psite software showed that VscX protein contained three casein ki- nase lI phosphorylation sites, one N-myristoylation site and three C-terminal targeting signal sites. Subcellular localization revealed that VscX might be located in cytoplasm with the possibility of 56.5%. According to SMART prediction, VscX had one Pfam （ 1 - 125 aa） domain. Phylogenetic analysis revealed that VscX from V. alginolyticus and VscX from E parahemolyticus were clustered into the same group. Network interaction analysis showed that vscX was adjacent to vseY, vopB and sycN. By real-time fluorescent quantitative PCR technique and 2-△△△ method, the differences in expression levels of VscX mRNA in V. alginolyticus strain HY9901, T3SS deletion strain AvscO and complementary strain C-vscO at different growth stages were analyzed. The results showed that the expression levels of VscX mRNA in V. algianlyticus strain HY9901 and C-vscO were significantly up-regulated at stable growth stage （ P 〈0.01 ） ; the expression levels of VscX mRNA in deletion strain △vscO were significantly up-regulated at late growth stage （ P 〈0.01 ）. This study provided the basis for revealing the transport mechanism of T3SS injectisome of E alginolyticus.
文摘BACKGROUND Human milk oligosaccharides(HMOs)are bioactive components of breast milk with diverse health benefits,including shaping the gut microbiota,modulating the immune system,and protecting against infections.HMOs exhibit dynamic secretion patterns during lactation,influenced by maternal genetics and environ-mental factors.Their direct and indirect antimicrobial properties have garnered significant research interest.However,a comprehensive understanding of the secretion dynamics of HMOs and their correlation with antimicrobial efficacy remains underexplored.AIM To synthesize current evidence on the secretion dynamics of HMOs during lactation and evaluate their antimicrobial roles against bacterial,viral,and protozoal pathogens.METHODS A systematic search of PubMed,Scopus,Web of Science,and Cochrane Library focused on studies investigating natural and synthetic HMOs,their secretion dynamics,and antimicrobial properties.Studies involving human,animal,and in vitro models were included.Data on HMO composition,temporal secretion patterns,and mechanisms of antimicrobial action were extracted.Quality assess-ment was performed using validated tools appropriate for study design.RESULTS A total of 44 studies were included,encompassing human,animal,and in vitro research.HMOs exhibited dynamic secretion patterns,with 2′-fucosyllactose(2′-FL)and lacto-N-tetraose peaking in early lactation and declining over time,while 3-fucosyllactose(3-FL)increased during later stages.HMOs demonstrated significant antimicrobial properties through pathogen adhesion inhibition,biofilm disruption,and enzymatic activity impairment.Synthetic HMOs,including bioengineered 2′-FL and 3-FL,were structurally and functionally comparable to natural HMOs,effectively inhibiting pathogens such as Pseudomonas aeruginosa,Escherichia coli,and Campylobacter jejuni.Additionally,HMOs exhibited synergistic effects with antibiotics,enhancing their efficacy against resistant pathogens.CONCLUSION HMOs are vital in antimicrobial defense,supporting infant health by targeting various pathogens.Both natural and synthetic HMOs hold significant potential for therapeutic applications,particularly in infant nutrition and as adjuncts to antibiotics.Further research,including clinical trials,is essential to address gaps in knowledge,validate findings,and explore the broader applicability of HMOs in improving maternal and neonatal health.
基金supported by the Youth innovation Program of Chinese Academy of Agricultural Sciences(No.Y2023QC32)the foundation of Tianjin Natural Science Foundation(No.22JCQNJC01460)the Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences(Agro-Environmental Protection Institute,Ministry of Agricultural and Rural Affairs)and the Youth Talent Project of Agro-Environmental Protection Institute,Ministry of Agricultural and Rural Affairs(Xu Yan).
文摘The exponential growth of antibiotic-resistant bacteria and antibiotic-resistant genes(ARGs)in soil-crop systems in recent years has posed a great challenge to ecological security and human health.While many studies have documented the residues of ARGs in soils and crops,but little is known about who drives the proliferation of ARGs in farming systems and what their underlying mechanisms are.Herein,we explored the occurrence and proliferating behavior of ARGs in soil-crop environments in terms of root secretions and plant volatiles.This review highlighted that plant root secretions and volatile organic compounds(VOCs)served as key substances mediating the development of antibiotic resistance in the soil-crop system.Still,there is controversy here as to plant root secretions promote the ARGs proliferation or inhibit.Some studies indicated that root secretions can suppress the colonization of ARGs,mainly attributed by the production of bluntedmetabolic enzymes and blocking of cellular exocytosis systems.Whereas the others have evidenced that root secretions can promote ARGs proliferation,primarily by altering the structure of microbial communities to influence species interactions and thus indirectly affect the proliferation of ARGs.Also,VOCs can act as molecular signals to convey antibiotic resistance information to their neighbors,which in turn drive the up-regulation of ARGs expression.Even so,the mechanism by which VOC-driven antibiotic resistance acquisition and proliferation need to be further probed.Overall,this review contributed to the development of products and technologies to impede the ARGs proliferation in agricultural environment.
基金the Research Plan of Jiangsu Provincial Technology Commission (No.BS2004021)the Advanced Talent Research Plan of Jiangsu University(No.JDG2004008).
文摘Objective To review the research progress on Type Ⅳ secretion system （T4SS） in HelicobacterpylorL Data sources The data used in this review were identified by searching of PUBMED （1995-2007） online resources using the key terms ＇Type Ⅳ secretion system＇ and ＇Helicobacter pylon. Study selection Mainly original articles and critical reviews written by major pioneer investigators of this field were selected. Results The research progress on T4SS in Helicobacter pylori was summarized. The structure and function was discussed. Conclusions T4SS is not only involved in toxin secretion and injection of virulence factors into eukaryotic host target cells, but also involved in horizontal DNA transfer to other bacteria and eukaryotic cells, through DNA uptake from or release into the extracellular milieu. It provides a new insight into the pathogenicity of Helicobacter pylori and a novel target for antimicrobials development. However, many challenges remain for us in understanding the biological role of T4SS in Helicobacter pylori.
基金supported by the Science and Technology Commission of Shanghai Municipality(19430750600,19JC1413000)the National Natural Science Foundation of China(31670074)+1 种基金the Medical Excellence Award Funded by the Creative Research Development Grant from the First Affiliated Hospital of Guangxi Medical University(XK2019025)the Science Fund of the Republic of Serbia(7750294,q-bio BDS)。
文摘TypeⅥSecretion System(T6SS)plays significant roles in microbial activities via injecting effectors into adjacent cells or environments.T6SS increasingly gained attention due to its important influence on pathogenesis,microbial competition,etc.T6SS-associated research is explosively expanding on numerous grounds that call for an efficient resource.The SecReT6 version3 provides comprehensive information on T6SS and the interactions between T6SS and T6SS-related proteins such as T6SS regulators and T6SS effectors.To assist T6SS researches like microbial competition and regulatory mechanisms,SecReT6 v3developed online tools for detection and analysis of T6SS and T6SS-related proteins and estimation of T6SS-dependent killing risk.We have identified a novel T6SS regulator and T6SS-dependent killing capacity in Acinetobacter baumannii clinical isolates with the aid of SecReT6 v3.17,212 T6SSs and plentiful T6SS-related proteins in 26,573 bacterial complete genomes were also detected,analyzed and incorporated into the database.The database is freely available at https://bioinfo-mml.sjtu.edu.cn/SecReT6/.
基金supported by the grant of the National Key R&D Program of China(2018YFA0901200)the National Natural Science Foundation of China(31725003,32070103,31860012 and 31800113).L.X.is supported by China Postdoctoral Science Foundation(2018 M631201)and Shaanxi Postdoctoral Science Foundation(2018BSHTDZZ20).
文摘Bacteria inhabit diverse and dynamic environments,where nutrients may be limited and toxic chemicals can be prevalent.To adapt to these stressful conditions,bacteria have evolved specialized protein secretion systems,such as the type VI secretion system(T6SS)to facilitate their survival.As a molecular syringe,the T6SS expels various effectors into neighboring bacterial cells,eukaryotic cells,or the extracellular environment.These effectors improve the competitive fitness and environmental adaption of bacterial cells.Although primarily recognized as antibacterial weapons,recent studies have demonstrated that T6SSs have functions beyond interspecies competition.Here,we summarize recent research on the role of T6SSs in microbiome modulation,pathogenesis,and stress resistance.
基金This work was supported by funds from the National Basic Research Program(973 Program)(Nos.2011CB911104 and 2012CB917202)the National Natural Science Foundation of China(Grant No.31100538)to F.W.,(Grant No.31170817)to C.T.
文摘Mycosin-1 protease(MycP1)is a serine protease anchored to the inner membrane of Mycobacterium tuberculosis,and is essential in virulence factor secretion through the ESX-1 type VII secretion system(T7SS).Bacterial physiology studies demonstrated that MycP1 plays a dual role in the regulation of ESX-1 secretion and virulence,primarily through cleavage of its secretion substrate EspB.MycP1 contains a putative N-terminal inhibitory propeptide and a catalytic triad of Asp-His-Ser,classic hallmarks of a sub-tilase family serine protease.The MycP1 propeptide was previously reported to be initially inactive and activated after prolonged incubation.In this study,we have deter-mined crystal structures of MycP1 with(MycP124-422)and without(MycP1^(63-422))the propeptide,and conducted EspB cleavage assays using the two proteins.Very high struc-tural similarity was observed in the two crystal structures.Interestingly,protease assays demonstrated positive EspB cleavage for both proteins,indicating that the putative propeptide does not inhibit protease activity.Molecu-lar dynamic simulations showed higher rigidity in regions guarding the entrance to the catalytic site in MycP124-422 than in MycP1^(63-422),suggesting that the putative propeptide might contribute to the conformational stability of the active site cleft and surrounding regions.
基金supported by grants of the National Key R&D Program of China(Grants 2018YFA0901200)National Natural Science Foundation of China(Grants 31725003,31970114,32100034,and 32100149)+2 种基金Scientific Startup Foundation for Doctors of Northwest A and F University(Z1090122001 and Z1090122002)the China Postdoctoral Science Foundation(Grant 2020 M673501)Young Talent Support Program of Shaanxi Province University(20220206).
文摘The type Ⅵ secretion system(T6SS)is a widespread protein secretion apparatus deployed by many Gram-negative bacterial species to interact with competitor bacteria,host organisms,and the environment.Yersinia pseudotuber-culosis T6SS4 was recently reported to be involved in manganese acquisition;however,the underlying regulatory mechanism still remains unclear.In this study,we discovered that T6SS4 is regulated by ferric uptake regulator(Fur)in response to manganese ions(Mn^(2+)),and this negative regulation of Fur was proceeded by specifically recogniz-ing the promoter region of T6SS4 in Y.pseudotuberculosis.Furthermore,T6SS4 is induced by low Mn^(2+)and oxidative stress conditions via Fur,acting as a Mn^(2+)-responsive transcriptional regulator to maintain intracellular manganese homeostasis,which plays important role in the transport of Mn^(2+)for survival under oxidative stress.Our results pro-vide evidence that T6SS4 can enhance the oxidative stress resistance and virulence for Y.pseudotuberculosis.This study provides new insights into the regulation of T6SS4 via the Mn^(2+)-dependent transcriptional regulator Fur,and expands our knowledge of the regulatory mechanisms and functions of T6SS from Y.pseudotuberculosis.
文摘Many bacterial pathogens utilize specialized secretion systems to deliver virulence factors into the extracellular milieu. These exported effectors act to manipulate various processes of targeted cells in order to create a suitable niche for bacterial growth. Currently, seven different types of secretion system have been described, of which Type I - VI are mainly present in Gram-negative bacteria and the newly discovered Type VII system seems exclusive to Gram-positive species. This review summaries our current understanding on the architecture and transport mechanisms of each secretion apparatus. We also discuss recent studies revealing the roles that these secretion systems and their substrates play in microbial pathogenesis.
基金supported by the National Natural Science Foundation of China(32070103)the Qinchuang Yuan“Scientist+Engineer”Team Construction Project of Shaanxi Province(2023KXJ-019)+2 种基金the Regional Development Talent Project of the“Special Support Plan”of Shaanxi Province 2020-44a grant from the Outstanding Young Talent Support Plan of the Higher Education Institutions of Shaanxi Province 2018-111the Youth Innovation Team of Shaanxi Universities 2022-943.
文摘The type VI secretion system(T6SS)is a powerful bacterial molecular weapon that can inject effector proteins into prokaryotic or eukaryotic cells,thereby participating in the competition between bacteria and improving bacterial environmental adaptability.Although most current studies of the T6SS have focused on animal bacteria,this system is also significant for the adaptation of plant-associated bacteria.This paper briefly introduces the structure and biological functions of the T6SS.We summarize the role of plant-associated bacterial T6SS in adaptability to host plants and the external environment,including resistance to biotic stresses such as host defenses and competition from other bacteria.We review the role of the T6SS in response to abiotic factors such as acid stress,oxidation stress,and osmotic stress.This review provides an important reference for exploring the functions of the T6SS in plantassociated bacteria.In addition,characterizing these anti-stress functions of the T6SS may provide new pathways toward eliminating plant pathogens and controlling agricultural losses.
基金supported by the National Key Research and Development Program of China(2022YFD1800904)the National Natural Science Foundation of China(31972650 and 32102673)+1 种基金the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(KYCX22_0780)the China Postdoctoral Science Foundation(2020M682297)。
文摘Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization of numerous TA systems in various bacteria,the investigation of these systems within Streptococcus suis is still limited.Here,we systematically analyzed the type Ⅱ TA systems of 95 S.suis genomes available in the GenBank database using TAfinder.A total of 612 putative type Ⅱ TA systems were retrieved and classified into 10 categories by phylogenetic analysis.Notably,an elevated occurrence of these TA systems was observed among the important prevalent serotypes 2,4,5,9,14,Chz,NCL1,and NCL3 strains.The following study identified the activities of TA systems using 2 strategies and confirmed the regulatory effect of HigBA on the type Ⅶ secretion system in S.suis by measuringβ-galactosidase activity and transcriptional changes.Moreover,we unveiled a hitherto uncharacterized,highly prevalent novel TA system,with the composition of antitoxin–toxin–antitoxin(SS-ATA),which regulates the downstream two-component signaling system.Altogether,this study systematically analyzed the type Ⅱ TA systems within S.suis,highlighting the widespread distribution of Hig BA and SS-ATA as important regulatory elements in S.suis.
基金We are extremely grateful to the National Centre for Protein Science Shanghai(Protein Expression and Purification System)for their instrumental support and technical assistance.We thank the staff from beamlines BL18U and BL19U1 at Shanghai Synchrotron Radiation Facility(Shanghai,China)and beamline BL41XU at SPring-8(Hyogo,Japan)for assistance during data collection.We also thank Prof.Rongguang Zhang and Dr.Jinwei Zhu for providing laboratory resources.This work was supported by Grants from the National Key Research and Development Program of China(Grant No.2017YFC0840300)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB08020200)the National Natural Science Foundation of China(Grant Nos.81520108019,31500607).
文摘Type VII secretion systems(T7SSs)are found in many disease related bacteria including Mycobacterium tuberculosis(Mtb).ESX-1[early secreted antigen 6 kilodaltons(ESAT-6)system 1]is one of the five subtypes(ESX-1?5)of T7SSs in Mfb,where it delivers virulence factors into host macrophages during infection.However,little is known about the molecular details as to how this occurs.Here,we provide high-resolution crystal structures of the C-terminal ATPase3 domains of EccC subunits from four different Mtb T7SS subtypes.These structures adopt a classic RecA-like a/p fold with a conserved Mg-ATP binding site.The structure of EccCbl in complex with the C-terminal peptide of EsxB identifies the location of substrate recognition site and shows how the specific signaling module XxxxMxF"for Mtb ESX-1 binds to this site resulting in a translation of the bulge loop.A comparison of all the ATPase3 structures shows there are significant differences in the shape and composition of the signal recognition pockets across the family,suggesting that distinct signaling sequences of substrates are required to be specifically recognized by different T7SSs.A hexameric model of the EccC-ATPase3 is proposed and shows the recognition pocket is located near the central substrate translocation channel.The diameter of the channel is?25-A,with a size that would allow helix-bundle shaped substrate proteins to bind and pass through.Thus,our work provides new molecular insights into substrate recognition for Mtb T7SS subtypes and also a possible transportation mechanism for substrate and/or virulence factor secretion.
基金funding from the National Key R&D Program of China(2020YFA0907200)National Natural Science Foundation of China(31770082,32030001).
文摘The type VI secretion system(T6SS)is a double-tubular nanomachine widely found in gram-negative bacteria.Its spear-like Hcp tube is capable of penetrating a neighboring cell for cytosol-to-cytosol protein delivery.However,gram-positive bacteria have been considered impenetrable to such T6SS action.Here we report that the T6SS of a plant pathogen,Acidovorax citrulli(AC),could deliver an Rhsfamily nuclease effector RhsB to kill not only gram-negative but also gram-positive bacteria.Using bioinformatic,biochemical,and genetic assays,we systematically identified T6SS-secreted effectors and determined that RhsB is a crucial antibacterial effector.RhsB contains an N-terminal PAAR domain,a middle Rhs domain,and an unknown C-terminal domain.RhsB is subject to self-cleavage at both its N-and C-terminal domains and its secretion requires the upstream-encoded chaperone EagT2 and VgrG3.The toxic Cterminus of RhsB exhibits DNase activities and such toxicity is neutralized by either of the two downstream immunity proteins,RimB1 and RimB2.Deletion of rhsB significantly impairs the ability of killing Bacillus subtilis while ectopic expression of immunity proteins RimB1 or RimB2 confers protection.We demonstrate that the AC T6SS not only can effectively outcompete Escherichia coli and B.subtilis in planta but also is highly potent in killing other bacterial and fungal species.Collectively,these findings highlight the greatly expanded capabilities of T6SS in modulating microbiome compositions in complex environments.
文摘A pressure controlled mechanical ventilator with an automatic secretion clearance function can improve secretion clearance safely and efficiently.Studies on secretion clearance by pressure controlled systems show that these are suited for clinical applications.However,these studies are based on a single lung electric model and neglect the coupling between the two lungs.The research methods applied are too complex for the analysis of a multi-parameter system.In order to understand the functioning of the human respiratory system,this paper develops a dimensionless mathematical model of doublelung mechanical ventilation system with a secretion clearance function.An experiment is designed to verify the mathematical model through comparison of dimensionless experimental data and dimensionless simulation data.Finally,the coupling between the two lungs is studied,and an orthogonal experiment designed to identify the impact of each parameter on the system.
文摘Tannic acid (TA) and TA containing beverage have been proved to inhibit Ca2+-activated Cl- channel located apical membrane of the secretory cells. However, their effect on salivary fluid secretion is not well investigated. We used mouse ex Vivo submandibular gland perfusion technique to identify the general effect of TA and related beverage samples on muscarinic agonist carbachol induced fluid secretion. Green tea inhibited fluid secretion by 64% from the control, where oolong tea was by 53%, and red wine by 43% which was linked with their TA concentration. On the other hand, though TA was contained at 4.7 μM in white wine sample and 33 μM in coffee extract, no adverse effect was observed. In addition, coffee induced salivation in the absence of carbachol. TA had a negative effect on fluid secretion with a concentration dependent manner. The effects of TA on carbachol induced calcium increase showed identical as fluid secretion, which was initially no effect, and then gradually decreased over the time. These results demonstrate that TA directly inhibits the salivary fluid secretion and it affects not only Ca2+-activated Cl- channel but also intracellular Ca2+ increasing mechanisms.
基金supported by the National Natural Science Foundation of China(81673680)the Fundamental Research Funds for the Central Public Welfare Research Institutes(YZX-202306).
文摘Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction during type 2 diabetes mellitus(T2DM)progression.Methods:T2DM rat model was established using a high-fat diet and streptozotocin injection.JTP,BBR,and Metformin were intragastrically administered for 35 days.The analyzed indices included blood glucose,blood lipids,islet hormones,and proteins related to 5-HT synthesis,secretion,and transport.Additionally,an in vitro model of glucose injury in islet cells was established to study the effects of JTP and BBR on islet hormone secretion following tryptophan hydroxylase 1(TPH1)inhibition.Results:JTP and BBR significantly improved blood glucose and lipid levels and islet morphology in T2DM rats.Both models exhibited reduced islet 5-HT levels and impaired islet hormone secretion.However,the administration of JTP and BBR reversed these effects.Furthermore,JTP and BBR upregulated the expression of TPH1(P=.0194,P=.0413)transglutaminase 2(TGase2;P=.0492,P=.0349),serotonin transporter(SERT,P=.0090),and 5-hydroxytryptamine 1F receptor(5-HT1FR)in the islet 5-HT pathway(P=.0194).In the cell model,the regulatory effects of JTP and BBR on islet hormone levels were significantly weakened after TPH1 inhibition(P=.001),suggesting that JTP and BBR influence islet hormone secretion through the pancreatic 5-HT system.Conclusion:The islet 5-HT system is correlated with islet hormone secretion dysfunction in T2DM.JTP and BBR can improve islet hormone secretion by activating the TPH1/TGase2/SERT/5-HT1FR pathway in the islet 5-HT system in T2DM rats.
基金Supported by National Natural Science Foundation of China(General Program),No.82073909Four‘Batches’Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province,No.2023XM022The Shanxi Provincial Central Leading Local Science and Technology Development Fund Project,No.YDZJSX2022A059 and No.YDZJSX20231A059。
文摘BACKGROUND Autonomous cortisol secretion(ACS)is linked to a higher prevalence of metabolic abnormalities and an increased risk of major adverse cardiovascular events.AIM To evaluate glucose and bone metabolism in patients with ACS using a continuous glucose monitoring system(CGMS)and dual-energy X-ray absorptiometry(DXA).METHODS Patients diagnosed with ACS,including Cushing syndrome,mild ACS(MACS),and nonfunctional adrenal incidentaloma(NFAI),were recruited for this study.Glucose variability and glycemic status were assessed using CGMS.Regional bone mineral content(BMC),bone mineral density(BMD),and bone area(BA)were evaluated using DXA.CGMS-and DXA-derived parameters were compared across the subgroups of ACS.Correlation analysis was performed to examine relationships between varying degrees of cortisol secretion,measured by cortisol after 1 mg overnight dexamethasone suppression test(DST)or 24-hour urine free cortisol(24h UFC),and CGMS-or DXA-derived parameters.RESULTS A total of 64 patients with ACS were included in this study:19 with Cushing syndrome,11 with MACS,and 34 with NFAI.Glucose variability,time above range(TAR),and time in range(TIR)along with specific areal BMC,BMD,and BA,differed significantly between groups of Cushing syndrome and NFAI.A significant positive correlation was observed between glucose variability or TAR and cortisol after 1 mg overnight DST or 24h UFC.By contrast,TIR,along with regional BMC,BMD,and BA,were negatively correlated with varying degrees of cortisol secretion.CONCLUSION Glucose and bone metabolism impairments are on a continuum alteration from NFAI to MACS and Cushing syndrome.Prompt attention should be given to these patients with ACS,especially those with mild hormone secretion.Parameters of glucose variability and glycemic status along with bone condition in regions rich in cancellous bone will provide valuable information.
基金supported by the National Natural Science Foundation of China(32401919)the Department of Science and Technology of Henan Province(242102111126).
文摘Recent studies have shown that mucilage secretion from aerial roots is an essential feature of modern maize inbred lines,with some retaining the nitrogen-fixing capabilities of ancient landraces.To explore the genetic basis of nitrogen fixation in mucilage and its evolution from teosinte(Zea mays ssp.mexicana)to modern maize,we developed a recombinant inbred line(RIL)population from teosinte and cultivated it under low-nitrogen conditions.Large-scale,multi-year,and multi-environment analyses of RIL-Teo,Doubled Haploid-A(DH-A),Doubled Haploid-B(DH-B),and association populations led to the identification of 15 quantitative trait loci(QTL),68 quantitative trait nucleotides(QTN),and 59 candidate genes linked to mucilage secretion from aerial roots.Functional verification of the candidate gene ZmAco3,which is associated with mucilage secretion in aerial roots,demonstrated that deletion of this gene resulted in a reduction in mucilage secretion in aerial roots.In addition,most maize inbred lines exhibited stronger mucilage secretion from aerial roots under low-nitrogen conditions than under normal-nitrogen conditions.We categorized mucilage secretion into constitutive and low-nitrogen-inducible types.Through genotype-by-environment interaction studies,8 QTL,16 QTN,and 19 candidate genes were identified,revealing the genetic mechanisms underlying mucilage secretion under low-nitrogen conditions.These findings provide a comprehensive genetic analysis of the mucilage-secreting ability of maize aerial roots,contributing to our understanding of nitrogen fixation and offering potential avenues for enhancing nitrogen fixation in modern maize lines.This research advances knowledge of plant nutrient acquisition strategies and has implications for sustainable agricultural practices.
