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BACKGROUND/AIMS: Roxadustat, an oral medication for treating renal anemia, is a hypoxia-inducible factor prolyl hydroxylase inhibitor used for regulating iron metabolism and promoting erythropoiesis. To investigate the efficacy and safety of roxadustat in patients undergoing peritoneal dialysis (PD) with erythropoietin hyporesponsiveness. METHODS: Single-center, retrospective study, 81 PD patients (with erythropoietin hyporesponsiveness) were divided into the roxadustat group (n = 61) and erythropoiesis-stimulating agents (ESAs) group (n = 20). Hemoglobin (Hb), total cholesterol, intact parathyroid hormone (iPTH), brain natriuretic peptide (BNP), related indicators of cardiac function and high-sensitivity C-reactive protein (hs-CRP) were collected. Additionally, adverse events were also recorded. The follow-up period was 16 weeks. RESULTS: The two groups exhibited similar baseline demographic and clinical characteristics. At baseline, the roxadustat group had a mean Hb level of 89.8 ± 18.9 g/L, while the ESAs group had a mean Hb level of 95.2 ± 16.0 g/L. By week 16, the Hb levels had increased to 118 ± 19.8 g/L (p < 0.05) in the roxadustat group and 101 ± 19.3 g/L (p > 0.05) in the ESAs group. The efficacy of roxadustat in improving anemia was not influenced by baseline levels of hs-CRP and iPTH. Cholesterol was decreased in the roxadustat group without statin use. An increase in left ventricular ejection fraction and stabilization of BNP were observed in the roxadustat group. CONCLUSION: For PD patients with erythropoietin hyporesponsiveness, roxadustat can significantly improve renal anemia. The efficacy of roxadustat in improving renal anemia was not affected by baseline levels of hs-CRP0 and iPTH.
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Anemia , Eritropoetina , Glicina , Hematínicos , Hemoglobinas , Isoquinolinas , Diálise Peritoneal , Humanos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Anemia/tratamento farmacológico , Anemia/etiologia , Anemia/sangue , Eritropoetina/uso terapêutico , Eritropoetina/efeitos adversos , Resultado do Tratamento , Glicina/análogos & derivados , Glicina/uso terapêutico , Glicina/efeitos adversos , Idoso , Isoquinolinas/uso terapêutico , Isoquinolinas/efeitos adversos , Diálise Peritoneal/efeitos adversos , Hematínicos/uso terapêutico , Hematínicos/efeitos adversos , Hemoglobinas/metabolismo , Adulto , Fatores de Tempo , Biomarcadores/sangue , Inibidores de Prolil-Hidrolase/uso terapêutico , Inibidores de Prolil-Hidrolase/efeitos adversosRESUMO
As a representative of the fourth-generation light sources, the High Energy Photon Source (HEPS) in Beijing, China, utilizes a multi-bend achromat lattice to obtain an approximately 100 times emittance reduction compared with third-generation light sources. New technologies bring new challenges to operate the storage ring. In order to meet the beam commissioning requirements of HEPS, a new framework for the development of high-level applications (HLAs) has been created. The key part of the new framework is a dual-layer physical module to facilitate the seamless fusion of physical simulation models with the real machine, allowing for fast switching between different simulation models to accommodate the various simulation scenarios. As a framework designed for development of physical applications, all variables are based on physical quantities. This allows physicists to analytically assess measurement parameters and optimize machine parameters in a more intuitive manner. To enhance both extensibility and adaptability, a modular design strategy is utilized, partitioning the entire framework into discrete modules in alignment with the requirements of HLA development. This strategy not only facilitates the independent development of each module but also minimizes inter-module coupling, thereby simplifying the maintenance and expansion of the entire framework. To simplify the development complexity, the design of the new framework is implemented using Python and is called Python-based Accelerator Physics Application Set (Pyapas). Taking advantage of Python's flexibility and robust library support, we are able to develop and iterate quickly, while also allowing for seamless integration with other scientific computing applications. HLAs for both the HEPS linac and booster have been successfully developed. During the beam commissioning process at the linac, Pyapas's ease of use and reliability have significantly reduced the time required for the beam commissioning operators. As a development framework for HLA designed for the new-generation light sources, Pyapas has the versatility to be employed with HEPS, as well as with other comparable light sources, due to its adaptability.
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Globally, gastric cancer (GC) is a major cause of cancer death. This study is aimed at investigating the biological functions of activating transcription factor 2 (ATF2) and the underlying mechanism in GC. In the present work, GEPIA, UALCAN, Human Protein Atlas and StarBase databases were adopted to analyze ATF2 expression characteristics in GC tissues and normal gastric tissues, and its relationships with tumor grade and patients' survival time. Quantitative real-time polymerase chain reaction (qRT-PCR) method was employed to examine ATF2 mRNA expression in normal gastric tissues, GC tissues, and GC cell lines. Cell counting kit-8 (CCK-8) and EdU assays were utilized for detecting GC cell proliferation. Cell apoptosis was detected by flow cytometry. PROMO database was applied to predict the binding site of ATF2 with the METTL3 promoter region. The binding relationship between ATF2 and the METTL3 promoter region was verified through dual-luciferase reporter gene assay and chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) assay. Western blot was performed to evaluate the effect of ATF2 on METTL3 expression. METTL3-related signaling pathways were predicted using Gene Set Enrichment Analysis (GSEA) in the LinkedOmics database. It was found that, ATF2 level was elevated in GC tissues and cell lines in comparison with normal tissues and correlated with short patients' survival time. ATF2 overexpression facilitated GC cell growth and suppressed the apoptosis, whereas ATF2 knockdown suppressed GC cell proliferation and facilitated the apoptosis. ATF2 bound to the METTL3 promoter region, and ATF2 overexpression promoted the transcription of METTL3, and ATF2 knockdown restrained the transcription of METTL3. METTL3 was associated with cell cycle progression, and ATF2 overexpression enhanced cyclin D1 expression, and METTL3 knockdown reduced cyclin D1 expression. In summary, ATF2 facilitates GC cell proliferation and suppresses the apoptosis via activating the METTL3/cyclin D1 signaling pathway, and ATF2 is promising to be an anti-drug target for GC.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Fatores de Transcrição/genética , Ciclina D1/genética , Ciclina D1/metabolismo , Fator 2 Ativador da Transcrição/genética , Fator 2 Ativador da Transcrição/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Metiltransferases/genéticaRESUMO
In situ and on-site analysis of trace components, such as methanol and ethyl acetate, in distilled spirits poses significant challenges. In this study, we have proposed a simple, yet effective and rapid approach that combines Raman spectroscopy with Raman integrating sphere technology to accurately detect trace constituents in distilled spirits. An external standard method to effectively separate overlapping Raman peaks from different substances are developed. Experimental results demonstrate that with an exposure time of 180 s under normal temperature and pressure, the detection limits for methanol, acetic acid, and ethyl acetate in proportioned distilled spirits are below 0.1 g/L. Importantly, the detection limit of methanol and acetic acid remains unaffected by the concentration of distilled spirits and the types of trace substances. Notably, the concentration of trace solute exhibits a highly linear relationship with its corresponding Raman intensity, offering a reliable probe for identifying unknown components in distilled spirits.
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Bebidas Alcoólicas , Metanol , Metanol/análise , Bebidas Alcoólicas/análise , Análise Espectral Raman , Ácido Acético/análiseRESUMO
BACKGROUND: Henoch-Schönlein purpura (HSP) with refractory gastrointestinal (GI) symptoms is always difficult to handle because of its resistance to supportive therapies and glucocorticoid. This study aimed to evaluate the efficacy of hemoperfusion (HP) and intravenous immunoglobulins (IVIG) therapies in this population. METHODS: Sixty-four HSP patients with refractory GI involvement (R-GI group) and 64 cases with mild GI symptoms (control group) were retrospectively analyzed in our center from March 2016 to October 2019. In R-GI group, 42 cases (subgroup A) were treated with IVIG and steroid, 13 cases (subgroup B) used HP and steroid, 9 cases (subgroup C) executed a combination of IVIG, HP and steroid. Demographic characteristics, clinical features, laboratory indexes and treatment outcomes were recorded. t-test, One-way ANOVA, Mann-Whitney U test, and multivariate logistic regression were used in comparing differences among subgroups and predicting independent risk factors. RESULTS: Compared with the control group, R-GI cases experienced higher risk of renal involvement (P = 0.000), more steroid exposure (P = 0.000), six times expenses (P = 0.000) and 2.3 times length of hospitalization (P = 0.000). The independent risk factors of R-GI group were elevated neutrophils (OR 1.250 [95% CI 1.130-1.383]) and the percentage of B lymphocytes (OR 1.100 [95% CI 1.026-1.179]) as well as decreased IgG (OR 0.847 [95% CI 0.732-0.98]). In R-GI group, increased age (OR 1.039 [95% CI 1.016-1.062]) and IgM (OR 5.994 [95% CI 1.403-27.611]) were verified to be risk factors of HSP nephritis. All three subgroups could alleviate the symptoms effectively. Compared with those in subgroup A, patients in subgroup B were elder (P = 0.004), had less relapse (P = 0.002), steroid exposure (P = 0.033) and expenses (P = 0.031), more significant decrease of WBC (P = 0.026) after treatment. CONCLUSION: The HSP with refractory GI involvement had much higher risk of medical burden and renal involvement. Both IVIG and HP therapies could ameliorate refractory GI symptoms efficiently. HP therapy tended to reduce the relapse, costs and steroid exposure in its audiences who were cooperated and with stable hemodynamics, while IVIG had better use in younger children.
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Glomerulonefrite , Hemoperfusão , Vasculite por IgA , Criança , Humanos , Vasculite por IgA/complicações , Vasculite por IgA/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Estudos RetrospectivosRESUMO
OBJECTIVES: The standard definition of pediatric acute kidney injury (AKI) is evolving, especially for critically ill in the PICU. We sought to validate the application of the Pediatric Reference Change Value Optimized for Acute Kidney Injury in Children (pROCK) criteria in critically ill children. DESIGN: Multicenter retrospective study. SETTING: Six PICUs in mainland China. PATIENTS: One thousand six hundred seventy-eight hospitalized children admitted to the PICU with at least two creatinine values within 7 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: AKI was diagnosed and staged according to the Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease (pRIFLE), the Kidney Disease Improving Global Outcomes (KDIGO), and the pROCK criteria. Multiple clinical parameters were assessed and analyzed along with 90-day follow-up outcomes. According to the definitions of pRIFLE, KDIGO, and pROCK, the prevalence of AKI in our cohort of 1,678 cases was 52.8% (886), 39.0% (655), and 19.0% (318), respectively. The presence of AKI, as defined by pROCK, was associated with increased number of injured organs, occurrence of sepsis, use of mechanical ventilation, use of continuous renal replace therapy ( p < 0.05), higher Pediatric Risk of Mortality III score, and higher Pediatric Logistic Organ Dysfunction-2 score ( p < 0.001). The survival curve of 90-day outcomes showed that pROCK was associated with shorter survival time (LogRank p < 0.001), and pROCK definition was associated with better separation of the different stages of AKI from non-AKI ( p < 0.001). CONCLUSIONS: In this retrospective analysis of AKI criteria in PICU admissions in China, pROCK is better correlated with severity and outcome of AKI. Hence, the pROCK criteria for AKI may have better utility in critically ill children.
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Injúria Renal Aguda , Estado Terminal , Criança , Humanos , Estudos Retrospectivos , Estado Terminal/terapia , Mortalidade Hospitalar , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/terapia , China/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Therapeutic studies against human immunodeficiency virus type 1 (HIV-1) infection have become one of the important works in global public health. METHODS: Differential expression analysis was performed between HIV-positive (HIV+) and HIV-negative (HIV-) patients for GPL6947 and GPL10558 of GSE29429. Coexpression analysis of common genes with the same direction of differential expression identified modules. Module genes were subjected to enrichment analysis, Short Time-series Expression Miner (STEM) analysis, and PPI network analysis. The top 100 most connected genes in the PPI network were screened to construct the LASSO model, and AUC values were calculated to identify the key genes. Methylation modification of key genes were identified by the chAMP package. Differences in immune cell infiltration between HIV + and HIV- patients, as well as between antiretroviral therapy (ART) and HIV + patients, were calculated using ssGSEA. RESULTS: We obtained 3610 common genes, clustered into nine coexpression modules. Module genes were significantly enriched in interferon signalling, helper T-cell immunity, and HIF-1-signalling pathways. We screened out module genes with gradual changes in expression with increasing time from HIV enrolment using STEM software. We identified 12 significant genes through LASSO regression analysis, especially proteasome 20S subunit beta 8 (PSMB8) and interferon alpha inducible protein 27 (IFI27). The expression of PSMB8 and IFI27 were then detected by quantitative real-time PCR. Interestingly, IFI27 was also a persistently dysregulated gene identified by STEM. In addition, 10 of the key genes were identified to be modified by methylation. The significantly infiltrated immune cells in HIV + patients were restored after ART, and IFI27 was significantly associated with immune cells. CONCLUSION: The above results provided potential target genes for early diagnosis and treatment of HIV + patients. IFI27 may be associated with the progression of HIV infection and may be a powerful target for immunotherapy.
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Infecções por HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/uso terapêuticoRESUMO
Ubiquitin C-terminal hydrolase-L3 (UCHL3) is a deubiquitinating enzyme involved in the repair mechanism of homologous recombinations of DNA double strand breaks (DBS). However, the role of UCHL3 in crustacean immune regulation has not been studied. In this experiment, we cloned and analyzed the expression profile of the UCHL3 gene from Macrobrachium nipponense (MnUCHL3). The obtained full-length cDNA of the MnUCHL3 transcript was 1192 bp, and it had a 687 bp open reading frame encoding a 228 amino acid protein, and the structure of UCHL3 is highly similar to that of other invertebrates. Real-time PCR results indicated that MnUCHL3 was expressed in all detected tissues, with the highest expression levels in the hepatopancreas, and the expression of MnUCHL3 in the gill and hepatopancreas was downregulated to different degrees within 48 h after the infection of viruses and bacteria. Furthermore, knockdown of MnUCHL3 expression by double-stranded RNA (dsRNA) injection in Aeromonas hydrophila-infected prawns increased prawn mortality and bacterial growth. In addition, overexpression of MnUCHL3 in HEK293T cells in vitro suggested that MnUCHL3 could activate the NF-κB signal path and the expression levels of NF-κB signaling cascade members and AMPs, exhibiting remarkable downregulation in the MnUCHL3-silenced group. The above experimental conclusions revealed that UCHL3 gene might be involved in the innate immune response to bacterial infection by regulating the synthesis of a series of AMPs, and these results might provide new insights into UCHL3 in invertebrates.
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Proteínas de Artrópodes , Imunidade Inata , Palaemonidae , Ubiquitina Tiolesterase , Animais , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Clonagem Molecular , Células HEK293 , Humanos , NF-kappa B/metabolismo , Palaemonidae/enzimologia , Palaemonidae/genética , Filogenia , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/imunologiaRESUMO
We herein report a novel, reliable and inexpensive method for detecting esophageal cancer using blood plasma resonance Raman spectroscopy combined with multivariate analysis methods. The blood plasma samples were divided into late stage cancer group (n = 164), early stage cancer group (n = 35) and normal group (n = 135) based on clinical pathological diagnosis. Using a specially designed quartz capillary tube as sample holder, we obtained higher quality resonance Raman spectra of blood plasma than existing method. The study demonstrated that the carotenoids levels in blood plasma were reduced in esophageal cancer patients. The area under the receiver operating characteristic curve (and 95% confidence interval) calculated by wavenumber selection and principal component analysis combined with linear discriminant analysis (PC-LDA) algorithm were 0.894 (0.858-0.929), 0.901 (0.841-0.960) and 0.871 (0.799-0.942) for differentiating late cancer from normal, late cancer from early cancer, and early cancer from normal respectively. The contribution from the two carotenoids wavenumber regions of 1155 and 1515 cm-1 were more than 84.2%. The results show that the plasma carotenoids could be a potential biomarker for screening esophageal cancer using resonance Raman spectroscopy combined with wavenumber selection and PC-LDA algorithms.
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Neoplasias Esofágicas , Análise Espectral Raman , Análise Discriminante , Neoplasias Esofágicas/diagnóstico , Humanos , Análise Multivariada , Plasma , Análise de Componente PrincipalRESUMO
The present study evaluated the anticancer potential of celastrol through down-regulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. HeLa cells were incubated with different concentrations of celastrol (1, 10 and 100 µM) for 48h. Doxorubicin was used as a reference drug. Cancer cell migration, apoptosis, cell viability and mitochondrial fragmentation were evaluated following celastrol treatment. In addition, the expression level of MMP-2, MMP-9 and caspase-3 was evaluated following celastrol treatment. HeLa cell viability was 94.1 ± 7, 53.4 ± 4 and 36.3 ± 2% at 1-100 µM of celastrol, respectively. Apoptotic cell numbers were increased, and inhibition of larger wounds in cancer cells was observed following celastrol treatment. Celastrol-treated cells showed condensed nuclei and clumped mitochondria. Reduced expression of MMP-2 and MMP-9 and increased expression of caspase-3 were observed following celastrol treatment. Based on the experimental results, we are concluding that the celastrol was effective against HeLa cervical cancer cells.
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Proliferação de Células , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Metaloproteinase 2 da Matriz/química , Metaloproteinase 9 da Matriz/química , Triterpenos Pentacíclicos/farmacologia , Neoplasias do Colo do Útero/patologia , Apoptose , Movimento Celular , Feminino , Células HeLa , Humanos , Invasividade Neoplásica , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismoRESUMO
The polymeric immunoglobulin receptor (pIgR) is one of the most vital components of mucosal immunity that plays a pivotal role in mediating transcytosis of polymeric immunoglobulin (pIg) on epithelial surfaces for protection against invading pathogens. Herein, we cloned the full-length cDNA of Pelodiscus sinensis pIgR, designated as P. sinensis pIgR, made of an open reading frame (ORF) of 1848 bp, molecular weight of 68.2 kDa and estimated isoelectric point of 7.00. The deduced P. sinensis pIgR sequence had a leader peptide, extracellular region containing four immunoglobulin-like domains (Ig like domains), transmembrane and intracellular regions comparable with other vertebrates. P. sinensis pIgR contained four Ig like domains that corresponded with mammalian D1, D3, D4 and D5 similar with reptile and avian Ig like domains. It had 40 potential phosphorylation sites, four putative N-glycosylation sites and several motifs resembling mammalian pIgR motifs. Phylogenetic analysis showed a close relationship between P. sinensis pIgR with avian and reptile pIgRs. P. sinensis pIgR basal levels were higher in the esophagus, small intestine and intestinnum crissum than in other organs of health turtles. Intragastric delivery of LPS and Aeromonassobria led to significant upregulation of P. sinensis pIgR in tissues of the gastrointestinal tract. A polyclonal anti- P. sinensis pIgR antibody produced in rabbit reacted with the recombinant P. sinensis pIgR protein expressed in Escherichia coli in Western blot. These studies demonstrate the existence and immune response of P. sinensis pIgR to stimulation in mucosal organs in Chinese soft-shelled turtles.
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Aeromonas/imunologia , Imunidade nas Mucosas , Receptores de Imunoglobulina Polimérica/metabolismo , Tartarugas/imunologia , Animais , Trato Gastrointestinal , Lipopolissacarídeos/imunologia , Filogenia , Domínios Proteicos/genética , Receptores de Imunoglobulina Polimérica/análise , Receptores de Imunoglobulina Polimérica/genética , Tartarugas/genética , Tartarugas/metabolismo , Tartarugas/microbiologia , Regulação para Cima/imunologiaRESUMO
Cardamonin (CAR), a flavone existing in the Alpinia plant, has been found to modulate multiple biological activities, including antioxidant, anti-inflammatory, and anti-tumor effects. Nevertheless, the influence of CAR on pancreatic cancer (PC) is less understood. Here, we conducted in vitro and in vivo experiments to explore the functions of CAR on PC cells' proliferation, apoptosis and chemosensitivity to gemcitabine (GEM). The growth of PC cells (including PANC-1 and SW1990) was evaluated by the cell counting kit-8 assay, colony formation assay and xenograft tumor experiment. Besides, the apoptosis was determined by flow cytometry and western blot (WB). Moreover, the FOXO3a-FOXM1 pathway expression was tested by reverse transcription-polymerase chain reaction and WB. Our data suggested that CAR restrained cell proliferation, growth and expedited apoptosis both in vitro and in vivo. Moreover, CAR sensitized PC cells to GEM. Mechanistically, CAR heightened FOXO3a while repressed FOXM1. Further loss-of-function assays revealed that down-regulating FOXO3a markedly dampened the anti-tumor effect induced by CAR and accelerated the FOXM1 expression. Our data confirmed that CAR exerted an anti-tumor function in PC dependently by modulating the FOXO3a-FOXM1 axis.
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The four-and-a-half LIM-only protein family of transcription co-factors participates in various cellular processes, such as cell proliferation, cell differentiation, apoptosis, cell adhesion, migration, transcription and signal transduction. However, the knowledge of the structural characteristics and immune functions of its ancestor Lmpt, which contains six LIM domains at the C-terminus and a PET domain at the N-terminus, is limited in invertebrates, especially in crustaceans. In the present study, a novel Lmpt from oriental river prawn (Macrobrachium nipponense) was identified, and its role in the immune response was investigated. Its full-length cDNA sequence was 6407 bp, which contained a 2595 bp ORF encoding 865 amino acids, exhibiting high similarity to the structure of Lmpt derived from other invertebrates. Tissue distribution analysis revealed that MnLmpt was widely expressed in all examined tissues, and high expression levels were observed in muscle, heart and intestine in M. nipponense. After experimental challenges with bacteria and virus, the transcription levels of MnLmpt significantly fluctuated in gill and hepatopancreas, indicating that it might play a role in the innate immune response in M. nipponense. Silencing of MnLmpt by dsRNA injection in vivo could promote bacterial growth, suggesting that MnLmpt exerted an antibacterial immune function in prawn. Immunocytochemistry assay results demonstrated that MnLmpt was able to translocate from the cytoplasm to the nucleus after being stimulated with pathogens. The expression levels of NF-κB signalling cascade members, such as dorsal, relish, TAK1, TAB1, Ikkß, and Ikkε, and AMPs, including ALF4, Cru1, and Cru2, exhibited significant downregulation in the MnLmpt silenced group. Similarly, dual-luciferase reporter assays also demonstrated that MnLmpt could stimulate an NF-κB signalling cascade. Meanwhile, all of the LIM domains of MnLmpt could trigger NF-κB signalling; however, their cumulative effect on NF-κB promoter activation was hardly observed. These results showed that MnLmpt might play a crucial role in the innate immune response in M. nipponense, and these findings paved the way for a better understanding of the immune system in crustacean species.
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Proteínas com Domínio LIM/imunologia , NF-kappa B/metabolismo , Palaemonidae/imunologia , Transporte Ativo do Núcleo Celular , Aeromonas hydrophila/fisiologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Proteínas de Artrópodes/metabolismo , Núcleo Celular/metabolismo , Clonagem Molecular , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Imunidade Inata/genética , Proteínas com Domínio LIM/genética , Proteínas com Domínio LIM/metabolismo , NF-kappa B/genética , Filogenia , Regiões Promotoras Genéticas , Alinhamento de Sequência , Transdução de Sinais , Distribuição TecidualRESUMO
The Decapentaplegic (Dpp) gene, which belongs to the TGF-ß superfamily, is involved in multiple developmental processes in eukaryotic species. In this study, we firstly identified and characterized Dpp from Macrobrachium nipponense. Its full-length open reading frame (ORF) cDNA was 1332 bp, encoding 443 amino acids. The putative MnDpp protein contained a signal peptide, a TGF-ß propeptide region and a TGF-ß domain. Its TGF-ß domain was highly conserved from vertebrates to invertebrates, and exhibited highly similarity to Dpp derived from Bombyx mori. qRT-PCR analysis suggested that MnDpp expressed in all tested tissues and responded to both bacterial and virus pathogens, indicating MnDpp was involved in the innate immune response of M. nipponense. Knockdown of MnDppin vivo significantly increased bacteria growth and markedly decreased the expressions of NF-κB signaling genes including dorsal, relish, TAK1, TAB1, Ikkß and Ikkε as well as antimicrobial peptides (AMPs) including ALF2, ALF3, ALF4, ALF5, Cru1 and Cru2. Moreover, in vitro overexpression of MnDpp protein in HEK293T cells further demonstrated that it exerted antibacterial immune response by activation of NF-κB signaling cascade. In summary, these results indicated that MnDpp played an important role in the innate immunity in M. nipponense by modulating NF-κB signaling pathway, which might provide new insights about Dpp in crustaceans and paved the way for a better understanding of the crustacean innate immune system.
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Proteínas de Artrópodes/imunologia , NF-kappa B/imunologia , Palaemonidae/imunologia , Fator de Crescimento Transformador beta/imunologia , Aeromonas hydrophila , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/genética , Sequência de Bases , Clonagem Molecular , Infecções por Vírus de DNA/imunologia , Infecções por Vírus de DNA/veterinária , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Células HEK293 , Humanos , Palaemonidae/genética , Palaemonidae/microbiologia , Filogenia , Fator de Crescimento Transformador beta/genética , Vírus da Síndrome da Mancha Branca 1RESUMO
Bx42, the homologue of SNW1 in mammals, is involved in pre-mRNA splicing and transcriptional regulation. However, the presence and function of Bx42 have remained poorly understood in invertebrates until now. In the current study, a novel SNW domain-containing protein (MnBx42) from Macrobrachium nipponense was identified, and its potential role in the immune response was investigated. The full-length MnBx42 was 7467 bp with an open reading frame of 1653 bp, encoding 550 amino acids. Real-time PCR analysis suggested that MnBx42 was predominantly expressed in the intestine, gills and hepatopancreas, and immunofluorescence assays indicated that it was located in the nucleus. Its expression level was significantly decreased in M. nipponense post-challenge with white spot syndrome virus (WSSV) as well as Aeromonas hydrophila and Staphylococcus aureus, implying its participation in the innate immune response. The knockdown of MnBx42 in vivo notably increased the susceptibility of the prawns to bacterial infection, markedly increased the bacterial load in the gills, and significantly attenuated the phagocytic activity of haemocytes. Dual-luciferase reporter assays illustrated that MnBx42 could activate the NF-κB pathway. Consistent with this, when MnBx42 was silenced in vivo, the expression levels of antimicrobial peptides (AMPs), including ALF2, ALF3, ALF4, ALF5, Cru1 and Cru2, and NF-κB signalling genes, including dorsal, relish, TAK1, TAB1, Ikkß, and Ikkε, were significantly reduced. Taken together, these findings may provide new insights about Bx42 in crustaceans and pave the way for a better understanding of the crustacean innate immune system.
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Aeromonas hydrophila/fisiologia , Proteínas de Artrópodes/genética , Infecções por Vírus de DNA/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Coativadores de Receptor Nuclear/genética , Palaemonidae/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/fisiologia , Vírus da Síndrome da Mancha Branca 1/fisiologia , Animais , Proteínas de Artrópodes/metabolismo , Clonagem Molecular , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Imunidade Inata/genética , NF-kappa B/metabolismo , Coativadores de Receptor Nuclear/metabolismo , Especificidade de Órgãos , Interferência de RNA , Transdução de Sinais , TranscriptomaRESUMO
BACKGROUND: Circular RNAs (circRNAs), proven as single-stranded closed RNA molecules, have been implicated in the onset and development of multiple cancers. This study aimed to summarize existing evidences regarding the clinicopathologic, diagnostic, and prognostic significances of circRNAs in gastric cancer (GC). METHODS: Eligible studies were identified using online databases. The quality of the included studies was judged, and patients' clinical characteristics, diagnostic data, and overall survival (OS) were extracted from the electronic medical record. Fisher's method was adopted to determine P values for clinicopathologic features. The diagnostic and prognostic data from all included studies were merged. RESULTS: Thirty eligible studies were comprised of 2687 GC patients were enrolled in the meta-analyses. Altered expressions of circRNAs in GC tissues were significantly associated with worse clinicopathologic features. Abnormally expressed circRNAs yielded a pooled sensitivity of 0.76 (95% CI: 0.69-0.81) and a specificity of 0.77 (95% CI: 0.70-0.83) in distinguishing GC from noncancerous controls, which corresponded to an area under the curve (AUC) of 0.83. The survival analysis showed that the oncogenic circRNA signature could be an independent risk factor of OS (HR = 2.11, 95% CI: 1.60-2.78, P = .000). Patients with down-regulated circRNAs (tumor suppressor genes) presented a significantly shorter OS time than those with high-level circRNAs (HR = 0.33, 95% CI: 0.27-0.42, P = .000). Stratified analyses based on sample type, control source, circRNA expression status, and cutoff setting also produced robust results. CONCLUSIONS: CircRNAs may play an important role as potential diagnostic and prognostic biomarkers of GC.
Assuntos
RNA Circular , Neoplasias Gástricas , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Humanos , Prognóstico , RNA Circular/análise , RNA Circular/genética , Sensibilidade e Especificidade , Estômago/química , Estômago/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologiaRESUMO
Solar-blind deep ultraviolet photodetectors (DUVPDs) based on conventional inorganic ultrawide bandgap semiconductors (UWBS) have shown promising application in various civil and military fields and yet they can hardly be used in wearable optoelectronic devices and systems for lack of mechanical flexibility. In this study, we report a non-UWBS solar-blind DUVPD by designing ultrathin polymer nanofibrils with a virtual ultrawide bandgap, which was obtained by grafting P3HT with PHA via a polymerization process. Optoelectronic analysis reveals that the P3HT-b-PHA nanofibrils are sensitive to DUV light with a wavelength of 254 nm but are virtually blind to both 365 nm and other visible light illuminations. The responsivity is 120 A/W with an external quantum efficiency of up to 49700%, implying a large photoconductive gain in the photoresponse process. The observed solar-blind DUV photoresponse is associated with the resonant mode due to the leakage mode of the ultrathin polymer nanofibrils. Moreover, a flexible image sensor composed of 10 × 10 pixels can also be fabricated to illustrate their capability for image sensing application. These results signify that the present ultrathin P3HT-b-PHA nanofibrils are promising building blocks for assembly of low-cost, flexible, and high-performance solar-blind DUVPDs.
RESUMO
Metasurfaces are capable of tailoring the amplitude, phase, and polarization of incident light to design various polarization devices. Here, we propose a metasurface based on the novel dielectric material gallium nitride (GaN) to realize high-efficiency modulation for both of the orthogonal linear polarizations simultaneously in the visible range. Both modulated transmitted phases of the orthogonal linear polarizations can almost span the whole 2π range by tailoring geometric sizes of the GaN nanobricks, while maintaining high values of transmission (almost all over 90%). At the wavelength of 530 nm, we designed and realized the beam splitter and the focusing lenses successfully. To further prove that our proposed method is suitable for arbitrary orthogonal linear polarization, we also designed a three-dimensional (3D) metalens that can simultaneously focus the X-, Y-, 45°, and 135° linear polarizations on spatially symmetric positions, which can be applied to the linear polarization measurement. Our work provides a possible method to achieve high-efficiency multifunctional optical devices in visible light by extending the modulating dimensions.
RESUMO
Pelodiscus sinensis, which is one of the important reptile species in the aquaculture industry in China, frequently suffers from serious infectious diseases caused by viruses. However, there is a lack of biological knowledge about its antiviral innate immunity. In this study, we identified and characterized the open reading frame (ORF) of PsMAVS cDNA in P. sinensis. It consisted of 2691 nucleotides encoding a protein of 896 amino acid residues, which were composed of an N-terminal CARD, a central proline-rich domain and a C-terminal TM domain. Based on the amino acid sequence, phylogenetic analyses revealed a closer relationship of PsMAVS with those of Chelonia. qRT-PCR analysis indicated that PsMAVS was ubiquitously expressed in all of the examined healthy tissues with different expression levels; it was expressed at high levels in spleen, muscle and heart and at moderate levels in kidney, liver, intestine, intestinum crissum and oesophagus. PsMAVS was detected in embryos at 10 days post hatching, and it gradually upregulated with the embryonic development stage. Its expression levels in the examined tissues were all upregulated significantly after challenge with Poly I:C. The PsMAVS protein was detected in the intestinal tissues from both the challenge and the control groups, and it was distributed widely in the cytoplasm of the intestinal cells, suggesting PsMAVS plays multiple roles in the complicated mechanisms of immune defence against virus invasion in P. sinensis.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Imunidade Inata , Tartarugas/genética , Tartarugas/imunologia , Proteínas Adaptadoras de Transdução de Sinal/química , Sequência de Aminoácidos , Animais , Injeções Intraperitoneais/veterinária , Filogenia , Poli I-C/farmacologia , Proteínas de Répteis/química , Proteínas de Répteis/genética , Proteínas de Répteis/imunologia , Alinhamento de Sequência/veterinária , Tartarugas/metabolismoRESUMO
The characteristics of ferroelectric capacitors with poly(vinylidene fluoride-trifluoroethlene) (P(VDF-TrFE)) films have been studied at different structures of cell electrodes. It is suggested that the effect of electrode structures could induce changes of performance. Remarkably, cells with line electrodes display a better polarization and fatigue resistance than those with flat electrodes. For P(VDF-TrFE) ultrathin films with different electrode structures, the models of charge compensation mechanism for depolarization field and domain fatigue decomposition are used to explain the effect of electrode structure. Furthermore, the driving voltage based on normal speed-functionality is designed, and the testing results show that the line electrode structure could induce a robust switching, which is determined by the free charges concentration in active layer. These findings provide an effective route to design the optimum structure for a ferroelectric capacitor based on P(VDF-TrFE) copolymer ultrathin film.