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1.
Hepatobiliary Pancreat Dis Int ; 23(1): 43-51, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36966125

RESUMO

BACKGROUND: Acute liver failure (ALF) is an unpredictable and life-threatening critical illness. The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ failure. METHODS: Animals were divided into 3 groups, normal, thioacetamide (TAA, ALF model) and TAA + AGK2. Cultured L02 cells were divided into 5 groups, normal, TAA, TAA + mitofusin 2 (MFN2)-siRNA, TAA + AGK2, and TAA + AGK2 + MFN2-siRNA groups. The liver histology was evaluated with hematoxylin and eosin staining, inositol-requiring enzyme 1 (IRE1), activating transcription factor 6ß (ATF6ß), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) and phosphorylated-PERK (p-PERK). C/EBP homologous protein (CHOP), reactive oxygen species (ROS), MFN2 and glutathione peroxidase 4 (GPX4) were measured with Western blotting, and cell viability and liver chemistry were also measured. Mitochondria-associated endoplasmic reticulum membranes (MAMs) were measured by immunofluorescence. RESULTS: The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis, which were reduced by AGK2 pre-treatment. In comparison to the normal group, apoptosis rate and levels of IRE1, ATF6ß, p-PERK, CHOP, ROS and Fe2+ in the TAA-induced ALF model group were significantly increased, which were decreased by AGK2 pre-treatment. The levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group, which were enhanced by AGK2 pre-treatment. Compared with the TAA-induced L02 cell, apoptosis rate and levels of IRE1, ATF6ß, p-PERK, CHOP, ROS and Fe2+ were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA group. AGK2 pre-treatment decreased the apoptosis rate and levels of IRE1, ATF6ß, p-PERK, CHOP, ROS and Fe2+ and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 cell. Immunofluorescence observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced group in both mice and L02 cells. CONCLUSIONS: The data suggested that AGK2 pre-treatment had hepatoprotective role in TAA-induced ALF via upregulating the expression of MFN2 and then inhibiting PERK and ferroptosis pathway in ALF.


Assuntos
Ferroptose , Falência Hepática Aguda , Camundongos , Animais , Tioacetamida/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/prevenção & controle , Transdução de Sinais , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/efeitos adversos , Proteínas Serina-Treonina Quinases/metabolismo , Apoptose , Necrose , RNA Interferente Pequeno/efeitos adversos , Estresse do Retículo Endoplasmático/genética
2.
BMC Med Imaging ; 23(1): 18, 2023 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717773

RESUMO

BACKGROUND: Chest radiography is the standard investigation for identifying rib fractures. The application of artificial intelligence (AI) for detecting rib fractures on chest radiographs is limited by image quality control and multilesion screening. To our knowledge, few studies have developed and verified the performance of an AI model for detecting rib fractures by using multi-center radiographs. And existing studies using chest radiographs for multiple rib fracture detection have used more complex and slower detection algorithms, so we aimed to create a multiple rib fracture detection model by using a convolutional neural network (CNN), based on multi-center and quality-normalised chest radiographs. METHODS: A total of 1080 radiographs with rib fractures were obtained and randomly divided into the training set (918 radiographs, 85%) and the testing set (162 radiographs, 15%). An object detection CNN, You Only Look Once v3 (YOLOv3), was adopted to build the detection model. Receiver operating characteristic (ROC) and free-response ROC (FROC) were used to evaluate the model's performance. A joint testing group of 162 radiographs with rib fractures and 233 radiographs without rib fractures was used as the internal testing set. Furthermore, an additional 201 radiographs, 121 with rib fractures and 80 without rib fractures, were independently validated to compare the CNN model performance with the diagnostic efficiency of radiologists. RESULTS: The sensitivity of the model in the training and testing sets was 92.0% and 91.1%, respectively, and the precision was 68.0% and 81.6%, respectively. FROC in the testing set showed that the sensitivity for whole-lesion detection reached 91.3% when the false-positive of each case was 0.56. In the joint testing group, the case-level accuracy, sensitivity, specificity, and area under the curve were 85.1%, 93.2%, 79.4%, and 0.92, respectively. At the fracture level and the case level in the independent validation set, the accuracy and sensitivity of the CNN model were always higher or close to radiologists' readings. CONCLUSIONS: The CNN model, based on YOLOv3, was sensitive for detecting rib fractures on chest radiographs and showed great potential in the preliminary screening of rib fractures, which indicated that CNN can help reduce missed diagnoses and relieve radiologists' workload. In this study, we developed and verified the performance of a novel CNN model for rib fracture detection by using radiography.


Assuntos
Fraturas das Costelas , Humanos , Fraturas das Costelas/diagnóstico por imagem , Inteligência Artificial , Estudos de Viabilidade , Sensibilidade e Especificidade , Radiografia , Redes Neurais de Computação , Estudos Retrospectivos
3.
J Cell Mol Med ; 26(21): 5528-5538, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36226351

RESUMO

Acute liver failure (ALF) is life-threatening and often associated with high mortality rates. The aim of the present study was to investigate whether extracellular histone H3 could induce ferroptosis in hepatic macrophages in ALF and explore its potential mechanism. RAW264.7 macrophages and C57BL/6 mice were used in this study. LPS, D-galactosamine (D-Gal), histone H3, histone H3 antibody, NOD2 agonist Muramyl Dipeptide (MDP) and HDAC6-siRNA were administered in this study. The key molecules of ferroptosis, NOD2, HDAC6 and the NF-κb pathway, were detected. In vitro, histone H3 was released into the extracellular environment from cell nucleus after LPS exposure. In addition, histone H3 could induce ferroptosis in RAW264.7 macrophages with increased level of Fe2+ and ROS and decreased levels of GPX4 and GSH. MDP further aggravated ferroptosis in RAW264.7 macrophages stimulated by histone H3, which was accompanied by elevated NOD2, HDAC6, p-P65 and IκBα. HDAC6-siRNA ameliorated ferroptosis in RAW264.7 macrophages induced by histone H3, which was accompanied by decreased levels of HDAC6, p-P65 and IκBα. However, HDAC6-siRNA did not alter NOD2 levels in RAW264.7 macrophages administered histone H3. In vivo, the levels of NOD2, HDAC6 the NF-κb pathway and ferroptosis were increased in ALF mice, which were downregulated by histone H3 antibody and upregulated by histone H3. Extracellular histone H3 could induce ferroptosis in hepatic macrophages in ALF by regulating theNOD2-mediated HDAC6/NF-κb signalling pathway.


Assuntos
Ferroptose , Falência Hepática Aguda , Animais , Camundongos , Acetilmuramil-Alanil-Isoglutamina/farmacologia , Histonas , Lipopolissacarídeos , Falência Hepática Aguda/induzido quimicamente , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , RNA Interferente Pequeno/genética
4.
Biochem Biophys Res Commun ; 594: 1-7, 2022 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-35065293

RESUMO

Evidence shows that trimethylamine (TMA)/trimethylamine-N-oxide (TMAO) is closely related to non-alcoholic fatty liver disease (NAFLD). The conversion of TMA to TMAO is mainly catalyzed by flavin-containing monooxygenases 3 (FMO3) and FMO1. In this study, we explored the role of TMA in the process of NAFLD. The human NAFLD liver puncture data set GSE89632 and rat TMAO gene chip GSE135856 was downloaded for gene differential expression analysis. Besides, oleic acid (OA) combined with palmitate were used to establish high-fat cell model. TMA, TMAO and FMO1-siRNA were used to stimulate L02 cells. Contents of free fatty acid (FFA), triglyceride (TG), TMAO, FMO1 and unfolded protein response (UPR) related proteins GRP78, XBP1, Derlin-1 were detected. Our results showed that FMO1 and PEG10 were important in the progression of NAFLD. Immunohistochemistry showed that FMO1 in NAFLD liver was increased. In addition, the contents of FFA, TG, FMO1 expression, and TMAO were significantly increased after OA + palmitate and TMA stimulation. However, after silencing FMO1 with siRNA, the expressions of these molecules were decreased. Besides, the protein levels of GRP78, XBP1, Derlin-1 were increased after TMAO treatment (all P < 0.05). In Conclusion, high fat and TMA could induce the expression of FMO1 and its metabolite TMAO. When FMO1 is silenced, the effects of high fat and TMA on TMAO are blocked. And the role of TMAO in NAFLD may be through the activation of UPR.


Assuntos
Microbioma Gastrointestinal , Metilaminas/química , Hepatopatia Gordurosa não Alcoólica/metabolismo , Oxigenases/biossíntese , Animais , Linhagem Celular , Chaperona BiP do Retículo Endoplasmático/biossíntese , Inativação Gênica , Humanos , Imuno-Histoquímica , Inflamação , Masculino , Proteínas de Membrana/biossíntese , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína 1 de Ligação a X-Box/biossíntese
5.
Microb Pathog ; 170: 105689, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35917990

RESUMO

Edwardsiella tarda is reported as the causative agent of the systemic disease Edwardsiellosis in fish, which lead to huge economic losses in aquaculture. The pathogenicity and immune response to a highly virulent E. tarda isolate responsible for mass mortality in hybrid snakehead were performed. After species identification, morphology and virulence gene detection of Edwardsiella isolated from hybrid snakehead, the pathogenicity of the strain and histopathological changes in infected fish were analyzed. The infected fish exhibited typical acute hemorrhagic symptoms and enlarged internal organs. Histopathology revealed that the liver, spleen, kidney and intestinal tissues of diseased fish exhibited marked inflammatory with vacuolar degeneration and cell necrosis. Subsequently, humoral immune factors such as superoxide dismutase, lysozyme and acid phosphatase activities were detected as serum indicators, and real-time quantitative PCR was used to investigate immune-related genes (STAT1, HSP70, IgM, IL-6, IL-8, TRAF2, CD40, HLA-DMA and LCK) expression patterns in liver, spleen and head kidney. The results showed that these enzyme activity indicators and immune-related gene expression were significantly activated compared with healthy fish. These data provide insight into the pathogenic mechanisms and host immune responses of E. tarda, which could be useful for the future prevention and treatment of Edwardsiellosis in fish.


Assuntos
Infecções por Enterobacteriaceae , Doenças dos Peixes , Animais , Aquicultura , Edwardsiella tarda , Infecções por Enterobacteriaceae/veterinária , Peixes/genética , Imunidade , Virulência
6.
Int J Mol Sci ; 23(9)2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35563386

RESUMO

Soybean is a major crop that provides essential protein and oil for food and feed. Since its origin in China over 5000 years ago, soybean has spread throughout the world, becoming the second most important vegetable oil crop and the primary source of plant protein for global consumption. From early domestication and artificial selection through hybridization and ultimately molecular breeding, the history of soybean breeding parallels major advances in plant science throughout the centuries. Now, rapid progress in plant omics is ushering in a new era of precision design breeding, exemplified by the engineering of elite soybean varieties with specific oil compositions to meet various end-use targets. The assembly of soybean reference genomes, made possible by the development of genome sequencing technology and bioinformatics over the past 20 years, was a great step forward in soybean research. It facilitated advances in soybean transcriptomics, proteomics, metabolomics, and phenomics, all of which paved the way for an integrated approach to molecular breeding in soybean. In this review, we summarize the latest progress in omics research, highlight novel findings made possible by omics techniques, note current drawbacks and areas for further research, and suggest that an efficient multi-omics approach may accelerate soybean breeding in the future. This review will be of interest not only to soybean breeders but also to researchers interested in the use of cutting-edge omics technologies for crop research and improvement.


Assuntos
Glycine max , Melhoramento Vegetal , Embaralhamento de DNA , Genômica/métodos , Melhoramento Vegetal/métodos , Proteômica/métodos , Glycine max/genética
7.
Geriatr Nurs ; 47: 247-253, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36007425

RESUMO

This single-arm observational study explored the feasibility and efficacy of a 12-week personalised physical activity and dietary protein intervention programme for older adults undergoing peritoneal dialysis. Older adults undergoing peritoneal dialysis received eight individualised nutrition and physical activity advice sessions provided by trained nurses. Protein intake and physical activity were regarded as primary outcomes. All data were collected at baseline and at week 12. The enrolment rate was 78.4%. Twenty-nine patients participated in the study. Of these, 86.2% (25/29) completed the intervention. There was a significant increase in protein intake (t = -4.453, P< 0.001) and physical activity levels (Z = -2.929, P = 0.004). Of the participants, 56.0% achieved the targeted protein goal, and 41.4% met the physical activity goal. The timed up-and-go performance (t = 4.135, P = 0.001) increased after intervention. Trained nurses can successfully implement personalised diet and physical activity advice, and achieve promising patient outcomes.


Assuntos
Exercício Físico , Diálise Peritoneal , Idoso , Proteínas Alimentares , Estudos de Viabilidade , Humanos , Estado Nutricional
8.
J Cell Mol Med ; 25(15): 7218-7228, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34180140

RESUMO

Acute liver failure (ALF) is a rare and critical medical condition. This study was designed to investigate the protective effects and underlying mechanism of ACY1215 in ALF mice. Our findings suggested that ACY1215 treatment ameliorates the pathological hepatic damage of ALF and decreases the serum levels of ALT and AST. Furthermore, ACY1215 pretreatment increased the level of ATM, γ-H2AX, Chk2, p53, p21, F-actin and vinculin in ALF. Moreover, ACY1215 inhibited the level of NLRP3, ASC, caspase-1, IL-1ß and IL-18 in ALF. The ATM inhibitor KU55933 could decrease the level of ATM, γ-H2AX, Chk2, p53, p21, F-actin and vinculin in ALF with ACY1215 pretreatment. The F-actin inhibitor cytochalasin B decreased the level of F-actin and vinculin in ALF with ACY1215 pretreatment. However, cytochalasin B had no effect on protein levels of ATM, Chk2, p53 and p21 in ALF with ACY1215 pretreatment. Cytochalasin B could dramatically increase the level of NLRP3, ASC, caspase-1, IL-1ß and IL-18 in ALF with ACY1215 pretreatment. These results indicated that ACY1215 exhibited hepatoprotective properties, which was associated with the inhibition of NLRP3 inflammasome, and this effect of ACY1215 was connected with upregulation of the ATM/F-actin mediated signalling pathways.


Assuntos
Inibidores de Histona Desacetilases/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Inflamassomos/metabolismo , Falência Hepática/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pirimidinas/uso terapêutico , Actinas/metabolismo , Animais , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Linhagem Celular , Quinase do Ponto de Checagem 2/metabolismo , Desacetilase 6 de Histona/antagonistas & inibidores , Desacetilase 6 de Histona/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Humanos , Ácidos Hidroxâmicos/farmacologia , Inflamassomos/efeitos dos fármacos , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Falência Hepática/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pirimidinas/farmacologia , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo
9.
PLoS Pathog ; 15(8): e1007983, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31433824

RESUMO

Recognition of viral RNA by the retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), including RIG-I and MDA5, initiates innate antiviral responses. Although regulation of RLR-mediated signal transduction has been extensively investigated, how the recognition of viral RNA by RLRs is regulated remains enigmatic. In this study, we identified heterogeneous nuclear ribonucleoprotein M (hnRNPM) as a negative regulator of RLR-mediated signaling. Overexpression of hnRNPM markedly inhibited RNA virus-triggered innate immune responses. Conversely, hnRNPM-deficiency increased viral RNA-triggered innate immune responses and inhibited replication of RNA viruses. Viral infection caused translocation of hnRNPM from the nucleus to the cytoplasm. hnRNPM interacted with RIG-I and MDA5, and impaired the binding of the RLRs to viral RNA, leading to inhibition of innate antiviral response. Our findings suggest that hnRNPM acts as an important decoy for excessive innate antiviral immune response.


Assuntos
Proteína DEAD-box 58/antagonistas & inibidores , Ribonucleoproteínas Nucleares Heterogêneas Grupo M/metabolismo , Infecções por Vírus de RNA/imunologia , Vírus de RNA/imunologia , RNA Viral/metabolismo , Replicação Viral/imunologia , Proteína DEAD-box 58/genética , Proteína DEAD-box 58/metabolismo , Células HEK293 , Células HeLa , Ribonucleoproteínas Nucleares Heterogêneas Grupo M/genética , Humanos , Ligação Proteica , Infecções por Vírus de RNA/metabolismo , Infecções por Vírus de RNA/virologia , RNA Viral/genética , Transdução de Sinais
10.
J Pathol ; 250(2): 170-182, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31610014

RESUMO

Accumulating evidence links Fusobacterium nucleatum with ulcerative colitis (UC). The mechanism by which F. nucleatum promotes intestinal inflammation in UC remains poorly defined. Here, we first examined the abundance and impact of F. nucleatum on disease activity in UC tissues. Next, we isolated a strain of F. nucleatum from UC tissues and explored whether F. nucleatum aggravates the intestinal inflammatory response in vitro and in vivo. We also examined whether F. nucleatum infection involves the NF-κB or IL-17F signaling pathways. Our data showed that F. nucleatum was enriched in 51.78% of UC tissues and was correlated with the clinical course, clinical activity and refractory behavior of UC (p < 0.05). Furthermore, we demonstrated that F. nucleatum promoted intestinal epithelial damage and the expression of the inflammatory cytokines IL-1ß, Il-6, IL-17F and TNF-α. Mechanistically, F. nucleatum targeted caspase activation and recruitment domain 3 (CARD3) through NOD2 to activate the IL-17F/NF-κB pathway in vivo and in vitro. Thus, F. nucleatum orchestrates a molecular network involving CARD3 and IL-17F to control the UC process. Measuring and targeting F. nucleatum and its associated pathways will yield valuable insight into the prevention and treatment of UC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Colite Ulcerativa/microbiologia , Infecções por Fusobacterium/complicações , Fusobacterium nucleatum/patogenicidade , Interleucina-17/metabolismo , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/biossíntese , Adolescente , Adulto , Idoso , Animais , Estudos de Casos e Controles , Células Cultivadas , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Feminino , Infecções por Fusobacterium/metabolismo , Fusobacterium nucleatum/isolamento & purificação , Humanos , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , NF-kappa B/metabolismo , RNA Mensageiro/genética , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/deficiência , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/genética , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/fisiologia , Índice de Gravidade de Doença , Transdução de Sinais/fisiologia , Regulação para Cima/fisiologia , Adulto Jovem
11.
J Integr Plant Biol ; 63(6): 1036-1053, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33768659

RESUMO

There is growing interest in expanding the production of soybean oils (mainly triacylglycerol, or TAG) to meet rising feed demand and address global energy concerns. We report that a plastid-localized glycerol-3-phosphate dehydrogenase (GPDH), encoded by GmGPDHp1 gene, catalyzes the formation of glycerol-3-phosphate (G3P), an obligate substrate required for TAG biosynthesis. Overexpression of GmGPDHp1 increases soybean seed oil content with high levels of unsaturated fatty acids (FAs), especially oleic acid (C18:1), without detectably affecting growth or seed protein content or seed weight. Based on the lipidomic analyses, we found that the increase in G3P content led to an elevated diacylglycerol (DAG) pool, in which the Kennedy pathway-derived DAG was mostly increased, followed by PC-derived DAG, thereby promoting the synthesis of TAG containing relatively high proportion of C18:1. The increased G3P levels induced several transcriptional alterations of genes involved in the glycerolipid pathways. In particular, genes encoding the enzymes responsible for de novo glycerolipid synthesis were largely upregulated in the transgenic lines, in-line with the identified biochemical phenotype. These results reveal a key role for GmGPDHp1-mediated G3P metabolism in enhancing TAG synthesis and demonstrate a strategy to modify the FA compositions of soybean oils for improved nutrition and biofuel.


Assuntos
Glicerol-3-Fosfato Desidrogenase (NAD+)/metabolismo , Glycine max/metabolismo , Ácido Oleico/metabolismo , Óleos de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Glicerol-3-Fosfato Desidrogenase (NAD+)/genética , Ácido Oleico/genética , Plantas Geneticamente Modificadas/genética , Triglicerídeos/metabolismo
12.
Angew Chem Int Ed Engl ; 59(10): 4075-4081, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-31829491

RESUMO

The role of endogenous serotonin (5-HT) in gastrointestinal motility is still highly controversial. Although electrochemical techniques allow for direct and real-time recording of biomolecules, the dynamic monitoring of 5-HT release from elastic and tubular intestine during motor reflexes remains a great challenge because of the specific peristalsis patterns and inevitable passivation of the sensing interface. A stretchable sensor with antifouling and decontamination properties was assembled from gold nanotubes, titanium dioxide nanoparticles, and carbon nanotubes. The sandwich-like structure endowed the sensor with satisfying mechanical stability and electrochemical performance, high resistance against physical adsorption, and superior efficiency in the photodegradation of biofouling molecules. Insertion of the sensor into the lumen of rat ileum (the last section of the small intestine) successfully mimics intestinal peristalsis, and simultaneous real-time monitoring of distension-evoked 5-HT release was possible for the first time. Our results unambiguously reveal that mechanical distension of the intestine induces endogenous 5-HT overflow, and 5-HT level is closely associated with the physiological or pathological states of the intestine.


Assuntos
Técnicas Eletroquímicas , Intestinos/química , Serotonina/metabolismo , Animais , Ratos , Serotonina/química , Estresse Mecânico
13.
PLoS Pathog ; 13(11): e1006693, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29155878

RESUMO

VISA (also known as MAVS, IPS-1 and Cardif) is an essential adaptor protein in innate immune response to RNA virus. The protein level of VISA is delicately regulated before and after viral infection to ensure the optimal activation and timely termination of innate antiviral response. It has been reported that several E3 ubiquitin ligases can mediate the degradation of VISA, but how the stability of VISA is maintained before and after viral infection remains enigmatic. In this study, we found that the ER-associated inactive rhomboid protein 2 (iRhom2) plays an essential role in mounting an efficient innate immune response to RNA virus by maintaining the stability of VISA through distinct mechanisms. In un-infected and early infected cells, iRhom2 mediates auto-ubiquitination and degradation of the E3 ubiquitin ligase RNF5 and impairs the assembly of VISA-RNF5-GP78 complexes, thereby antagonizes ER-associated degradation (ERAD) of VISA. In the late phase of viral infection, iRhom2 mediates proteasome-dependent degradation of the E3 ubiquitin ligase MARCH5 and impairs mitochondria-associated degradation (MAD) of VISA. Maintenance of VISA stability by iRhom2 ensures efficient innate antiviral response at the early phase of viral infection and ready for next round of response. Our findings suggest that iRhom2 acts as a checkpoint for the ERAD/MAD of VISA, which ensures proper innate immune response to RNA virus.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Transporte/imunologia , Degradação Associada com o Retículo Endoplasmático , Imunidade Inata , Infecções por Vírus de RNA/imunologia , Vírus de RNA/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Proteólise , Infecções por Vírus de RNA/genética , Infecções por Vírus de RNA/metabolismo , Infecções por Vírus de RNA/virologia , Vírus de RNA/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
14.
Int J Mol Sci ; 19(3)2018 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-29522493

RESUMO

Modification of metal surfaces with antimicrobial peptides is a promising approach to reduce bacterial adhesion. Here, cyclic peptides or cycloids, possessing remarkable stability and antimicrobial activities, were extracted and purified from Viola philippica Cav., and identified using mass spectrometry. Cyclotides were subsequently utilized to modify stainless steel surfaces via polydopamine-mediated coupling. The resulting cyclotide-modified surfaces were characterized by Fourier transform infrared (FTIR) spectroscopy and contact angle analysis. The antibacterial capacity of these cyclotides against Staphylococcus aureus was assessed by Alamar blue assay. The antibiofilm capacity of the modified surfaces was assessed by crystal violet assay, and scanning electron microscopy (SEM). A composite of Kalata b1, Varv A, Viba 15 and Viba 17 (P1); Varv E (P2); and Viphi G (P3) were isolated and identified. FTIR analysis of the modified surfaces demonstrated that cyclotides bound to the surfaces and induced reduction of contact angles. Antimicrobial effects showed an order P3 > P1 and P2, with P3-treated surfaces demonstrating the strongest antibiofilm capacity. SEM confirmed reduced biofilm formation for P3-treated surfaces. This study provides novel evidence for cyclotides as a new class for development of antibacterial and antibiofilm agents.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Ciclotídeos/farmacologia , Metais/química , Extratos Vegetais/farmacologia , Viola/química , Sequência de Aminoácidos , Antibacterianos/química , Ciclotídeos/química , Ciclotídeos/isolamento & purificação , Indóis/química , Microscopia Eletrônica de Varredura , Extratos Vegetais/química , Proteínas de Plantas/química , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/farmacologia , Polímeros/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia
15.
Opt Express ; 23(2): 1249-55, 2015 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-25835883

RESUMO

We propose and experimentally demonstrate a distance-adaptive bandwidth allocation scheme to realize high-capacity long-reach orthogonal frequency division multiple access passive optical network (OFDMA PON) with cost-effective electro-absorption modulator (EAM). In our scheme, the subcarriers in downstream OFDM signal are properly allocated to the optical network units (ONUs) with different fiber transmission lengths. By this means, the detrimental influence of power fading induced by dispersion and chirp can be avoided, thus all OFDM subcarriers can be modulated with high-order quadrature amplitude modulation (QAM) format, leading to a high transmission capacity. A proof-of-concept experiment is performed, in which three ONUs with transmission distances of 25, 50, and 100 km are assigned with different subcarriers, respectively. By using distance-adaptive bandwidth allocation technique, an OFDM signal of 34.5 Gb/s is successfully delivered to the ONUs with a bit error ratio (BER) lower than 2 × 10(-3).

16.
Opt Express ; 22(12): 14433-40, 2014 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-24977540

RESUMO

We propose and experimentally demonstrate a new scheme for photonic generation of microwave frequency shift keying (FSK) signal by employing one single-drive Mach-Zehnder modulator (MZM). In the proposed method, an electrical signal with different radio frequency (RF) amplitudes and direct current (DC) components for bit '0' and bit '1' is generated. After amplification, the signal is fed into a single-drive MZM which is biased at the quadrature and null points of its transmission curve for bit '0' and bit '1', respectively. Due to the different RF amplitudes, a microwave FSK signal can be obtained after photodetection, where the space frequency is the same as the RF frequency and the mark frequency is twice as large as the RF frequency. The feasibility of the proposed scheme is verified by a proof-of-concept experiment. 5/10-GHz and 10/20-GHz microwave FSK signals with different bit rates are successfully demonstrated.

17.
Opt Express ; 22(11): 13043-9, 2014 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-24921501

RESUMO

We propose and experimentally demonstrate a new scheme to reduce the energy consumption of optical network units (ONUs) in orthogonal frequency division multiplexing passive optical networks (OFDM PONs) by using time-domain interleaved OFDM (TI-OFDM) technique. In a conventional OFDM PON, each ONU has to process the complete downstream broadcast OFDM signal with a high sampling rate and a large FFT size to retrieve its required data, even if it employs a portion of OFDM subcarriers. However, in our scheme, the ONU only needs to sample and process one data group from the downlink TI-OFDM signal, effectively reducing the sampling rate and the FFT size of the ONU. Thus, the energy efficiency of ONUs in OFDM PONs can be greatly improved. A proof-of-concept experiment is conducted to verify the feasibility of the proposed scheme. Compared to the conventional OFDM PON, our proposal can save 17.1% and 26.7% energy consumption of ONUs by halving and quartering the sampling rate and the FFT size of ONUs with the use of the TI-OFDM technology.

18.
Opt Express ; 22(21): 26254-64, 2014 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-25401658

RESUMO

We propose and experimentally demonstrate an all-optical temporal differential-equation solver that can be used to solve ordinary differential equations (ODEs) characterizing general linear time-invariant (LTI) systems. The photonic device implemented by an add-drop microring resonator (MRR) with two tunable interferometric couplers is monolithically integrated on a silicon-on-insulator (SOI) wafer with a compact footprint of ~60 µm × 120 µm. By thermally tuning the phase shifts along the bus arms of the two interferometric couplers, the proposed device is capable of solving first-order ODEs with two variable coefficients. The operation principle is theoretically analyzed, and system testing of solving ODE with tunable coefficients is carried out for 10-Gb/s optical Gaussian-like pulses. The experimental results verify the effectiveness of the fabricated device as a tunable photonic ODE solver.


Assuntos
Interferometria/instrumentação , Processamento de Sinais Assistido por Computador/instrumentação , Silício , Telecomunicações/instrumentação , Fótons
19.
J Funct Biomater ; 15(6)2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38921526

RESUMO

Silver nanoparticles (AgNPs) are known for their antibacterial properties and their ability to promote wound healing. By incorporating silver nanoparticles into medical gauze, the resulting composite material shows promise as an advanced wound dressing. However, clinical applications are hindered by challenges related to the stability of silver nanoparticle loading on the gauze as nanoparticle leaching can compromise antibacterial efficacy. In this study, silver nanoparticles were immobilized onto polydopamine (PDA) submicron particles, which were then used to modify medical gauze. Energy dispersive spectroscopy (EDS) was employed to analyze the elemental distribution on the modified gauze, confirming successful surface modification. The antibacterial properties of the modified gauze were assessed using a laser scanning confocal microscope (CLSM). The results demonstrated a significant reduction in the adhesion rates of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by 99.1% and 63%, respectively, on the PDA-Ag-modified gauze. Optical density (OD) measurements at 590 nm indicated that the modified gauze effectively inhibited biofilm formation, underscoring its potent antimicrobial capabilities. Further antibacterial efficacy was evaluated by diluting and plating co-cultured bacterial solutions with the modified dressing, followed by 24 h incubation and colony counting. The gauze exhibited an antibacterial efficiency of 99.99% against E. coli and 99.8% against S. aureus. Additionally, cell compatibility tests, involving the co-culture of PDA-Ag composites with human cells, demonstrated excellent biocompatibility. These findings suggest that PDA-Ag-modified medical gauze holds significant potential for the treatment of infected wounds, offering a promising solution to improve wound care through enhanced antimicrobial activity and biocompatibility.

20.
Waste Manag ; 179: 12-21, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38447255

RESUMO

Sn ash recycling is an industry with positive development prospects, as it provides better-protected resources, promotes sustainable development, and lays a solid foundation for future development. In this study, an innovative vacuum carbothermal reduction-directional condensation process was developed. The thermodynamic analysis results indicated that the initial reaction pressure and temperature for the carbothermal reduction of the system was 1-10 Pa and 998-1063 K, respectively. The saturation vapor pressure, separation coefficient, and condensation temperature of Sn, Pb, and Zn in the reduced products differed significantly, and their separation could be achieved by controlling the volatilization and condensation temperatures. A single-factor experiment investigated the effects of carbon ratio, temperature, and time on the reduction efficiency, direct yield, and recovery rate. The optimal experimental conditions were the ratio of MeO to C of 4:1, temperature of 1373 K, and time of 120 min. Sn, Pb, and Zn products were obtained at different positions. This process shortens the traditional process, reduces the reduction cost of Sn, and enables the implementation of the process, making it environmentally friendly.


Assuntos
Chumbo , Metais Pesados , Vácuo , Reciclagem/métodos , Temperatura , Cinza de Carvão
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