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1.
Cell Rep Med ; 5(5): 101573, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38776874

RESUMEN

Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1. These antibodies effectively neutralize EBV infection in vitro and in vivo while preserving gp42's interaction with the human leukocyte antigen class II (HLA-II) receptor. Structural analysis unveils their distinct binding epitopes on gp42, different from the HLA-II binding site. Furthermore, both 2B7 and 2C1 demonstrate potent neutralization of EBV infection in HLA-II-positive epithelial cells, expanding our understanding of gp42's role. Overall, this study introduces two human anti-gp42 antibodies with potential implications for developing EBV vaccines targeting gp42 epitopes, addressing a critical gap in EBV research.


Asunto(s)
Anticuerpos Monoclonales , Epítopos , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Humanos , Herpesvirus Humano 4/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Anticuerpos Monoclonales/inmunología , Epítopos/inmunología , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Ratones , Antígenos de Histocompatibilidad Clase II/inmunología , Antígenos de Histocompatibilidad Clase II/metabolismo , Proteínas Virales/inmunología , Linfocitos B/inmunología
2.
Magn Reson Imaging ; 111: 21-27, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38582100

RESUMEN

Muscle hyperemia in exercise is usually the combined result of increased cardiac output and local muscle vasodilation, with the latter reflecting muscle's capacity for increased blood perfusion to support exercise. In this study, we aim to quantify muscle's vasodilation capability with dynamic BOLD imaging. A deoxyhemoglobin-kinetics model is proposed to analyze dynamic BOLD signals acquired during exercise recovery, deriving a hyperemia index (HI) for a muscle group of interest. We demonstrated the method's validity with calf muscles of healthy subjects who performed plantar flexion for muscle stimulation. In a test with exercise load incrementally increasing from 0 to 16 lbs., gastrocnemius HI showed considerable variance among the 4 subjects, but with a consistent trend, i.e. low at light load (e.g. 0-6 lbs) and linearly increasing at heavy load. The high variability among different subjects was confirmed with the other 10 subjects who exercised with a same moderate load of 8 lbs., with coefficient of variance among subjects' medial gastrocnemius 87.8%, lateral gastrocnemius 111.8% and soleus 132.3%. These findings align with the fact that intensive exercise induces high muscle hyperemia, but a comparison among different subjects is hard to make, presumably due to the subjects' different rate of oxygen utilization. For the same 10 subjects who exercised with load of 8 lbs., we also performed dynamic contrast enhanced (DCE) MRI to measure muscle perfusion (F). With a moderate correlation of 0.654, HI and F displayed three distinctive responses of calf muscles: soleus of all the subjects were in the cluster of low F and low HI, and gastrocnemius of most subjects had high F and either low or high HI. This finding suggests that parameter F encapsulates blood flow through vessels of all sizes, but BOLD-derived HI focuses on capillary flow and therefore is a more specific indicator of muscle vasodilation. In conclusion, the proposed hyperemia index has the potential of quantitatively assessing muscle vasodilation induced with exercise.

3.
Sensors (Basel) ; 24(4)2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38400448

RESUMEN

Accurate fault diagnosis is essential for the safe operation of rotating machinery. Recently, traditional deep learning-based fault diagnosis have achieved promising results. However, most of these methods focus only on supervised learning and tend to use small convolution kernels non-effectively to extract features that are not controllable and have poor interpretability. To this end, this study proposes an innovative semi-supervised learning method for bearing fault diagnosis. Firstly, multi-scale dilated convolution squeeze-and-excitation residual blocks are designed to exact local and global features. Secondly, a classifier generative adversarial network is employed to achieve multi-task learning. Both unsupervised and supervised learning are performed simultaneously to improve the generalization ability. Finally, supervised learning is applied to fine-tune the final model, which can extract multi-scale features and be further improved by implicit data augmentation. Experiments on two datasets were carried out, and the results verified the superiority of the proposed method.

4.
Spectrochim Acta A Mol Biomol Spectrosc ; 312: 124054, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38382221

RESUMEN

Breast cancer is a significant cause of death among women worldwide. It is crucial to quickly and accurately diagnose breast cancer in order to reduce mortality rates. While traditional diagnostic techniques for medical imaging and pathology samples have been commonly used in breast cancer screening, they still have certain limitations. Surface-enhanced Raman spectroscopy (SERS) is a fast, highly sensitive and user-friendly method that is often combined with deep learning techniques like convolutional neural networks. This combination helps identify unique molecular spectral features, also known as "fingerprint", in biological samples such as serum. Ultimately, this approach is able to accurately screen for cancer. The Gramian angular field (GAF) algorithm can convert one-dimensional (1D) time series into two-dimensional (2D) images. These images can be used for data visualization, pattern recognition and machine learning tasks. In this study, 640 serum SERS from breast cancer patients and healthy volunteers were converted into 2D spectral images by Gramian angular field (GAF) technique. These images were then used to train and test a two-dimensional convolutional neural network-GAF (2D-CNN-GAF) model for breast cancer classification. We compared the performance of the 2D-CNN-GAF model with other methods, including one-dimensional convolutional neural network (1D-CNN), support vector machine (SVM), K-nearest neighbor (KNN) and principal component analysis-linear discriminant analysis (PCA-LDA), using various evaluation metrics such as accuracy, precision, sensitivity, F1-score, receiver operating characteristic (ROC) curve and area under curve (AUC) value. The results showed that the 2D-CNN model outperformed the traditional models, achieving an AUC value of 0.9884, an accuracy of 98.13%, sensitivity of 98.65% and specificity of 97.67% for breast cancer classification. In this study, we used conventional nano-silver sol as the SERS-enhanced substrate and a portable laser Raman spectrometer to obtain the serum SERS data. The 2D-CNN-GAF model demonstrated accurate and automatic classification of breast cancer patients and healthy volunteers. The method does not require augmentation and preprocessing of spectral data, simplifying the processing steps of spectral data. This method has great potential for accurate breast cancer screening and also provides a useful reference in more types of cancer classification and automatic screening.


Asunto(s)
Neoplasias de la Mama , Detección Precoz del Cáncer , Humanos , Femenino , Neoplasias de la Mama/diagnóstico , Espectrometría Raman , Redes Neurales de la Computación , Mama
5.
Materials (Basel) ; 17(2)2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38255567

RESUMEN

The preheating of the substrate in laser additive superalloys can reduce residual stress and minimize cracking. However, this preheating process can lead to changes in the heat transfer conditions, ultimately affecting the resulting microstructure and mechanical properties. In order to explore the influence of substrate preheating on the formation of laser cladding, this research focuses on investigating the characteristics of Inconel 718, a nickel-based superalloy, as the subject of study. To simulate the temperature and flow field of laser cladding, a 3D computational fluid dynamics (CFD) model is employed. By varying the initial preheating conditions, an investigation is conducted into the distribution of the temperature field under different parameters. This leads to the acquisition of varying temperature gradients, G, and solidification speeds, R. Subsequently, an analysis is carried out on both the flow field and solidification microstructure in the melt pool. The results demonstrate that the preheating of the substrate results in a slower cooling rate, ultimately leading to the formation of a coarser microstructure.

6.
Adv Sci (Weinh) ; 10(35): e2302116, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37890462

RESUMEN

Epstein-Barr virus (EBV) is associated with various malignancies and infects >90% of the global population. EBV latent proteins are expressed in numerous EBV-associated cancers and contribute to carcinogenesis, making them critical therapeutic targets for these cancers. Thus, this study aims to develop mRNA-based therapeutic vaccines that express the T-cell-epitope-rich domain of truncated latent proteins of EBV, including truncatedlatent membrane protein 2A (Trunc-LMP2A), truncated EBV nuclear antigen 1 (Trunc-EBNA1), and Trunc-EBNA3A. The vaccines effectively activate both cellular and humoral immunity in mice and show promising results in suppressing tumor progression and improving survival time in tumor-bearing mice. Furthermore, it is observed that the truncated forms of the antigens, Trunc-LMP2A, Trunc-EBNA1, and Trunc-EBNA3A, are more effective than full-length antigens in activating antigen-specific immune responses. In summary, the findings demonstrate the effectiveness of mRNA-based therapeutic vaccines targeting the T-cell-epitope-rich domain of EBV latent proteins and providing new treatment options for EBV-associated cancers.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Neoplasias , Ratones , Animales , Herpesvirus Humano 4/genética , Infecciones por Virus de Epstein-Barr/terapia , Epítopos de Linfocito T , Vacunas de ARNm , Proteínas de la Membrana , ARN Mensajero/genética
7.
Cell Host Microbe ; 31(11): 1882-1897.e10, 2023 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-37848029

RESUMEN

Epstein-Barr virus (EBV) is a global public health concern, as it is known to cause multiple diseases while also being etiologically associated with a wide range of epithelial and lymphoid malignancies. Currently, there is no available prophylactic vaccine against EBV. gB is the EBV fusion protein that mediates viral membrane fusion and participates in host recognition, making it critical for EBV infection in both B cells and epithelial cells. Here, we present a gB nanoparticle, gB-I53-50 NP, that displays multiple copies of gB. Compared with the gB trimer, gB-I53-50 NP shows improved structural integrity and stability, as well as enhanced immunogenicity in mice and non-human primate (NHP) preclinical models. Immunization and passive transfer demonstrate a robust and durable protective antibody response that protects humanized mice against lethal EBV challenge. This vaccine candidate demonstrates significant potential in preventing EBV infection, providing a possible platform for developing prophylactic vaccines for EBV.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Vacunas , Cricetinae , Animales , Ratones , Herpesvirus Humano 4 , Infecciones por Virus de Epstein-Barr/prevención & control , Formación de Anticuerpos , Células CHO , Anticuerpos Neutralizantes , Anticuerpos Antivirales
8.
In Vitro Cell Dev Biol Anim ; 59(7): 550-563, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37639049

RESUMEN

Conservation of genetic resources is an important way to protect endangered species. At present, mesenchymal stem cells (MSCs) have been isolated from the bone marrow and umbilical cords of giant pandas. However, the types and quantities of preserved cell resources were rare and limited, and none of MSCs was derived from female reproductive organs. Here, we first isolated MSCs from the endometrium of giant panda. These cells showed fibroblast morphology and expressed Sox2, Klf4, Thy1, CD73, CD105, CD44, CD49f, and CD105. Endometrium mesenchymal stem cells (eMSCs) of giant panda could induce differentiation into three germ layers in vitro. RNA-seq analysis showed that 833 genes were upregulated and 716 genes were downregulated in eMSCs compared with skin fibroblast cells. The results of GO and the KEGG analysis of differentially expressed genes (DEGs) were mainly focused on transporter activity, signal transducer activity, pathways regulating pluripotency of stem cells, MAPK signaling pathway, and PI3K-Akt signaling pathway. The genes PLCG2, FRK, JAK3, LYN, PIK3CB, JAK2, CBLB, and MET were identified as hub genes by PPI network analysis. In addition, the exosomes of eMSCs were also isolated and identified. The average diameter of exosomes was 74.26 ± 13.75 nm and highly expressed TSG101 and CD9 but did not express CALNEXIN. A total of 277 miRNAs were detected in the exosomes; the highest expression of miRNA was the has-miR-21-5p. A total of 14461 target genes of the whole miRNAs were predicted and proceeded with functional analysis. In conclusion, we successfully isolated and characterized the giant panda eMSCs and their exosomes, and analyzed their functions through bioinformatics techniques. It not only enriched the conservation types of giant panda cell resources and promoted the protection of genetic diversity, but also laid a foundation for the application of eMSCs and exosomes in the disease treatment of giant pandas.


Asunto(s)
Exosomas , Células Madre Mesenquimatosas , MicroARNs , Ursidae , Femenino , Animales , Ursidae/genética , Exosomas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , Endometrio/metabolismo
9.
Materials (Basel) ; 16(9)2023 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-37176361

RESUMEN

Primary dendrite arm spacing (PDAS) is a crucial microstructural feature in nickel-based superalloys produced by laser cladding. In order to investigate the effects of process parameters on PDAS, a multi-scale model that integrates a 3D transient heat and mass transfer model with a quantitative phase-field model was proposed to simulate the dendritic growth behavior in the molten pool for laser cladding Inconel 718. The values of temperature gradient (G) and solidification rate (R) at the S/L interface of the molten pool under different process conditions were obtained by multi-scale simulation and used as input for the quantitative phase field model. The influence of process parameters on microstructure morphology in the deposition layer was analyzed. The result shows that the dendrite morphology is in good agreement with the experimental result under varying laser power (P) and scanning velocity (V). PDAS was found to be more sensitive to changes in laser scanning velocity, and as the scanning velocity decreased from 12 mm/s to 4 mm/s, the PDAS increased by 197% when the laser power was 1500 W. Furthermore, smaller PDAS can be achieved by combining higher scanning velocity with lower laser power.

10.
Polymers (Basel) ; 15(4)2023 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-36850323

RESUMEN

Segregated conductive polymer composites exhibit excellent electrical properties with a low percolation threshold. However, the mechanical properties of the segregated conductive polymer composites were always poor because the conductive fillers at the interfaces hinder polymer chain diffusion and thus lead to weak interfacial interaction between the conductive fillers and the polymer matrix. In this paper, polyamide-6 and polyamide-612 microspheres were synthesized via the in situ anionic ring opening of caprolactam and laurolactam. Segregated graphite sheets/polyamide-6(GS/PA6) and polyamide-612(PA612) composites with good mechanical properties were realized via high-pressure solid-phase compression molding. The microstructures of the composite samples were observed by scanning electron microscopy, which showed that the formation of a GS-conductive network at the PA6 granule interfaces in the segregated conductive structures and the adopting of PA612 considerably improved the interfacial adhesion of the composites. A superior impact strength of 5.1 kJ/m2 was achieved with 50 wt% PA612 loading owing to improvements in the interface compatibility between PA6 and GS. The composites possessed an ultralow percolation threshold, which was ascribed to the segregated network structure being successfully constructed inside the material. As for GS/PA6 composites, the combination of segregated GS-conductive networks achieved an ultralow percolation of 2.8 vol%. The percolation of 80PA6/20PA612-GS composites was slightly higher, measuring up to 3.2 vol%. Moreover, the thermal conductivity of the 80PA6/20PA612-GS composites increased from 0.26 to around 0.5 W/(m·K), which was 1.9 times larger than the pure polyamide.

11.
Front Psychol ; 13: 1017775, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36478923

RESUMEN

Based on the General Strain Theory and the moderating role model of social support, the present study explored the relationship between cyber upward social comparison and cyberbullying and further explored the mediating role of moral justification and the moderating role of online social support. This model was examined with 660 Chinese college students. Participants completed questionnaires regarding cyber upward social comparison, cyberbullying, moral justification, and online social support. After basic demographic variables were controlled, cyber upward social comparison was significantly and positively associated with cyberbullying. Moral justification played a mediating role in the relationship between cyber upward social comparison and cyberbullying. The mediating effect of moral justification on the relationship between cyber upward social comparison and cyberbullying was moderated by online social support. The results of this study will provide references for the prevention and intervention of cyberbullying.

12.
Molecules ; 27(24)2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36558075

RESUMEN

During drilling in deep shale gas reservoirs, drilling fluid losses, hole wall collapses, and additional problems occur frequently due to the development of natural fractures in the shale formation, resulting in a high number of engineering accidents such as drilling fluid leaks, sticking, mud packings, and buried drilling tools. Moreover, the horizontal section of horizontal well is long (about 1500 m), and the problems of friction, rock carrying, and reservoir pollution are extremely prominent. The performance of drilling fluids directly affects drilling efficiency, the rate of engineering accidents, and the reservoir protection effect. In order to overcome the problems of high filtration in deep shale formations, collapse of borehole walls, sticking of pipes, mud inclusions, etc., optimization studies of water-based drilling fluid systems have been conducted with the primary purpose of controlling the rheology and water loss of drilling fluid. The experimental evaluation of the adsorption characteristics of "KCl + polyamine" anti-collapse inhibitor on the surface of clay particles and its influence on the morphology of bentonite was carried out, and the mechanism of inhibiting clay mineral hydration expansion was discussed. The idea of controlling the rheology and water loss of drilling fluid with high temperature resistant modified starch and strengthening the inhibition performance of drilling fluid with "KCl + polyamine" was put forward, and a high temperature-resistant modified starch polyamine anti-sloughing drilling fluid system with stable performance and strong plugging and strong inhibition was optimized. The temperature resistance of the optimized water-based drilling fluid system can reach 180 °C. Applied to on-site drilling of deep shale gas horizontal wells, it effectively reduces the rate of complex accidents such as sticking, mud bagging, and reaming that occur when resistance is encountered during shale formation drilling. The time for a single well to trip when encountering resistance decreases from 2-3 d in the early stages to 3-10 h. The re-use rate of the second spudded slurry is 100 percent, significantly reducing the rate of complex drilling accidents and saving drilling costs. It firmly supports the optimal and rapid construction of deep shale gas horizontal wells.


Asunto(s)
Gas Natural , Agua , Temperatura , Arcilla , Minerales , Almidón
13.
Proc Natl Acad Sci U S A ; 119(32): e2202371119, 2022 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-35917353

RESUMEN

Epstein-Barr virus (EBV) infects more than 90% of the world's adult population and accounts for a significant cancer burden of epithelial and B cell origins. Glycoprotein B (gB) is the primary fusogen essential for EBV entry into host cells. Here, we isolated two EBV gB-specific neutralizing antibodies, 3A3 and 3A5; both effectively neutralized the dual-tropic EBV infection of B and epithelial cells. In humanized mice, both antibodies showed effective protection from EBV-induced lymphoproliferative disorders. Cryoelectron microscopy analyses identified that 3A3 and 3A5 bind to nonoverlapping sites on domains D-II and D-IV, respectively. Structure-based mutagenesis revealed that 3A3 and 3A5 inhibit membrane fusion through different mechanisms involving the interference with gB-cell interaction and gB activation. Importantly, the 3A3 and 3A5 epitopes are major targets of protective gB-specific neutralizing antibodies elicited by natural EBV infection in humans, providing potential targets for antiviral therapies and vaccines.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Proteínas Virales , Animales , Anticuerpos Neutralizantes/química , Anticuerpos Neutralizantes/aislamiento & purificación , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/química , Anticuerpos Antivirales/aislamiento & purificación , Anticuerpos Antivirales/uso terapéutico , Microscopía por Crioelectrón , Infecciones por Virus de Epstein-Barr/prevención & control , Infecciones por Virus de Epstein-Barr/terapia , Herpesvirus Humano 4/inmunología , Humanos , Fusión de Membrana , Ratones , Proteínas Virales/inmunología
14.
Materials (Basel) ; 15(15)2022 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-35897590

RESUMEN

Direct laser deposition (DLD) is widely used in precision manufacturing, but the process parameters (e.g., laser power, scanning patterns) easily lead to changes in dimensional accuracy and structural properties. Many methods have been proposed to analyze the principle of distortion and residual stress generation, but it is difficult to evaluate the involvement of temperature and stress in the process of rapid melting and solidification. In this paper, a three-dimensional finite element model is established based on thermal-mechanical relationships in multilayer DLD. Differences in temperature and residual stress between continuous laser deposition (CLD) and pulsed laser deposition (PLD) are compared with the numerical model. To validate the relationship, the temperature and residual stress values obtained by numerical simulation are compared with the values obtained by the HIOKI-LR8431 temperature logger and the Pulstec µ-X360s X-ray diffraction (XRD) instrument. The results indicate that the temperature and residual stress of the deposition part can be evaluated by the proposed simulation model. The proposed PLD process, which includes continuous pulsed laser deposition (CPLD) and interval pulsed laser deposition (IPLD), were found more effective to improve the homogeneity of temperature and residual stress than the CLD process. This study is expected to be useful in the distortion control and microstructure consistency of multilayer deposited parts.

15.
J Virol ; 96(9): e0033622, 2022 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-35404082

RESUMEN

Epstein-Barr virus (EBV), the first identified human tumor virus, is etiologically associated with various kinds of malignant and benign diseases, accounting for 265,000 cancer incident cases and 164,000 cancer deaths in 2017. EBV prophylactic vaccine development has been gp350 centered for several decades. However, clinical studies show that gp350-centered vaccines fail to prevent EBV infection. Advances in the EBV infection mechanisms shed light on gB and gHgL, the two key components of the infection apparatus. In this study, for the first time, we utilized recombinant vesicular stomatitis virus (VSV) to display EBV gB (VSV-ΔG-gB/gB-G) or gHgL (VSV-ΔG-gHgL). In vitro studies confirmed successful virion production and glycoprotein presentation on the virion surface. In mouse models, VSV-ΔG-gB/gB-G or VSV-ΔG-gHgL elicited potent humoral responses. Neutralizing antibodies elicited by VSV-ΔG-gB/gB-G were prone to prevent B cell infection, while those elicited by VSV-ΔG-gHgL were prone to prevent epithelial cell infection. Combinatorial vaccination yields an additive effect. The ratio of endpoint neutralizing antibody titers to the endpoint total IgG titers immunized with VSV-ΔG-gHgL was approximately 1. The ratio of IgG1/IgG2a after VSV-ΔG-gB/gB-G immunization was approximately 1 in a dose-dependent, adjuvant-independent manner. Taken together, VSV-based EBV vaccines can elicit a high ratio of epithelial and B lymphocyte neutralizing antibodies, implying their unique potential as EBV prophylactic vaccine candidates. IMPORTANCE Epstein-Barr virus (EBV), one of the most common human viruses and the first identified human oncogenic virus, accounted for 265,000 cancer incident cases and 164,000 cancer deaths in 2017 as well as millions of nonmalignant disease cases. So far, no prophylactic vaccine is available to prevent EBV infection. In this study, for the first time, we reported the VSV-based EBV vaccines presenting two key components of the EBV infection apparatus, gB and gHgL. We confirmed potent antigen-specific antibody generation; these antibodies prevented EBV from infecting epithelial cells and B cells, and the IgG1/IgG2a ratio indicated balanced humoral-cellular responses. Taken together, we suggest VSV-based EBV vaccines are potent prophylactic candidates for clinical studies and help eradicate numerous EBV-associated malignant and benign diseases.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Vesiculovirus , Vacunas Virales , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Infecciones por Virus de Epstein-Barr/prevención & control , Herpesvirus Humano 4/fisiología , Inmunidad Humoral , Inmunoglobulina G/sangre , Ratones , Vesiculovirus/genética , Vacunas Virales/inmunología
16.
Signal Transduct Target Ther ; 7(1): 42, 2022 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-35136040

RESUMEN

SARS-CoV-2 variants have evolved a variety of critical mutations, leading to antigenicity changes and immune escape. The recent emerging SARS-CoV-2 Omicron variant attracted global attention due to its significant resistance to current antibody therapies and vaccines. Here, we profiled the mutations of Omicron and other various circulating SARS-CoV-2 variants in parallel by computational interface analysis and in vitro experimental assays. We identified critical mutations that lead to antigenicity changes and diminished neutralization efficiency of a panel of 14 antibodies due to diverse molecular mechanisms influencing the antigen-antibody interaction. Our study identified that Omicron exhibited extraordinary potency in immune escape compared to the other variants of concern, and explores the application of computational interface analysis in SARS-CoV-2 mutation surveillance and demonstrates its potential for the early identification of concerning variants, providing preliminary guidance for neutralizing antibody therapy.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Antígenos Virales , COVID-19 , Evasión Inmune , SARS-CoV-2 , Antígenos Virales/genética , Antígenos Virales/inmunología , COVID-19/genética , COVID-19/inmunología , Células HEK293 , Humanos , SARS-CoV-2/genética , SARS-CoV-2/inmunología
17.
Front Microbiol ; 12: 667637, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34054776

RESUMEN

Many Pseudomonas protegens strains produce the antibiotics pyoluteorin (PLT) and 2,4-diacetylphloroglucinol (2,4-DAPG), both of which have antimicrobial properties. The biosynthesis of these metabolites is typically controlled by multiple regulatory factors. Virulence factor regulator (Vfr) is a multifunctional DNA-binding regulator that modulates 2,4-DAPG biosynthesis in P. protegens FD6. However, the mechanism by which Vfr regulates this process remains unclear. In the present study, chromatin immunoprecipitation of FLAG-tagged Vfr and nucleotide sequencing analysis were used to identify 847 putative Vfr binding sites in P. protegens FD6. The consensus P. protegens Vfr binding site predicted from nucleotide sequence alignment is TCACA. The qPCR data showed that Vfr positively regulates the expression of phlF and phlG, and the expression of these genes was characterized in detail. The purified recombinant Vfr bound to an approximately 240-bp fragment within the phlF and phlG upstream regions that harbor putative Vfr consensus sequences. Using electrophoretic mobility shift assays, we localized Vfr binding to a 25-bp fragment that contains part of the Vfr binding region. Vfr binding was eliminated by mutating the TACG and CACA sequences in phlF and phlG, respectively. Taken together, our results show that Vfr directly regulates the expression of the 2,4-DAPG operon by binding to the upstream regions of both the phlF and phlG genes. However, unlike other Vfr-targeted genes, Vfr binding to P. protegens FD6 does not require an intact binding consensus motif. Furthermore, we demonstrated that vfr expression is autoregulated in this bacterium. These results provide novel insights into the regulatory role of Vfr in the biocontrol agent P. protegens.

18.
Opt Express ; 29(6): 9618-9623, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33820385

RESUMEN

We theoretically investigate the evolution of optical beams in nonlocal nonlinear media of gradual nonlocality, which is governed by the nonlocal nonlinear Schrödinger equation with variable coefficient. With the variational approach, the evolution equation of beam width is derived. When the characteristic length of response function gradually changes with any functional forms, beams can exhibit a kind of adiabatic evolution. The variational results are well confirmed by numerical simulations.

19.
J Colloid Interface Sci ; 597: 242-259, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33872881

RESUMEN

In the present study, ({2-[2-(7-Isopropyl-1,4-dimethyl-9,10-octahydro-phenanthren-1-yl)-4,5-dihydro-1-yl]-ethylamino}-methyl)-phosphonicimidazole (GSIM) was synthesized by introducing phosphonate (-PH2O3) group into imidazoline derivatives and its corrosion inhibition performance was studied for Q345 steel in acidic medium along with SIM using potentiodynamic polarization, EIS and SECM analysis. Surface analysis of steel samples was also performed by optical microscopy and SEM-EDS analysis after polarization tests. XPS was used to detect chemical composition of the surface passive films. It was observed that introducing -PH2O3 group not only improved the adsorption capacity on the metal surface by coordinating with iron ions, but also inhibited the interference of hydrogen bond formed by -NH2 group and water molecules on the adsorption. GSIM not only inhibited intercrystalline corrosion and pitting corrosion, but also reduced uniform corrosion. Thermodynamics studies demonstrated that GSIM followed the Langmuir adsorption isotherm and had a larger adsorption equilibrium constant than SIM, which indicated that it had a stronger adsorption capacity. XPS and UV confirmed that the coordination between GSIM and Fe3+ and hydrogen bonding between SIM and water molecules. The quantum chemical study further clarified that the site and strength of hydrogen bond between SIM and H2O and the dominant configuration and coordination stability of GSIM with Fe3+.

20.
Nano Lett ; 21(6): 2476-2486, 2021 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-33683126

RESUMEN

Epstein-Barr virus (EBV) infection is a global health concern infecting over 90% of the population. However, there is no currently available vaccine. EBV primarily infects B cells, where the major glycoprotein 350 (gp350) is the main target of neutralizing antibodies. Given the advancement of nanoparticle vaccines, we describe rationally designed vaccine modalities presenting 60 copies of gp350 on self-assembled nanoparticles in a repetitive array. In a mouse model, gp350s on lumazine synthase (LS) and I3-01 adjuvanted with MF59 or aluminum hydroxide (Alhydrogel) elicited over 65- to 133-fold higher neutralizing antibody titers than the corresponding gp350 monomer to EBV. Furthermore, immunization with gp350D123-LS and gp350D123-I3-01 vaccine induced a Th2-biased response. For the nonhuman primate model, gp350D123-LS in MF59 elicited higher titers of total IgG and neutralizing antibodies than the monomeric gp350D123. Overall, these results support gp350D123-based nanoparticle vaccine design as a promising vaccine candidate for potent protection against EBV infection.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Nanopartículas , Vacunas , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Infecciones por Virus de Epstein-Barr/prevención & control , Herpesvirus Humano 4 , Inmunización , Ratones
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