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1.
Comput Biol Chem ; 86: 107261, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32361585

RESUMO

Mutant isocitrate dehydrogenase 2 (mIDH2) is an emerging target for the treatment of cancer. AG-221 is the first mIDH2 inhibitor approved by the FDA for acute myeloid leukemia treatment, but its acquired resistance has recently been observed, necessitating the development of new inhibitor. In this study, a multi-step virtual screening protocol was employed for the analysis of a large database of compounds to identify potential mIDH2 inhibitors. To this end, we firstly utilized molecular dynamics (MD) simulations and binding free energy calculations to elucidate the key factors affecting ligand binding and drug resistance. Based on these findings, the receptor-ligand interaction-based pharmacophore (IBP) model and hierarchical docking-based virtual screening were sequentially carried out to assess 212,736 compounds from the Specs database. The resulting hits were finally ranked by PAINS filter and ADME prediction and the top compounds were obtained. Among them, six molecules were identified as mIDH2 putative inhibitors with high selectivity by interacting with the capping residue Asp312. Furthermore, subsequent docking and MD experiments demonstrated that compound V2 might have potential inhibitory activity against the AG-221-resistant mutants, thereby making it a promising lead for the development of novel mIDH2 inhibitors.

2.
ChemSusChem ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32394542

RESUMO

The recent emerging generation of flexible energy storage devices has accelerated the research pace in terms of new materials, new processing techniques and new designs that can meet the demands of mechanical stability upon bending or stretching at an acceptable cost, without compromising their electrochemical performance. Among all the materials currently explored, biomass derived materials have received extensive attention due to their attractive properties such as renewable, low-cost, earth-abundant and multitudinous structures. Herein, in this review, we focus on fundamentals and applications of the special biomass material-bacterial cellulose (BC) in flexible electrochemical energy storage systems. Specifically, we summarized the recent advances of the attractive utilization of BC as stretchable substrates, carbonaceous species and scaffolds for flexible core components construction. Finally, several perspectives related to BC based materials for flexible electrochemical energy storages are proposed based on the current researches and our own evaluation, aiming to provide possible research directions in these fields.

3.
Front Immunol ; 11: 560, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32425924

RESUMO

Cell-based immunotherapies have tremendous potential to treat many diseases, such as activating immunity in cancer or suppressing it in autoimmune diseases. Most cell-based cancer immunotherapies in the clinic provide adjuvant signals through genetic engineering to enhance T cell functions. However, genetically encoded signals have minimal control over dosing and persist for the life of a cell lineage. These properties make it difficult to balance increasing therapeutic efficacy with reducing toxicities. Here, we demonstrated the potential of phospholipid-coupled ligands as a non-genetic system for immune cell engineering. This system provides simple, controlled, non-genetic adjuvant delivery to immune cells via lipid-mediated insertion into plasma membranes. Lipid-mediated insertion (termed depoting) successfully delivered Toll-like receptor (TLR) ligands intracellularly and onto cell surfaces of diverse immune cells. These ligands depoted into immune cells in a dose-controlled fashion and did not compete during multiplex pairwise loading. Immune cell activation could be enhanced by autocrine and paracrine mechanisms depending on the biology of the TLR ligand tested. Depoted ligands functionally persisted on plasma membranes for up to 4 days in naïve and activated T cells, enhancing their activation, proliferation, and skewing cytokine secretion. Our data showed that depoted ligands provided a persistent yet non-permanent adjuvant signal to immune cells that may minimize the intensity and duration of toxicities compared to permanent genetic delivery. Altogether, these findings demonstrate potential for lipid-mediated depoting as a universal cell engineering approach with unique, complementary advantages to other cell engineering methods.

4.
Am J Nephrol ; : 1-10, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349004

RESUMO

BACKGROUND: The lack of consensus criteria of acute on chronic kidney injury (ACKI) affects the judgment for its clinical prognosis. METHODS: In this study, we analyzed the data from 711,615 hospitalized adults who had at least 2 serum creatinine (SCr) tests within 30 days. We estimated the reference change value (RCV) of SCr given initial SCr level in adults without known risks of acute kidney injury other than chronic kidney disease (CKD). We proposed a criterion for ACKI based on the RCV of SCr (cROCK), which defined ACKI as a ≥25% increase in SCr in 7 days. We validated cROCK by its association with the risks of in-hospital mortality, death after discharge, and CKD progression in a large cohort of patients with CKD stage 3. RESULTS: In 21,661 patients with CKD stage 3, a total of 3,145 (14.5%), 1,512 (7.0%), and 221 (1.0%) ACKI events were detected by both cROCK and Kidney Disease Improving Global Outcomes (KDIGO), cROCK only, and KDIGO only, respectively. cROCK detected 40% more ACKI events than KDIGO. Compared with patients without ACKI by both definitions, those with cROCK- but not KDIGO-defined ACKI had a significantly increased risk of in-hospital mortality (hazard ratio [HR] 5.53; 95% CI 3.75-8.16), death after discharge (HR 1.51; 95% CI 1.21-1.83), and CKD progression (OR 5.65; 95% CI 3.05-10.48). CONCLUSIONS: RCV-based criterion (cROCK) for ACKI is clinically valid in that it has a substantially improved sensitivity in identifying patients with high risk of adverse outcomes.

5.
Biomed Eng Online ; 19(1): 21, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32295576

RESUMO

BACKGROUND: As one of the major complications of diabetes, diabetic retinopathy (DR) is a leading cause of visual impairment and blindness due to delayed diagnosis and intervention. Microaneurysms appear as the earliest symptom of DR. Accurate and reliable detection of microaneurysms in color fundus images has great importance for DR screening. METHODS: A microaneurysms' detection method using machine learning based on directional local contrast (DLC) is proposed for the early diagnosis of DR. First, blood vessels were enhanced and segmented using improved enhancement function based on analyzing eigenvalues of Hessian matrix. Next, with blood vessels excluded, microaneurysm candidate regions were obtained using shape characteristics and connected components analysis. After image segmented to patches, the features of each microaneurysm candidate patch were extracted, and each candidate patch was classified into microaneurysm or non-microaneurysm. The main contributions of our study are (1) making use of directional local contrast in microaneurysms' detection for the first time, which does make sense for better microaneurysms' classification. (2) Applying three different machine learning techniques for classification and comparing their performance for microaneurysms' detection. The proposed algorithm was trained and tested on e-ophtha MA database, and further tested on another independent DIARETDB1 database. Results of microaneurysms' detection on the two databases were evaluated on lesion level and compared with existing algorithms. RESULTS: The proposed method has achieved better performance compared with existing algorithms on accuracy and computation time. On e-ophtha MA and DIARETDB1 databases, the area under curve (AUC) of receiver operating characteristic (ROC) curve was 0.87 and 0.86, respectively. The free-response ROC (FROC) score on the two databases was 0.374 and 0.210, respectively. The computation time per image with resolution of 2544×1969, 1400×960 and 1500×1152 is 29 s, 3 s and 2.6 s, respectively. CONCLUSIONS: The proposed method using machine learning based on directional local contrast of image patches can effectively detect microaneurysms in color fundus images and provide an effective scientific basis for early clinical DR diagnosis.

6.
Dev Comp Immunol ; 107: 103665, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32147597

RESUMO

Invertebrates rely solely on the innate immune system to protect against virus infection, while the viral infection must rely on the transcriptional system of the host cell to achieve the expression of viral genes, which is naturally regulated by the host's transcriptional system. However, the mechanism of the host against viral transcription in host cells is still poorly understood in crustaceans. Previously, we found that the partial transcript sequence of a negative elongation factor E (named as CqNELF-E) was up-regulated in a differentially expressed transcriptome library of the haematopietic tissue (Hpt) cells from red claw crayfish Cherax quadricarinatus upon white spot syndrome virus (WSSV) infection, suggesting a possible role of CqNELF-E in WSSV-host interaction. In the present study, we revealed the function of CqNELF-E. The full-length cDNA sequence of CqNELF-E was identified with 1726 bp from red claw crayfish, which contained an open reading frame of 816 bp, encoding 271 amino acids. Amino acid sequencing analysis revealed that the CqNELF-E had a conserved RNA recognition motif (RRM) and a leucine zipper motif (LZM). Tissue distribution analysis showed that CqNELF-E was widely expressed in various tissues with the highest expression in muscle, relatively abundant in Hpt and the lowest presence in heart. Interestingly, the gene expression of CqNELF-E was significantly up-regulated at both 6 and 12 hpi after WSSV infection in Hpt cell cultures in red claw crayfish. In addition, the expression of both the viral immediately early gene (IE) 1 (IE1) and a late gene envelope protein VP28 were significantly increased after gene silencing of CqNELF-E in Hpt cells, indicating the potential suppression role of CqNELF-E against the viral infection. Further study revealed that the CqNELF-E had an inhibitory effect on the promoter activity of WSSV IE genes WSV051, WSV069 (IE1) and WSV083 by a dual luciferase reporter gene assay. Taken together, these results suggest that CqNELF-E plays an antiviral role, probably via inhibition on the viral transcription activity in WSSV infection in a crustacean.

7.
Front Immunol ; 11: 268, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194551

RESUMO

Phagocytosis is an ancient, highly conserved process in all multicellular organisms, through which the host can protect itself against invading microorganisms and environmental particles, as well as remove self-apoptotic cells/cell debris to maintain tissue homeostasis. In crustacean, phagocytosis by hemocyte has also been well-recognized as a crucial defense mechanism for the host against infectious agents such as bacteria and viruses. In this review, we summarized the current knowledge of hemocyte-mediated phagocytosis, in particular focusing on the related receptors for recognition and internalization of pathogens as well as the downstream signal pathways and intracellular regulators involved in the process of hemocyte phagocytosis. We attempted to gain a deeper understanding of the phagocytic mechanism of different hemocytes and their contribution to the host defense immunity in crustaceans.

8.
Dev Comp Immunol ; 107: 103640, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32078959

RESUMO

In contrast to that hypoacetylation of histones is associated with condensed chromatin and gene silencing, the hyperacetylation of histones can promote an "open chromatin" conformation and transcriptional activation, which is recruited by some viruses to enhance the viral genome replication in host cells. However, the function of histone acetylation modification in the infection of white spot syndrome virus (WSSV), one of the most virulent pathogens for crustaceans like shrimp and crayfish at present, is still unknown. Previously, we found that the transcript of a histone K-Lysine acetyltransferase CqKAT2A-like gene was down-regulated in a differentially expressed transcriptome library of the haematopietic tissue (Hpt) cells from red claw crayfish Cherax quadricarinatus upon WSSV infection at 12 hpi. To further reveal its possible role in anti-WSSV response, CqKAT2A-like gene was then identified with an open reading frame (ORF) of 2523 bp encoding 840 amino acids, which contained a conserved PCAF-N domain, acetyltransf1 domain and bromo domain. Gene expression analysis showed that CqKAT2A-like was distributed in all tissues examined with high presence in haemocyte and muscle, and the transcript was significantly down-regulated after WSSV infection in Hpt cells. Furthermore, the level of histone H3 acetylation (H3ac) was strongly reduced by gene silencing of CqKAT2A-like, which was accompanied with the significantly decreased gene expression of WSSV in Hpt cells, suggesting that CqKAT2A-like gene can promote the activity H3ac and the replication of WSSV. When the H3ac was induced by histone deacetyltransferase inhibitor TSA, the transcription of WSSV genes including both IE1 and VP28 genes was significantly increased, indicating that H3ac participated in WSSV infection in Hpt cells. Taken together, these data suggest that CqKAT2A-like gene might promote the replication of WSSV by regulating H3ac, which sheds new light on the pathogenesis of WSSV in crustaceans.

9.
J Clin Monit Comput ; 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32088910

RESUMO

The respiration rate (RR) is a vital sign in physiological measurement and clinical diagnosis. RR can be measured using stretchable and wearable strain gauge sensors which detect the respiratory movements in the abdomen or thorax areas caused by volumetric changes. In different body locations, the accuracy of RR detection might differ due to different respiratory movement amplitudes. Few studies have quantitatively investigated the effect of the measurement location on the accuracy of new sensors in RR detection. Using a stretchable and wearable inkjet-printed strain gauge (IPSG) sensor, RR was measured from five body locations (umbilicus, upper abdomen, xiphoid process, upper thorax, and diagonal) on 30 healthy test subjects while sitting on an armless chair. At each location, reference RR was simultaneously detected by the e-Health sensor, and the measurement was repeated twice. Subjects were asked about the comfortableness of locations. Based on Levene's test, ANOVA was performed to investigate if there is a significant difference in RR between sensors, measurement locations, and two repeated measurements. Bland-Altman analysis was applied to the RR measurements at different locations. The effects of measurement site and measurement trials on RR difference between sensors were also investigated. There was no significant difference between IPSG and reference sensors, between any locations, and between the two measurements (all p > 0.05). As to the RR deviation between IPSG and reference sensors, there was no significant difference between any locations, or between two measurements (all p > 0.05). All the 30 subjects agreed that diagonal and upper thorax positions were the most uncomfortable and most comfortable locations for measurement, respectively. The IPSG sensor could accurately detect RR at five different locations with good repeatability. Upper thorax was the most comfortable location.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32097281

RESUMO

Wiskott-Aldrich syndrome (WAS) and osteopetrosis are 2 different, rare hereditary diseases. Here we report clinical and molecular genetics investigations on an infant patient with persistent thrombocytopenia and prolonged fever. He was clinical diagnosed as osteopetrosis according to clinical presentation, radiologic skeletal features, and bone biopsy results. Gene sequencing demonstrated a de novo homozygous mutation in 5'-untranslated region of TNFRSF11A, c.-45A>G, which is relating to osteopetrosis. Meanwhile, a hemizygous transition mutation in WAS gene, c.400G>A diagnosed the infant with WAS. This is the first clinical report for the diagnosis of osteopetrosis coinheritance with WAS in a single patient.

11.
Nature ; 577(7792): 682-688, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31942069

RESUMO

Mycobacterium tuberculosis is an intracellular pathogen that uses several strategies to interfere with the signalling functions of host immune molecules. Many other bacterial pathogens exploit the host ubiquitination system to promote pathogenesis1,2, but whether this same system modulates the ubiquitination of M. tuberculosis proteins is unknown. Here we report that the host E3 ubiquitin ligase ANAPC2-a core subunit of the anaphase-promoting complex/cyclosome-interacts with the mycobacterial protein Rv0222 and promotes the attachment of lysine-11-linked ubiquitin chains to lysine 76 of Rv0222 in order to suppress the expression of proinflammatory cytokines. Inhibition of ANAPC2 by specific short hairpin RNA abolishes the inhibitory effect of Rv0222 on proinflammatory responses. Moreover, mutation of the ubiquitination site on Rv0222 impairs the inhibition of proinflammatory cytokines by Rv0222 and reduces virulence during infection in mice. Mechanistically, lysine-11-linked ubiquitination of Rv0222 by ANAPC2 facilitates the recruitment of the protein tyrosine phosphatase SHP1 to the adaptor protein TRAF6, preventing the lysine-63-linked ubiquitination and activation of TRAF6. Our findings identify a previously unrecognized mechanism that M. tuberculosis uses to suppress host immunity, and provide insights relevant to the development of effective immunomodulators that target M. tuberculosis.


Assuntos
Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Ubiquitinação , Ciclossomo-Complexo Promotor de Anáfase/química , Animais , Subunidade Apc2 do Ciclossomo-Complexo Promotor de Anáfase/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Células Cultivadas , Citocinas/antagonistas & inibidores , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Lisina/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Transdução de Sinais , Fator 6 Associado a Receptor de TNF/antagonistas & inibidores , Fator 6 Associado a Receptor de TNF/metabolismo , Fator de Transcrição AP-1/metabolismo , Tuberculose/microbiologia , Virulência/imunologia
12.
J Cereb Blood Flow Metab ; 40(1): 126-134, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30351176

RESUMO

We aimed to investigate the roles of antegrade residual flow and leptomeningeal collateral flow in sustaining cerebral perfusion distal to an intracranial atherosclerotic stenosis (ICAS). Patients with apparently normal cerebral perfusion distal to a symptomatic middle cerebral artery (MCA)-M1 stenosis were enrolled. Computational fluid dynamics models were built based on CT angiography to obtain a translesional pressure ratio (PR) to gauge the residual antegrade flow. Leptomeningeal collaterals (LMCs) were scaled on CT angiography. Cerebral perfusion metrics were obtained in CT perfusion maps. Among 83 patients, linear regression analyses revealed that both translesional PR and LMC scale were independently associated with relative ipsilesional mean transit time (rMTT). Subgroup analyses showed that ipsilesional rMTT was significantly associated with translesional PR (p < 0.001) rather than LMC scale in those with a moderate (50-69%) MCA stenosis, which, however, was only significantly associated with LMC scale (p = 0.051) in those with a severe (70-99%) stenosis. Antegrade residual flow and leptomeningeal collateral flow have complementary effects in sustaining cerebral perfusion distal to an ICAS, while cerebral perfusion may rely more on the collateral circulation in those with a severe stenosis.

13.
Pharmacotherapy ; 40(1): 4-16, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31742742

RESUMO

BACKGROUND: The pathogenic mechanism of antituberculous drug-induced liver injury (ATDILI) is associated with antioxidant enzymes. The objective of the present study was to investigate the associations of ATDILI susceptibility with genetic polymorphisms of antioxidant enzyme genes including nitric oxide synthase 2 (NOS2), thioredoxin reductase 1 (TXNRD1), superoxide dismutase 2 (SOD2), BTB domain and CNC homolog 1 (BACH1), and MAF bZIP transcription factor K (MAFK). METHODS: Thirty tag single nucleotide polymorphisms (tag-SNPs) from the all candidate genes were genotyped in a 2-stage cohort study including an initial discovery stage with 461 ATDILI patients and 466 controls and a replication stage with 216 ATDILI patients and 432 controls. The frequencies and distributions of genotypes and haplotypes were compared between the case and control groups. Three different genetic models including dominant, recessive, and additive models were used to determine the associations with susceptibility to ATDILI. RESULTS: The SNPs rs9906835, rs944725, and rs3794764 of the NOS2 gene were significantly associated with an increased risk of ATDILI. The MAFK rs3735656 SNP was significantly associated with a decreased risk for ATDILI. The AAA haplotype of the NOS2 gene was associated with susceptibility to ATDILI. The treatment outcomes of patients with tuberculosis were further affected by genetic variants of the NOS2 and MAFK genes. CONCLUSIONS: Genetic polymorphisms of NOS2 and MAFK are associated with ATDILI susceptibility in Chinese patients with tuberculosis. The variants in NOS2 and MAFK affect treatment outcomes of tuberculosis patients. Further studies are needed to better understand the molecular mechanisms of ATDILI susceptibility via regulation of the expression of ATDILI-susceptibility genes and proteins.

14.
Ann Surg Oncol ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776702

RESUMO

PURPOSE: This study evaluated the additional value of lymph node ratio (LNR) when used in combination with the 8th American Joint Committee on Cancer (AJCC) staging system for gastric cancer (GC) to establish a new LNR-based AJCC (rAJCC) staging system. METHODS: We searched the Surveillance, Epidemiology, and End Results database to identify patients who had undergone surgery to resect nonmetastatic GC during the period from 2004 to 2013. Recursive partitioning analysis was used to identify the optimal cutoff points for LNR, and an LNR-based N classification system was designed accordingly. The two staging systems were compared in terms of discriminatory ability, as measured by the concordance index. The likelihood ratio Chi square test was used to assess prognostic homogeneity. RESULTS: A total of 13,027 patients were included in the final analysis. All of the included patients, who belonged to the 8th AJCC IIIA category, could be further classified into the rIIB, rIIIA, rIIIB, and rIIIC subgroups using the proposed rAJCC classification system. A difference in 5-year overall survival rate was found between patients classified as having rIIA disease and those classified as having rIIIC disease (66.7% vs. 5.1%). The rAJCC staging system was superior to the 8th AJCC staging system in terms of discriminatory capacity and prognostic homogeneity. CONCLUSIONS: A new rAJCC staging system is proposed, with prognostic superiority to the 8th AJCC staging system for patients with GC. The rAJCC staging system may serve as a useful tool in clinical practice.

16.
Biomed Res Int ; 2019: 3168541, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737659

RESUMO

Background: Uterine contraction (UC) is the tightening and shortening of the uterine muscles which can indicate the progress of pregnancy towards delivery. Electrohysterogram (EHG), which reflects uterine electrical activities, has recently been studied for UC monitoring. In this paper, we aimed to evaluate different EHG segments for recognizing UCs using the convolutional neural network (CNN). Materials and Methods: In the open-access Icelandic 16-electrode EHG database (122 recordings from 45 pregnant women), 7136 UC and 7136 non-UC EHG segments with the duration of 60 s were manually extracted from 107 recordings of 40 pregnant women to develop a CNN model. A fivefold cross-validation was applied to evaluate the CNN based on sensitivity (SE), specificity (SP), and accuracy (ACC). Then, 1056 UC and 1056 non-UC EHG segments were extracted from the other 15 recordings of 5 pregnant women. Furthermore, the developed CNN model was applied to identify UCs using different EHG segments with the durations of 10 s, 20 s, and 30 s. Results: The CNN achieved the average SE, SP, and ACC of 0.82, 0.93, and 0.88 for a 60 s EHG segment. The EHG segments of 10 s, 20 s, and 30 s around the TOCO peak achieved higher SE and ACC than the other segments with the same duration. The values of SE from 20 s EHG segments around the TOCO peak were higher than those from 10 s to 30 s EHG segments on the same side of the TOCO peak. Conclusion: The proposed method could be used to determine the efficient EHG segments for recognizing UC with the CNN.

17.
Fish Shellfish Immunol ; 94: 934-943, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31600596

RESUMO

Really Interesting New Gene (RING) finger proteins are highly conserved molecules that participate in a variety of biological processes such as regulation of development, apoptosis and antiviral immunity in vertebrates. However, the functions of RING finger proteins are still poorly understood in crustaceans. Previously, we found that the transcript of a homolog of RING finger protein 152 (CqRNF152-like) was up-regulated in a differentially expressed transcriptome library of the haematopietic tissue (Hpt) cells from red claw crayfish Cherax quadricarinatus upon white spot syndrome virus (WSSV) infection, which is one of the most devastating viral diseases for crustaceans like shrimp and crayfish. The full-length cDNA sequence of CqRNF152-like was then identified with 975 bp, including an ORF of 685 bp that encoded a 195 amino acids protein, a 5'- UTR of 180 bp, and a 3'-UTR with a poly (A) tail of 207 bp. The conserved domain prediction showed that CqRNF152-like contained a conserved RING-finger domain. Gene expression analysis showed that CqRNF152-like was distributed in all tissues examined and the transcript is significantly up-regulated after WSSV challenge both in vivo in Hpt tissue and in vitro in cultured Hpt cells. Furthermore, the transcripts of both an immediate early gene ie1 and a late envelope protein gene vp28 of WSSV were clearly increased in the Hpt tissues, hemocytes and cultured Hpt cells after gene silencing of CqRNF152-like, which were further proved to be significantly decreased after overloading of recombinant CqRNF152-like protein in Hpt cell cultures. Meanwhile, CqRNF152-like was found to bind with WSSV envelope protein VP28 by proteins pull-down assay. Similar to most of RNF proteins, CqRNF152-like protein sequence contained a conserved RING-finger domain and showed self-ubiquitination activity in a RING finger domain dependent manner. Taken together, CqRNF152-like is likely to function as an antiviral molecular against WSSV infection through interaction with the envelope protein VP28 in a crustacean C. quadricarinatus. This is the first report that a RING finger protein with directly antiviral functions via interaction with viral protein and self-ubiquitination activity in crustacean, which sheds new light on the molecular mechanism of WSSV infection and the control of white spot disease.


Assuntos
Astacoidea/genética , Astacoidea/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/imunologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Sequência de Bases , Perfilação da Expressão Gênica , Filogenia , Alinhamento de Sequência , Ubiquitina-Proteína Ligases/química
18.
Materials (Basel) ; 12(20)2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31635405

RESUMO

Conventional carburizing has disadvantages, such as high energy consumption, large deformation of parts, and an imperfect structure of the carburizing layer. Hence, a rare earth ion pre-implantation method was used to catalyze and strengthen the carburized layer of 20Cr2Ni4A alloy steel. In this study, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), optical microscopy (OM), scanning electron microscopy (SEM), energy dispersive microanalysis (EDS), transmission electron microscopy (TEM), and Rockwell/Vickers hardness testing were used to analyze the microstructure, phase composition, retained austenite content, hardness, carburized layer thickness, and carbon diffusion. The results showed that lanthanum and yttrium ions implanted into the 20Cr2Ni4A steel formed solid solutions of rare earth ions and a large number of dislocations, which improved the diffusion coefficient of carbon elements on the carburized surface and the uniformity of the carbon distribution. Simultaneously, rare earth ion implantation improved the structure and hardness of the vacuum carburized layer. Compared to the lanthanum ion implantation, yttrium ion implantation caused the structure of the carburized layer to be finer, and the carbon diffusion coefficient increased by 1.17 times; in addition, the surface hardness of the carburized layer was 61.8 HRC.

19.
Polymers (Basel) ; 11(9)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31540494

RESUMO

The respiration rate (RR) is a key vital sign that links to adverse clinical outcomes and has various important uses. However, RR signals have been neglected in many clinical practices for several reasons and it is still difficult to develop low-cost RR sensors for accurate, automated, and continuous measurement. This study aims to fabricate, develop and evaluate a novel stretchable and wearable RR sensor that is low-cost and easy to use. The sensor is fabricated using the soft lithography technique of polydimethylsiloxane substrates (PDMS) for the stretchable sensor body and inkjet printing technology for creating the conductive circuit by depositing the silver nanoparticles on top of the PDMS substrates. The inkjet-printed (IJP) PDMS-based sensor was developed to detect the inductance fluctuations caused by respiratory volumetric changes. The output signal was processed in a Wheatstone bridge circuit to derive the RR. Six different patterns for a IJP PDMS-based sensor were carefully designed and tested. Their sustainability (maximum strain during measurement) and durability (the ability to go bear axial cyclic strains) were investigated and compared on an automated mechanical stretcher. Their repeatability (output of the sensor in repeated tests under identical condition) and reproducibility (output of different sensors with the same design under identical condition) were investigated using a respiratory simulator. The selected optimal design pattern from the simulator evaluation was used in the fabrication of the IJP PDMS-based sensor where the accuracy was inspected by attaching it to 37 healthy human subjects (aged between 19 and 34 years, seven females) and compared with the reference values from e-Health nasal sensor. Only one design survived the inspection procedures where design #6 (array consists of two horseshoe lines) indicated the best sustainability and durability, and went through the repeatability and reproducibility tests. Based on the best pattern, the developed sensor accurately measured the simulated RR with an error rate of 0.46 ± 0.66 beats per minute (BPM, mean ± SD). On human subjects, the IJP PDMS-based sensor and the reference e-Health sensor showed the same RR value, without any observable differences. The performance of the sensor was accurate with no apparent error compared with the reference sensor. Considering its low cost, good mechanical property, simplicity, and accuracy, the IJP PDMS-based sensor is a promising technique for continuous and wearable RR monitoring, especially under low-resource conditions.

20.
Fish Shellfish Immunol ; 93: 580-588, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31398395

RESUMO

Enveloped virus usually utilizes the receptor-mediated multiple endocytic routes to enter permissive host cells for successful infection. Cellular receptors are cell surface molecules, either by helping viral attachment to cell surface followed by internalization or by triggering antiviral immunity, participate in the viral-host interaction. White spot syndrome virus (WSSV), the most lethally viral pathogen with envelope and double strand DNA genome in crustacean farming, including shrimp and crayfish, has been recently found to recruit various endocytic routes for cellular entry into host cells. Meanwhile, other than the typical pattern recognition receptors for recognition of WSSV, more and more putative cellular receptors have lately been characterized to facilitate or inhibit WSSV entry. In this review, recent findings on the endocytosis-dependent WSSV entry, viral entry mediated by putative cellular receptors, the molecular interplay between WSSV and cellular receptors, and the following anti-WSSV immunity are summarized and discussed, which may provide us a better understanding of the WSSV pathogenesis and further possible antiviral control of white spot disease in crustacean farming.


Assuntos
Crustáceos/genética , Crustáceos/imunologia , Imunidade Inata/genética , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/imunologia , Vírus da Síndrome da Mancha Branca 1/fisiologia , Animais , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Internalização do Vírus
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