In this study,circular dichroism(CD)and molecular dynamics(MD)simulation were used to investigate the thermal unfolding pathway of staphylococcal enterotoxin B(SEB)at temperatures of 298–371 and 298–500 K,and the re...In this study,circular dichroism(CD)and molecular dynamics(MD)simulation were used to investigate the thermal unfolding pathway of staphylococcal enterotoxin B(SEB)at temperatures of 298–371 and 298–500 K,and the relationship between the experimental and simulation results were explored.Our computational findings on the secondary structure of SEB showed that at room temperature,the CD spectroscopic results were highly consistent with the MD results.Moreover,under heating conditions,the changing trends of helix,sheet and random coil obtained by CD spectral fitting were highly consistent with those obtained by MD.In order to gain a deeper understanding of the thermal stability mechanism of SEB,the MD trajectories were analyzed in terms of root mean square deviation(RMSD),secondary structure assignment(SSA),radius of gyration(R_(g)),free energy surfaces(FES),solvent-accessible surface area(SASA),hydrogen bonds and salt bridges.The results showed that at low heating temperature,domain Ⅰ without loops(omitting the mobile loop region)mainly relied on hydrophobic interaction to maintain its thermal stability,whereas the thermal stability of domain Ⅱ was mainly controlled by salt bridges and hydrogen bonds.Under high heating temperature conditions,the hydrophobic interactions in domain Ⅰ without loops were destroyed and the secondary structure was almost completely lost,while domain Ⅱ could still rely on salt bridges as molecular staples to barely maintain the stability of the secondary structure.These results help us to understand the thermodynamic and kinetic mechanisms that maintain the thermal stability of SEB at the molecular level,and provide a direction for establishing safer and more effective food sterilization processes.展开更多
Seven electron-deficient A_2 B type H_3-triarylcorroles have been synthesized and characterized. The solvent dependence of the electronic absorption and magnetic circular dichroism（MCD） spectra and a series of TD-DF...Seven electron-deficient A_2 B type H_3-triarylcorroles have been synthesized and characterized. The solvent dependence of the electronic absorption and magnetic circular dichroism（MCD） spectra and a series of TD-DFT calculations have been used to analyze trends in the electronic structures. Significant differences are observed in the optical spectra when solvents of differing polarity are used,which can be assigned to the effect of NH-tautomerism.展开更多
Objective To observe the role of superantigen staphylococcal enterotoxin B(SEB) andD - galactosamine (D - GalN) on Balb/c mouse hepatocytes and its mechanism. Methods After Balb/c mice wereinjected intraperitoneally w...Objective To observe the role of superantigen staphylococcal enterotoxin B(SEB) andD - galactosamine (D - GalN) on Balb/c mouse hepatocytes and its mechanism. Methods After Balb/c mice wereinjected intraperitoneally with SEB, D- GalN or both, blood samples were collected and livers were removed at 2,6, 12, 24h. Patterns of hepatocellular death were studied morphologically and biochemically, circulating cytokines(TNF, IFN-γ) were determined, and mice mortality within 24h was assessed. Results SEB could induce thetypical apoptotic changes of hepatocytes morphologically and biochemically. The mechanism is probably associatedwith the production and release of Cytokines (such as TNF, IFN- γ, etc).D - GalN could induce hepatocytesapoptosis and degeneration at the same time. Besides this, we confirmed hepatocytes of the mice which wereadministered SEB and D - GalN developing apoptosis at 2, 6h, but after 12h hepatocytes were characterized bysevere injury, the mice mortality within 24h is 50%. Conclusion SEB or D - GalN alone could induce the typicalapoptotic changes of hepatocytes. SEB+D-GalN developed hepatocytes apoptosis in the early stage and necrosisin the later. It suggests that there is some relationship between hepatic cell apoptosis and necrosis, and massivehepatocyte apoptosis is the probably initiating step of acute hepatic necrosis in mice.展开更多
Staphylococcal Enterotoxin B (SEB) is considered a potential biological weapon. It is toxic by both inhalation and ingestion. Effects of ingestion include fever, vomiting and diarrhoea, while inhalation may additional...Staphylococcal Enterotoxin B (SEB) is considered a potential biological weapon. It is toxic by both inhalation and ingestion. Effects of ingestion include fever, vomiting and diarrhoea, while inhalation may additionally result in chest pain, dyspnoea, pulmonary oedema and respiratory failure. Severe exposure may be fatal and treatment relies on symptomatic support. At a cellular level, SEB up-regulates T-cell proliferation leading to a pathological inflammatory response. Deguelin, a rotenoid isolated from the African plant Mundulea sericea (Leguminosae), has been shown to reduce cellular proliferation by inhibiting the phosphoinositide 3-kinase/Akt (PI3K/Akt) signalling pathway. Using isolated murine splenocytes, we have demonstrated that treatment with deguelin reduces SEB inducing T cell proliferation by 60%. Deguelin treatment also decreased IL-2 and CCL2 secretion by splenocytes exposed to SEB. We demonstrate that targeting cellular proliferation can significantly reduce inflammation after SEB exposure and suggest that anti-proliferatives may have a role as potential generic medical counter measures if superantigens are used as biological weapons.展开更多
Objective ： To construct plant transformation vector containing Escherichia coli heat-labile enterotoxin B subunit （LT-B） gene and generate LT-B transgenic tobacco plants. Methods： The LT-B coding sequence was amp...Objective ： To construct plant transformation vector containing Escherichia coli heat-labile enterotoxin B subunit （LT-B） gene and generate LT-B transgenic tobacco plants. Methods： The LT-B coding sequence was amplified from pMMB68 by PCR, subcloned into middle vector pUCmT and binary vector pBI121 to obtain plant expression vector pBI-LTB, in which LT-B expression was controlled under the Cauliflower mosaic virus （CaMV） 35S promoter. The tobacco plants （Nicotiana tobacum L. Cuttivar Xanthi） were transformed by co-cultivating leaf discs method via Agrobacterium tumefaciens LBA4404 harboring the plant expression vector. The regenerated transgenic tobacco plants were selected by kanamycin and confirmed by PCR, Southern blot, Western blot and ELISA. Resuits： LT-B gene integrated in the tobacco genomic DNA and were expressed in 9 strains of transgenic tobacco plants. The yield was varied from 3. 36-10. 56 ng/mg total soluble tobacco leaf protein. Conclusion： The plant binary expression vector pBI-LTB was constructed successfully, and transgenic LT-B tobacco plants was generated, and confirmed by Southern blot. The protein LT-B expressed by engineered plants was identified by Western blot analysis and had the expected molecular weight of LT-B pentamer protein. This result is an important step close to developing an edible vaccine and supplying a mucasal immunoajuvant, which will contribute to the preven- tion of mucosaroute evading pathogen.展开更多
The scavenger receptor class B type I (SR-BI) is a high-density lipoprotein (HDL) receptor involved in reverse cholesterol transport. Some studies reported the association to be stronger in the presence of diabetes. T...The scavenger receptor class B type I (SR-BI) is a high-density lipoprotein (HDL) receptor involved in reverse cholesterol transport. Some studies reported the association to be stronger in the presence of diabetes. The full length gene encoding SR-BI is comprised in 13 exons that are alternatively spliced to produce two major transcripts: the full length SR-BI and the splice variant SR-BII, in which exon 12 is skipped. Considering that type 2 diabetes status is characterized by changes in the concentration of plasma lipids, modifications in lipoprotein size and composition, which may be important modulators of the SR-BI expression;the aims of the study were to examine the influence of SR-BI polymorphism (rs838895) on lipid profile and SR-BI mRNA expression in a population of diabetic patients living in Juana Koslay City. Blood samples were drawn from controls (n = 40) and Type 2 diabetic patients (n = 66) and DNA and total RNA were obtained. SR-BI mRNA expression was measured by RT-PCR and SR-BI polymorphism was detected by Tetra Primer ARMSPCR. Compared to controls, diabetic patients had higher fasting serum glucose, glycated hemoglobin, triglycerides, total cholesterol, lowdensity lipoprotein cholesterol, and lower highdensity lipoprotein cholesterol. SR-BI mRNA expression was lower in T2DM when compared to controls, suggesting that the hyperglycemia presents in T2DM patients down-regulates SR-BI mRNA expression. Interestingly, we found that decreased SR-BI expression resulted in markedly increased plasma LDL concentrations in T2DM subjects, and the overexpression of SRBII isoform is responsible for the markedly increased plasma LDL-c concentrations. The polymorphism (rs838895) did not modify the mRNA level of SR-BI in leucocytes from control and diabetic patients. This study provides novel evidence suggesting that hyperglycemia may affect reverse cholesterol transport by controlling SRBI expression in diabetic patients. LDL cholesterol levels are associated with low SR-BI mRNA expression in T2DM.展开更多
Introduction:On September 16,2024,the Puyang City CDC received a report of a suspected foodborne disease outbreak involving 14 individuals who developed nausea,vomiting,and diarrhea following attendance at a hotel ban...Introduction:On September 16,2024,the Puyang City CDC received a report of a suspected foodborne disease outbreak involving 14 individuals who developed nausea,vomiting,and diarrhea following attendance at a hotel banquet.Upon notification,the District CDC immediately deployed a specialized investigation team to characterize the epidemiological features of the outbreak,identify the causative pathogen,assess potential transmission risks,and implement effective control and prevention measures.Methods:We integrated comprehensive on-site epidemiological investigations,clinical symptom analyses,and laboratory diagnostics to isolate and identify pathogenic agents from retained food samples,environmental specimens,and anal swabs collected from affected cases.The recovered isolates underwent enterotoxin-virulence-gene profiling,antimicrobialsusceptibility testing,and phylogenetic analyses.Additionally,we characterized the architecture of the enterotoxin-A-linked pathogenicity island vSaβ.Results:A total of 4 S.aureus strains were successfully isolated from 22 leftover food samples,2 environmental swabs,and 2 patient anal swabs.Contaminated donkey and goose meat was identified as the outbreak source.All isolates harbored sea and seb enterotoxin genes,exhibited PEN-OXA-ERY-CLI resistance patterns,and were identified as clonal ST59-spa t441-SCCmec IVa CA-MRSA strains.Phylogenetic analysis positioned the outbreak strains within the Asia-Pacific clade,distinguishing them from the North American ST59 sublineage.Comprehensive analysis of the sea-associated virulence island vSaβidentified a novel structural arrangement containing a type A IEC cluster(sea-sak-chp-scn).Conclusions:The detection of foodborne ST59 CAMRSA clones in this outbreak underscores the prevalence and transmission risks associated with this hypervirulent lineage.These findings emphasize the critical need to strengthen surveillance measures for CA-MRSA among food industry workers.展开更多
BACKGROUND C-X-C chemokine receptor type 5(CXCR5)^(+)CD8^(+)T cells represent a unique immune subset with dual roles,functioning as cytotoxic cells in persistent viral infections while promoting B cell responses.Despi...BACKGROUND C-X-C chemokine receptor type 5(CXCR5)^(+)CD8^(+)T cells represent a unique immune subset with dual roles,functioning as cytotoxic cells in persistent viral infections while promoting B cell responses.Despite their importance,the specific role of CXCR5^(+)CD8^(+)T cells in chronic hepatitis B(CHB),particularly during interferon-alpha(IFN-α)treatment,is not fully understood.This study aims to elucidate the relationship between CXCR5^(+)CD8^(+)T cells and sustained serologic response(SR)in patients undergoing 48 weeks of pegylated IFN-α(peg-IFN-α)treatment for CHB.AIM To elucidate the relationship between CXCR5^(+)CD8^(+)T cells and sustained SR in patients undergoing 48 weeks of peg-IFN-αtreatment for CHB.METHODS This study enrolled 60 patients with hepatitis Be antigen(HBeAg)-positive CHB undergoing 48 weeks of peg-IFN-αtreatment.Participants were assessed for eligibility based on criteria such as persistent HBsAg-positive status for at least six months,HBeAb-negative,hepatitis B virus DNA levels exceeding 2×10^(4) copies/mL,and alanine aminotransferase(ALT)levels between 2 and 10 times the upper limit of normal.Blood samples were collected at baseline and at weeks 12,24,48,and a 24-week treatment-free follow-up(week 72)to measure serum interleukin(IL)-21 concentration via ELISA and to analyze CXCR5 and programmed death-ligand 1(PD-L1)expression on CD8^(+)T cells by flow cytometry,CXCR5 is a chemokine receptor that directs immune cells to specific tissues,while PD-L1 is a protein that regulates immune responses by inhibiting T cell activity.RESULTS Patients with CHB exhibited significantly lower levels of circulating CXCR5^(+)CD8^(+)T cells compared to healthy controls(P<0.01).Notably,CXCR5^(+)CD8^(+)T cells were prominently expressed in patients who achieved sustained SR compared to non-SR(NSR).A significant correlation was observed between CXCR5 and PD-L1 expression(r=-0.189,P=0.002).However,there was no significant correlation between serum IL-21 levels and CXCR5+CD8+lymphocytes(r=-0.03,P=0.625)or serum ALT levels(r=0.026,P=0.678).CONCLUSION The enhanced expression of CXCR5^(+)CD8^(+)T cells in patients achieving HBeAg seroconversion during IFN-αtreatment suggests that these cells play a crucial role in antiviral immune responses against hepatitis B.This study highlights the potential of CXCR5^(+)CD8^(+)T cells as immune regulators in CHB,which may inform future therapeutic strategies to optimize antiviral treatments.展开更多
Type I interferon(IFN-I)is highly prevalent in autoimmune disorders and is intricately involved in disease pathogenesis,including Sjögren's disease(SjD),also known as Sjögren's syndrome.Although the ...Type I interferon(IFN-I)is highly prevalent in autoimmune disorders and is intricately involved in disease pathogenesis,including Sjögren's disease(SjD),also known as Sjögren's syndrome.Although the T follicular helper(Tfh)cell response has been shown to drive SjD development in a mouse model of experimental Sjögren's syndrome(ESS),the connection between IFN-I and the Tfh cell response remains unclear.As the activation of stimulator of interferon genes(STING)induces IFN-I production,we first demonstrated that mice deficient in STING or IFN-I signaling presented diminished Tfh cells and were completely resistant to ESS development.However,the STING-IFN-I axis does not directly influence Tfh cell differentiation.Instead,IFN-I signaling in B cells was essential for mounting Tfh cell responses,as evidenced in Cd19CreIfnar1flox mice,which also showed resistance to ESS development.Mechanistic analyses revealed that IFN-I drove CXCR5 expression in innate-like marginal zone B cells via the MEKK3-OCT2 axis,facilitating their migration into the follicular area.Additionally,IFN-I promoted interleukin-6 production in B cells via the MEKK3-ERK5 axis,resulting in hyperactive Tfh cell responses.In SjD patients,STING activation was predominantly observed in circulating CD14+monocytes and was positively correlated with disease activity and effector T-cell responses.Pharmaceutical inhibition of either STING or IFNAR1 yielded moderate improvements in ESS mice with chronic inflammation,but combination therapy markedly improved outcomes and led to signs of disease remission.Our findings elucidate a novel mechanism by which IFN-I bridges innate and Tfh cell responses,suggesting new therapeutic avenues for SjD and related autoimmune disorders.展开更多
BACKGROUND Sex disparities in clinical outcomes following thoracic endovascular aortic repair(TEVAR)for acute complicated type B aortic dissection(TBAD)are not well understood.AIM To evaluates the impact of sex on pri...BACKGROUND Sex disparities in clinical outcomes following thoracic endovascular aortic repair(TEVAR)for acute complicated type B aortic dissection(TBAD)are not well understood.AIM To evaluates the impact of sex on primary and secondary outcomes by comparing male and female cohorts undergoing TEVAR.METHODS A systematic search of PubMed,EMBASE,Cochrane Library,and ScienceDirect identified five studies involving 2572 patients(1153 males and 1419 females).The primary outcome was hospital mortality.Secondary outcomes included reintervention rates,acute kidney injury(AKI),ischemic stroke,limb ischemia,and spinal cord ischemia.Odds ratios(OR)with 95%confidence intervals(CI)were calculated using a random-effects model.Heterogeneity was assessed using the I²statistic.RESULTS The primary outcome showed no significant difference between males and females for hospital mortality(OR:1.13,95%CI:0.81-1.59,P=0.47,I2=0).Among secondary outcomes,males had a significantly higher risk of AKI(OR:1.55,95%CI:1.21-2.00,P=0.0006,I²=0).No differences were observed for reintervention rates,ischemic stroke,limb ischemia,or spinal cord ischemia.CONCLUSION Male patients undergoing TEVAR for complicated TBAD are at increased risk of AKI but show comparable outcomes to females for mortality,ischemic events,reintervention,and other complications.Future research should explore mechanisms and strategies to optimize outcomes.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
BACKGROUND The interplay between abnormal glucose metabolism and the progression of liver fibrosis in patients with both chronic hepatitis B(CHB)and type 2 diabetes mellitus(T2DM)remains unclear.Previous studies have ...BACKGROUND The interplay between abnormal glucose metabolism and the progression of liver fibrosis in patients with both chronic hepatitis B(CHB)and type 2 diabetes mellitus(T2DM)remains unclear.Previous studies have suggested that the coexistence of these conditions may exacerbate liver inflammation and fibrosis;however,the impacts of dynamic changes in glucose metabolism indicators,hypoglycemic medication regimens,and glycemic control status on liver fibrosis require further elucidation.AIM To explore the effect of glycemic control on hepatic fibrosis in patients with CHB and T2DM.METHODS A total of 420 patients with CHB and T2DM admitted to the Public Health Clinical Center of Chengdu between October 2018 and January 2022 were retrospectively included and classified according to liver stiffness measurement and glycemic control for between-group comparisons.RESULTS Significant differences were observed in the alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase,AST/ALT ratio,total bilirubin,direct bilirubin,diabetes treatment program,and thrombin time values among the liver fibrosis groups(adjusted P<0.05).Significant differences in albumin and gamma-glutamyl transferase levels were observed among the groups categorized by glucose status at admission(adjusted P<0.05).A positive correlation between fasting plasma glucose(FPG)and liver stiffness measurement was found to be mediated by ALT and AST.Fibrinogen and the international normalized ratio were positively correlated with glycated hemoglobin A1c,while the fibrosis-4 score,ALT,AST/ALT ratio,type III procollagen N-terminal peptide,ferritin,and activated partial thromboplastin time were correlated with FPG at admission.Additionally,AST was positively correlated with FPG at discharge(P<0.05).CONCLUSION Specific glucose metabolic parameters,hypoglycemic agents,and glycemic control status markers are associated with hepatic fibrosis in patients with both CHB and T2DM.Close blood glucose monitoring,optimized use of hypoglycemic agents,and continuous maintenance of good glycemic control may slow the progression of liver fibrosis in patients with CHB and T2DM.展开更多
Background and Objective The natural history of type B aortic intramural hematoma(IMH)is highly heterogeneous.A computational fluid dynamics(CFD)model can be utilized to calculate a range of data pertinent to flow dyn...Background and Objective The natural history of type B aortic intramural hematoma(IMH)is highly heterogeneous.A computational fluid dynamics(CFD)model can be utilized to calculate a range of data pertinent to flow dynamics,including flow rates,blood velocity,pressure,and wall shear stress.This study presents a series of CFD simulations that model the dynamic progression from type B aortic IMH to false lumen formation.Methods A 66-year-old male patient presenting with chest and back pain underwent aortic computed tomography angiography(CTA),and a 3D patient-specific model was constructed.To evaluate the hemodynamic environment,the velocity,pressure,time-averaged wall shear stress(TAWSS),and oscillatory shear index(OSI)were calculated.Results A modest quantity of slow flow and recirculation flow was observed in the vicinity of the ulcer-like protrusion(ULP).During the formation of the false lumen,low-velocity blood flow entered the false lumen and resulted in vortex flow.ULPs were located in the region with higher TAWSS,and some high OSIs were found on the ULPs.Conclusion This preliminary study suggests a potential association between the TAWSS or OSI and progression from type B aortic IMH to aortic dissection.展开更多
Objective:To investigate the influence and underlying mechanisms of imrecoxib on liver damage in rats with type 2 diabetes mellitus(T2DM).Methods:A rat model of T2DM was established by a high-fat diet and streptozotoc...Objective:To investigate the influence and underlying mechanisms of imrecoxib on liver damage in rats with type 2 diabetes mellitus(T2DM).Methods:A rat model of T2DM was established by a high-fat diet and streptozotocin administration.Rats were then treated with imrecoxib 10,20,or 40 mg/kg for 5 weeks.Body weight and fasting blood glucose levels were measured.The analysis included serum liver function,blood lipid profiles,and the levels of inflammatory factors in the rats.Liver tissue histology was evaluated using hematoxylin and eosin staining.Western blotting was conducted to measure the liver expression of proteins such as AKT,PI3K,NF-κB,p-AKT,p-PI3K,and p-NF-κB.Results:Rats treated with imrecoxib showed a greater weight gain compared to untreated diabetic rats.Compared to untreated diabetic rats,imrecoxib at all three doses reduced alanine aminotransferase,aspartate aminotransferase,triglycerides,cholesterol,tumor necrosis factor-α,interleukin(IL)-6,and IL-1β,and significantly increased the levels of IL-10 and IL-4.In imrecoxib-treated rats,the expression levels of AKT,PI3K,p-AKT,and p-PI3K were higher in comparison to the diabetes group,whereas the expression of p-NF-κB was lower.Conclusions:Imrecoxib could alleviate hepatic damage in T2DM rats by modulating PI3K/AKT/NF-κB signaling.展开更多
Diabetes mellitus(DM)is a metabolic disorder characterized by persistent hyperglycemia and other symptoms,which pose significant challenges to individual health,life expectancy,and public healthcare systems.The escala...Diabetes mellitus(DM)is a metabolic disorder characterized by persistent hyperglycemia and other symptoms,which pose significant challenges to individual health,life expectancy,and public healthcare systems.The escalating global prevalence of diabetes underscores the need for innovative therapeutic interventions.In this article,we critically comment on the study by Wang et al,published in the World Journal of Diabetes,which elucidates the therapeutic potential of Plantamajoside(PMS)in type 2 DM(T2DM)management.The authors provide evidence for the mechanism of action of PMS in T2DM models,demonstrating prevention of endoplasmic reticulum stress and apoptosis of pancreaticβ-cells via activation of DNAJC1.This manuscript provides a brief review of the pathogenesis of T2DM,explores the various roles of PMS in disease therapy in addition to the DNAJC-related apoptotic and autophagic functions,critically evaluates the experimental approaches employed by Wang et al,and provides recommendations for advancing future research.展开更多
文摘In this study,circular dichroism(CD)and molecular dynamics(MD)simulation were used to investigate the thermal unfolding pathway of staphylococcal enterotoxin B(SEB)at temperatures of 298–371 and 298–500 K,and the relationship between the experimental and simulation results were explored.Our computational findings on the secondary structure of SEB showed that at room temperature,the CD spectroscopic results were highly consistent with the MD results.Moreover,under heating conditions,the changing trends of helix,sheet and random coil obtained by CD spectral fitting were highly consistent with those obtained by MD.In order to gain a deeper understanding of the thermal stability mechanism of SEB,the MD trajectories were analyzed in terms of root mean square deviation(RMSD),secondary structure assignment(SSA),radius of gyration(R_(g)),free energy surfaces(FES),solvent-accessible surface area(SASA),hydrogen bonds and salt bridges.The results showed that at low heating temperature,domain Ⅰ without loops(omitting the mobile loop region)mainly relied on hydrophobic interaction to maintain its thermal stability,whereas the thermal stability of domain Ⅱ was mainly controlled by salt bridges and hydrogen bonds.Under high heating temperature conditions,the hydrophobic interactions in domain Ⅰ without loops were destroyed and the secondary structure was almost completely lost,while domain Ⅱ could still rely on salt bridges as molecular staples to barely maintain the stability of the secondary structure.These results help us to understand the thermodynamic and kinetic mechanisms that maintain the thermal stability of SEB at the molecular level,and provide a direction for establishing safer and more effective food sterilization processes.
基金financially supported by the National Natural Science Foundation of China(No.21171076)Natural Science Foundation of Jiangsu Province(No.BK20160499)to XL and WZ and an NRF of South Africa CSUR grant(uid:93627)to JM
文摘Seven electron-deficient A_2 B type H_3-triarylcorroles have been synthesized and characterized. The solvent dependence of the electronic absorption and magnetic circular dichroism（MCD） spectra and a series of TD-DFT calculations have been used to analyze trends in the electronic structures. Significant differences are observed in the optical spectra when solvents of differing polarity are used,which can be assigned to the effect of NH-tautomerism.
文摘Objective To observe the role of superantigen staphylococcal enterotoxin B(SEB) andD - galactosamine (D - GalN) on Balb/c mouse hepatocytes and its mechanism. Methods After Balb/c mice wereinjected intraperitoneally with SEB, D- GalN or both, blood samples were collected and livers were removed at 2,6, 12, 24h. Patterns of hepatocellular death were studied morphologically and biochemically, circulating cytokines(TNF, IFN-γ) were determined, and mice mortality within 24h was assessed. Results SEB could induce thetypical apoptotic changes of hepatocytes morphologically and biochemically. The mechanism is probably associatedwith the production and release of Cytokines (such as TNF, IFN- γ, etc).D - GalN could induce hepatocytesapoptosis and degeneration at the same time. Besides this, we confirmed hepatocytes of the mice which wereadministered SEB and D - GalN developing apoptosis at 2, 6h, but after 12h hepatocytes were characterized bysevere injury, the mice mortality within 24h is 50%. Conclusion SEB or D - GalN alone could induce the typicalapoptotic changes of hepatocytes. SEB+D-GalN developed hepatocytes apoptosis in the early stage and necrosisin the later. It suggests that there is some relationship between hepatic cell apoptosis and necrosis, and massivehepatocyte apoptosis is the probably initiating step of acute hepatic necrosis in mice.
文摘Staphylococcal Enterotoxin B (SEB) is considered a potential biological weapon. It is toxic by both inhalation and ingestion. Effects of ingestion include fever, vomiting and diarrhoea, while inhalation may additionally result in chest pain, dyspnoea, pulmonary oedema and respiratory failure. Severe exposure may be fatal and treatment relies on symptomatic support. At a cellular level, SEB up-regulates T-cell proliferation leading to a pathological inflammatory response. Deguelin, a rotenoid isolated from the African plant Mundulea sericea (Leguminosae), has been shown to reduce cellular proliferation by inhibiting the phosphoinositide 3-kinase/Akt (PI3K/Akt) signalling pathway. Using isolated murine splenocytes, we have demonstrated that treatment with deguelin reduces SEB inducing T cell proliferation by 60%. Deguelin treatment also decreased IL-2 and CCL2 secretion by splenocytes exposed to SEB. We demonstrate that targeting cellular proliferation can significantly reduce inflammation after SEB exposure and suggest that anti-proliferatives may have a role as potential generic medical counter measures if superantigens are used as biological weapons.
基金Supported by the National Natural Science Foundation ofChina (No. 30070848)
文摘Objective ： To construct plant transformation vector containing Escherichia coli heat-labile enterotoxin B subunit （LT-B） gene and generate LT-B transgenic tobacco plants. Methods： The LT-B coding sequence was amplified from pMMB68 by PCR, subcloned into middle vector pUCmT and binary vector pBI121 to obtain plant expression vector pBI-LTB, in which LT-B expression was controlled under the Cauliflower mosaic virus （CaMV） 35S promoter. The tobacco plants （Nicotiana tobacum L. Cuttivar Xanthi） were transformed by co-cultivating leaf discs method via Agrobacterium tumefaciens LBA4404 harboring the plant expression vector. The regenerated transgenic tobacco plants were selected by kanamycin and confirmed by PCR, Southern blot, Western blot and ELISA. Resuits： LT-B gene integrated in the tobacco genomic DNA and were expressed in 9 strains of transgenic tobacco plants. The yield was varied from 3. 36-10. 56 ng/mg total soluble tobacco leaf protein. Conclusion： The plant binary expression vector pBI-LTB was constructed successfully, and transgenic LT-B tobacco plants was generated, and confirmed by Southern blot. The protein LT-B expressed by engineered plants was identified by Western blot analysis and had the expected molecular weight of LT-B pentamer protein. This result is an important step close to developing an edible vaccine and supplying a mucasal immunoajuvant, which will contribute to the preven- tion of mucosaroute evading pathogen.
文摘The scavenger receptor class B type I (SR-BI) is a high-density lipoprotein (HDL) receptor involved in reverse cholesterol transport. Some studies reported the association to be stronger in the presence of diabetes. The full length gene encoding SR-BI is comprised in 13 exons that are alternatively spliced to produce two major transcripts: the full length SR-BI and the splice variant SR-BII, in which exon 12 is skipped. Considering that type 2 diabetes status is characterized by changes in the concentration of plasma lipids, modifications in lipoprotein size and composition, which may be important modulators of the SR-BI expression;the aims of the study were to examine the influence of SR-BI polymorphism (rs838895) on lipid profile and SR-BI mRNA expression in a population of diabetic patients living in Juana Koslay City. Blood samples were drawn from controls (n = 40) and Type 2 diabetic patients (n = 66) and DNA and total RNA were obtained. SR-BI mRNA expression was measured by RT-PCR and SR-BI polymorphism was detected by Tetra Primer ARMSPCR. Compared to controls, diabetic patients had higher fasting serum glucose, glycated hemoglobin, triglycerides, total cholesterol, lowdensity lipoprotein cholesterol, and lower highdensity lipoprotein cholesterol. SR-BI mRNA expression was lower in T2DM when compared to controls, suggesting that the hyperglycemia presents in T2DM patients down-regulates SR-BI mRNA expression. Interestingly, we found that decreased SR-BI expression resulted in markedly increased plasma LDL concentrations in T2DM subjects, and the overexpression of SRBII isoform is responsible for the markedly increased plasma LDL-c concentrations. The polymorphism (rs838895) did not modify the mRNA level of SR-BI in leucocytes from control and diabetic patients. This study provides novel evidence suggesting that hyperglycemia may affect reverse cholesterol transport by controlling SRBI expression in diabetic patients. LDL cholesterol levels are associated with low SR-BI mRNA expression in T2DM.
文摘Introduction:On September 16,2024,the Puyang City CDC received a report of a suspected foodborne disease outbreak involving 14 individuals who developed nausea,vomiting,and diarrhea following attendance at a hotel banquet.Upon notification,the District CDC immediately deployed a specialized investigation team to characterize the epidemiological features of the outbreak,identify the causative pathogen,assess potential transmission risks,and implement effective control and prevention measures.Methods:We integrated comprehensive on-site epidemiological investigations,clinical symptom analyses,and laboratory diagnostics to isolate and identify pathogenic agents from retained food samples,environmental specimens,and anal swabs collected from affected cases.The recovered isolates underwent enterotoxin-virulence-gene profiling,antimicrobialsusceptibility testing,and phylogenetic analyses.Additionally,we characterized the architecture of the enterotoxin-A-linked pathogenicity island vSaβ.Results:A total of 4 S.aureus strains were successfully isolated from 22 leftover food samples,2 environmental swabs,and 2 patient anal swabs.Contaminated donkey and goose meat was identified as the outbreak source.All isolates harbored sea and seb enterotoxin genes,exhibited PEN-OXA-ERY-CLI resistance patterns,and were identified as clonal ST59-spa t441-SCCmec IVa CA-MRSA strains.Phylogenetic analysis positioned the outbreak strains within the Asia-Pacific clade,distinguishing them from the North American ST59 sublineage.Comprehensive analysis of the sea-associated virulence island vSaβidentified a novel structural arrangement containing a type A IEC cluster(sea-sak-chp-scn).Conclusions:The detection of foodborne ST59 CAMRSA clones in this outbreak underscores the prevalence and transmission risks associated with this hypervirulent lineage.These findings emphasize the critical need to strengthen surveillance measures for CA-MRSA among food industry workers.
基金Supported by Changsha Science and Technology Program,No.kq2022397Natural Science Foundation of Hunan Province(Departmental Joint Fund),No.2023JJ60440+2 种基金Research Program of Health Commission of Hunan Province,No.202303088786Clinical Medical Research Center for Viral Hepatitis of Hunan Province,No.2023SK4009the Scientific Research Program of FuRong Laboratory,No.2023SK2108.
文摘BACKGROUND C-X-C chemokine receptor type 5(CXCR5)^(+)CD8^(+)T cells represent a unique immune subset with dual roles,functioning as cytotoxic cells in persistent viral infections while promoting B cell responses.Despite their importance,the specific role of CXCR5^(+)CD8^(+)T cells in chronic hepatitis B(CHB),particularly during interferon-alpha(IFN-α)treatment,is not fully understood.This study aims to elucidate the relationship between CXCR5^(+)CD8^(+)T cells and sustained serologic response(SR)in patients undergoing 48 weeks of pegylated IFN-α(peg-IFN-α)treatment for CHB.AIM To elucidate the relationship between CXCR5^(+)CD8^(+)T cells and sustained SR in patients undergoing 48 weeks of peg-IFN-αtreatment for CHB.METHODS This study enrolled 60 patients with hepatitis Be antigen(HBeAg)-positive CHB undergoing 48 weeks of peg-IFN-αtreatment.Participants were assessed for eligibility based on criteria such as persistent HBsAg-positive status for at least six months,HBeAb-negative,hepatitis B virus DNA levels exceeding 2×10^(4) copies/mL,and alanine aminotransferase(ALT)levels between 2 and 10 times the upper limit of normal.Blood samples were collected at baseline and at weeks 12,24,48,and a 24-week treatment-free follow-up(week 72)to measure serum interleukin(IL)-21 concentration via ELISA and to analyze CXCR5 and programmed death-ligand 1(PD-L1)expression on CD8^(+)T cells by flow cytometry,CXCR5 is a chemokine receptor that directs immune cells to specific tissues,while PD-L1 is a protein that regulates immune responses by inhibiting T cell activity.RESULTS Patients with CHB exhibited significantly lower levels of circulating CXCR5^(+)CD8^(+)T cells compared to healthy controls(P<0.01).Notably,CXCR5^(+)CD8^(+)T cells were prominently expressed in patients who achieved sustained SR compared to non-SR(NSR).A significant correlation was observed between CXCR5 and PD-L1 expression(r=-0.189,P=0.002).However,there was no significant correlation between serum IL-21 levels and CXCR5+CD8+lymphocytes(r=-0.03,P=0.625)or serum ALT levels(r=0.026,P=0.678).CONCLUSION The enhanced expression of CXCR5^(+)CD8^(+)T cells in patients achieving HBeAg seroconversion during IFN-αtreatment suggests that these cells play a crucial role in antiviral immune responses against hepatitis B.This study highlights the potential of CXCR5^(+)CD8^(+)T cells as immune regulators in CHB,which may inform future therapeutic strategies to optimize antiviral treatments.
基金supported by the General Research Fund,Hong Kong Research Grants Council(17109123,17116521 and 27111820)the Mainland-Hong Kong Joint Funding Scheme(MHP/104/22)and the Health and Medical Research Fund(20212601 and 19201121).
文摘Type I interferon(IFN-I)is highly prevalent in autoimmune disorders and is intricately involved in disease pathogenesis,including Sjögren's disease(SjD),also known as Sjögren's syndrome.Although the T follicular helper(Tfh)cell response has been shown to drive SjD development in a mouse model of experimental Sjögren's syndrome(ESS),the connection between IFN-I and the Tfh cell response remains unclear.As the activation of stimulator of interferon genes(STING)induces IFN-I production,we first demonstrated that mice deficient in STING or IFN-I signaling presented diminished Tfh cells and were completely resistant to ESS development.However,the STING-IFN-I axis does not directly influence Tfh cell differentiation.Instead,IFN-I signaling in B cells was essential for mounting Tfh cell responses,as evidenced in Cd19CreIfnar1flox mice,which also showed resistance to ESS development.Mechanistic analyses revealed that IFN-I drove CXCR5 expression in innate-like marginal zone B cells via the MEKK3-OCT2 axis,facilitating their migration into the follicular area.Additionally,IFN-I promoted interleukin-6 production in B cells via the MEKK3-ERK5 axis,resulting in hyperactive Tfh cell responses.In SjD patients,STING activation was predominantly observed in circulating CD14+monocytes and was positively correlated with disease activity and effector T-cell responses.Pharmaceutical inhibition of either STING or IFNAR1 yielded moderate improvements in ESS mice with chronic inflammation,but combination therapy markedly improved outcomes and led to signs of disease remission.Our findings elucidate a novel mechanism by which IFN-I bridges innate and Tfh cell responses,suggesting new therapeutic avenues for SjD and related autoimmune disorders.
文摘BACKGROUND Sex disparities in clinical outcomes following thoracic endovascular aortic repair(TEVAR)for acute complicated type B aortic dissection(TBAD)are not well understood.AIM To evaluates the impact of sex on primary and secondary outcomes by comparing male and female cohorts undergoing TEVAR.METHODS A systematic search of PubMed,EMBASE,Cochrane Library,and ScienceDirect identified five studies involving 2572 patients(1153 males and 1419 females).The primary outcome was hospital mortality.Secondary outcomes included reintervention rates,acute kidney injury(AKI),ischemic stroke,limb ischemia,and spinal cord ischemia.Odds ratios(OR)with 95%confidence intervals(CI)were calculated using a random-effects model.Heterogeneity was assessed using the I²statistic.RESULTS The primary outcome showed no significant difference between males and females for hospital mortality(OR:1.13,95%CI:0.81-1.59,P=0.47,I2=0).Among secondary outcomes,males had a significantly higher risk of AKI(OR:1.55,95%CI:1.21-2.00,P=0.0006,I²=0).No differences were observed for reintervention rates,ischemic stroke,limb ischemia,or spinal cord ischemia.CONCLUSION Male patients undergoing TEVAR for complicated TBAD are at increased risk of AKI but show comparable outcomes to females for mortality,ischemic events,reintervention,and other complications.Future research should explore mechanisms and strategies to optimize outcomes.
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 Natural Science Foundation of Sichuan Province,No.2023NSFSC0682.
文摘BACKGROUND The interplay between abnormal glucose metabolism and the progression of liver fibrosis in patients with both chronic hepatitis B(CHB)and type 2 diabetes mellitus(T2DM)remains unclear.Previous studies have suggested that the coexistence of these conditions may exacerbate liver inflammation and fibrosis;however,the impacts of dynamic changes in glucose metabolism indicators,hypoglycemic medication regimens,and glycemic control status on liver fibrosis require further elucidation.AIM To explore the effect of glycemic control on hepatic fibrosis in patients with CHB and T2DM.METHODS A total of 420 patients with CHB and T2DM admitted to the Public Health Clinical Center of Chengdu between October 2018 and January 2022 were retrospectively included and classified according to liver stiffness measurement and glycemic control for between-group comparisons.RESULTS Significant differences were observed in the alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase,AST/ALT ratio,total bilirubin,direct bilirubin,diabetes treatment program,and thrombin time values among the liver fibrosis groups(adjusted P<0.05).Significant differences in albumin and gamma-glutamyl transferase levels were observed among the groups categorized by glucose status at admission(adjusted P<0.05).A positive correlation between fasting plasma glucose(FPG)and liver stiffness measurement was found to be mediated by ALT and AST.Fibrinogen and the international normalized ratio were positively correlated with glycated hemoglobin A1c,while the fibrosis-4 score,ALT,AST/ALT ratio,type III procollagen N-terminal peptide,ferritin,and activated partial thromboplastin time were correlated with FPG at admission.Additionally,AST was positively correlated with FPG at discharge(P<0.05).CONCLUSION Specific glucose metabolic parameters,hypoglycemic agents,and glycemic control status markers are associated with hepatic fibrosis in patients with both CHB and T2DM.Close blood glucose monitoring,optimized use of hypoglycemic agents,and continuous maintenance of good glycemic control may slow the progression of liver fibrosis in patients with CHB and T2DM.
文摘Background and Objective The natural history of type B aortic intramural hematoma(IMH)is highly heterogeneous.A computational fluid dynamics(CFD)model can be utilized to calculate a range of data pertinent to flow dynamics,including flow rates,blood velocity,pressure,and wall shear stress.This study presents a series of CFD simulations that model the dynamic progression from type B aortic IMH to false lumen formation.Methods A 66-year-old male patient presenting with chest and back pain underwent aortic computed tomography angiography(CTA),and a 3D patient-specific model was constructed.To evaluate the hemodynamic environment,the velocity,pressure,time-averaged wall shear stress(TAWSS),and oscillatory shear index(OSI)were calculated.Results A modest quantity of slow flow and recirculation flow was observed in the vicinity of the ulcer-like protrusion(ULP).During the formation of the false lumen,low-velocity blood flow entered the false lumen and resulted in vortex flow.ULPs were located in the region with higher TAWSS,and some high OSIs were found on the ULPs.Conclusion This preliminary study suggests a potential association between the TAWSS or OSI and progression from type B aortic IMH to aortic dissection.
基金funded by the“Hengrui-Tianqing Medical Education Fund”of the Second Affiliated Hospital of Wannan Medical College(grant no.HXKT2022026)Natural Science Research Program for Universities in Anhui Province(grant no.2023AH051739).
文摘Objective:To investigate the influence and underlying mechanisms of imrecoxib on liver damage in rats with type 2 diabetes mellitus(T2DM).Methods:A rat model of T2DM was established by a high-fat diet and streptozotocin administration.Rats were then treated with imrecoxib 10,20,or 40 mg/kg for 5 weeks.Body weight and fasting blood glucose levels were measured.The analysis included serum liver function,blood lipid profiles,and the levels of inflammatory factors in the rats.Liver tissue histology was evaluated using hematoxylin and eosin staining.Western blotting was conducted to measure the liver expression of proteins such as AKT,PI3K,NF-κB,p-AKT,p-PI3K,and p-NF-κB.Results:Rats treated with imrecoxib showed a greater weight gain compared to untreated diabetic rats.Compared to untreated diabetic rats,imrecoxib at all three doses reduced alanine aminotransferase,aspartate aminotransferase,triglycerides,cholesterol,tumor necrosis factor-α,interleukin(IL)-6,and IL-1β,and significantly increased the levels of IL-10 and IL-4.In imrecoxib-treated rats,the expression levels of AKT,PI3K,p-AKT,and p-PI3K were higher in comparison to the diabetes group,whereas the expression of p-NF-κB was lower.Conclusions:Imrecoxib could alleviate hepatic damage in T2DM rats by modulating PI3K/AKT/NF-κB signaling.
文摘Diabetes mellitus(DM)is a metabolic disorder characterized by persistent hyperglycemia and other symptoms,which pose significant challenges to individual health,life expectancy,and public healthcare systems.The escalating global prevalence of diabetes underscores the need for innovative therapeutic interventions.In this article,we critically comment on the study by Wang et al,published in the World Journal of Diabetes,which elucidates the therapeutic potential of Plantamajoside(PMS)in type 2 DM(T2DM)management.The authors provide evidence for the mechanism of action of PMS in T2DM models,demonstrating prevention of endoplasmic reticulum stress and apoptosis of pancreaticβ-cells via activation of DNAJC1.This manuscript provides a brief review of the pathogenesis of T2DM,explores the various roles of PMS in disease therapy in addition to the DNAJC-related apoptotic and autophagic functions,critically evaluates the experimental approaches employed by Wang et al,and provides recommendations for advancing future research.
