Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23
Filtrar
1.
BMC Genomics ; 25(1): 188, 2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38368335

RESUMEN

BACKGROUND: Haemonchus contortus (H. contortus) is the most common parasitic nematode in ruminants and is prevalent worldwide. H. contortus resistance to albendazole (ABZ) hinders the efficacy of anthelmintic drugs, but little is known about the molecular mechanisms that regulate this of drug resistance. Recent research has demonstrated that long noncoding RNAs (lncRNAs) can exert significant influence as pivotal regulators of the emergence of drug resistance. RESULTS: In this study, transcriptome sequencing was conducted on both albendazole-sensitive (ABZ-sensitive) and albendazole-resistant (ABZ-resistant) H. contortus strains, with three biological replicates for each group. The analysis of lncRNA in the transcriptomic data revealed that there were 276 differentially expressed lncRNA (DElncRNA) between strains with ABZ-sensitive and ABZ-resistant according to the criteria of |log2Foldchange|≥ 1 and FDR < 0.05. Notably, MSTRG.12969.2 and MSTRG.9827.1 exhibited the most significant upregulation and downregulation, respectively, in the resistant strains. The potential roles of the DElncRNAs included catalytic activity, stimulus response, regulation of drug metabolism, and modulation of the immune response. Moreover, we investigated the interactions between DElncRNAs and other RNAs, specifically MSTRG.12741.1, MSTRG.11848.1, MSTRG.5895.1, and MSTRG.14070.1, involved in regulating drug stimulation through cis/trans/antisense/lncRNA‒miRNA-mRNA interaction networks. This regulation leads to a decrease (or increase) in the expression of relevant genes, consequently enhancing the resistance of H. contortus to albendazole. Furthermore, through comprehensive analysis of competitive endogenous RNAs (ceRNAs) involved in drug resistance-related pathways, such as the mTOR signalling pathway and ABC transporter signalling pathway, the relevance of the MSTRG.2499.1-novel-m0062-3p-HCON_00099610 interaction was identified to mainly involve the regulation of catalytic activity, metabolism, ubiquitination and transcriptional regulation of gene promoters. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) validation indicated that the transcription profiles of six DElncRNAs and six DEmRNAs were consistent with those obtained by RNA-seq. CONCLUSIONS: The results of the present study allowed us to better understand the changes in the lncRNA expression profile of ABZ-resistant H. contortus. In total, these results suggest that the lncRNAs MSTRG.963.1, MSTRG.12741.1, MSTRG.11848.1 and MSTRG.2499.1 play important roles in the development of ABZ resistance and can serve as promising biomarkers for further study.


Asunto(s)
Antihelmínticos , Haemonchus , ARN Largo no Codificante , Animales , Albendazol/farmacología , Albendazol/análisis , Albendazol/metabolismo , Haemonchus/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Transcriptoma , Antihelmínticos/farmacología , Antihelmínticos/metabolismo , Antihelmínticos/uso terapéutico
2.
Respir Res ; 25(1): 180, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664797

RESUMEN

BACKGROUND: Pulmonary ionocytes have been identified in the airway epithelium as a small population of ion transporting cells expressing high levels of CFTR (cystic fibrosis transmembrane conductance regulator), the gene mutated in cystic fibrosis. By providing an infinite source of airway epithelial cells (AECs), the use of human induced pluripotent stem cells (hiPSCs) could overcome some challenges of studying ionocytes. However, the production of AEC epithelia containing ionocytes from hiPSCs has proven difficult. Here, we present a platform to produce hiPSC-derived AECs (hiPSC-AECs) including ionocytes and investigate their role in the airway epithelium. METHODS: hiPSCs were differentiated into lung progenitors, which were expanded as 3D organoids and matured by air-liquid interface culture as polarised hiPSC-AEC epithelia. Using CRISPR/Cas9 technology, we generated a hiPSCs knockout (KO) for FOXI1, a transcription factor that is essential for ionocyte specification. Differences between FOXI1 KO hiPSC-AECs and their wild-type (WT) isogenic controls were investigated by assessing gene and protein expression, epithelial composition, cilia coverage and motility, pH and transepithelial barrier properties. RESULTS: Mature hiPSC-AEC epithelia contained basal cells, secretory cells, ciliated cells with motile cilia, pulmonary neuroendocrine cells (PNECs) and ionocytes. There was no difference between FOXI1 WT and KO hiPSCs in terms of their capacity to differentiate into airway progenitors. However, FOXI1 KO led to mature hiPSC-AEC epithelia without ionocytes with reduced capacity to produce ciliated cells. CONCLUSION: Our results suggest that ionocytes could have role beyond transepithelial ion transport by regulating epithelial properties and homeostasis in the airway epithelium.


Asunto(s)
Células Madre Pluripotentes Inducidas , Mucosa Respiratoria , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/citología , Diferenciación Celular/fisiología , Células Cultivadas , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Células Epiteliales/metabolismo , Organoides/metabolismo
3.
Parasitol Res ; 123(5): 226, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38814484

RESUMEN

In this study, 858 novel long non-coding RNAs (lncRNAs) were predicted as sensitive and resistant strains of Haemonchus contortus to ivermectin. These lncRNAs underwent bioinformatic analysis. In total, 205 lncRNAs significantly differed using log2 (difference multiplicity) > 1 or log2 (difference multiplicity) < - 1 and FDR < 0.05 as the threshold for significant difference analysis. We selected five lncRNAs based on significant differences in expression, cis-regulation, and their association with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. These expressions of lncRNAs, namely MSTRG.12610.1, MSTRG.8169.1, MSTRG.6355.1, MSTRG.980.1, and MSTRG.9045.1, were significantly downregulated. These findings were consistent with the results of transcriptomic sequencing. We further investigated the relative expression of target gene mRNAs and the regulation of mRNA and miRNA, starting with lncRNA cis-regulation of mRNA, and constructed a lncRNA-mRNA-miRNA network regulation. After a series of statistical analyses, we finally screened out UGT8, Unc-116, Fer-related kinase-1, GGPP synthase 1, and sart3, which may be involved in developing drug resistance under the regulation of their corresponding lncRNAs. The findings of this study provide a novel direction for future studies on drug resistance targets.


Asunto(s)
Resistencia a Medicamentos , Haemonchus , Ivermectina , ARN Largo no Codificante , Animales , Haemonchus/genética , Haemonchus/efectos de los fármacos , ARN Largo no Codificante/genética , Ivermectina/farmacología , Resistencia a Medicamentos/genética , Hemoncosis/parasitología , Hemoncosis/veterinaria , Antihelmínticos/farmacología , MicroARNs/genética , Biología Computacional , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos
4.
Environ Sci Technol ; 54(9): 5498-5508, 2020 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-32275414

RESUMEN

The sulfur cycle is an important part of constructed wetland biogeochemistry because it is intimately intertwined with the carbon, nitrogen, and iron cycles. However, to date, no quantitative investigation has been conducted on the sulfur cycle in constructed wetlands because of the complexity of wetland systems and the deficiencies in experimental methodology. In this study, 34S-stable isotope analysis was extended in terms of the calculation for the enrichment factor and the kinetic analysis for bacterial sulfate reduction. With this extended method, we attempted for the first time to assess the true rate of bacterial sulfate reduction when sulfide oxidation co-occurs. The joint application of the extended 34S-stable isotope and mass balance analyses made it possible to quantitatively investigate the primary sulfur transformation in a wetland microcosm. Accordingly, a sulfur cycle model for constructed wetlands was quantified and validated. Approximately 75% of the input sulfur was discharged. The remainder was mainly removed through deposition as acid volatile sulfide, pyrite, and elemental sulfur. Plant uptake was negligible. These findings improve our understanding of the physical, chemical, and biological transformations of sulfur among plants, sediments, and microorganisms, and their interactions with carbon, nitrogen, and iron cycles, in constructed wetlands and similar systems.


Asunto(s)
Azufre , Humedales , Isótopos , Cinética , Nitrógeno
5.
J Food Sci ; 89(6): 3183-3193, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38767932

RESUMEN

The stems of Cynomorium songaricum are used in traditional Chinese medicine as a tonic and also used locally as a food material and livestock feed. It is known that some of the falvan-3-ol monomers and dimers that entered the milk of dairy sheep fed with C. songaricum stems are biotransformation products of the original flavan-3-ol polymers in C. songaricum stems. This study was performed to investigate the biotransformation process of the flavan-3-ols in dairy sheep and to evaluate the bioactivities. The results showed that procyanidin A2 and epicatechin could be released from the polymeric flavan-3-ols of C. songaricum through rumen microbial metabolism. On traumatic and lipopolysaccharide (LPS)-induced inflammation models of Tg (mpx: EGFP) zebrafish larvae and LPS-induced liver injury models of Tg (fabp10a: DsRed) zebrafish larvae, the milk from sheep fed with C. songaricum stems showed stronger anti-inflammatory and hepatoprotective activities compared to blank milk. The absorbed chemical constituents of C. songaricum stems and the metabolites also exhibited anti-inflammatory and hepatoprotective activities, with the dimeric flavan-3-ols being more effective than the monomers. The milk, the absorbed chemical constituents of C. songaricum stems, and the metabolites alleviated the increased level of reactive oxygen species induced by LPS in zebrafish larvae. PRACTICAL APPLICATION: This study found that C. songaricum stems as livestock feed could produce milk that has a beneficial impact on consumer and livestock health in terms of anti-inflammation and hepatoprotection.


Asunto(s)
Alimentación Animal , Biotransformación , Flavonoides , Hígado , Pez Cebra , Animales , Flavonoides/farmacología , Flavonoides/metabolismo , Ovinos , Hígado/metabolismo , Hígado/efectos de los fármacos , Alimentación Animal/análisis , Inflamación/metabolismo , Leche/química , Proantocianidinas/farmacología , Antiinflamatorios/farmacología , Extractos Vegetales/farmacología , Femenino , Rumen/metabolismo , Tallos de la Planta/química
6.
Adv Mater ; 36(8): e2306679, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38061027

RESUMEN

Air liquid interfaced (ALI) epithelial barriers are essential for homeostatic functions such as nutrient transport and immunological protection. Dysfunction of such barriers are implicated in a variety of autoimmune and inflammatory disorders and, as such, sensors capable of monitoring barrier health are integral for disease modelling, diagnostics and drug screening applications. To date, gold-standard electrical methods for detecting barrier resistance require rigid electrodes bathed in an electrolyte, which limits compatibility with biological architectures and is non-physiological for ALI. This work presents a flexible all-planar electronic device capable of monitoring barrier formation and perturbations in human respiratory and intestinal cells at ALI. By interrogating patient samples with electrochemical impedance spectroscopy and simple equivalent circuit models, disease-specific and patient-specific signatures are uncovered. Device readouts are validated against commercially available chopstick electrodes and show greater conformability, sensitivity and biocompatibility. The effect of electrode size on sensing efficiency is investigated and a cut-off sensing area is established, which is one order of magnitude smaller than previously reported. This work provides the first steps in creating a physiologically relevant sensor capable of mapping local and real-time changes of epithelial barrier function at ALI, which will have broad applications in toxicology and drug screening applications.


Asunto(s)
Electrónica , Humanos , Electrodos
7.
Opt Express ; 21(9): 11349-55, 2013 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-23669991

RESUMEN

A sensitive surface enhanced Raman scattering (SERS) substrate with metallic nanogap array (MNGA) is fabricated by etching of an assembled polystyrene (PS) spheres array, followed by the coating of a metal film. The substrate is reproducible in fabrication and sensitive due to the nanogap coupling resonance (NGCR) enhancement. The NGCR is analyzed with the finite difference time domain (FDTD) method, and the relationship between the gap parameter and the field enhancement is obtained. Experimental measurements of R6G on demonstrate that the enhancement factor (EF) of the MNGA SERS substrate is increased by more than two fold compared with the control sample.


Asunto(s)
Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Poliestirenos/química , Espectrometría Raman/métodos , Luz , Ensayo de Materiales , Nanopartículas del Metal/efectos de la radiación , Microesferas , Poliestirenos/efectos de la radiación , Dispersión de Radiación , Propiedades de Superficie
8.
Braz J Microbiol ; 54(2): 975-981, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36964325

RESUMEN

Coastal wetlands are subjected to increasing tetrabromobisphenol A (TBBPA) pollution, whereas knowledge of TBBPA degradation in marine environments is lacking. The changes of bacterial communities in TBBPA-polluted soil covered with halophytes were investigated. TBBPA could be degraded in the halophyte-covered saline-alkali soil in a microcosm experiment. Higher TBBPA removal occurred in the soil of Kandelia obovata compared with soils covered with Suaeda australis and Phragmites australis within 56 days of cultivation. The rhizosphere soils of S. australis, P. australis, and K. obovata mainly involved the classes of Bacteroidia, Gammaproteobacteria, Alphaproteobacteria, and Anaerolineae. Additionally, manganese oxidation, aerobic anoxygenic phototrophy, and fermentation functions were higher in the rhizosphere soil of K. obovata after TBBPA addition. This study supports that using suitable local halophytic plants is a promising approach for degrading TBBPA-contaminated coastal soil.


Asunto(s)
Microbiota , Suelo , Plantas Tolerantes a la Sal , Humedales
9.
Genes (Basel) ; 14(10)2023 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-37895211

RESUMEN

Dkks have inhibitory effects on the Wnt signaling pathway, which is involved in the development of skin and its appendages and the regulation of hair growth. The nucleotide sequences were compared and analyzed to further investigate the relationship between the structure and function of the Dkk gene family and vertebrate epidermal hair. The analysis of the molecular evolution of the Dkk family revealed that the evolution rate of the genes changed significantly after speciation, with the Aves and Reptilia branches showing accelerated evolution. Additionally, positive selection was observed at specific sites. The tertiary structure of the protein was also predicted. The analysis of the functional divergence of the Dkk family revealed that the functional divergence coefficient of each gene was greater than 0, with most of the functional divergence sites were located in the Cys-2 domain and a few in the Cys-1 domain. This suggests that the amino acid and functional divergence sites may play a role in regulating the binding of the Dkk family to LRP5/6, and thus affect the inhibition of Wnt signaling, leading to different functions of Dkk1, Dkk2, and Dkk4 in the development of skin hair follicles. In addition, the Dkk families of Aves and Reptilia may have undergone adaptive evolution and functional divergence.


Asunto(s)
Péptidos y Proteínas de Señalización Intercelular , Vía de Señalización Wnt , Péptidos y Proteínas de Señalización Intercelular/genética , Vía de Señalización Wnt/genética , Secuencia de Bases , Evolución Molecular
10.
Heliyon ; 9(3): e14383, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36938474

RESUMEN

Cigarette smoking has many serious negative health consequences. The relationship between smoking and SARS-CoV-2 infection is controversial, specifically whether smokers are at increased risk of infection. We investigated the impact of cigarette smoke on ACE2 isoform expression and SARS-CoV-2 infection in differentiated primary human bronchial epithelial cells at the air-liquid-interface (ALI). We assessed the expression of ACE2 in response to CSE and therapeutics reported to modulate ACE2. We exposed ALI cultures to cigarette smoke extract (CSE) and then infected them with SARS-CoV-2. We measured cellular infection using flow cytometry and whole-transwell immunofluorescence. We found that CSE increased expression of full-length ACE2 (flACE2) but did not alter the expression of a Type I-interferon sensitive truncated isoform (dACE2) that lacks the capacity to bind SARS-CoV-2. CSE did not have a significant impact on key mediators of the innate immune response. Importantly, we show that, despite the increase in flACE2, CSE did not alter airway cell infection after CSE exposure. We found that nicotine does not significantly alter flACE2 expression but that NRF2 agonists do lead to an increase in flACE2 expression. This increase was not associated with an increase in SARS-CoV-2 infection. Our results are consistent with the epidemiological data suggesting that current smokers do not have an excess of SARS-CoV-2 infection. but that those with chronic respiratory or cardiovascular disease are more vulnerable to severe COVID-19. They suggest that, in differentiated conducting airway cells, flACE2 expression levels may not limit airway SARS-CoV-2 infection.

11.
Vet Sci ; 10(9)2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37756065

RESUMEN

Cell types have been established during organogenesis based on early mouse embryos. However, our understanding of cell types and molecular mechanisms in the early embryo development of Mongolian sheep has been hampered. This study presents the first comprehensive single-cell transcriptomic characterization at E16 in Ujumqin sheep and Hulunbuir short-tailed sheep. Thirteen major cell types were identified at E16 in Ujumqin sheep, and eight major cell types were identified at E16 in Hulunbuir short-tailed sheep. Function enrichment analysis showed that several pathways were significantly enriched in the TGF-beta signaling pathway, the Hippo signaling pathway, the platelet activation pathway, the riboflavin metabolism pathway, the Wnt signaling pathway, regulation of the actin cytoskeleton, and the insulin signaling pathway in the notochord cluster. Glutathione metabolism, glyoxylate, and dicarboxylate metabolism, the citrate cycle, thyroid hormone synthesis, pyruvate metabolism, cysteine and methionine metabolism, thermogenesis, and the VEGF signaling pathway were significantly enriched in the spinal cord cluster. Steroid biosynthesis, riboflavin metabolism, the cell cycle, the Hippo signaling pathway, the Hedgehog signaling pathway, the FoxO signaling pathway, the JAK-STAT signaling pathway, and the Wnt signaling pathway were significantly enriched in the paraxial mesoderm cluster. The notochord cluster, spinal cord cluster, and paraxial mesoderm cluster were found to be highly associated with tail development. Pseudo-time analysis demonstrated that the mesenchyme can translate to the notochord in Ujumqin sheep. Molecular assays revealed that the Hippo signaling pathway was enriched in Ujumqin sheep. This comprehensive single-cell map revealed previously unrecognized signaling pathways that will further our understanding of the mechanism of short-tailed sheep formation.

12.
Anim Biosci ; 35(4): 614-623, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34991228

RESUMEN

OBJECTIVE: The objective of this study was to investigate the effects of sheep slaughter age on myogenic characteristics in skeletal muscle satellite cells (SMSCs). METHODS: Primary SMSCs were isolated from hind leg biceps femoris muscles of Wurank lambs (slaughtered at three months, Mth-3) and adults (slaughtered at fifteen months, Mth-15). SMSCs were selected by morphological observation and fluorescence staining. Myogenic regulatory factors (MRF) and myosin heavy chain (MyHC) expressions of SMSCs were analyzed on days 1, 3, 4, and 5. RESULTS: The expressions of myogenic factor 5 (Myf5), myogenic differentiation (MyoD), Myf6, and myogenin (MyoG) in Mth-15 were significantly higher in Mth-15 than in Mth-3 on days 1, 3, and 4 (p<0.05). However, MyoG expression in Mth-15 was significantly lower than in Mth-3 on day 5 (p<0.05). The expressions of MyHC I, MyHC IIa, and MyHC IIx in Mth-15 were significantly higher than in Mth-3 on days 1 and 3 (p<0.05), and MyHC IIb were significantly lower than in Mth-3 on days 3 and 4 (p<0.05). In contrast, the expression of MyHC IIx in Mth-15 was significantly lower and MyHC IIb was significantly higher than in Mth-3 on days 5 (p<0.05). CONCLUSION: The slaughter age altered the expression of MRFs and MyHCs in SMSCs while differentiation, which caused the variation of myogenic characteristics, and thus may affect the meat quality of Wurank sheep.

13.
Foods ; 11(10)2022 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-35627044

RESUMEN

Anthocyanins have great health benefits, especially malvidin. Vitis amurensis Rupr are rich in malvidin, and malvidin-3-O-glucoside (Mv3G) monomer is the most abundant. However, natural anthocyanins are unstable, which limits their wide application in the food field. Soybean insoluble dietary fiber (SIDF) has high stability, and it can be used as an inert substrate to construct a stable system, which may improve the stability of anthocyanins. The optimal condition to construct a stable system of SIDF and Mv3G at pH 3.0 was determined by an orthogonal experiment. The results indicated that SIDF effectively improved the stability of Mv3G under different pH values (1.0~7.0), high temperature (100 °C for 100 min), and sunlight (20 ± 2 °C for 30 d) conditions. The absorption peak intensity of the UV-VIS spectrum of SIDF-Mv3G was enhanced, which indicated that there was interaction between SIDF and Mv3G. Fourier transform infrared spectroscopy analyses revealed that the -OH stretching vibration peak of SIDF-Mv3G was changed, which indicated that the interaction between SIDF and Mv3G was due to hydrogen bonding. X-ray diffraction analysis showed that the crystalline morphology of SIDF was opened, which was combined with Mv3G, and SIDF made Mv3G change to a more stable state. Scanning electron microscope analysis showed that SIDF and Mv3G were closely combined to form an inclusion complex. Overall, this study provides valuable information for enhancing the color stability of anthocyanins, which will further expand the application of anthocyanins in the food field.

14.
Life Sci Alliance ; 5(4)2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35110354

RESUMEN

BACKGROUND: There are limited effective prophylactic/early treatments for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Viral entry requires spike protein binding to the angiotensin-converting enzyme-2 receptor and cleavage by transmembrane serine protease 2 (TMPRSS2), a cell surface serine protease. Targeting of TMPRSS2 by either androgen blockade or direct inhibition is in clinical trials in early SARS-CoV-2 infection. METHODS: We used differentiated primary human airway epithelial cells at the air-liquid interface to test the impact of targeting TMPRSS2 on the prevention of SARS-CoV-2 infection. RESULTS: We first modelled the systemic delivery of compounds. Enzalutamide, an oral androgen receptor antagonist, had no impact on SARS-CoV-2 infection. By contrast, camostat mesylate, an orally available serine protease inhibitor, blocked SARS-CoV-2 entry. However, oral camostat is rapidly metabolised in the circulation, with poor airway bioavailability. We therefore modelled local airway administration by applying camostat to the apical surface of differentiated airway cultures. We demonstrated that a brief exposure to topical camostat effectively restricts SARS-CoV-2 infection. CONCLUSION: These experiments demonstrate a potential therapeutic role for topical camostat for pre- or post-exposure prophylaxis of SARS-CoV-2, which can now be evaluated in a clinical trial.


Asunto(s)
Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/virología , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/fisiología , Serina Endopeptidasas/metabolismo , Inhibidores de Serina Proteinasa/administración & dosificación , Administración Tópica , Andrógenos/metabolismo , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , Antivirales/farmacología , COVID-19/prevención & control , COVID-19/virología , Células Cultivadas , Células Epiteliales , Ésteres/farmacología , Expresión Génica , Células Caliciformes/inmunología , Células Caliciformes/metabolismo , Guanidinas/farmacología , Interacciones Huésped-Patógeno/efectos de los fármacos , Humanos , Serina Endopeptidasas/genética , Transducción de Señal , Internalización del Virus/efectos de los fármacos , Replicación Viral/efectos de los fármacos
15.
Wellcome Open Res ; 7: 224, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36483314

RESUMEN

Background: Quantitative proteomics is able to provide a comprehensive, unbiased description of changes to cells caused by viral infection, but interpretation may be complicated by differential changes in infected and uninfected 'bystander' cells, or the use of non-physiological cellular models. Methods: In this paper, we use fluorescence-activated cell sorting (FACS) and quantitative proteomics to analyse cell-autonomous changes caused by authentic SARS-CoV-2 infection of respiratory epithelial cells, the main target of viral infection in vivo. First, we determine the relative abundance of proteins in primary human airway epithelial cells differentiated at the air-liquid interface (basal, secretory and ciliated cells). Next, we specifically characterise changes caused by SARS-CoV-2 infection of ciliated cells. Finally, we compare temporal proteomic changes in infected and uninfected 'bystander' Calu-3 lung epithelial cells and compare infection with B.29 and B.1.1.7 (Alpha) variants. Results: Amongst 5,709 quantified proteins in primary human airway ciliated cells, the abundance of 226 changed significantly in the presence of SARS-CoV-2 infection (q <0.05 and >1.5-fold). Notably, viral replication proceeded without inducing a type-I interferon response. Amongst 6,996 quantified proteins in Calu-3 cells, the abundance of 645 proteins changed significantly in the presence of SARS-CoV-2 infection (q < 0.05 and > 1.5-fold). In contrast to the primary cell model, a clear type I interferon (IFN) response was observed. Nonetheless, induction of IFN-inducible proteins was markedly attenuated in infected cells, compared with uninfected 'bystander' cells. Infection with B.29 and B.1.1.7 (Alpha) variants gave similar results. Conclusions: Taken together, our data provide a detailed proteomic map of changes in SARS-CoV-2-infected respiratory epithelial cells in two widely used, physiologically relevant models of infection. As well as identifying dysregulated cellular proteins and processes, the effectiveness of strategies employed by SARS-CoV-2 to avoid the type I IFN response is illustrated in both models.

16.
Sci Adv ; 6(39)2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32967829

RESUMEN

As a superior self-protection strategy, invisibility has been a topic of long-standing interest in both academia and industry, because of its potential for intriguing applications that have only appeared thus far in science fiction. However, due to the strong dispersion of passive materials, achieving cross-wavelength invisibility remains an open challenge. Inspired by the natural ecological relationship between transparent midwater oceanic animals and the cross-wavelength detection strategy of their predators, we propose a cross-wavelength invisibility concept that integrates various invisibility tactics, where a Boolean metamaterial design procedure is presented to balance divergent material requirements over cross-scale wavelengths. As proof of concept, we experimentally demonstrate longwave cloaking and shortwave transparency simultaneously through a nanoimprinting technique. Our work extends the concept of stealth techniques from individual invisibility tactics targeting a single-wavelength spectrum to an integrated invisibility tactic targeting a cross-wavelength applications and may pave the way for development of cross-wavelength integrated metadevices.

17.
Nanoscale ; 10(2): 614-622, 2018 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-29235605

RESUMEN

Fabrication and application of hybrid functional circuits have become a hot research topic in the field of printed electronics. In this study, a novel flexible diode-transistor logic (DTL) driving circuit is proposed, which was fabricated based on a light emitting diode (LED) integrated with printed high-performance single-walled carbon nanotube (SWCNT) thin-film transistors (TFTs). The LED, which is made of AlGaInP on GaAs, is commercial off-the-shelf, which could generate free electrical charges upon white light illumination. Printed top-gate TFTs were made on a PET substrate by inkjet printing high purity semiconducting SWCNTs (sc-SWCNTs) ink as the semiconductor channel materials, together with printed silver ink as the top-gate electrode and printed poly(pyromellitic dianhydride-co-4,4'-oxydianiline) (PMDA/ODA) as gate dielectric layer. The LED, which is connected to the gate electrode of the TFT, generated electrical charge when illuminated, resulting in biased gate voltage to control the TFT from "ON" status to "OFF" status. The TFTs with a PMDA/ODA gate dielectric exhibited low operating voltages of ±1 V, a small subthreshold swing of 62-105 mV dec-1 and ON/OFF ratio of 106, which enabled DTL driving circuits to have high ON currents, high dark-to-bright current ratios (up to 105) and good stability under repeated white light illumination. As an application, the flexible DTL driving circuit was connected to external quantum dot LEDs (QLEDs), demonstrating its ability to drive and to control the QLED.

18.
ACS Appl Mater Interfaces ; 9(42): 37048-37054, 2017 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-28967742

RESUMEN

Metal-mesh is one of the contenders to replace indium tin oxide (ITO) as transparent conductive electrodes (TCEs) for optoelectronic applications. However, considerable surface roughness accompanying metal-mesh type of transparent electrodes has been the root cause of electrical short-circuiting for optoelectronic devices, such as organic light-emitting diode (OLED) and organic photovoltaic (OPV). In this work, a novel approach to making metal-mesh TCE has been proposed that is based on hybrid printing of silver (Ag) nanoparticle ink and electroplating of nickel (Ni). By polishing back the electroplated Ni, an extremely smooth surface was achieved. The fabricated Ag/Ni metal-mesh TCE has a surface roughness of 0.17 nm, a low sheet resistance of 2.1 Ω/□, and a high transmittance of 88.6%. The figure of merit is 1450, which is 30 times better than ITO. In addition, the Ag/Ni metal-mesh TCE shows outstanding mechanical flexibility and environmental stability at high temperature and humidity. Using the polished Ag/Ni metal-mesh TCE, a flexible quantum dot light-emitting diode (QLED) was fabricated with an efficiency of 10.4 cd/A and 3.2 lm/W at 1000 cd/m2.

19.
ACS Appl Mater Interfaces ; 9(44): 38716-38727, 2017 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-28994279

RESUMEN

Film morphology has predominant influence on the performance of multilayered organic light-emitting diodes (OLEDs), whereas there is little reported literature from the angle of the molecular level to investigate the impact on film-forming ability and device performance. In this work, four isomeric cross-linkable electron-transport materials constructed with pyridine, 1,2,4-triazole, and vinylbenzyl ether groups were developed for inkjet-printed OLEDs. Their lowest unoccupied molecular orbital (∼3.20 eV) and highest occupied molecular orbital (∼6.50 eV) levels are similar, which are mainly determined by the 1,2,4-triazole groups. The triplet energies of these compounds can be tuned from 2.51 to 2.82 eV by different coupling modes with the core of pyridine, where the 2,6-pyridine-based compound has the highest value of 2.82 eV. Film formation and solubility of the compounds were investigated. It was found that the 2,6-pyridine-based compound outperformed the 2,4-pyridine, 2,5-pyridine, and 3,5-pyridine-based compounds. The spin-coated blue OLEDs based on the four compounds have achieved over 14.0% external quantum efficiencies (EQEs) at the luminance of 100 cd m-2, and a maximum EQE of 12.1% was obtained for the inkjet-printed device with 2,6-pyridine-based compound.

20.
Artículo en Zh | MEDLINE | ID: mdl-16600091

RESUMEN

OBJECTIVE: To investigate the systemic changes of iron metabolism following manganese exposure. METHODS: Ninety-seven welders and 91 workers with no history of exposure to manganese were recruited from the same factory in Beijing serving as the exposure group and the control group respectively. The welding rods used were type J422. The concentration of the manganese in the air of the work place was determined respectively with the national standard method. The serum iron and manganese, ferritin, transferrin and transferrin receptors were measured with the graphite furnace atomic absorption spectrophotometry and ELISA in both groups. RESULTS: The permissible concentration-STEL of ambient Mn in welders' breathing zone ranged from 0.53 mg/m(3) to 2.19 mg/m(3), while the permissible concentration-TWA of ambient Mn was between 0.29 mg/m(3) and 0.92 mg/m(3) in the breathing zone of the workplace. Serum Mn and Fe concentrations in welders were about 1.40 times (P < 0.0l) and 1.2 times (P < 0.01), respectively, higher than those of control subjects. At the same time, the transferrin concentrations in serum were significantly higher (about 1.2 times, P < 0.05) in welders than in controls. In contrast, transferrin receptors were significantly lower (about 1.2 times) in exposed subjects than controls (P = 0.001). There was no difference in serum ferritin between the two groups (P = 0.112). Although there was no significant trend, the serum ferritin level was increased by 18% in comparison with that of the control. The abnormal percentage of serum Fe and Serum Mn in welders were 55.67% and 67.01% respectively, higher than those of control subjects. In addition, the correlations between all indicators and the duration of employment were not observed. CONCLUSION: The long term exposure to the manganese can induce the disorder of the iron metabolism, which is found in the expression of increase of the serum iron and transferrin as well as the decrease of transferrin receptors.


Asunto(s)
Hierro/metabolismo , Manganeso/efectos adversos , Exposición Profesional/efectos adversos , Femenino , Ferritinas/sangre , Humanos , Trastornos del Metabolismo del Hierro/inducido químicamente , Masculino , Receptores de Transferrina/sangre , Transferrina/análisis , Soldadura
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA