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The downy mildew of grapevine (Vitis vinifera L.) is caused by Plasmopara viticola and is a major production problem in most grape-growing regions. The vast majority of effectors act as virulence factors and sabotage plant immunity. Here, we describe in detail one of the putative P. viticola Crinkler (CRN) effector genes, PvCRN11, which is highly transcribed during the infection stages in the downy mildew-susceptible grapevine V. vinifera cv. 'Pinot Noir' and V. vinifera cv. 'Thompson Seedless'. Cell death-inducing activity analyses reveal that PvCRN11 was able to induce spot cell death in the leaves of Nicotiana benthamiana but did not induce cell death in the leaves of the downy mildew-resistant V. riparia accession 'Beaumont' or of the downy mildew-susceptible 'Thompson Seedless'. Unexpectedly, stable expression of PvCRN11 inhibited the colonization of P. viticola in grapevine and Phytophthora capsici in Arabidopsis. Both transgenic grapevine and Arabidopsis constitutively expressing PvCRN11 promoted plant immunity. PvCRN11 is localized in the nucleus and cytoplasm, whereas PvCRN11-induced plant immunity is nucleus-independent. The purified protein PvCRN11Opt initiated significant plant immunity extracellularly, leading to enhanced accumulations of reactive oxygen species, activation of MAPK and up-regulation of the defense-related genes PR1 and PR2. Furthermore, PvCRN11Opt induces BAK1-dependent immunity in the apoplast, whereas PvCRN11 overexpression in intracellular induces BAK1-independent immunity. In conclusion, the PvCRN11 protein triggers resistance against P. viticola in grapevine, suggesting a potential for the use of PvCRN11 in grape production as a protectant against downy mildew.
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Arabidopsis , Oomicetos , Phytophthora , Vitis , Resistência à Doença/genética , Proteínas/metabolismo , Imunidade Vegetal , Doenças das Plantas , Vitis/metabolismoRESUMO
Chloroplasts play a crucial role in plant defense against pathogens, making them primary targets for pathogen effectors that suppress host immunity. This study characterizes the Plasmopara viticola CRN-like effector, PvCRN20, which interacts with DEG5 in the cytoplasm but not with its interacting protein, DEG8, which is located in the chloroplast. By transiently overexpressing in tobacco leaves, we show that PvCRN20 could inhibit INF1- and Bax-triggered cell death. Constitutive expression of PvCRN20 suppresses the accumulation of reactive oxygen species (ROS) and promotes pathogen colonization. PvCRN20 reduces DEG5 entry into chloroplasts, thereby disrupting DEG5 and DEG8 interactions in chloroplasts. Overexpression of VvDEG5 and VvDEG8 induces ROS accumulation and enhances grapevine resistance to P. viticola, whereas knockout of VvDEG8 represses ROS production and promotes P. viticola colonization. Consistently, ectopic expression of VvDEG5 and VvDEG8 in tobacco promotes chloroplast-derived ROS accumulation, whereas co-expression of PvCRN20 counteracted this promotion by VvDEG5. Therefore, DEG5 is essential for the virulence function of PvCRN20. Although PvCRN20 is located in both the nucleus and cytoplasm, only cytoplasmic PvCRN20 suppresses plant immunity and promotes pathogen infection. Our results reveal that PvCRN20 dampens plant defenses by repressing the chloroplast import of DEG5, thus reducing host ROS accumulation and facilitating pathogen colonization.
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Peel browning is a natural phenomenon that adversely affects the appearance of fruits. Research on the regulation of browning in apples (Malus × domestica Borkh.) has mainly focused on postharvest storage, while studies at the preharvest stage are relatively rare. Apple is an economically important horticultural crop prone to peel browning during growth, especially when the fruits are bagged (dark conditions). The present study's integrated transcriptomics and metabolomics analysis revealed that preharvest apple peel browning was primarily due to changes in phenolics and flavonoids. The detailed analysis identified MdLAC7's (laccase 7) role in the preharvest apple peel browning process. Transient injection, overexpression, and CRISPR/Cas9 knockout of the MdLAC7 gene in apple fruit and calli identified vallinic acid, anthocyanidin, tannic acid, sinapic acid, and catechinic acid as its catalytic substrates. In addition, yeast one-hybrid assay, electrophoretic mobility shift assay, luciferase reporter assay, and ChIP-PCR analysis revealed that MdWRKY31 binds to the promoter of MdLAC7 and positively regulates its activity to promote peel browning of bagged fruits (dark conditions). Interestingly, upon light exposure, the light-responsive transcription factor MdHY5 (ELONGATED HYPOCOTYL 5) bound to the promoter of MdWRKY31 and inhibited the gene's expression, thereby indirectly inhibiting the function of MdLAC7. Subsequent analysis showed that MdHY5 binds to the MdLAC7 promoter at the G-box1/2 site and directly inhibits its expression in vivo. Thus, the study revealed the MdLAC7-mediated mechanism regulating preharvest apple peel browning and demonstrated the role of light in inhibiting MdLAC7 activity and subsequently reducing peel browning. These results provide theoretical guidance for producing high-quality apple fruits.
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Malus , Malus/genética , Malus/metabolismo , Transcriptoma/genética , Frutas/genética , Frutas/metabolismo , Perfilação da Expressão Gênica , MetabolômicaRESUMO
BACKGROUND: Branch retinal vein occlusion (BRVO) is a common retinal vascular disease leading to severe vision loss and blindness. This study aimed to investigate and reveal the pathophysiological mechanisms underlying macular edema (ME) recurrence in patients with BRVO through a proteomic approach. METHODS: We detected proteins in the aqueous humor of 14 untreated, four refractory, and four post-operative patients with BRVO-ME and 12 age-matched cataract controls using four-dimensional label-free proteomic and bioinformatics analyses. RESULTS: In total, 84 proteins exhibited significant differential expression between the BRVO and control samples (fold change [FC] ≥ 1.2 and adjusted p-value < 0.05). Compared to the control group, 43 and 41 proteins were upregulated and downregulated, respectively, in the BRVO group. These proteins were involved in cell adhesion, visual perception, retina homeostasis, and platelet activation. Several significantly enriched signaling pathways included complement and coagulation cascades and platelet activation. In the protein-protein interaction networks generated using the search tool for retrieval of interacting genes (STRING), the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. Many common protein expression trends, such as the fibrinogen alpha chain and fibrinogen beta chain, were observed in both the recurrent and refractory groups. Differentially expressed proteins in the two groups were involved in complement activation, acute-phase response, platelet activation, and platelet aggregation. Important signaling pathways include the complement and coagulation cascades, and platelet activation. Protein-protein interaction analysis suggested that the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. The expression of some differentially expressed proteins shared by the BRVO and the recurrent and refractory groups was reversed in the post-operative group. CONCLUSIONS: Our study is the first to analyze the proteomics of recurrent, refractory, and post-operative groups treated for BRVO-ME, and may potentially provide novel therapeutic interventions for the recurrence of ME.
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Edema Macular , Oclusão da Veia Retiniana , Humanos , Oclusão da Veia Retiniana/tratamento farmacológico , Edema Macular/tratamento farmacológico , Proteômica/métodos , Fibrinogênio/uso terapêuticoRESUMO
PURPOSE: This study aimed to investigate the incidence of meibomian gland dysfunction (MGD) in postmenopausal women with primary acquired nasolacrimal duct obstruction (PANDO) and enables ophthalmologists to pay attention to ocular surface damage before surgery. METHODS: 165 postmenopausal women with PANDO and 115 postmenopausal women with a normal lacrimal drainage system were enrolled in this prospective study. Based on the results of lacrimal duct irrigation and age, the participants were further subdivided. The incidence of different severities of MGD in different groups was calculated and analyzed by the chi-squared test. RESULTS: The incidence of MGD in the PANDO group was 81.21%, and in the control group, it was 46.96%, which was significantly higher in the presence of PANDO (p < 0.001). The incidence of severe MGD in the complete and incomplete PANDO groups was higher than that in the control group (all p < 0.05), and no significant differences were observed between the complete and incomplete PANDO groups. The incidence of moderate MGD was significantly higher in the complete PANDO group than in the control group (p < 0.001). When age was considered an independent variable, the results revealed a significant value for patients aged < 70 years (p < 0.001). CONCLUSIONS: Our study revealed a prodominantly high incidence of MGD in postmenopausal women with PANDO, especially in a complete PANDO or aged < 70 years. Ophthalmologists need to pay close attention to MGD in postmenopausal women with PANDO.
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Obstrução dos Ductos Lacrimais , Disfunção da Glândula Tarsal , Ducto Nasolacrimal , Humanos , Feminino , Incidência , Obstrução dos Ductos Lacrimais/diagnóstico , Obstrução dos Ductos Lacrimais/epidemiologia , Pós-Menopausa , Estudos Prospectivos , PálpebrasRESUMO
Grapevine downy mildew, caused by Plasmopara viticola, is one of the most devastating diseases in viticulture. Plasmopara viticola secretes RxLR effectors to modulate immune responses in grapevine. Here, we report an RxLR effector RxLR50253 from P. viticola that can interfere with plant immune response and thus promote pathogen colonization. RxLR50253 was induced at an early stage of P. viticola infection and could suppress elicitor (INF1 and Bax)-triggered cell death. RxLR50253 promote pathogen colonization in both tobacco and grapevine leaves. VpBPA1 was found to be the host target of RxLR50253 by yeast two-hybrid screening, and interaction between RxLR50253 and VpBPA1 was confirmed by multiple in vivo and in vitro assays. Further analysis revealed that VpBPA1 promoted pathogen colonization and decreased H2 O2 accumulation in transgenic tobacco and grapevine, while there was enhanced resistance and H2 O2 accumulation in NbBPA1-silenced Nicotiana benthamiana leaves. Moreover, transient expression of VpBPA1 in NbBPA1-silenced N. benthamiana leaves could reduce the accumulation of H2 O2 . Experiments in vivo demonstrated that RxLR50253 inhibits degradation of VpBPA1. Taken together, our findings showed that RxLR50253 targets and stabilizes VpBPA1 to attenuate plant immunity through decreasing H2 O2 accumulation during pathogen infection.
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Oomicetos , Phytophthora infestans , Vitis , Doenças das Plantas , Imunidade Vegetal , Nicotiana/genética , Vitis/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Grapevine downy mildew, caused by the oomycete Plasmopara viticola, is one of the most significant production challenges for the grape and wine industry. P. viticola injects a plethora of effectors into its host cells to disrupt immune processes, but the mechanisms by which these effectors act at the molecular level have not been well characterized. Herein, we show that a candidate P. viticola avirulence homolog (Avh) RxLR effector gene, designated PvAvh77, was strongly up-regulated during the initial stages of P. viticola infection in Vitis vinifera. Further experiments demonstrated that PvAvh77 could trigger non-specific cell death when expressed in the wild grapevine Vitis riparia and in tobacco (Nicotiana benthamiana and Nicotiana tabacum). In addition, a truncated form of PvAvh77, designated PvAvh77-M2, was more active in inducing cell death in N. benthamiana and V. riparia than full-length PvAvh77. Ectopic expression of PvAvh77 in V. vinifera 'Thompson Seedless' leaves neutralized host immunity and enhanced colonization by P. viticola, and the immune-inhibiting activity of PvAvh77 on susceptible Eurasian grapevine depended on its nuclear localization. Using a yeast signal sequence trap approach, we showed that the signal peptide of PvAvh77 is functional in yeast. Moreover, PvAvh77 with a signal peptide stimulated plant immune responses in the apoplast. Notably, application of exogenous purified PvAvh77-M2 effectively initiated defence responses in grapevine extracellularly, as evidenced by increased accumulation of salicylic acid and H2O2, and reduced infection of inoculated P. viticola. In summary, we identified a novel effector, PvAvh77, from P. viticola, which has the potential to serve as an inducer of plant immunity.
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Oomicetos , Phytophthora infestans , Vitis , Saccharomyces cerevisiae , Peróxido de Hidrogênio/metabolismo , Doenças das Plantas , Nicotiana/genética , Vitis/genética , Vitis/metabolismo , Morte Celular , Sinais Direcionadores de Proteínas , Resistência à DoençaRESUMO
BACKGROUND: Hippocampal alterations have been implicated in the pathophysiology of cognitive impairment in hemodialysis patients. The hippocampus consists of several distinct subfields, and the molecular mechanisms underlying cognition might be associated with specific hippocampal subfield volume changes. However, this has not yet been investigated in hemodialysis patients. This study aimed to explore volumetric abnormalities in hippocampal subfields in regular hemodialysis patients. METHODS: High-resolution T1-weighted structural images were collected in 61 subjects including 36 hemodialysis patients and 25 healthy controls. A state-of-the-art hippocampal segmentation approach was adopted to segment the hippocampal subfields. Group differences in hippocampal subfield volumes were assessed in Python with a statsmodels module using an ordinary least squares regression with age and sex as nuisance effects. RESULTS: Hemodialysis patients had significantly smaller volumes in the bilateral hippocampus (P < .05/2, Bonferroni corrected), cornu ammonis 1 (CA1), CA4, granule cell and molecular layer of the dentate gyrus, hippocampus-amygdala transition area and molecular layer of the hippocampus than healthy controls (P < .05/24, Bonferroni corrected). Hemodialysis patients also had lower volumes in the left hippocampal tail and right fimbria than healthy controls (P < .05/24, Bonferroni corrected). Hippocampal subfield volumes were associated with neuropsychological test scores, the duration of disease and hemoglobin levels. CONCLUSIONS: We found smaller hippocampal subfield volumes in hemodialysis patients, which were associated with impaired cognition, supporting their role in memory disturbance in the hemodialysis population. However, multiple clinical factors may have confounded the results, and therefore, the interpretation of these results needs to be cautious.
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Disfunção Cognitiva , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Hipocampo/diagnóstico por imagem , Cognição , Testes NeuropsicológicosRESUMO
The major challenges in producing highly electrically conductive copper films are the oxide content and the porosity of the sintered films. This study developed a multilayer sintering method to remove the copper oxides and reduce copper film porosity. We used a self-built arc discharge reactor to produce copper nanoparticles. Copper nanoparticles produced by arc discharge synthesis have many advantages, such as low cost and a high production rate. Conductive inks were prepared from copper nanoparticles to obtain thin copper films on glass substrates. As demonstrated by scanning electron microscopy analyses and electrical resistivity measurements, the copper film porosity and electrical resistivity cannot be significantly reduced by prolonged sintering time or increasing single film thickness. Instead, by applying the multilayer sintering method, where the coating and sintering process was repeated up to four times in this study, the porosity of copper films could be effectively reduced from 33.6% after one-layer sintering to 3.7% after four-layer sintering. Copper films with an electrical resistivity of 3.49 ± 0.35µΩ·cm (two times of the bulk copper) have been achieved after four-layer sintering, while one-layer sintered copper films were measured to possess resistivity of 11.17 ± 2.17µΩ·cm.
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BACKGROUND: Abnormal white matter has been reported in patients with end-stage renal disease (ESRD). However, few studies have investigated the relationship between specific damage segments and cognition in ESRD. This study aimed to delineate white matter alterations in ESRD and its relationship with cognition. METHODS: A total of 36 patients undergoing hemodialysis and 25 healthy controls underwent diffusion tensor imaging (DTI) and a series of neuropsychiatric tests. Automated fiber quantification was used to extract distinct DTI indices, and the relationship between the specific segment of the white matter and clinical properties was investigated. Furthermore, a support vector machine was applied to differentiate patients with ESRD from healthy controls. RESULTS: Fractional anisotropy values decreased in multiple fiber bundles, including bilateral thalamic radiata, cingulum cingulate, inferior fronto-occipital fasciculus (IFOF), uncinate, Callosum_Forceps_Major/Callosum_Forceps_Minor (CFMaj/CFMin), and left uncinate from the tract level in patients with ESRD. Specific damaged segments were detected in 8 fiber bundles, including bilateral thalamic radiation, cingulum cingulate, IFOF, CFMin, and left corticospinal tract. Few alterations in these fiber bundles were correlated with cognition impairment and hemoglobin levels. The tract profiles of the left thalamic radiata and left cingulum cingulate could be used to differentiate hemodialysis patients from healthy controls, with an accuracy of 76.9% and 67.6%, respectively. CONCLUSIONS: This study revealed white matter damage in hemodialysis patients. This damage occurred in specific segments of the tract, especially in the left thalamic radiata and left cingulum cingulate, which might become a new biomarker for patients with ESRD and cognition impairment.
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Falência Renal Crônica , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Corpo Caloso , Diálise Renal/efeitos adversos , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico por imagem , Falência Renal Crônica/terapia , Encéfalo/diagnóstico por imagem , AnisotropiaRESUMO
Pathogens secrete a large number of effectors that manipulate host processes to create an environment conducive to pathogen colonization. However, the underlying mechanisms by which Plasmopara viticola effectors manipulate host plant cells remain largely unclear. In this study, we reported that RXLR31154, a P. viticola RXLR effector, was highly expressed during the early stages of P. viticola infection. In our study, stable expression of RXLR31154 in grapevine (Vitis vinifera) and Nicotiana benthamiana promoted leaf colonization by P. viticola and Phytophthora capsici, respectively. By yeast two-hybrid screening, the 23-kDa oxygen-evolving enhancer 2 (VpOEE2 or VpPsbP), encoded by the PsbP gene, in Vitis piasezkii accession Liuba-8 was identified as a host target of RXLR31154. Overexpression of VpPsbP enhanced susceptibility to P. viticola in grapevine and P. capsici in N. benthamiana, and silencing of NbPsbPs, the homologs of PsbP in N. benthamiana, reduced P. capcisi colonization, indicating that PsbP is a susceptibility factor. RXLR31154 and VpPsbP protein were co-localized in the chloroplast. Moreover, VpPsbP reduced H2 O2 accumulation and activated the 1 O2 signaling pathway in grapevine. RXLR31154 could stabilize PsbP. Together, our data revealed that RXLR31154 reduces H2 O2 accumulation and activates the 1 O2 signaling pathway through stabilizing PsbP, thereby promoting disease.
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Cloroplastos/parasitologia , Oomicetos/metabolismo , Doenças das Plantas/parasitologia , Proteínas de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Vitis/parasitologia , Clorofila/química , Clorofila/metabolismo , Fluorescência , Peróxido de Hidrogênio , Nicotiana/parasitologiaRESUMO
BACKGROUND: Antimicrobial peptides including various defensins have been attracting considerable research interest worldwide, as they have potential to substitute for antibiotics. Moreover, AMPs also have immunomodulatory activity. In this study, we explored the role and its potential mechanisms of ß-defensin 118 (DEFB118) in alleviating inflammation and injury of IPEC-J2 cells (porcine jejunum epithelial cell line) upon the enterotoxigenic Escherichia coli (ETEC) challenge. RESULTS: The porcine jejunum epithelial cell line (IPEC-J2) pretreated with or without DEFB118 (25 µg/mL) were challenged by ETEC (1×106 CFU) or culture medium. We showed that DEFB118 pretreatment significantly increased the cell viability (P<0.05) and decreased the expressions of inflammatory cytokines such as the interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in IPEC-J2 cells exposure to ETEC (P<0.05). Interestingly, DEFB118 pretreatment significantly elevated the abundance of the major tight-junction protein zonula occludens-1 (ZO-1), but decreased the number of apoptotic cells upon ETEC challenge (P<0.05). The expression of caspase 3, caspase 8, and caspase 9 were downregulated by DEFB118 in the IPEC-J2 cells exposure to ETEC (P<0.05). Importantly, DEFB118 suppressed two critical inflammation-associated signaling proteins, nuclear factor-kappa-B inhibitor alpha (IκB-α) and nuclear factor-kappaB (NF-κB) in the ETEC-challenged IPEC-J2 cells. CONCLUSIONS: DEFB118 can alleviate ETEC-induced inflammation in IPEC-J2 cells through inhibition of the NF-κB signaling pathway, resulting in reduced secretion of inflammatory cytokines and decreased cell apoptosis. Therefore, DEFB118 can act as a novel anti-inflammatory agent.
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Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Inflamação , Doenças dos Suínos , beta-Defensinas , Animais , Citocinas/metabolismo , Escherichia coli Enterotoxigênica/fisiologia , Células Epiteliais/metabolismo , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/veterinária , Inflamação/metabolismo , Inflamação/veterinária , Mucosa Intestinal/metabolismo , NF-kappa B/metabolismo , Suínos , Doenças dos Suínos/patologia , beta-Defensinas/metabolismoRESUMO
BACKGROUND AND OBJECTIVES: Ablative fractional laser treatment has been used to improve the color and texture of hypertrophic scars with safe and effective results. However, no consensus on the optimal time to initiate fractional laser treatment is available. The effect on early-stage scars remains controversial. This study was designed to assess the efficacy and safety of ablative fractional carbon dioxide (CO2 ) laser treatments for hypertrophic burn scars and to analyze the efficacy and safety in the early period within 3 months after injury. STUDY DESIGN/MATERIALS AND METHODS: We performed a retrospective study of 221 hypertrophic scar patients. According to the time of the first laser treatment after injury, patients were divided into five subgroups, including less than 1 month, 1-3 months, 3-6 months, 6-12 months, and more than 12 months postinjury. One month after the last laser treatment, the scars were assessed by photography, the Vancouver Scar Scale (VSS), durometry, and spectrocolorimetry. RESULTS: The patients included 118 males and 103 females. The average age was 33.6 years. Fire/flame was the primary injury source. Thirty-six percent of the patients underwent at least one fractional CO2 laser treatment. All the included patients, including those treated within 1 month after injury, had significantly decreased VSS scores after laser treatment. We also noted that hardness and redness scores were decreased after treatment for both scars treated within 3 months and those treated more than 12 months after injury. Seepage (17.6%), bleeding (22.2%), and swelling (9.0%) were the main adverse events after laser treatment. CONCLUSIONS: This study demonstrated the safety and efficacy of ablative fractional CO2 laser treatment applied to early-stage burn scars. The optimal time for laser application for burn patients can be within 1 month after injury. Durometry and spectrocolorimetry were effective for assessing scars as objective modalities. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.
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Queimaduras , Cicatriz Hipertrófica , Lasers de Gás , Adulto , Queimaduras/complicações , Dióxido de Carbono , Cicatriz , Cicatriz Hipertrófica/etiologia , Cicatriz Hipertrófica/patologia , Cicatriz Hipertrófica/cirurgia , Feminino , Humanos , Lasers de Gás/uso terapêutico , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Porcine NK-Lysine (PNKL) is a new antimicrobial peptide (AMP) identified in the small intestine. In this study, PNKL protein was obtained through heterologous expression in Escherichia coli and was estimated by SDS-PAGE at 33 kDa. The antibacterial activities of PNKL were determined using various bacterial strains and showed broad-spectrum antimicrobial activity against Gram-negative and Gram-positive bacteria. Furthermore, E. coli K88-challenged IPEC-J2 cells were used to determine PNKL influences on inflammatory responses. Hemolytic assays showed that PNKL had no detrimental impact on cell viability. Interestingly, PNKL elevated the viability of IPEC-J2 cells exposure to E. coli K88. PNKL significantly decreased the cell apoptosis rate, and improved the distribution and abundance of tight junction protein ZO-1 in IPEC-J2 cells upon E. coli K88-challenge. Importantly, PNKL not only down regulated the expressions of inflammatory cytokines such as the IL-6 and TNF-α, but also down regulated the expressions of NF-κB, Caspase3, and Caspase9 in the E. coli K88-challenged cells. These results suggest a novel function of natural killer (NK)-lysin, and the anti-bacterial and anti-inflammatory properties of PNKL may allow it a potential substitute for conventionally used antibiotics or drugs.
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Fatores Imunológicos/metabolismo , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Proteolipídeos/metabolismo , Suínos/metabolismo , Animais , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Linhagem Celular , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Modelos Moleculares , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Proteolipídeos/química , Proteolipídeos/farmacologia , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologiaRESUMO
A novel approach for the detection and separation of toxic ions was successfully developed via the introduction of competitive reactions into a long-alkyl-chained acylhydrazone-based coumarin supramolecular polymer, chemosensor OGC (3%, n-BuOH/H2O), which showed sequential detection and separation of CN-, Fe3+ and S2-, Ag+ in the gel state with high selectivity and sensitivity. Moreover, the ion-responsive films were prepared for the convenient and continuous detection of CN-, Fe3+ and S2-, Ag+ in water solution.
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Copper nanoparticles (NPs) are considered as a promising alternative for silver and gold NPs in conductive inks for the application of printing electronics, since copper shows a high electrical conductivity but is significantly cheaper than silver and gold. In this study, copper NPs were synthesized in the gas phase by transferred arc discharge, which has demonstrated scale-up potential. Depending on the production parameters, copper NPs can be continuously synthesized at a production rate of 1.2-5.5 g h-1, while their Brunauer-Emmett-Teller sizes were maintained below 100 nm. To investigate the suitability in electronic printing, we use ball milling technique to produce copper conductive inks. The effect of ball milling parameters on ink stability was discussed. In addition, the electrical resistivity of copper films sintered at 300 °C in reducing atmosphere was measured to be 5.4 ± 0.6 µΩ cm which is about three times higher than that of bulk copper (1.7 µΩ cm). This indicates that conductive inks prepared from gas-phase synthesized copper NPs are competitive to the conductive inks prepared from chemically synthesized copper NPs.
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BACKGROUND: The mechanism of chronic migraine (CM) is complex, central sensitization is considered as one of the pathological mechanism. Synaptic plasticity is the basis of central sensitization. Metabotropic glutamate receptor 5 (mGluR5) plays a vital role in the synaptic plasticity of the central nervous system. However, whether mGluR5 can promote the central sensitization by regulating synaptic plasticity in CM is unknown. METHODS: Male Wistar rats were used to establish a CM rat model, and the expression of mGluR5 mRNA and protein were detected by qRT-PCR and western blot. The allodynia was assessed by mechanical and thermal thresholds, and central sensitization was assessed by expression of the phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) at Serine 133(pCREB-S133) and c-Fos. The synaptic-associated protein postsynaptic density protein 95 (PSD), synaptophysin (Syp), and synaptophysin-1(Syt-1), synaptic ultrastructure, and dendritic spines were detected to explore synaptic plasticity. The expression of PKC, total NR2B(tNR2B), and phosphorylation of NR2B at Tyr1472(pNR2B-Y1472) were detected by western blot. RESULTS: We found that the expression of mGluR5 was upregulated in CM rats. Downregulated the mGluR5 with MPEP alleviated the allodynia and reduced the expression of CGRP, pCREB-S133, c-Fos, PSD, Syp and Syt-1 and synaptic transmission. Moreover, the administration of MPEP inhibited the upregulation of PKC and pNR2B-Y1472. CONCLUSIONS: These results indicate that mGluR5 contributes to central sensitization by regulating synaptic plasticity in CM through the PKC/NR2B signal, which suggests that mGluR5 may be a potential therapeutic candidate for CM.
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Transtornos de Enxaqueca , Plasticidade Neuronal , Animais , Hiperalgesia , Masculino , Ratos , Ratos Wistar , Receptor de Glutamato Metabotrópico 5RESUMO
By rationally introducing multi-self-assembly driving forces and coordination binding sites into the same molecule, a designed functional gelator, G, was synthesized. Next, a novel supramolecular polymer material, OGV (1% DMSO), was constructed and used for the ultrasensitive detection and separation of multianalytes in gel states. Interestingly, OGV showed a fluorescent ultrasensitive response for the Hg2+ and Fe3+ ions in water. Moreover, by introducing these metal ions into the OGV, stable metal ion-coordinated supramolecular metallogels (HgG and FeG) were formed, which could sense CN- and H2PO4- in water with high selectivity and sensitivity.
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Enabled by piezoceramic transducers, ultrasonic logging images often suffer from low contrast and indistinct local details, which makes it difficult to analyze and interpret geologic features in the images. In this work, we propose a novel partially overlapped sub-block histogram-equalization (POSHE)-based optimum clip-limit contrast enhancement (POSHEOC) method to highlight the local details hidden in ultrasonic well logging images obtained through piezoceramic transducers. The proposed algorithm introduces the idea of contrast-limited enhancement to modify the cumulative distribution functions of the POSHE and build a new quality evaluation index considering the effects of the mean gradient and mean structural similarity. The new index is designed to obtain the optimal clip-limit value for histogram equalization of the sub-block. It makes the choice of the optimal clip-limit automatically according to the input image. Experimental results based on visual perceptual evaluation and quantitative measures demonstrate that the proposed method yields better quality in terms of enhancing the contrast, emphasizing the local details while preserving the brightness and restricting the excessive enhancement compared with the other seven histogram equalization-based techniques from the literature. This study provides a feasible and effective method to enhance ultrasonic logging images obtained through piezoceramic transducers and is significant for the interpretation of actual ultrasonic logging data.
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BACKGROUND: Although the mechanism of chronic migraine (CM) is unclear, it might be related to central sensitization and neuronal persistent hyperexcitability. The tyrosine phosphorylation of NR2B (NR2B-pTyr) reportedly contributes to the development of central sensitization and persistent pain in the spinal cord. Central sensitization is thought to be associated with an increase in synaptic efficiency, but the mechanism through which NR2B-pTyr regulates synaptic participation in CM-related central sensitization is unknown. In this study, we aim to investigate the role of NR2B-pTyr in regulating synaptic plasticity in CM-related central sensitization. METHODS: Male Sprague-Dawley rats were subjected to seven inflammatory soup (IS) injections to model recurrent trigeminovascular or dural nociceptor activation, which is assumed to occur in patients with CM. We used the von Frey test to detect changes in mechanical withdrawal thresholds, and western blotting and immunofluorescence staining assays were performed to detect the expression of NR2B-pTyr in the trigeminal nucleus caudalis (TNC). NR2B-pTyr was blocked with the Src family kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)-pyrazolo [3,4-d] pyrimidine (PP2) and the protein tyrosine kinase inhibitor genistein to detected the changes in calcitonin gene-related peptide (CGRP), substance P (SP), and the synaptic proteins postsynaptic density 95 (PSD95), synaptophysin (Syp), synaptotagmin1 (Syt-1). The synaptic ultrastructures were observed by transmission electron microscopy (TEM), and the dendritic architecture of TNC neurons was observed by Golgi-Cox staining. RESULTS: Statistical analyses revealed that repeated infusions of IS induced mechanical allodynia and significantly increased the expression of NR2B Tyr-1472 phosphorylation (pNR2B-Y1472) and NR2B Tyr-1252 phosphorylation (pNR2B-Y1252) in the TNC. Furthermore, the inhibition of NR2B-pTyr by PP2 and genistein relieved allodynia and reduced the expression of CGRP, SP, PSD95, Syp and Syt-1 and synaptic transmission. CONCLUSIONS: These data indicate that NR2B-pTyr might regulate synaptic plasticity in central sensitization in a CM rat model. The inhibition of NR2B tyrosine phosphorylation has a protective effect on threshold dysfunction and migraine attacks through the regulation of synaptic plasticity in central sensitization.