Plant stomata close rapidly in response to a rise in the plant hormone abscisic acid(ABA)or salicylic acid(SA)and after recognition of pathogenassociated molecular patterns(PAMPs).Stomatal closure is the result of vac...Plant stomata close rapidly in response to a rise in the plant hormone abscisic acid(ABA)or salicylic acid(SA)and after recognition of pathogenassociated molecular patterns(PAMPs).Stomatal closure is the result of vacuolar convolution,ion efflux,and changes in turgor pressure in guard cells.Phytopathogenic bacteria secrete typeⅢeffectors(T3Es)that interfere with plant defense mechanisms,causing severe plant disease symptoms.Here,we show that the virulence and infection of Xanthomonas oryzae pv.oryzicola(Xoc),which is the causal agent of rice bacterial leaf streak disease,drastically increased in transgenic rice(Oryza sativa L.)plants overexpressing the Xoc T3E gene Xop AP,which encodes a protein annotated as a lipase.We discovered that Xop AP binds to phosphatidylinositol 3,5-bisphosphate(Ptd Ins(3,5)P_(2)),a memb rane phospholipid that functions in p H control in lysosomes,membrane dynamics,and protein trafficking.Xop AP inhibited the acidification of vacuoles by competing with vacuolar H^(+)-pyrophosphatase(V-PPase)for binding to Ptd Ins(3,5)P_(2),leading to stomatal opening.Transgenic rice overexpressing Xop AP also showed inhibition of stomatal closure when challenged by Xoc infection and treatment with the PAMP flg22.Moreover,Xop AP suppressed flg22-induced gene expression,reactive oxygen species burst and callose deposition in host plants,demonstrating that Xop AP subverts PAMP-triggered immunity during Xoc infection.Taken together,these findings demonstrate that Xop AP overcomes stomatal immunity in plants by binding to lipids.展开更多
The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of pro...The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of proinflammatory cytokines and reactive oxygen species, phagocytosis, and induced programmed cell death are processes initiated by innate immune cells in order to combat invading pathogens. However, pathogens have evolved various virulence mechanisms to subvert these responses. One strategy utilized by Gram-negative bacterial pathogens is the deployment of a complex machine termed the type Ⅲ secretion system(T3SS). The T3SS is composed of a syringe-like needle structure and the effector proteins that are injected directly into a target host cell to disrupt a cellular response. The three human pathogenic Yersinia spp.(Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis) are Gramnegative bacteria that share in common a 70 kb virulence plasmid which encodes the T3 SS. Translocation of the Yersinia effector proteins(YopE, YopH, YopT, YopM, YpkA/YopO, and YopP/J) into the target host cell results in disruption of the actin cytoskeleton to inhibit phagocytosis, downregulation of proinflammatory cytokine/chemokine production, and induction of cellular apoptosis of the target cell. Over the past 25 years, studies on the Yersinia effector proteins have unveiled tremendous knowledge of how the effectors enhance Yersinia virulence. Recently, the long awaited crystal structure of YpkA has been solved providing further insights into the activation of the YpkA kinase domain. Multisite autophosphorylation by YpkA to activate its kinase domain was also shown and postulated to serve as a mechanism to bypass regulation by host phosphatases. In addition, novel Yersinia effector protein targets, such as caspase-1, and signaling pathways including activation of the inflammasome were identified. In this review, we summarize the recent discoveries made on Yersinia effector proteins and their contribution to Yersinia pathogenesis.展开更多
Ralstonia solanacearum is a widespread plant bacterial pathogen that can launch a range of type Ⅲ effectors(T3Es)to cause disease.In this study,we isolate a pathogenic R.solanacearum strain named P380 from tomato rhi...Ralstonia solanacearum is a widespread plant bacterial pathogen that can launch a range of type Ⅲ effectors(T3Es)to cause disease.In this study,we isolate a pathogenic R.solanacearum strain named P380 from tomato rhizosphere.Five out of 12 core T3Es of strain P380 are introduced into Pseudomonas syringae DC3000D36E separately to determine their functions in interacting with plants.DC3000D36E that harbors each effector suppresses FliC-triggered Pti5 and ACRE31 expression,ROS burst,and callose deposition.RipAE,RipU,and RipW elicit cell death as well as upregulate the MAPK cascades in Nicotiana benthamiana.The derivatives RipC1^(△DDXDX(T/V))and RipW^(△DDKXXQ)but not RipAE^(K310R) fail to suppress ROS burst.Moreover,RipAE^(K310R) and RipW^(△DDKXXQ) retain the cell death elicitation ability.RipAE and RipW are associated with salicylic acid and jasmonic acid pathways,respectively.RipAE and RipAQ significantly promote the propagation of DC3000D36E in plants.The five core T3Es localize in diverse subcellular organelles of nucleus,plasma membrane,endoplasmic reticulum,and Golgi network.The suppressor of G2 allele of Skp1 is required for RipAE but not RipU-triggered cell death in N.benthamiana.These results indicate that the core T3Es in R.solanacearum play diverse roles in plantpathogen interactions.展开更多
In this study, Va 1686 gene was cloned from Vibrio alginolyticus . The total length of the gene is 1 164 bp, and it could encode 387 amino acids. The physicochemical properties, protein structure, genetic evolutionary...In this study, Va 1686 gene was cloned from Vibrio alginolyticus . The total length of the gene is 1 164 bp, and it could encode 387 amino acids. The physicochemical properties, protein structure, genetic evolutionary relationship and antigenic characteristics of the effect protein Va1686 of V. alginolyticus HY9901 type Ⅲ secretion system were studied and analyzed by bioinformatics methods and tools. The results showed that Va1686 is a stable hydrophilic and acidic protein without a transmembrane region and a signal peptide, and secondary structure to α-helix. The evolutionary analysis showed that V. alginolyticus HY9901 and V. harveyi were clustered together, which indicated that the genetic relationship between the two species was the closest. Va1686 contains a Fic superfamily conserved domain associated with cell division. Bioinformatics analysis showed that the B-cell preponderant epitopes of Va1686 might be localized in the regions of 48-49, 82-85, 125-126, 150-153, 185-186, 236-237 and so on. The 3D structure model of Va1686 subunit was simulated by SWISS-MODEL software and it was found that the vopS of V. parahaemolyticus was similar and the similarity was 89.46%. In this study, the feasibility of Va1686 as a common antigen of Vibrio was verified from the perspective of bioinformatics, which laid the foundation for the next step in vaccine development.展开更多
BACKGROUND Managing Gustilo type ⅢB fractures in patients with type 2 diabetes is challenging due to delayed healing and elevated complication risks.This retro-spective study highlights the successful use of free-fla...BACKGROUND Managing Gustilo type ⅢB fractures in patients with type 2 diabetes is challenging due to delayed healing and elevated complication risks.This retro-spective study highlights the successful use of free-flap transfer combined with plate fixation,contributing insights into effective management strategies for these complex cases.AIM To evaluate free-flap transfer with plate fixation for managing Gustilo ⅢB fractures in diabetic patients,focusing on outcomes.METHODS A retrospective analysis of six cases was conducted with a minimum follow-up period of three years.Patients underwent free-flap transfer and plate fixation for fracture management.Outcomes assessed included bone union,flap viability,and complications requiring intervention or plate removal.The follow-up period ranged from three to four years.Persistent infections beneath the flap developed in two patients,necessitating daily wound care.RESULTS Bone healing occurred within 17 to 34 months,with plate removal required in three patients after fracture consolidation.Traumatic osteomyelitis was observed in at least one patient.Despite challenges such as sinus formation and variations in flap pedicle anatomy,successful bone union and flap viability were achieved in all cases.Freeflap transfer combined with plate fixation shows promise for treating Gustilo type ⅢB fractures in patients with diabetes.While infection and the need for plate removal surgeries were observed,consistent success in bone healing and flap viability highlights the potential of this approach.CONCLUSION Free-flap transfer with plate fixation effectively manages Gustilo ⅢB fractures in diabetics,achieving bone/flap healing despite infection risks.Careful patient selection and further validation are critical.展开更多
In this study,Hy322 gene was cloned from Vibrio alginolyticus.The total length of its gene was 969 bp,and it could encode 322 amino acids.The physicochemical properties,protein structure,genetic evolutionary relations...In this study,Hy322 gene was cloned from Vibrio alginolyticus.The total length of its gene was 969 bp,and it could encode 322 amino acids.The physicochemical properties,protein structure,genetic evolutionary relationship and antigenic characteristics of the effector protein Hy322 of V.alginolyticus HY9901 type Ⅲ secretion system were studied and analyzed by bioinformatics methods and tools.The results showed that Hy322 is an unstable hydrophilic and acidic protein without a transmembrane region and a signal peptide,and secondary structure to α-helix.The evolutionary analysis showed that V.alginolyticus HY9901 and V.harveyi were clustered together,which indicated that the genetic relationship between the two species was closest.HY322 contains a FliN super family conserved domain associated with Flagellar motor switch.Bioinformatics analysis showed that the B-cell preponderant epitopes of Hy322 might be localized in the regions of 32-33,100-102,138-140,215-216,235-238 and 246-249.The 3D structure model of Hy322 subunit was simulated by SWISS-MODEL software and itwas found that the yscQ of Yersinia were similar and the similarity was 42.25%.In this study,the feasibility of Hy322 as a common antigen of Vibrio was verified from the perspective of bioinformatics,which laid the foundation for the next step in vaccine development.展开更多
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
目的:基于上皮细胞-间充质细胞转分化(EMT)学说观察化纤Ⅳ号方、艾灸以及二者相配合治疗肺纤维化大鼠Collagen TypeⅢ(Ⅲ-C)和PDGF的变化,探讨其治疗效应及生物学机制。方法:将鼠龄约为6周的SD大鼠随机分为空白组、模型组、化纤Ⅳ号方...目的:基于上皮细胞-间充质细胞转分化(EMT)学说观察化纤Ⅳ号方、艾灸以及二者相配合治疗肺纤维化大鼠Collagen TypeⅢ(Ⅲ-C)和PDGF的变化,探讨其治疗效应及生物学机制。方法:将鼠龄约为6周的SD大鼠随机分为空白组、模型组、化纤Ⅳ号方组、艾灸组、化纤Ⅳ号方与艾灸配合治疗组(简称为"灸药组"),治疗30 d后处死观察其肺组织病理改变,并检测其Collagen TypeⅢ、PDGF的基因和蛋白表达情况。结果:实时荧光定量结果显示:与空白组相比,各组Ⅲ-C和PDGF m RNA表达增高(P<0.05)。与模型组相比,各组的Ⅲ-C和PDGF m RNA表达有明显降低(P<0.01)。而各组中,灸药组疗效最明显,Ⅲ-C和PDGF的表达最低。蛋白免疫印迹法检测结果显示:与模型组相比各组的Ⅲ-C蛋白表达有差异。结论:1艾灸、化纤Ⅳ号方均可减轻博莱霉素诱导肺纤维化大鼠的肺纤维化程度。2艾灸配合化纤Ⅳ号方可减轻博莱霉素诱导肺纤维化大鼠的肺纤维化程度,且其效果优于单用艾灸或单用化纤Ⅳ号方。3艾灸、化纤Ⅳ号方及其二者配合使用不同程度阻抑博莱霉素诱导肺纤维化大鼠肺纤维化进程的效应机制,可能与通过调控其EMT过程中的Ⅲ-C和PDGF表达环节紧密相关。展开更多
OBJECTIVE: To assess the significance of serum hyaluronic acid (HA), proeollagen type Ⅲ (PCⅢ), collagen type Ⅳ (CⅣ) in the histological diagnosis of liver fibrosis. METHODS: The concentrations of serum HA, PCⅢ, C...OBJECTIVE: To assess the significance of serum hyaluronic acid (HA), proeollagen type Ⅲ (PCⅢ), collagen type Ⅳ (CⅣ) in the histological diagnosis of liver fibrosis. METHODS: The concentrations of serum HA, PCⅢ, CⅣ in 253 patients with chronic liver diseases were measured by radioimmunoassay. Liver biopsies were performed in all patients at the same time. The liver was pathologically evaluated by a pathologist according to a scoring system. Combined with the results of liver pathological diagnosis, the accuracy of serum HA, PCⅢ, CⅣ in diagnosing patients with hepatic fibrosis (staging≥S_2) or cirrhosis (S_4) was assessed using the receiver operating curve (ROC). RESULTS: The cutoff values of serum HA, PCⅢ and CⅣ for identifying patients with hepatic fibrosis (≥S_2) or cirrhosis (S_4) were determined. The cutoff values of serum HA, PCⅢ and CⅣ for detecting patients with fibrosis (stage≥S_2) were 90μg/L, 90μg/L, 75μg/L, respectively; their sensitivity (Se) was 80.4%, 82%, 63.1%; their specificity (Spe) was 70.2%, 60.8%, 83.8%; their positive predictive values (PPV) were 86.7%, 83.5%, 90.4%; their negative predictive values (NPV) were 59.8%, 58.4%, 48.4%, respectively. The cutoff values for detecting patients with liver cirrhosis were 210μg/L for HA, 96.2% for Se, 85.3% for Spe, 65.4% for PPV, 98.8% for NPV; 150μg/L for PCⅢ, 76.4% for Se, 68.7% for Spe, 40.4% for PPV, 91.3% for NPV; 90μg/L for CⅣ, 80% for Se, 75.8% for Spe, 47.8% for PPV, 93.2% for NPV, respectively. CONCLUSIONS: Serum HA, PCⅢ and CⅣ can be determined for an accurate diagnosis of hepatic fibrosis in various stages. HA is the best for screening liver cirrhosis.展开更多
Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an ...Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an environment that provides animals with multi-sensory stimulation and movement opportunities. An enriched environment has been shown to promote the regeneration of nerve cells, synapses, and blood vessels in the animal brain after cerebral ischemia;however, the exact mechanisms have not been clarified. This study aimed to determine whether an enriched environment could improve neurobehavioral functions after the experimental inducement of cerebral ischemia and whether neurobehavioral outcomes were associated with the expression of FDNC5 and BDNF. This study established ischemic mouse models using permanent middle cerebral artery occlusion(pMCAO) on the left side. On postoperative day 1, the mice were randomly assigned to either enriched environment or standard housing condition groups. Mice in the standard housing condition group were housed and fed under standard conditions. Mice in the enriched environment group were housed in a large cage, containing various toys, and fed with a standard diet. Sham-operated mice received the same procedure, but without artery occlusion, and were housed and fed under standard conditions. On postoperative days 7 and 14, a beam-walking test was used to assess coordination, balance, and spatial learning. On postoperative days 16–20, a Morris water maze test was used to assess spatial learning and memory. On postoperative day 15, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex were analyzed by western blot assay. The results showed that compared with the standard housing condition group, the motor balance and coordination functions(based on beam-walking test scores 7 and 14 days after operation), spatial learning abilities(based on the spatial learning scores from the Morris water maze test 16–19 days after operation), and memory abilities(based on the memory scores of the Morris water maze test 20 days after operation) of the enriched environment group improved significantly. In addition, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex increased in the enriched environment group compared with those in the standard housing condition group. Furthermore, the Pearson correlation coefficient showed that neurobehavioral functions were positively associated with the expression levels of FDNC5 and BDNF(r = 0.587 and r = 0.840, respectively). These findings suggest that an enriched environment upregulates FDNC5 protein expression in the ipsilateral cerebral cortex after cerebral ischemia, which then activates BDNF protein expression, improving neurological function. BDNF protein expression was positively correlated with improved neurological function. The experimental protocols were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval Nos. 20160858 A232, 20160860 A234) on February 24, 2016.展开更多
AIM To evaluate whether a high risk macroscopic appearance(Type Ⅳ and giant Type Ⅲ) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological sta...AIM To evaluate whether a high risk macroscopic appearance(Type Ⅳ and giant Type Ⅲ) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage Ⅱ/Ⅲ(p Stage Ⅱ/Ⅲ) gastric cancer.METHODS One hundred and seventy-two advanced gastric cancer(defined as pT2 or beyond) patients with p Stage Ⅱ/Ⅲ who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined. RESULTS Advanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival(RFS)(35.7%) and overall survival(OS)(34%) than an average risk appearance(P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13^(th) Japanese Gastric Cancer Association(JGCA) pT(P = 0.01), but not with the 13^(th) JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13^(th) JGCA p Stage(P < 0.0001)and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified highrisk macroscopic appearance(P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator. CONCLUSION A high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13^(th) JGCA stage in p Stage Ⅱ/Ⅲ advanced gastric cancer.展开更多
AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response media...AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response mediators. METHODS: The study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the Endemic Disease Hospital at Cairo University. Patients were compared with 25 ageand sexmatched healthy individuals. Inclusion criteria were based on a history of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under followup). Based on ultrasonography, patients were classified into four subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC).Total Vit D (i.e., 25-OH-Vit D) and active Vit D [i.e., 1,25-(OH) 2 -Vit D] assays were carried out using commercial kits. IL-17, IL-23 and PⅢNP levels were assayed using enzyme linked immunosorbent assay kits, while HCV virus was measured by quantitative and qualitative polymerase chain reaction. RESULTS: Levels of Vit D and its active form were significantly lower in advanced liver disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PⅢNP levels were markedly increased in HCV patients and correlated with the progression of hepatic damage. The decrease in Vit D and active Vit D was concomitant with an increase in viral load, as well as levels of IL-17, IL-23 and PⅢNP among all subgroups of HCV-infected patients, compared to normal healthy controls. A significant negative correlation was evident between active Vit D and each of IL-17, IL-23 and PⅢNP (r = -0.679, -0.801 and -0.920 at P < 0.001, respectively). HCV-infected men and women showed no differences with respect to Vit D levels. The viral load was negatively correlated with Vit D and active Vit D (r = -0.084 and -0.846 at P < 0.001, respectively), and positively correlated with IL-17, IL-23 and PⅢNP (r = 0.951, 0.922 and 0.94 at P < 0.001, respectively). Whether the deficiency in Vit D was related to HCVinduced chronic liver disease or was a predisposing factor for a higher viral load remains to be elucidated. CONCLUSION: The negative correlations between Vit D and IL-17, IL-23 and PⅢNP highlight their involvement in the immune response in patients with HCV-4related liver diseases in Egypt.展开更多
BACKGROUND Invaginated teeth pose greater challenges in clinical management because of their complex configuration.With advancements in equipment and materials,such as the dental operation microscope,cone-beam compute...BACKGROUND Invaginated teeth pose greater challenges in clinical management because of their complex configuration.With advancements in equipment and materials,such as the dental operation microscope,cone-beam computed tomography and mineral trioxide aggregate,the preservation rate of type Ⅲ dens invaginatus could be greatly increased.CASE SUMMARY This case report presented a 31-year-old woman with complaints of spontaneous swelling and pain in the right maxillary lateral tooth.With the aid of cone-beam computed tomography,type Ⅲ dens invaginatus with apical periodontitis was diagnosed and confirmed.Three-visit endodontic treatment was performed.In the first visit,the invagination was carefully removed under the dental operation microscope,and chemomechanical preparation was done.In the second visit,mineral trioxide aggregate apical barrier surgery was performed in this tooth.In the third visit,the canal was finally obturated with thermoplastic gutta-percha to recover the crown morphology.A 26-mo follow-up revealed a satisfied outcome both in the radiographic and oral examinations.CONCLUSION In this case,removal of the entire abnormal structure provided great convenience for the follow-up treatment.When confronted with the same clinical case in the future,we can take a similar approach to address it.展开更多
TypeⅢinterferons(IFNs)represent the most recently discovered group of IFNs.Together with typeⅠIFNs(e.g.IFN-α/β),typeⅢIFNs(IFN-λ)are produced as part of the innate immune response to virus infection,and elicit an...TypeⅢinterferons(IFNs)represent the most recently discovered group of IFNs.Together with typeⅠIFNs(e.g.IFN-α/β),typeⅢIFNs(IFN-λ)are produced as part of the innate immune response to virus infection,and elicit an anti-viral state by inducing expression of interferon stimulated genes(ISGs).It was initially thought that typeⅠIFNs and typeⅢIFNs perform largely redundant functions.However,it has become evident that typeⅢIFNs particularly play a major role in antiviral protection of mucosal epithelial barriers,thereby serving an important role in the first-line defense against virus infection and invasion at contact areas with the outside world,versus the generally more broad,potent and systemic antiviral effects of typeⅠIFNs.Herpesviruseses are large DNA viruses,which enter their host via mucosal surfaces and establish lifelong,latent infections.Despite the importance of mucosal epithelial cells in the pathogenesis of herpesviruses,our current knowledge on the interaction of herpesviruses with typeⅢIFN is limited and largely restricted to studies on the alphaherpesvirus herpes simplex virus(HSV).This review summarizes the current understanding about the role of IFN-λin the immune response against herpesvirus infections.展开更多
The main purpose of this paper is to study the persistence of the general multispecies competition predator-pray system with Holling Ⅲ type functional response. In this system, the competition among predator species ...The main purpose of this paper is to study the persistence of the general multispecies competition predator-pray system with Holling Ⅲ type functional response. In this system, the competition among predator species and among prey species are simultaneously considered. By using the comparison theory and qualitative analysis, the sufficient conditions for uniform strong persistence are obtained.展开更多
基金supported by the Shanghai Agriculture Applied Technology Development Program,China(2020-02-08-00-08-F01462)the National Natural Science Foundation of China(31830072,32102147)。
文摘Plant stomata close rapidly in response to a rise in the plant hormone abscisic acid(ABA)or salicylic acid(SA)and after recognition of pathogenassociated molecular patterns(PAMPs).Stomatal closure is the result of vacuolar convolution,ion efflux,and changes in turgor pressure in guard cells.Phytopathogenic bacteria secrete typeⅢeffectors(T3Es)that interfere with plant defense mechanisms,causing severe plant disease symptoms.Here,we show that the virulence and infection of Xanthomonas oryzae pv.oryzicola(Xoc),which is the causal agent of rice bacterial leaf streak disease,drastically increased in transgenic rice(Oryza sativa L.)plants overexpressing the Xoc T3E gene Xop AP,which encodes a protein annotated as a lipase.We discovered that Xop AP binds to phosphatidylinositol 3,5-bisphosphate(Ptd Ins(3,5)P_(2)),a memb rane phospholipid that functions in p H control in lysosomes,membrane dynamics,and protein trafficking.Xop AP inhibited the acidification of vacuoles by competing with vacuolar H^(+)-pyrophosphatase(V-PPase)for binding to Ptd Ins(3,5)P_(2),leading to stomatal opening.Transgenic rice overexpressing Xop AP also showed inhibition of stomatal closure when challenged by Xoc infection and treatment with the PAMP flg22.Moreover,Xop AP suppressed flg22-induced gene expression,reactive oxygen species burst and callose deposition in host plants,demonstrating that Xop AP subverts PAMP-triggered immunity during Xoc infection.Taken together,these findings demonstrate that Xop AP overcomes stomatal immunity in plants by binding to lipids.
基金Supported by the ASM Robert D Watkins Graduate FellowshipUC Davis Hellman Fellowship
文摘The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of proinflammatory cytokines and reactive oxygen species, phagocytosis, and induced programmed cell death are processes initiated by innate immune cells in order to combat invading pathogens. However, pathogens have evolved various virulence mechanisms to subvert these responses. One strategy utilized by Gram-negative bacterial pathogens is the deployment of a complex machine termed the type Ⅲ secretion system(T3SS). The T3SS is composed of a syringe-like needle structure and the effector proteins that are injected directly into a target host cell to disrupt a cellular response. The three human pathogenic Yersinia spp.(Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis) are Gramnegative bacteria that share in common a 70 kb virulence plasmid which encodes the T3 SS. Translocation of the Yersinia effector proteins(YopE, YopH, YopT, YopM, YpkA/YopO, and YopP/J) into the target host cell results in disruption of the actin cytoskeleton to inhibit phagocytosis, downregulation of proinflammatory cytokine/chemokine production, and induction of cellular apoptosis of the target cell. Over the past 25 years, studies on the Yersinia effector proteins have unveiled tremendous knowledge of how the effectors enhance Yersinia virulence. Recently, the long awaited crystal structure of YpkA has been solved providing further insights into the activation of the YpkA kinase domain. Multisite autophosphorylation by YpkA to activate its kinase domain was also shown and postulated to serve as a mechanism to bypass regulation by host phosphatases. In addition, novel Yersinia effector protein targets, such as caspase-1, and signaling pathways including activation of the inflammasome were identified. In this review, we summarize the recent discoveries made on Yersinia effector proteins and their contribution to Yersinia pathogenesis.
基金supported by the National Key R&D Program of China(2019YFD1002000)the Science and Technology Programs of the Shandong Tobacco(KN273)Zunyi Tobacco(2021XM03).
文摘Ralstonia solanacearum is a widespread plant bacterial pathogen that can launch a range of type Ⅲ effectors(T3Es)to cause disease.In this study,we isolate a pathogenic R.solanacearum strain named P380 from tomato rhizosphere.Five out of 12 core T3Es of strain P380 are introduced into Pseudomonas syringae DC3000D36E separately to determine their functions in interacting with plants.DC3000D36E that harbors each effector suppresses FliC-triggered Pti5 and ACRE31 expression,ROS burst,and callose deposition.RipAE,RipU,and RipW elicit cell death as well as upregulate the MAPK cascades in Nicotiana benthamiana.The derivatives RipC1^(△DDXDX(T/V))and RipW^(△DDKXXQ)but not RipAE^(K310R) fail to suppress ROS burst.Moreover,RipAE^(K310R) and RipW^(△DDKXXQ) retain the cell death elicitation ability.RipAE and RipW are associated with salicylic acid and jasmonic acid pathways,respectively.RipAE and RipAQ significantly promote the propagation of DC3000D36E in plants.The five core T3Es localize in diverse subcellular organelles of nucleus,plasma membrane,endoplasmic reticulum,and Golgi network.The suppressor of G2 allele of Skp1 is required for RipAE but not RipU-triggered cell death in N.benthamiana.These results indicate that the core T3Es in R.solanacearum play diverse roles in plantpathogen interactions.
基金Supported by Shenzhen Science and Technology Project(JCYJ20170818111629778,JCYJ20170306161613251)National Natural Science Foundation of Guangdong Province(2017A030313174)+2 种基金Natural Science Foundation of Guangdong Ocean University(C17379)Undergraduate Innovative and Entrepreneurial Team Project(CCTD201802)Science and Technology Program of Guangdong Province(2015A020209163)
文摘In this study, Va 1686 gene was cloned from Vibrio alginolyticus . The total length of the gene is 1 164 bp, and it could encode 387 amino acids. The physicochemical properties, protein structure, genetic evolutionary relationship and antigenic characteristics of the effect protein Va1686 of V. alginolyticus HY9901 type Ⅲ secretion system were studied and analyzed by bioinformatics methods and tools. The results showed that Va1686 is a stable hydrophilic and acidic protein without a transmembrane region and a signal peptide, and secondary structure to α-helix. The evolutionary analysis showed that V. alginolyticus HY9901 and V. harveyi were clustered together, which indicated that the genetic relationship between the two species was the closest. Va1686 contains a Fic superfamily conserved domain associated with cell division. Bioinformatics analysis showed that the B-cell preponderant epitopes of Va1686 might be localized in the regions of 48-49, 82-85, 125-126, 150-153, 185-186, 236-237 and so on. The 3D structure model of Va1686 subunit was simulated by SWISS-MODEL software and it was found that the vopS of V. parahaemolyticus was similar and the similarity was 89.46%. In this study, the feasibility of Va1686 as a common antigen of Vibrio was verified from the perspective of bioinformatics, which laid the foundation for the next step in vaccine development.
文摘BACKGROUND Managing Gustilo type ⅢB fractures in patients with type 2 diabetes is challenging due to delayed healing and elevated complication risks.This retro-spective study highlights the successful use of free-flap transfer combined with plate fixation,contributing insights into effective management strategies for these complex cases.AIM To evaluate free-flap transfer with plate fixation for managing Gustilo ⅢB fractures in diabetic patients,focusing on outcomes.METHODS A retrospective analysis of six cases was conducted with a minimum follow-up period of three years.Patients underwent free-flap transfer and plate fixation for fracture management.Outcomes assessed included bone union,flap viability,and complications requiring intervention or plate removal.The follow-up period ranged from three to four years.Persistent infections beneath the flap developed in two patients,necessitating daily wound care.RESULTS Bone healing occurred within 17 to 34 months,with plate removal required in three patients after fracture consolidation.Traumatic osteomyelitis was observed in at least one patient.Despite challenges such as sinus formation and variations in flap pedicle anatomy,successful bone union and flap viability were achieved in all cases.Freeflap transfer combined with plate fixation shows promise for treating Gustilo type ⅢB fractures in patients with diabetes.While infection and the need for plate removal surgeries were observed,consistent success in bone healing and flap viability highlights the potential of this approach.CONCLUSION Free-flap transfer with plate fixation effectively manages Gustilo ⅢB fractures in diabetics,achieving bone/flap healing despite infection risks.Careful patient selection and further validation are critical.
基金Supported by Shenzhen Science and Technology Project(JCYJ20170818111629778,JCYJ20170306161613251)National Natural Science Foundation of Guangdong Province(2017A030313174)+1 种基金Natural Science Foundation of Guangdong Ocean University(C17379)Undergraduate Innovative and Entrepreneurial Team Project(CCTD201802)
文摘In this study,Hy322 gene was cloned from Vibrio alginolyticus.The total length of its gene was 969 bp,and it could encode 322 amino acids.The physicochemical properties,protein structure,genetic evolutionary relationship and antigenic characteristics of the effector protein Hy322 of V.alginolyticus HY9901 type Ⅲ secretion system were studied and analyzed by bioinformatics methods and tools.The results showed that Hy322 is an unstable hydrophilic and acidic protein without a transmembrane region and a signal peptide,and secondary structure to α-helix.The evolutionary analysis showed that V.alginolyticus HY9901 and V.harveyi were clustered together,which indicated that the genetic relationship between the two species was closest.HY322 contains a FliN super family conserved domain associated with Flagellar motor switch.Bioinformatics analysis showed that the B-cell preponderant epitopes of Hy322 might be localized in the regions of 32-33,100-102,138-140,215-216,235-238 and 246-249.The 3D structure model of Hy322 subunit was simulated by SWISS-MODEL software and itwas found that the yscQ of Yersinia were similar and the similarity was 42.25%.In this study,the feasibility of Hy322 as a common antigen of Vibrio was verified from the perspective of bioinformatics,which laid the foundation for the next step in vaccine development.
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.
文摘目的:基于上皮细胞-间充质细胞转分化(EMT)学说观察化纤Ⅳ号方、艾灸以及二者相配合治疗肺纤维化大鼠Collagen TypeⅢ(Ⅲ-C)和PDGF的变化,探讨其治疗效应及生物学机制。方法:将鼠龄约为6周的SD大鼠随机分为空白组、模型组、化纤Ⅳ号方组、艾灸组、化纤Ⅳ号方与艾灸配合治疗组(简称为"灸药组"),治疗30 d后处死观察其肺组织病理改变,并检测其Collagen TypeⅢ、PDGF的基因和蛋白表达情况。结果:实时荧光定量结果显示:与空白组相比,各组Ⅲ-C和PDGF m RNA表达增高(P<0.05)。与模型组相比,各组的Ⅲ-C和PDGF m RNA表达有明显降低(P<0.01)。而各组中,灸药组疗效最明显,Ⅲ-C和PDGF的表达最低。蛋白免疫印迹法检测结果显示:与模型组相比各组的Ⅲ-C蛋白表达有差异。结论:1艾灸、化纤Ⅳ号方均可减轻博莱霉素诱导肺纤维化大鼠的肺纤维化程度。2艾灸配合化纤Ⅳ号方可减轻博莱霉素诱导肺纤维化大鼠的肺纤维化程度,且其效果优于单用艾灸或单用化纤Ⅳ号方。3艾灸、化纤Ⅳ号方及其二者配合使用不同程度阻抑博莱霉素诱导肺纤维化大鼠肺纤维化进程的效应机制,可能与通过调控其EMT过程中的Ⅲ-C和PDGF表达环节紧密相关。
基金This study was supported by the grant from the Guangdong Provincial Science and Technology Foundation (No. A 1999--198).
文摘OBJECTIVE: To assess the significance of serum hyaluronic acid (HA), proeollagen type Ⅲ (PCⅢ), collagen type Ⅳ (CⅣ) in the histological diagnosis of liver fibrosis. METHODS: The concentrations of serum HA, PCⅢ, CⅣ in 253 patients with chronic liver diseases were measured by radioimmunoassay. Liver biopsies were performed in all patients at the same time. The liver was pathologically evaluated by a pathologist according to a scoring system. Combined with the results of liver pathological diagnosis, the accuracy of serum HA, PCⅢ, CⅣ in diagnosing patients with hepatic fibrosis (staging≥S_2) or cirrhosis (S_4) was assessed using the receiver operating curve (ROC). RESULTS: The cutoff values of serum HA, PCⅢ and CⅣ for identifying patients with hepatic fibrosis (≥S_2) or cirrhosis (S_4) were determined. The cutoff values of serum HA, PCⅢ and CⅣ for detecting patients with fibrosis (stage≥S_2) were 90μg/L, 90μg/L, 75μg/L, respectively; their sensitivity (Se) was 80.4%, 82%, 63.1%; their specificity (Spe) was 70.2%, 60.8%, 83.8%; their positive predictive values (PPV) were 86.7%, 83.5%, 90.4%; their negative predictive values (NPV) were 59.8%, 58.4%, 48.4%, respectively. The cutoff values for detecting patients with liver cirrhosis were 210μg/L for HA, 96.2% for Se, 85.3% for Spe, 65.4% for PPV, 98.8% for NPV; 150μg/L for PCⅢ, 76.4% for Se, 68.7% for Spe, 40.4% for PPV, 91.3% for NPV; 90μg/L for CⅣ, 80% for Se, 75.8% for Spe, 47.8% for PPV, 93.2% for NPV, respectively. CONCLUSIONS: Serum HA, PCⅢ and CⅣ can be determined for an accurate diagnosis of hepatic fibrosis in various stages. HA is the best for screening liver cirrhosis.
基金supported by the National Natural Science Foundation of China,Nos.81601961(to KWY),81672242(to YW)the Key Construction Projects of Shanghai Health and Family Planning on Weak Discipline,China,No.2015ZB0401(to YW)
文摘Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an environment that provides animals with multi-sensory stimulation and movement opportunities. An enriched environment has been shown to promote the regeneration of nerve cells, synapses, and blood vessels in the animal brain after cerebral ischemia;however, the exact mechanisms have not been clarified. This study aimed to determine whether an enriched environment could improve neurobehavioral functions after the experimental inducement of cerebral ischemia and whether neurobehavioral outcomes were associated with the expression of FDNC5 and BDNF. This study established ischemic mouse models using permanent middle cerebral artery occlusion(pMCAO) on the left side. On postoperative day 1, the mice were randomly assigned to either enriched environment or standard housing condition groups. Mice in the standard housing condition group were housed and fed under standard conditions. Mice in the enriched environment group were housed in a large cage, containing various toys, and fed with a standard diet. Sham-operated mice received the same procedure, but without artery occlusion, and were housed and fed under standard conditions. On postoperative days 7 and 14, a beam-walking test was used to assess coordination, balance, and spatial learning. On postoperative days 16–20, a Morris water maze test was used to assess spatial learning and memory. On postoperative day 15, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex were analyzed by western blot assay. The results showed that compared with the standard housing condition group, the motor balance and coordination functions(based on beam-walking test scores 7 and 14 days after operation), spatial learning abilities(based on the spatial learning scores from the Morris water maze test 16–19 days after operation), and memory abilities(based on the memory scores of the Morris water maze test 20 days after operation) of the enriched environment group improved significantly. In addition, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex increased in the enriched environment group compared with those in the standard housing condition group. Furthermore, the Pearson correlation coefficient showed that neurobehavioral functions were positively associated with the expression levels of FDNC5 and BDNF(r = 0.587 and r = 0.840, respectively). These findings suggest that an enriched environment upregulates FDNC5 protein expression in the ipsilateral cerebral cortex after cerebral ischemia, which then activates BDNF protein expression, improving neurological function. BDNF protein expression was positively correlated with improved neurological function. The experimental protocols were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval Nos. 20160858 A232, 20160860 A234) on February 24, 2016.
文摘AIM To evaluate whether a high risk macroscopic appearance(Type Ⅳ and giant Type Ⅲ) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage Ⅱ/Ⅲ(p Stage Ⅱ/Ⅲ) gastric cancer.METHODS One hundred and seventy-two advanced gastric cancer(defined as pT2 or beyond) patients with p Stage Ⅱ/Ⅲ who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined. RESULTS Advanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival(RFS)(35.7%) and overall survival(OS)(34%) than an average risk appearance(P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13^(th) Japanese Gastric Cancer Association(JGCA) pT(P = 0.01), but not with the 13^(th) JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13^(th) JGCA p Stage(P < 0.0001)and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified highrisk macroscopic appearance(P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator. CONCLUSION A high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13^(th) JGCA stage in p Stage Ⅱ/Ⅲ advanced gastric cancer.
文摘AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response mediators. METHODS: The study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the Endemic Disease Hospital at Cairo University. Patients were compared with 25 ageand sexmatched healthy individuals. Inclusion criteria were based on a history of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under followup). Based on ultrasonography, patients were classified into four subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC).Total Vit D (i.e., 25-OH-Vit D) and active Vit D [i.e., 1,25-(OH) 2 -Vit D] assays were carried out using commercial kits. IL-17, IL-23 and PⅢNP levels were assayed using enzyme linked immunosorbent assay kits, while HCV virus was measured by quantitative and qualitative polymerase chain reaction. RESULTS: Levels of Vit D and its active form were significantly lower in advanced liver disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PⅢNP levels were markedly increased in HCV patients and correlated with the progression of hepatic damage. The decrease in Vit D and active Vit D was concomitant with an increase in viral load, as well as levels of IL-17, IL-23 and PⅢNP among all subgroups of HCV-infected patients, compared to normal healthy controls. A significant negative correlation was evident between active Vit D and each of IL-17, IL-23 and PⅢNP (r = -0.679, -0.801 and -0.920 at P < 0.001, respectively). HCV-infected men and women showed no differences with respect to Vit D levels. The viral load was negatively correlated with Vit D and active Vit D (r = -0.084 and -0.846 at P < 0.001, respectively), and positively correlated with IL-17, IL-23 and PⅢNP (r = 0.951, 0.922 and 0.94 at P < 0.001, respectively). Whether the deficiency in Vit D was related to HCVinduced chronic liver disease or was a predisposing factor for a higher viral load remains to be elucidated. CONCLUSION: The negative correlations between Vit D and IL-17, IL-23 and PⅢNP highlight their involvement in the immune response in patients with HCV-4related liver diseases in Egypt.
基金the Priority Academic Program Development of Jiangsu Higher Education Institutions,No.PAPD2018-87.
文摘BACKGROUND Invaginated teeth pose greater challenges in clinical management because of their complex configuration.With advancements in equipment and materials,such as the dental operation microscope,cone-beam computed tomography and mineral trioxide aggregate,the preservation rate of type Ⅲ dens invaginatus could be greatly increased.CASE SUMMARY This case report presented a 31-year-old woman with complaints of spontaneous swelling and pain in the right maxillary lateral tooth.With the aid of cone-beam computed tomography,type Ⅲ dens invaginatus with apical periodontitis was diagnosed and confirmed.Three-visit endodontic treatment was performed.In the first visit,the invagination was carefully removed under the dental operation microscope,and chemomechanical preparation was done.In the second visit,mineral trioxide aggregate apical barrier surgery was performed in this tooth.In the third visit,the canal was finally obturated with thermoplastic gutta-percha to recover the crown morphology.A 26-mo follow-up revealed a satisfied outcome both in the radiographic and oral examinations.CONCLUSION In this case,removal of the entire abnormal structure provided great convenience for the follow-up treatment.When confronted with the same clinical case in the future,we can take a similar approach to address it.
基金Research of YY and HWF is supported by grants from the Special Research Fund of Ghent University(CSC-cofunding grant and Concerted Research Action GOA013-17).
文摘TypeⅢinterferons(IFNs)represent the most recently discovered group of IFNs.Together with typeⅠIFNs(e.g.IFN-α/β),typeⅢIFNs(IFN-λ)are produced as part of the innate immune response to virus infection,and elicit an anti-viral state by inducing expression of interferon stimulated genes(ISGs).It was initially thought that typeⅠIFNs and typeⅢIFNs perform largely redundant functions.However,it has become evident that typeⅢIFNs particularly play a major role in antiviral protection of mucosal epithelial barriers,thereby serving an important role in the first-line defense against virus infection and invasion at contact areas with the outside world,versus the generally more broad,potent and systemic antiviral effects of typeⅠIFNs.Herpesviruseses are large DNA viruses,which enter their host via mucosal surfaces and establish lifelong,latent infections.Despite the importance of mucosal epithelial cells in the pathogenesis of herpesviruses,our current knowledge on the interaction of herpesviruses with typeⅢIFN is limited and largely restricted to studies on the alphaherpesvirus herpes simplex virus(HSV).This review summarizes the current understanding about the role of IFN-λin the immune response against herpesvirus infections.
基金Supported by the National Natural Science Foundation of China (10701020)
文摘The main purpose of this paper is to study the persistence of the general multispecies competition predator-pray system with Holling Ⅲ type functional response. In this system, the competition among predator species and among prey species are simultaneously considered. By using the comparison theory and qualitative analysis, the sufficient conditions for uniform strong persistence are obtained.
