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1.
BMC Microbiol ; 24(1): 130, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643095

RESUMO

BACKGROUND: Mycobacteria bloodstream infections are common in immunocompromised people and usually have disastrous consequences. As the primary phagocytes in the bloodstream, monocytes and neutrophils play critical roles in the fight against bloodstream mycobacteria infections. In contrast to macrophages, the responses of monocytes infected with the mycobacteria have been less investigated. RESULTS: In this study, we first established a protocol for infection of non-adherent monocyte-like THP-1 cells (i.e. without the differentiation induced by phorbol 12-myristate 13-acetate (PMA) by bacillus Calmette-Guérin (BCG). Via the protocol, we were then capable of exploring the global transcriptomic profiles of non-adherent THP-1 cells infected with BCG, and found that NF-κB, MAPK and PI3K-Akt signaling pathways were enhanced, as well as some inflammatory chemokine/cytokine genes (e.g. CCL4, CXCL10, TNF and IL-1ß) were up-regulated. Surprisingly, the Akt-HIF-mTOR signaling pathway was also activated, which induces trained immunity. In this in vitro infection model, increased cytokine responses to lipopolysaccharides (LPS) restimulation, higher cell viability, and decreased Candida albicans loads were observed. CONCLUSIONS: We have first characterized the transcriptomic profiles of BCG-infected non-adherent THP-1 cells, and first developed a trained immunity in vitro model of the cells.


Assuntos
Monócitos , Mycobacterium bovis , Humanos , Vacina BCG , Imunidade Treinada , Proteínas Proto-Oncogênicas c-akt/genética , Células THP-1 , Fosfatidilinositol 3-Quinases , Citocinas
2.
Nucleic Acids Res ; 50(7): 3777-3798, 2022 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-35325196

RESUMO

Type III and type VI secretion systems (T3/T6SS) are encoded in horizontally acquired genomic islands (GIs) that play crucial roles in evolution and virulence in bacterial pathogens. T3/T6SS expression is subjected to tight control by the host xenogeneic silencer H-NS, but how this mechanism is counteracted remains to be illuminated. Here, we report that xenogeneic nucleoid-associated protein EnrR encoded in a GI is essential for virulence in pathogenic bacteria Edwardsiella and Salmonella. We showed that EnrR plays critical roles in T3/T6SS expression in these bacteria. Various biochemical and genetic analyses demonstrated that EnrR binds and derepresses the promoter of esrB, the critical regulator of T3/T6SS, to promote their expression by competing with H-NS. Additionally, EnrR targets AT-rich regions, globally modulates the expression of ∼363 genes and is involved in various cellular processes. Crystal structures of EnrR in complex with a specific AT-rich palindromic DNA revealed a new DNA-binding mode that involves conserved HTH-mediated interactions with the major groove and contacts of its N-terminal extension to the minor groove in the symmetry-related duplex. Collectively, these data demonstrate that EnrR is a virulence activator that can antagonize H-NS, highlighting a unique mechanism by which bacterial xenogeneic regulators recognize and regulate foreign DNA.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Ligação a DNA/metabolismo , Edwardsiella/patogenicidade , Ilhas Genômicas , Salmonella/patogenicidade , Sistemas de Secreção Bacterianos , Edwardsiella/genética , Regulação Bacteriana da Expressão Gênica , Inativação Gênica , Salmonella/genética , Virulência
3.
World J Surg Oncol ; 22(1): 39, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38297355

RESUMO

BACKGROUND: The peritoneal cancer index (PCI) has been used to predict surgical outcomes for pseudomyxoma peritonei (PMP). The present study aimed to establish the optimal cutoff point for PCI to predict surgical resectability of PMP. METHODS: A total of 366 PMP patients were included. The patients were divided into low-grade and high-grade groups. Based on the completeness of the cytoreduction (CC) score, both low-grade and high-grade PMP patients were further divided into complete cytoreductive surgery (CRS) and maximal tumor debulking (MTD) subgroups. The ability to predict surgical resectability of total and selected PCI (regions 2 + 9 to 12) was analyzed through receiver operating characteristic (ROC) curves. RESULTS: Both total and selected PCI demonstrated excellent discriminative ability in predicting surgical resectability for low-grade PMP patients (n = 266), with the ROC-AUC of 0.940 (95% CI: 0.904-0.965) and 0.927 (95% CI: 0.889-0.955). The corresponding optimal cutoff point was 21 and 5, respectively. For high-grade PMP patients (n = 100), both total and selected PCI exhibited good performance in predicting surgical resectability, with the ROC-AUC of 0.894 (95% CI: 0.816-0.946) and 0.888 (95% CI: 0.810-0.943); correspondingly, the optimal cutoff point was 25 and 8, respectively. The discriminative ability between total and selected PCI in predicting surgical resectability did not show a statistical difference. CONCLUSIONS: Both total and selected PCI exhibited good performance and similarity in predicting complete surgical resection for both low-grade and high-grade PMP patients. However, the selected PCI was simpler and time-saving in clinical practice. In the future, new imaging techniques or predictive models may be developed to better predict PCI preoperatively, which might assist in confirming whether complete surgical resection can be achieved.


Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Humanos , Pseudomixoma Peritoneal/patologia , Neoplasias Peritoneais/patologia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Estudos Retrospectivos
4.
BMC Cancer ; 23(1): 90, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36703100

RESUMO

BACKGROUND: To investigate the expression of carcinoembryonic antigen (CEA), cancer antigen 199 (CA199) and CA125 in serum and ascites of appendiceal pseudomyxoma peritonei (PMP) patients relative to their diagnostic and predictive value. METHODS: The study comprised 183 patients with pathologically confirmed appendiceal PMP, enrolled from May 2012 to June 2020, in Aerospace Center Hospital. Serum and ascites tumor markers were obtained, and their diagnostic values were compared by receiver operating characteristic (ROC) curves. The prognostic factors of appendiceal PMP with different pathologic subgroups were calculated by univariate and multivariate Cox proportional hazard regression models. RESULTS: There were significant differences between the numbers of patients with positive CEA and CA199 in serum vs. ascites: p = 0.034 in CEA and p = 0.006 in CA199, respectively. The sensitivities with optimal cut-off values for ascites markers of CEA, CA199 and CA125 were 83.5%, 88.9% and 72.6%, respectively. CEA in ascites showed significant difference in the diagnosis of appendiceal PMP (p = 0.000); the areas under the ROC curves (AUROCs) and specificity were 0.725, 70.7%, respectively. Univariate analysis showed that the higher the ascites tumor markers, the poorer the survival (p = 0.014). Multivariate analysis indicated that completeness of cytoreduction (CCR), ascites CEA and pathological grade were independent risk factors for overall survival (OS). CONCLUSION: CEA in ascites can be used to help specify the origin of PMP. Furthermore, elevation of ascites CEA, high pathological grade and incomplete cytoreduction predicted poor prognosis of appendiceal PMP.


Assuntos
Neoplasias do Apêndice , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Humanos , Pseudomixoma Peritoneal/diagnóstico , Pseudomixoma Peritoneal/patologia , Prognóstico , Antígeno Carcinoembrionário/metabolismo , Biomarcadores Tumorais , Ascite , Neoplasias do Apêndice/diagnóstico , Neoplasias do Apêndice/cirurgia , Antígeno Ca-125
5.
Eur Radiol ; 33(4): 2800-2808, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36418618

RESUMO

OBJECTIVES: This study aimed to identify the diagnostic accuracy of combined ultrasonography (US) and computed tomography (CT) in evaluating the tumor burden of pseudomyxoma peritonei (PMP). Besides, we assessed the ability of this combination to predict the likelihood of complete resection. METHODS: This retrospective study involved 504 patients diagnosed with PMP and scheduled for cytoreduction surgery. We compared tumor burden-quantified as peritoneal cancer index (PCI) by preoperative US and CT (US-CT-PCI)-with surgical findings. Next, we assessed the prognostic value of US-CT PCI and imaging features in determining the completeness of cytoreduction (CCR) score using multivariate analysis. RESULTS: US-CT PCI demonstrated a high PCI evaluation accuracy under moderate tumor burden. Higher US-CT PCI could predict incomplete resection. In addition, we identified imaging features such as mesenteric involvement as an independent predictor of incomplete resection (hazard ratio (HR) = 2.006; p = 0.007). CONCLUSIONS: US-CT PCI allowed us to predict the completeness of cytoreductive surgery in patients with PMP. Moreover, the combined US and CT imaging detected several features indicating incomplete cytoreduction. KEY POINTS: • Ultrasonography (US) can act as a complementary diagnostic modality in peritoneal cancer index (PCI) evaluation by combining CT in the small bowel area and US in the abdominal area. • A modified peritoneal cancer index (US-CT PCI) helps preoperatively evaluate tumor burden with high accuracy and allows to predict incomplete resection. • US-CT PCI of 20 or above and the involvement of particular structures such as mesentery, independently indicate incomplete resection.


Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Humanos , Pseudomixoma Peritoneal/diagnóstico por imagem , Pseudomixoma Peritoneal/cirurgia , Pseudomixoma Peritoneal/patologia , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/cirurgia , Neoplasias Peritoneais/patologia , Estudos Retrospectivos , Prognóstico , Tomografia Computadorizada por Raios X , Ultrassonografia/métodos , Procedimentos Cirúrgicos de Citorredução , Terapia Combinada
6.
Perception ; 52(4): 238-254, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36788004

RESUMO

Categorical color constancy has been widely investigated and found to be very robust. As one of object material properties, the surface gloss was found to barely contribute to color constancy in a natural viewing condition. In this study, the effect of surface gloss on categorical color constancy was investigated by asking eight observers to categorize 208 Munsell matte surfaces and 260 Munsell glossy surfaces under D65, F, and TL84 illuminants in a viewing chamber with a uniform gray background. A color constancy index based on the centroid shift of the color category was used to evaluate color constancy degree of each color category across illumination changes from D65 to F or TL84 illuminant. The result showed that both matte and glossy surfaces showed almost perfect color constancy on all color categories under F and TL84 illuminants, and there was no significant difference between them. This result suggests that surface gloss has little effect on categorical color constancy in a uniform gray background where the local surround cue was present, which is consistent with the previous findings.


Assuntos
Percepção de Cores , Iluminação , Humanos , Estimulação Luminosa , Cor
7.
Ann Surg Oncol ; 29(2): 885-892, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34480280

RESUMO

BACKGROUNDS: The completeness of cytoreduction is one of the most important prognostic factors for patients with pseudomyxoma peritonei (PMP). To date, no nomograms have been established to predict incomplete cytoreduction (IC) for patients with PMP. The current study therefore proposed a nomogram to predict individual IC risk for PMP patients. METHODS: Between 1 June 2013, and 22 November 2019, 144 consecutive PMP patients who underwent cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the first time in our center were included in a retrospective study. Possible predictors of cytoreducibility were analyzed using logistic regression modeling to predict IC for PMP patients. A nomogram was developed based on the multivariate analysis and further investigated for internal validation. RESULTS: After CRS, the 144 participants were divided into complete CRS (CCRS) (n = 46) and IC (n = 98) subgroups. Four independent predictors (sex, disease duration, anemia, and carbohydrate antigen 19-9 (CA 199)) were included in the prediction model. Then, a nomogram predicting IC was established based on the aforementioned variables, which demonstrated good predictive accuracy (C-index, 0.837; 95 % confidence interval [CI], 0.764-0.894). The predicted probability was close to the actual observed outcome according to the calibration plot. CONCLUSIONS: The current work led to the development of a nomogram capable of predicting IC for PMP patients who demonstrated good performance. Risk stratification by the established nomogram had ability to optimize individual IC prediction and help physicians to establish meticulous preoperative plans.


Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Nomogramas , Neoplasias Peritoneais/cirurgia , Pseudomixoma Peritoneal/cirurgia , Estudos Retrospectivos
8.
Opt Express ; 30(11): 18571-18588, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-36221656

RESUMO

Categorical color constancy in normal trichromats has been found to be very robust in real scenes. In this study, we investigated categorical color constancy in red-green dichromats and anomalous trichromats. Eight dichromats (two protanopes and six deuteranopes), eight anomalous trichromats (four protanomalous and four deuteranomalous trichromats), and eight normal trichromats sorted 208 Munsell matte surfaces into Berlin and Kay's basic color categories under D65 illuminant, F illuminant with correlated color temperature 4200 K, and TL84 illuminant with correlated color temperature 2700 K. Color constancy was quantified by a color constancy index. The results showed that the constancy index of dichromats (0.79) was considerable and significantly lower than that of normal trichromats (0.87) while that of anomalous trichromats (0.84) was not. The impairment of color constancy performance in dichromats was expected to be caused by their large intra-subject variabilities in color naming. The results indicate robust categorical color constancy along daylight locus in red-green dichromats and anomalous trichromats, which might be contributed by cone adaptation mechanism and be independent of color discrimination mechanism. It suggests that the color categorization by color vision deficient subjects can be reasonable without any assistants of artificial equipment in daily life under sunlight and common illuminations.


Assuntos
Defeitos da Visão Cromática , Visão de Cores , Cor , Percepção de Cores , Defeitos da Visão Cromática/genética , Humanos , Estimulação Luminosa/métodos , Células Fotorreceptoras Retinianas Cones
9.
J Chem Phys ; 156(5): 054703, 2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-35135281

RESUMO

Transient absorption (TA) and time-resolved photoluminescence (PL) spectroscopies have been used to elucidate the hole tunneling and Auger dynamics in biexcitons and negative trions in high-quality InP/ZnSe/ZnS quantum dots (QDs). In a previous paper [Nguyen et al., J. Phys. Chem. C 125, 15405-15414 (2021)], we showed that under high-intensity photoexcitation, two types of biexcitons are formed: those having two conduction band electrons and two valence band holes (designated as an XX state) and those having two conduction band electrons, one valence band hole, and an additional trapped hole (designated as an XT state). In the present paper, we show that both types of biexcitons can undergo Auger processes, with those of the XT state being a factor of four to five slower than those of the XX state. In addition, the trapped holes can undergo tunneling into the valence band, converting an XT state to an XX state. The relative amplitudes of the fast (XX) and slow (XT) components are different in the TA and PL kinetics, and these differences can be quantitatively understood in terms of oscillator strengths and electron-hole overlap integrals of each state. XT to XX hole tunneling rates are obtained from the comparison of the XT state lifetimes with those of the negative trions. This comparison shows that the tunneling times decrease with decreasing core size and shell thickness. These times are about 2 ns for the thinnest shell red-emitting QDs and decrease to 330 ps for QDs that luminesce in the yellow.

10.
BMC Surg ; 22(1): 372, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36316677

RESUMO

PURPOSE: Accurate assessment of preoperative tumor burden contribute to formulate a scientific surgical plan for patients with pseudomyxoma peritonei (PMP). Present study aimed to assess whether the preoperative plasma D-Dimer level could reflect tumor burden for PMP patients. METHODS: A total of 253 PMP patients were included between June 1, 2013 and March 1, 2022. According to the peritoneal cancer index (PCI), all participants were divided into extensive (PCI ≥ 28) and none-extensive (PCI < 28) subgroups. The D-Dimer and tumor markers were compared between the two subgroups. The correlation between the abovementioned biomarkers and PCI will be calculated, and further compared with each other. Two-sided P value less than 0.05 is considered statistically significant. RESULTS: The level of D-Dimer (ng/ml) between extensive and none-extensive subgroup were 600 (328, 1268) vs. 339 (128, 598), Z = -5.425, p < 0.001. The Spearman correlation between D-Dimer, carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA 125), CA 19 - 9 and PCI were 0.487, 0.509, 0.469, and 0.499, respectively (all p < 0.001). The correlation coefficients were compared with each other according to Meng, Rosenthal and Rubin's method, however, there was no significant difference. CONCLUSION: Preoperative plasma D-Dimer could moderately reflect tumor burden for PMP. In the future, a multivariate prediction model will be developed to help surgeons to formulate a more precise surgical plan for the PMP patients.


Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Humanos , Pseudomixoma Peritoneal/diagnóstico , Pseudomixoma Peritoneal/cirurgia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/cirurgia , Produtos de Degradação da Fibrina e do Fibrinogênio , Antígeno CA-19-9 , Estudos Retrospectivos
11.
Int J Cancer ; 148(8): 2036-2047, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33403690

RESUMO

Pseudomyxoma peritonei (PMP) is a rare disorder with unique pathological and genetic changes. Although several studies have reported the clinical features and mutational changes of PMP that originates from the appendix, few studies on PMP originating from the ovary have been reported due to its extreme rarity. In order to characterize the somatic mutational landscape and to investigate the prognosis predicting factors of ovary-originating PMP, we examined 830 cases of PMP and identified 16 patients with PMP that originated from the ovary. Whole-exome sequencing (WES) was performed on 12 cases using formalin-fixed, paraffin-embedded (FFPE) tissue samples. We found that 25% (3/12) of the patients carried mutations in cancer driver genes, including TP53, ATM and SETD2, and 16.7% (2/12) of the patients carried mutations in cancer driver genes, including ATRX, EP300, FGFR2, KRAS, NOCR1 and RB1. The MUC16 (58.33%), BSN (41.67%), PCNT (41.67%), PPP2R5A (41.67%), PRSS36 (41.67%), PTPRK (41.67%) and SBF1 (41.67%) genes presented the highest mutational frequencies. The PI3K-Akt signaling pathway, human papillomavirus infection pathway, cell skeleton, cell adhesion, and extracellular matrix and membrane proteins were the major pathways or functions that were affected. Patients were followed up to 174 months (median: 48.26 months). The 5-year OS rate for all patients was 71.2% and the median OS was not reached. PTPRK mutations, presurgical CA199 level, completeness of cytoreduction (CCR) and peritoneal cancer index (PCI) were identified as potential predictive factors for patient survival. In conclusion, the mutational landscape for ovary-originating PMP was revealed and exhibited unique features distinct from appendix-originating PMP. PTPRK, CA199, CCR and PCI may predict patient survival.


Assuntos
Sequenciamento do Exoma/métodos , Predisposição Genética para Doença/genética , Mutação , Ovário/metabolismo , Neoplasias Peritoneais/genética , Pseudomixoma Peritoneal/genética , Adulto , Idoso , Proteínas Mutadas de Ataxia Telangiectasia/genética , Feminino , Histona-Lisina N-Metiltransferase/genética , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Ovário/patologia , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/patologia , Prognóstico , Pseudomixoma Peritoneal/metabolismo , Pseudomixoma Peritoneal/patologia , Proteínas de Ligação a Retinoblastoma/genética , Estudos Retrospectivos , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/genética
12.
J Surg Oncol ; 124(8): 1459-1467, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34634135

RESUMO

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare disease, with the rate of overall survival (OS) influenced by many factors. The present study aimed to define independent predictors and establish a nomogram for individual risk prediction in PMP patients. METHODS: One hundred forty-seven PMP patients were consecutively included between June 1, 2013, and November 22, 2019. The log-rank test was used to compare the OS rate between groups; subsequently, variables with p < .10 were subjected to multivariate Cox modeling for defining independent prediction indicators. Finally, a nomogram was established based on independent prognosticators and assessed for internal validation. RESULTS: Multivariate Cox analysis showed that D-dimer level, carbohydrate antigen (CA) 125 level, CA 19-9 level, degree of radical surgery, and histological grade were all independently associated with OS in PMP patients. A nomogram was plotted and underwent internal validation. The discrimination ability of the nomogram revealed a good predictive ability as indicated by the C-index value (0.825), and calibration plots confirmed good consistency between the predicted and observed survival probabilities. CONCLUSIONS: Five independent prognostic factors for predicting the survival of PMP patients were identified, and the nomogram based on these independent indicators showed a reasonable discrimination ability for individual risk prediction.


Assuntos
Neoplasias do Apêndice/mortalidade , Biomarcadores Tumorais/análise , Nomogramas , Neoplasias Peritoneais/mortalidade , Pseudomixoma Peritoneal/mortalidade , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Prognóstico , Pseudomixoma Peritoneal/patologia , Pseudomixoma Peritoneal/terapia , Estudos Retrospectivos , Taxa de Sobrevida
13.
J Chem Phys ; 155(24): 244705, 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34972380

RESUMO

We have used time-correlated single photon counting to elucidate the radiative dynamics of InP/ZnSe/ZnS core/shell/shell quantum dots (QDs) that differ in the amount and distribution of excess indium. Stoichiometric QDs having an In:P atom ratio very near unity exhibit simple luminescence kinetics. The photoluminescence (PL) rises with the 40 ps instrument response function and exhibits a decay that is close to a single exponential with a time constant that decreases from 32 to 28 ns with increasing shell thickness. QDs having excess indium (In:P ratio of 1.15-1.63) show a significant component of a slower rise time assigned to transient population of indium-based hole traps in the ZnSe shell. They also have a slower PL decay, attributed to an equilibrium between these traps, which are optically dark, and the emissive valence-band state. This results in a radiative lifetime that increases from 32 to 48 ns with increasing shell thickness. Different treatments of the InP cores prior to shell deposition result in different core/shell interfaces as indicated by resonance Raman spectroscopy, as well as differences in the amplitude and timescale of the slow PL rise and the PL decay time. These are interpreted in terms of different radial distributions of the indium-based hole traps, which can be related to differences in the interfacial lattice strain.

14.
Planta Med ; 87(7): 538-549, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33545719

RESUMO

Influenza viral infections are prone to global outbreaks and cause pneumonia in affected populations. High morbidity and mortality caused by pneumonia occur during an influenza pandemic. Antivirals or control of inflammation is the primary means of influenza treatment. A compound cocktail composed of arctiin, daidzein, glycyrrhizic acid, and liquiritin inhibited mouse pneumonia resulting from a PR8 viral infection and caused a weight gain after oral administration. Natural killer cell activating receptors, both Ly49D and Ly49H in the lungs, were increased in the treatment in mice. In H3N2 virus-infected natural killer-92MI cells, the cocktail treatment had different effects on phosphorylation sites of phospholipase Cγ1 (PLCγ1) and killed infected cells through necroptosis or late apoptosis, in which RIP3 was increased and both caspase-3 and phosphorylated-JNK in the cells were downregulated. Acid phosphatase activity in viral-infected natural killer-92MI cells was induced by the compound cocktail treatment, which could be related to the p62 decrease in natural killer-92MI cells. In addition, an autophagic flux induction was observed in alveolar basal epithelial cells (A549). Protein p65, but not phosphorylated-p65, was significantly decreased by the treatment. Our results indicate that the compound cocktail strengthened the phosphorylation of PLCγ1-related necroptosis and partial autophagy in natural killer cells, which could yield an inhibitory effect on viral pneumonia in influenza.


Assuntos
Influenza Humana , Infecções por Orthomyxoviridae , Pneumonia Viral , Animais , Autofagia , Vírus da Influenza A Subtipo H3N2 , Células Matadoras Naturais , Camundongos , Necroptose , Fosfolipase C gama , Fosforilação , Pneumonia Viral/tratamento farmacológico
15.
PLoS Pathog ; 14(8): e1007272, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30169545

RESUMO

Edwardsiella piscicida is a leading fish pathogen that causes significant economic loses in the aquaculture industry. The pathogen depends on type III and type VI secretion systems (T3/T6SS) for growth and virulence in fish and the expression of both systems is controlled by the EsrB transcription activator. Here, we performed a Tn-seq-based screen to uncover factors that govern esrB expression. Unexpectedly, we discovered that RpoS antagonizes esrB expression and thereby inhibits production of E. piscicida's T3/T6SS. Using in vitro transcription assays, we showed that RpoS can block RpoD-mediated transcription of esrB. ChIP-seq- and RNA-seq-based profiling, as well as mutational and biochemical analyses revealed that RpoS-repressed promoters contain a -6G in their respective discriminator sequences; moreover, this -6G proved critical for RpoS to inhibit esrB expression. Mutation of the RpoS R99 residue, an amino acid that molecular modeling predicts interacts with -6G in the esrB discriminator, abolished RpoS' capacity for repression. In a turbot model, an rpoS deletion mutant was attenuated early but not late in infection, whereas a mutant expressing RpoSR99A exhibited elevated fitness throughout the infection period. Collectively, these findings deepen our understanding of how RpoS can inhibit gene expression and demonstrate the temporal variation in the requirement for this sigma factor during infection.


Assuntos
Proteínas de Bactérias/fisiologia , Edwardsiella/genética , Edwardsiella/patogenicidade , Doenças dos Peixes , Regiões Promotoras Genéticas/genética , Fator sigma/fisiologia , Virulência/genética , Animais , Aquicultura , Proteínas de Bactérias/metabolismo , Infecções por Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/microbiologia , Doenças dos Peixes/genética , Doenças dos Peixes/microbiologia , Linguados , Regulação Bacteriana da Expressão Gênica , Ligação Proteica , Fator sigma/metabolismo
16.
BMC Cancer ; 20(1): 280, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252683

RESUMO

BACKGROUND: To investigate the clinical and pathological characteristics of appendiceal mucinous adenocarcinoma with peritoneal metastasis and analyze the prognostic factors. METHODS: A retrospective analyses of clinicopathological features of 50 patients with appendiceal mucinous adenocarcinoma with peritoneal metastasis from January, 2013 to December, 2017 in Aerospace Central Hospital, Beijing, China. Survival data calculation and comparison were respectively performed with the Kaplan-Meier method and the log-rank test. The Cox proportional hazards regression method was used for multivariate survival analyses. RESULTS: Cytoreduction for appendiceal mucinous adenocarcinoma was conducted on 50 patients (24 males and 26 females), with a median age of 52.5 years at the time of surgery (range 31-71 years). The median overall survival (OS) time was 24 months, with 2-,3- and 5-year survival rates of 53, 24 and 8%, respectively. At the last follow-up in December 2018, 13 patients were still alive. Multivariate analysis revealed that patients who had low Ki-67 expression (less than 50%) and CCR (completeness of cytoreduction) 0/1/2 score had significantly better OS rate than their respective counterparts. CONCLUSIONS: Ki-67 expression statue and CCR score could be employed as the prognosis prediction in patients with appendiceal mucinous adenocarcinoma.


Assuntos
Adenocarcinoma Mucinoso/mortalidade , Neoplasias do Apêndice/mortalidade , Procedimentos Cirúrgicos de Citorredução/mortalidade , Hipertermia Induzida/mortalidade , Neoplasias Peritoneais/mortalidade , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/terapia , Adulto , Idoso , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/terapia , Biomarcadores Tumorais/metabolismo , China , Terapia Combinada , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
17.
Fish Shellfish Immunol ; 90: 65-72, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30946958

RESUMO

Edwardsiella piscicida is the aetiological agent of fish edwardsiellosis, causing huge economic losses in aquaculture industries. The use of a live attenuated vaccine (LAV) will be an effective strategy to control the disease in farmed fish. Thus, methods facilitating exploration of targets used for construction of an LAV will be of great significance. Previously, we devised an algorithm termed pattern analysis of conditional essentiality (PACE) to perform genome-wide analysis of the temporal dynamic behaviour of E. piscicida mutants colonizing turbot. Here, we correlated the conditional essentiality patterns of the PACE-derived colonization determinants with that of the aroC gene encoding chorismate synthase, the established target for LAV construction in E. piscicida, and identified ETAE_0023 as a novel valuable LAV target. ETAE_0023 encodes an uncharacterized DcrB family protein. Deletion of ETAE_0023 dramatically impaired E. piscicida invasion capability in ZF4 cells as well as colonization in fish and resulted in in vivo clearance at ∼30 days post-infection. ΔETAE_0023 showed an ∼2500-fold higher 50% lethal dose (LD50) than that of the wild type strain. Vaccination with ΔETAE_0023 by intraperitoneal (i.p.) injection upregulated expression of immune factors, i.e., IL-1ß, IgM, MHC-I and MHC-II, and produced significantly high levels of E. piscicida-specific IgM as well as serum bactericidal capacities in turbot. Moreover, a single i.p. inoculation with ΔETAE_0023 generated significant protection comparable to the established WED LAV strain in turbot against challenge with the wild type strain after 5 weeks of vaccination. Taken together, we demonstrated a PACE-based method for heuristic identification of targets for LAV construction and presented ΔETAE_0023 as a new LAV candidate against edwardsiellosis.


Assuntos
Vacinas Bacterianas/imunologia , Edwardsiella/imunologia , Edwardsiella/patogenicidade , Infecções por Enterobacteriaceae/veterinária , Doenças dos Peixes/imunologia , Linguados , Algoritmos , Animais , Edwardsiella/genética , Infecções por Enterobacteriaceae/imunologia , Vacinas Atenuadas/imunologia , Virulência/genética
18.
Opt Express ; 25(4): 3327-3335, 2017 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-28241547

RESUMO

We developed a novel light enhancing film for an organic light emitting diode (OLED) based on polymer dispersed liquid crystal (PDLC). In the film, the liquid crystal droplets are unidirectionally aligned along the film normal direction and exhibit selective scattering. The film scatters light emitted only in directions with large incident angles but not light emitted in directions with small incident angles. When the light is scattered, it changes propagation direction and exits the OLED. The PDLC film reduces the total internal reflection and thus can significantly increase the light efficiency of the OLED.

19.
J Opt Soc Am A Opt Image Sci Vis ; 33(3): A283-99, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26974935

RESUMO

We explored the color constancy mechanisms of color-deficient observers under red, green, blue, and yellow illuminations. The red and green illuminations were defined individually by the longer axis of the color discrimination ellipsoid measured by the Cambridge Colour Test. Four dichromats (3 protanopes and 1 deuteranope), two anomalous trichromats (2 deuteranomalous observers), and five color-normal observers were asked to complete the color constancy task by making a simultaneous paper match under asymmetrical illuminations in haploscopic view on a monitor. The von Kries adaptation model was applied to estimate the cone responses. The model fits showed that for all color-deficient observers under all illuminations, the adjustment of the S-cone response or blue-yellow chromatically opponent responses modeled with the simple assumption of cone deletion in a certain type (S-M, S-L or S-(L+M)) was consistent with the principle of the von Kries model. The degree of adaptation was similar to that of color-normal observers. The results indicate that the color constancy of color-deficient observers is mediated by the simplified blue-yellow color system with a von Kries-type adaptation effect, even in the case of brightness match, as well as by a possible cone-level adaptation to the S-cone when the illumination produces a strong S-cone stimulation, such as blue illumination.


Assuntos
Percepção de Cores/efeitos da radiação , Defeitos da Visão Cromática/parasitologia , Discriminação Psicológica/fisiologia , Discriminação Psicológica/efeitos da radiação , Luz , Adulto , Defeitos da Visão Cromática/patologia , Feminino , Humanos , Masculino , Modelos Biológicos , Estimulação Luminosa , Células Fotorreceptoras Retinianas Cones/patologia , Células Fotorreceptoras Retinianas Cones/efeitos da radiação , Adulto Jovem
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