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1.
Arch Oral Biol ; 109: 104570, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31568992

RESUMO

OBJECTIVE: The aim of this study is to investigate the effects of 17ß-Estradiol (E2) at different concentrations combined with cyclical compressive stress on the proliferation and differentiation of mandibular condylar chondrocytes (MCCs). DESIGN: MCCs, isolated from female Sprague-Dawley rats, were exposed to E2 at different concentration, cyclical compressive stress or the combination, effects of which on MCCs proliferation and differentiation were detected. RESULTS: E2 at physiological concentration (10-9 mol/L) has lower proliferative effects on MCCs, compared with non-physiological concentration (10-12 mol/L or 10-6 mol/L). For MCCs differentiation, effects of E2 at different concentration are totally opposite: E2 at 10-9 mol/L promotes MCCs differentiation, but at 10-12 mol/L or 10-6 mol/L, it inhibits MCCs differentiation. When combined with E2 at 10-9 mol/L, cyclical compressive stress shows synergistic effect on proliferation and differentiation. However, when combined with E2 at 10-12 mol/L or 10-6 mol/L cyclical compressive stress reverses the inhibition in MCCs differentiation provoked by E2 at 10-12 mol/L or 10-6 mol/L. CONCLUSION: Effects of E2 combined with cyclical compressive stress on MCCs proliferation and differentiation are different, which suggests that orthodontist should take fully consideration of the levels of E2 and adopt comprehensive strategies, so as to achieve better orthodontic effect.

2.
J Nanosci Nanotechnol ; 20(4): 2452-2459, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492261

RESUMO

A promising anode material for lithium-ion batteries (LIBs) consisting of ultrafine N-doped TiO2 nanoparticles and N-doped carbon composite has been prepared by an effective sol-gel-calcined strategy. The synergetic effect between N-doped TiO2 nanoparticles and N-doped carbon provides not only high conductivity paths and strong electron contact interface, but also supply a large surface area along with hindering the nanoparticles aggregation, resulting in excellent lithium-storage performance. When tested as an anode material for LIBs, a high capacity of 292.7 mAh g-1 can be retained after 50 cycles at 0.5 C. Even at 8 C, a satisfactory capacity of 160.3 mAh g-1 can be delivered. These features suggest the N-doped TiO2/C composite a viable choice for application as an anode material in high-power LIBs.

4.
Medicine (Baltimore) ; 98(45): e17852, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702645

RESUMO

RATIONALE: Fusidic acid (FA) is an active agent against gram-positive bacteria such as Staphylococcus, it is generally well tolerated and the major adverse effects are mild gastrointestinal discomfort, diarrhea, and headache. However, some rare side effects such as granulocytopenia and thrombocytopenia have also been reported. Here we report a case of FA-induced hepatotoxicity and hematologic toxicity. PATIENT CONCERNS: A 54-year-old woman with hepatitis B cirrhosis was referred to us because of fever, Staphylococcus aureus was identified in the twice blood culture, and intravenous FA was given (0.5 g, q8 hours). Twelve days after FA therapy, she developed nausea and jaundice. Meanwhile, complete blood cell count showed neutropenia (white blood cell count of 1360/µL, neutrophil of 619/µL) and aggravated thrombocytopenia (platelet count of 18,000/µL). Adverse drug reaction was suspected, and FA was stopped immediately, after 1 day of discontinuation of FA, nose bleeding occurred and the platelet count declined further and reached the lowest value of 4000/µL. DIAGNOSES: Hepatotoxicity and hematologic complications induced by FA were diagnosed. INTERVENTIONS AND OUTCOMES: The FA was stopped immediately, and concentrated platelet transfusion was used. Five days after withdrawal of FA, jaundice resolved and the hematologic index returned to the level before the medication. LESSONS: Hematologic adverse effect accompanying with hepatotoxicity may be induced by FA. Though the risk is rather low, it should not be overlooked.


Assuntos
Ácido Fusídico/administração & dosagem , Icterícia/induzido quimicamente , Neutropenia/induzido quimicamente , Infecções Estafilocócicas/tratamento farmacológico , Administração Intravenosa , Feminino , Ácido Fusídico/efeitos adversos , Hepatite B/complicações , Humanos , Cirrose Hepática/virologia , Pessoa de Meia-Idade , Neutropenia/terapia , Transfusão de Plaquetas , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus/isolamento & purificação , Resultado do Tratamento
5.
BMC Cardiovasc Disord ; 19(1): 262, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771509

RESUMO

BACKGROUND: Hypertension is an established risk factor for the development of atrial fibrillation (AF). We evaluated the association and population impact of hypertension, defined using the new 2017 guidelines, on risk of AF. METHODS: In this analysis, we included 14,915 participants in the Atherosclerosis Risk in Communities study without history of AF. Participants underwent blood pressure measurements at baseline and their antihypertensive medication use was assessed. Incident AF was ascertained from study electrocardiograms, hospital records and death certificates. Cox proportional models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of AF among individuals with hypertension based on the JNC7 and 2017 ACC/AHA guidelines. Poisson models were used to obtain risk ratios and calculate population-attributable fractions (PAFs). RESULTS: We identified 2891 cases of incident AF during 21.4 years of mean follow-up. Prevalence of hypertension was 34 and 48% under the JNC7 and 2017 ACC/AHA definitions, respectively. HRs (95%CI) of AF in hypertensives versus non-hypertensives were 1.44 (1.32, 1.56) and 1.37 (1.26, 1.48) after multivariable adjustment under the old and new guidelines, respectively. The corresponding PAF (95%CI) using the old and new guidelines were 11% (8, 13%) and 13% (9, 16%), respectively. CONCLUSIONS: Overall, our analysis shows that even though the prevalence of hypertension using the new criteria is 40% higher than with the old criteria, this does not translate into meaningful increases in AF attributable to hypertension. These results suggest that prevention or treatment of hypertension based on the new (versus old) guidelines may have limited impact on AF incidence.

6.
Am J Cardiol ; 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771759

RESUMO

The aim of the present study was to investigate the association between atrial fibrillation (AF) and total and regional brain volumes among participants in the community-based Atherosclerosis Risk in Communities Neurocognitive study (ARIC-NCS). A total of 1,930 participants (130 with AF) with a mean age of 76.3 ± 5.2, who underwent 3T brain MRI scans in 2011 to 2013 were included. Prevalent AF was ascertained from study ECGs and hospital discharge codes. Brain volumes were measured using FreeSurfer image analysis software. Markers of subclinical cerebrovascular disease included lobar microhemorrhages, subcortical microhemorrhages, cortical infarcts, subcortical infarcts, lacunar infarcts, and volume of white matter hyperintensities. Linear regression models were used to assess the associations between AF status and brain volumes. In adjusted analyses, AF was not associated with markers of subclinical cerebrovascular disease. However, AF was associated with smaller regional brain volumes (including temporal, occipital, and parietal lobes; deep gray matter; Alzheimer disease signature region; and hippocampus [all p <0.05]) after controlling for demographics, cardiovascular risk factors, prevalent cardiovascular disease, and markers of subclinical cerebrovascular disease. Subgroup analysis revealed a significant interaction between AF and total brain volume with respect to age (p = 0.02), with associations between AF and smaller brain volumes being stronger for older individuals. In conclusion, AF was associated with smaller brain volumes, and the association was stronger among older individuals. This finding may be related to the longer exposure period of the older population to AF or the possibility that older people are more susceptible to the effects of AF on brain volume.

7.
Opt Lett ; 44(23): 5764-5767, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31774774

RESUMO

Metasurfaces have shown great potential to manipulate electromagnetic waves, and hence have found numerous applications in photonics. However, the functionalities of most of the reported metasurfaces are polarization unfriendly after the fabrication process and cannot be reconfigured dynamically with switchable polarization. Here, graphene-based metasurfaces are proposed to exhibit polarization-switchable electromagnetic response before and after switch of the chemical potential of graphene. The phase shifts covering a considerable phase range (with respect to 2π) can be switched from x polarization to y polarization by tuning the chemical potential of graphene from one value to another one. High-performance polarization-switchable anomalous reflection and focusing have been demonstrated with the designed metasurfaces. The presented design strategy can be applied to make other polarization-switchable metadevices in different frequency domains, and impact numerous photonic applications.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31741422

RESUMO

The signal molecules in root exudates that are sensed by plant growth-promoting rhizobacteria (PGPRs) are critical to regulate their root colonization. Phosphorylated Spo0A is an important global transcriptional regulator that controls colonization and sporulation in Bacillus species. In this study, we found that deletion of kinD from PGPR strain Bacillus amyloliquefaciens SQR9, encoding an original phosphate donor of Spo0A, resulted in reduced biofilm formation in root exudates compared with the wild type strain, indicating that KinD is responsible for sensing root exudates. Ligands of B. amyloliquefaciens SQR9 KinD in cucumber root exudates were determined by both the non-targeted ligand fishing method and the targeted surface plasmon resonance (SPR) detection method. In total, we screened 80 compounds in root exudates for binding to KinD and found that spermine and guanosine could bind to KinD with KD values of 213 µM and 51 µΜ, respectively. In addition, calcium L-threonate, N-acetyl-L-aspartic acid, sodium decanoic acid and parabanic acid could also bind to KinD weakly. Then, the 3-dimensional binding models were constructed to demonstrate the interactions between the root secreted signals and KinD. It was observed that exogenous spermine reduced the wrinkles of biofilm when kinD was defected, indicating that KinD might be involved in sensing root-secreted spermine and stabilizing biofilm in response to this negative effector. This study provided a new insight of interaction between rhizobacterial sensor and root secreted signals.

9.
Am J Cardiol ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31706453

RESUMO

Atrial fibrillation (AF) is prevalent and strongly associated with higher cardiovascular disease (CVD) risk. Machine learning is increasingly used to identify novel predictors of CVD risk, but prediction improvements beyond established risk scores are uncertain. We evaluated improvements in predicting 5-year AF risk when adding novel candidate variables identified by machine learning to the CHARGE-AF Enriched score, which includes age, race/ethnicity, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes, and NT-proBNP. We included 3,534 participants (mean age, 61.3 years; 52.0% female) with complete data from the prospective Multi-Ethnic Study of Atherosclerosis. Incident AF was defined based on study electrocardiograms and hospital discharge diagnosis ICD-9 codes, supplemented by Medicare claims. Prediction performance was evaluated using Cox regression and a parsimonious model was selected using LASSO. Within 5 years of baseline, 124 participants had incident AF. Compared with the CHARGE-AF Enriched model (c-statistic, 0.804), variables identified by machine learning, including biomarkers, cardiac magnetic resonance imaging variables, electrocardiogram variables, and subclinical CVD variables, did not significantly improve prediction. A 23-item score derived by machine learning achieved a c-statistic of 0.806, whereas a parsimonious model including the clinical risk factors age, weight, current smoking, NT-proBNP, coronary artery calcium score, and cardiac troponin-T achieved a c-statistic of 0.802. This analysis confirms that the CHARGE-AF Enriched model and a parsimonious 6-item model performed similarly to a more extensive model derived by machine learning. In conclusion, these simple models remain the gold standard for risk prediction of AF, although addition of the coronary artery calcium score should be considered.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31683001

RESUMO

As molecular chaperones, heat shock proteins (HSPs) play essential roles in cells in response to stress conditions. Recent studies about immune functions of HSPs in fish have also been reported. In this study, based on the reported cDNA sequences of the four HSP genes, HSP70, HSC70, HSP90α and HSP90ß, the temporal expression patterns of the four genes during embryonic development of dojo loach(Misgurnus anguillicaudatus) was assayed with qRT-PCR. All of the four genes were ubiquitously expressed in all detected embryonic developmental stages. Among of them, HSP70, HSC70 and HSP90ß were highly expressed in the organ formation stage, while HSP90α was the highest expressed in myotome formation stage. Further, the immune responses of the four HSP genes were assayed when loach were infected with three different pathogens, bacterium (Flavobacterium cloumnare G4), parasite (Ichthyophthirius multifiliis) and fungus (Saprolegnia). All of the four genes were differentially expressed in four tissues such as skin, gills, spleen and kidney in response to the pathogenic invasion, but both HSP70 and HSP90α expressions were dramatically up-regulated. Further, the cellular responses of the loach skinand gill tissues were observed, in which the number of the skin goblet cells were significantly increased, and the gill lamellae became shorter and wider after infected. Thus, our work indicated that the HSPs may directly or indirectly involved in immune defense in fish, at least in the loach.

11.
Int Immunopharmacol ; : 105973, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31677992

RESUMO

Sepsis is a syndrome of life-threatening organ dysfunction caused by dysregulated host responses to infection. Macrophage polarization is a key process involved in the pathogenesis of sepsis. Recent evidence has demonstrated that autophagy participates in the regulation of macrophage polarization in different phases of inflammation. Here, we investigated whether trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, promotes the macrophage M2 phenotype by enhancing autophagy to counteract excessive inflammation in a cecal ligation and puncture (CLP) mouse model. TSA stimulation increased the proportions of M2 marker (CD206, CD124 and CD23)-labeled RAW264.7 macrophages. Furthermore, with increasing TSA doses, autophagy was enhanced gradually. Interestingly, the autophagy activator rapamycin (Rap), also known as an mTOR inhibitor, unexpectedly decreased the proportions of M2 marker-labeled macrophages. However, TSA treatment reversed the Rap-induced decreases in CD206-labeled macrophages. Next, we stimulated different groups of RAW264.7 cells with the autophagy inhibitors MHY1485 or 3-methyladenine (3-MA). Inhibition of autophagy at any stage in the process suppressed TSA-induced macrophage M2 polarization, but the effect was not associated with mTOR activity. In vivo, TSA administration promoted peritoneal macrophage M2 polarization, increased LC3 II expression, attenuated sepsis-induced organ (lung, liver and kidney) injury, and altered systemic inflammatory cytokine secretion. However, 3-MA abolished the protective effects of TSA in CLP mice and decreased the number of M2 peritoneal macrophages. Therefore, TSA promotes the macrophage M2 phenotype by enhancing autophagy to reduce systemic inflammation and ultimately improves the survival of mice with polymicrobial sepsis.

12.
Circulation ; : CIR0000000000000740, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31694402

RESUMO

The widespread use of cardiac implantable electronic devices and wearable monitors has led to the detection of subclinical atrial fibrillation in a substantial proportion of patients. There is evidence that these asymptomatic arrhythmias are associated with increased risk of stroke. Thus, detection of subclinical atrial fibrillation may offer an opportunity to reduce stroke risk by initiating anticoagulation. However, it is unknown whether long-term anticoagulation is warranted and in what populations. This scientific statement explores the existing data on the prevalence, clinical significance, and management of subclinical atrial fibrillation and identifies current gaps in knowledge and areas of controversy and consensus.

13.
Food Chem ; : 125755, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31704075

RESUMO

A simple, sensitive and environmentally-friendly method for determining organophosphorus and pyrethroid pesticides in vegetables was developed to better evaluate the risk of consuming them. The pesticides in vegetables were extracted, purified and concentrated by using the QuEChERS (quick, easy, cheap, effective, rugged and safe method) combined DLLME-SFO (dispersive liquid-liquid microextraction based on solidification of floating organic droplet) techniques. The key parameters were optimized through orthogonal array experimental design and statistical analysis. The linearity of the calibration curves was satisfied in matrix-matched standard solution with R2 ≥ 0.99. The limits of detection and limits of quantification were 0.3-1.5 and 0.9-4.7 µg/kg, respectively. The average recoveries of pesticides were 61.6-119.4% with relative standard deviations <16.1%. Furthermore, the method was applied successfully to analyse the pesticides in 15 pairs of organic and conventional vegetables. These results reflect the efficiency, reliability and robustness of the developed method.

14.
J Biol Chem ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31723028

RESUMO

Proteins of nuclear receptor subfamily 4 group A (NR4A), including NR4A1/NGFI-B, NR4A2/Nurr1, and NR4A3/NOR-1, are nuclear transcription factors that play important roles in metabolism, apoptosis, and proliferation. NR4A proteins recognize DNA response elements as monomers or dimers to regulate the transcription of a variety of genes involved in multiple biological processes. In this study, we determined two crystal structures of the NR4A2 DNA-binding domain (NR4A2-DBD) bound to two Nur-responsive elements (NurREs), namely, an inverted repeat and an everted repeat at 2.6-2.8 Å resolutions.  The structures revealed that two NR4A2-DBD molecules bind independently to the everted repeat, whereas two other NR4A2-DBD molecules form a novel dimer interface on the inverted repeat. Moreover, substitution of the interfacial residue Valine 298 to lysine, as well as mutation of DNA bases involved in the interactions, abolished the dimerization. Overall, our structural, biochemical, and bioinformatics analyses provide a molecular basis for the binding of the NR4A2 protein dimers to NurREs and advance our understanding of the dimerization specificity of nuclear receptors.

15.
Opt Lett ; 44(22): 5446-5449, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730079

RESUMO

Graphene has attracted the interest of researchers seeking to develop compact optical modulators with the flexible tunability of graphene conductivity by tuning the Fermi level. Plasmonic structures have provided a robust way to enhance the modulation depth (MD) of graphene optical modulators, but the available schemes suffer from low MD, fabrication complexities, or both. Here, an ultra-thin plasmonic metasurface structure capable of guiding slow surface plasmons (SPs) is proposed to construct graphene-based optical modulators. The designs take advantage of the strong field enhancement of slow SP modes as well as the orientation match between the electric field and the graphene plane. A typical 0.96-µm-long metasurface-based graphene modulator presents a significantly improved MD of 4.66 dB/µm and an acceptable insertion loss of 1.4 dB/µm, while still having ease of fabrication.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31765792

RESUMO

Complement is a complex component of innate immune system, playing an important role in defense against pathogens and host homeostasis. The complement system has been comprehensively studied in mammals, however less is known about complement in teleost, especially in tetraploid common carp (Cyprinus carpio). In this study, a total of 110 complement genes were identified and characterized in common carp, which include almost all the homologs of mammalian complement genes. These genes were classified into three pathways (alternative pathways, lectin pathways and classical pathways), similar to those in mammals. Phylogenetic and selection pressure analysis showed that the complement genes were evolving-constrained and the function was conserved. Most of the complement genes were highly expressed in spleen, liver, brain and skin among the tested 12 health tissues of common carp. After Aeromonas hydrophila infection in the common carp, many members of complement genes were activated to bring about an immune response and expressed to against any pathogenic encroachment. Gene expression divergences which were found between two homoeologous genes suggested the functional divergences of the homoeologous genes after the 4R WGD event, revealing the evolutionary fate of the tetraploid common carp after the recent WGD.

17.
J Am Heart Assoc ; 8(23): e013197, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31766970

RESUMO

Background Atrial fibrillation (AF) is associated with cognitive decline. Whether left atrial enlargement (LAE), a critical substrate for AF, is also associated is less well established. Therefore, we assessed the association of LAE and AF with cognitive decline in the ARIC-NCS (Atherosclerosis Risk in Communities Neurocognitive Study). Methods and Results Participants (n=3391; mean age, 75±5 years; 59% women) underwent cognitive tests and 2-dimensional echocardiograms at visit 5 (2011-2013) and follow-up cognitive tests at visit 6 (2016-2017). LAE was defined as left atrium volume index ≥34 mL/m2. AF was ascertained using study ECGs and hospitalization discharge codes. We assessed the association of AF and LAE with (a) cognitive domain scores at visit 5 and (b) cognitive domain score changes between visit 5 and visit 6. At visit 5, compared with the reference group (without AF, normal left atrium), participants with LAE and AF had significantly lower global cognition (Z score, -0.24; 95% CI, -0.38 to -0.10), whereas participants with AF and without LAE and participants with LAE and without AF did not have lower global cognition. In longitudinal analysis, compared with the reference group, participants with AF but without LAE had significantly greater decline in global cognition (Z score, -0.13; 95% CI, -0.21 to -0.06). However, LAE, with or without AF, was not associated with greater cognitive decline. Conclusion Although LAE with AF was significantly associated with lower cognitive function in cross-sectional analysis, LAE, with or without AF, was not associated with greater cognitive decline over 5 years, highlighting the importance of evaluating longitudinal cognitive function. Future studies should have longer follow-up and evaluate left atrium function.

18.
J Nanobiotechnology ; 17(1): 116, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767014

RESUMO

Tumor cells with heterogeneity and diversity can express different markers. At present, positive separation of circulating tumor cells (CTC) taking EpCAM as the marker was used in most cases which could be one-sided, while this study successfully prepared four antibody-modified magnetic immunoliposomes (MIL) by using the self-assembled liposome with antibody derivatives. This study aims to explore the separation efficiency and clinical detection feasibility of single or combined use of MIL with multi-tumor markers on different tumors. Captured CTC were stained with CK-FITC, CD45-PE and DAPI, and fluorescence microscope was used for the observation, analysis and calculation. The result indicated that the CTC number positive rate in blood samples of four different magnetic balls on the same patient could be up to 87.5% in 32 patients with 14 different kinds tumors. While the effect of directly mixed separation by four kinds of magnetic balls was not satisfying. It suggested that the MIL of multi-tumor markers could be a powerful tool for CTC separation in application of tumor screening and prognosis.

19.
Small ; : e1904369, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769618

RESUMO

2D transition metal dichalcogenides (TMDs) based photodetectors have shown great potential for the next generation optoelectronics. However, most of the reported MoS2 photodetectors function under the photogating effect originated from the charge-trap mechanism, which is difficult for quantitative control. Such devices generally suffer from a poor compromise between response speed and responsivity (R) and large dark current. Here, a dual-gated (DG) MoS2 phototransistor operating based on the interface coupling effect (ICE) is demonstrated. By simultaneously applying a negative top-gate voltage (VTG ) and positive back-gate voltage (VBG ) to the MoS2 channel, the photogenerated holes can be effectively trapped in the depleted region under TG. An ultrahigh R of ≈105 A W-1 and detectivity (D*) of ≈1014 Jones are achieved in several devices with different thickness under Pin of 53 µW cm-2 at VTG = -5 V. Moreover, the response time of the DG phototransistor can also be modulated based on the ICE. Based on these systematic measurements of MoS2 DG phototransistors, the results show that the ICE plays an important role in the modulation of photoelectric performances. The results also pave the way for the future optoelectrical application of 2D TMDs materials and prompt for further investigation in the DG structured phototransistors.

20.
Int J Med Microbiol ; : 151379, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31759864

RESUMO

The presence of bacterial species other than the pathogen at infection site can affect the progression of a bacterial infection. Based on the fact that Citrobacter freundii can coexist during Pseudomonas aeruginosa infection, this study aims to investigate the impact of the co-existing C. freundii on the pathogenesis of P. aeruginosa infection. A murine peritonitis model was used to compare the mortality rates and histopathology of P. aeruginosaPAO1 infection in the presence and absence of a C. freundii clinical isolate C9. We also investigated the intercellular interaction between PAO1 and C9 by examining pyocyanin production and comparing gene expression levels. The results demonstrate that co-infection with C9 significantly increased the mortality rate and tissue damages in PAO1 infected mice. At an inoculum of 106 CFU, no mortality was observed in the C9 infected group at three days post-infection, whereas the mortality rate in the PAO1-C9 co-infection group was 64%, compared with 24% in the PAO1 infected group. Pyocyanin production in P. aeruginosa PAO1 increased 8 folds approximately in the presence of C. freundii C9, and operons associated with phenazine synthesis, phzA1 and phzA2, were also upregulated. Disruption of the phzA1 and phzA2 eliminated the exacerbated pathogenicity in the co-infection group, indicating that the elevated pyocyanin production was the main contributing factor. The results suggest that co-existing C. freundii during P. aeruginosa infection can exacerbate the pathogenicity, which may have significant implications in patients infected with these bacteria.

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