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1.
J Virol ; 97(8): e0070023, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37578239

RESUMO

Human adenovirus (HAdV) is ubiquitous in the human population, constituting a significant burden of global respiratory diseases. Children and individuals with low immunity are at risk of developing severe infections without approved antiviral treatment for HAdV. Our study demonstrated that TRIM35 inhibited HAdV-C5 early gene transcription, early protein expression, genome replication, and infectious virus progeny production. Furthermore, TRIM35 was found to inhibit HAdV replication by attenuating E1A expression. Mechanistically, TRIM35 interacts with and degrades E1A by promoting its K48-linked ubiquitination. Additionally, K253 and K285 are the key sites necessary for TRIM35 degradation. Moreover, an oncolytic adenovirus carrying shTRIM35 was constructed and observed to exhibit improved oncolysis in vivo, providing new ideas for clinical tumor treatment. Our results expand the broad antiviral activity of TRIM35 and mechanically support its application as a HAdV replication inhibitor. IMPORTANCE E1A is an essential human adenovirus (HAdV) protein responsible for the early replication of adenovirus while interacting with multiple host proteins. Understanding the interaction between HAdV E1A and TRIM35 helps identify effective antiviral therapeutic targets. The viral E1A protein is a crucial activator and regulator of viral transcription during the early infection stages. We first reported that TRIM35 interacts with E1A to resist adenovirus infection. Our study demonstrated that TRIM35 targets E1A to resist adenovirus, indicating the applicability of targeting virus-dependent host factors as a suitable antiviral strategy.


Assuntos
Proteínas E1A de Adenovirus , Adenovírus Humanos , Proteínas Reguladoras de Apoptose , Replicação Viral , Humanos , Proteínas E1A de Adenovirus/genética , Proteínas E1A de Adenovirus/metabolismo , Adenovírus Humanos/fisiologia , Antivirais/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo
2.
J Digit Imaging ; 36(6): 2402-2410, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37620710

RESUMO

Large numbers of radiographic images are available in musculoskeletal radiology practices which could be used for training of deep learning models for diagnosis of knee abnormalities. However, those images do not typically contain readily available labels due to limitations of human annotations. The purpose of our study was to develop an automated labeling approach that improves the image classification model to distinguish normal knee images from those with abnormalities or prior arthroplasty. The automated labeler was trained on a small set of labeled data to automatically label a much larger set of unlabeled data, further improving the image classification performance for knee radiographic diagnosis. We used BioBERT and EfficientNet as the feature extraction backbone of the labeler and imaging model, respectively. We developed our approach using 7382 patients and validated it on a separate set of 637 patients. The final image classification model, trained using both manually labeled and pseudo-labeled data, had the higher weighted average AUC (WA-AUC 0.903) value and higher AUC values among all classes (normal AUC 0.894; abnormal AUC 0.896, arthroplasty AUC 0.990) compared to the baseline model (WA-AUC = 0.857; normal AUC 0.842; abnormal AUC 0.848, arthroplasty AUC 0.987), trained using only manually labeled data. Statistical tests show that the improvement is significant on normal (p value < 0.002), abnormal (p value < 0.001), and WA-AUC (p value = 0.001). Our findings demonstrated that the proposed automated labeling approach significantly improves the performance of image classification for radiographic knee diagnosis, allowing for facilitating patient care and curation of large knee datasets.


Assuntos
Articulação do Joelho , Radiologia , Humanos , Radiografia , Articulação do Joelho/diagnóstico por imagem , Artroplastia
3.
PLoS Pathog ; 16(10): e1008944, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33075108

RESUMO

Feline calicivirus (FCV) belongs to the Caliciviridae, which comprises small RNA viruses of both medical and veterinary importance. Once infection has occurred, FCV can persist in the cat population, but the molecular mechanism of how it escapes the innate immune response is still unknown. In this study, we found FCV strain 2280 to be relatively resistant to treatment with IFN-ß. FCV 2280 infection inhibited IFN-induced activation of the ISRE (Interferon-stimulated response element) promoter and transcription of ISGs (Interferon-stimulated genes). The mechanistic analysis showed that the expression of IFNAR1, but not IFNAR2, was markedly reduced in FCV 2280-infected cells by inducing the degradation of IFNAR1 mRNA, which inhibited the phosphorylation of downstream adaptors. Further, overexpression of the FCV 2280 nonstructural protein p30, but not p30 of the attenuated strain F9, downregulated the expression of IFNAR1 mRNA. His-p30 fusion proteins were produced in Escherichia coli and purified, and an in vitro digestion assay was performed. The results showed that 2280 His-p30 could directly degrade IFNAR1 RNA but not IFNAR2 RNA. Moreover, the 5'UTR of IFNAR1 mRNA renders it directly susceptible to cleavage by 2280 p30. Next, we constructed two chimeric viruses: rFCV 2280-F9 p30 and rFCV F9-2280 p30. Compared to infection with the parental virus, rFCV 2280-F9 p30 infection displayed attenuated activities in reducing the level of IFNAR1 and inhibiting the phosphorylation of STAT1 and STAT2, whereas rFCV F9-2280 p30 displayed enhanced activities. Animal experiments showed that the virulence of rFCV 2280-F9 p30 infection was attenuated but that the virulence of rFCV F9-2280 p30 was increased compared to that of the parental viruses. Collectively, these data show that FCV 2280 p30 could directly and selectively degrade IFNAR1 mRNA, thus blocking the type I interferon-induced activation of the JAK-STAT signalling pathway, which may contribute to the pathogenesis of FCV infection.


Assuntos
Antivirais/farmacologia , Infecções por Caliciviridae/tratamento farmacológico , Calicivirus Felino/patogenicidade , Imunidade Inata/efeitos dos fármacos , Interferon Tipo I/metabolismo , Animais , Infecções por Caliciviridae/virologia , Calicivirus Felino/efeitos dos fármacos , Calicivirus Felino/imunologia , Doenças do Gato/virologia , Gatos , Interferon Tipo I/imunologia , Interferon beta/genética , Vírus/efeitos dos fármacos , Vírus/genética
4.
Sensors (Basel) ; 22(12)2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35746106

RESUMO

This paper proposes a displacement sensing method based on magnetic flux measurement. A bridge-structured magnetic circuit, formed by permanent magnets and two ferromagnetic cores, is designed and discussed. The analyses of the equivalent magnetic circuit and three-dimensional finite element simulations showed that the magnetic flux density changes linearly with the reciprocal of the sum of a constant and the displacement. A prototype sensor of the bridge structure is developed that consists of four permanent magnets as excitation, a Hall sensor as reception, and two ferromagnetic cores as the connection. Experiments have validated the feasibility of this method. The measured results show a good linearity between the sensor's output and the reciprocal of the sum of a constant and the displacement, with a correlation coefficient greater than 0.9995 across different measurement ranges. Additionally, the measured results significantly indicate that the proposed sensor is compatible with different ferromagnetic materials with a worst-case error of less than 5%. The proposed sensor has the advantages of low cost and good linearity; however, the test object is limited to ferromagnetic materials.

5.
Bioinformatics ; 35(13): 2306-2308, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30445566

RESUMO

MOTIVATION: Modern bioinformatics tools for analyzing large-scale NGS datasets often need to include fast implementations of core sequence alignment algorithms in order to achieve reasonable execution times. We address this need by presenting the BGSA toolkit for optimized implementations of popular bit-parallel global pairwise alignment algorithms on modern microprocessors. RESULTS: BGSA outperforms Edlib, SeqAn and BitPAl for pairwise edit distance computations and Parasail, SeqAn and BitPAl when using more general scoring schemes for pairwise alignments of a batch of sequence reads on both standard multi-core CPUs and Xeon Phi many-core CPUs. Furthermore, banded edit distance performance of BGSA on a Xeon Phi-7210 outperforms the highly optimized NVBio implementation on a Titan X GPU for the seed verification stage of a read mapper by a factor of 4.4. AVAILABILITY AND IMPLEMENTATION: BGSA is open-source and available at https://github.com/sdu-hpcl/BGSA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Software , Alinhamento de Sequência , Análise de Sequência de DNA
6.
J Infect Dis ; 220(3): 392-399, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-30891604

RESUMO

BACKGROUND: This study tested the hypothesis that the immunogenicity and safety of the simultaneous administration of enterovirus 71 (EV71) vaccine (dose 1) with recombinant hepatitis B vaccine (HepB) on day 1 and EV71 vaccine (dose 2) with group A meningococcal polysaccharide vaccine (MenA) on day 30 is not inferior to separate administration of each vaccine. METHODS: The study was designed as a randomized, open-label, noninferiority trial. A total of 775 healthy infants aged 6 months were randomly assigned in a ratio of 1:1:1 to receive simultaneous administration of EV71 vaccine (dose 1) and HepB on day 1 and EV71 vaccine (dose 2) and MenA on day 30 (the SI group); administration of doses 1 and 2 of EV71 vaccine on days 1 and 30, respectively (the SE1 group); or administration of HepB and MenA on days 1 and 30, respectively (the SE2 group). RESULTS: According to the per protocol set, antibody responses against EV71, hepatitis B virus (HBV), and group A meningococcal polysaccharide were similar regardless of administration schedule. With the non-inferiority margin setting at 10%, the seroconversion rates of the three pathogens in the SI group (100% [98.25, 100], 44.84% [38.20, 51.63] and 27.83% [21.91, 34.38]) were not inferior to those in SE1 or SE2 group (100% [98.31, 100], 44.35% [37.82, 51.02] and 29.17% [23.20, 35.72], respectively). Frequencies of adverse reactions to each vaccination regimen were comparable (60.62% in the SI group vs 52.33% in the SE1 group and 56.98% in the SE2 group; P = .16). CONCLUSIONS: Simultaneous administration of combined EV71 vaccine with HepB and MenA has noninferior immunogenicity and safety, compared with separate administration of these vaccines. CLINICAL TRIALS REGISTRATION: NCT03274102.


Assuntos
Formação de Anticorpos/imunologia , Vacinas contra Hepatite B/imunologia , Vacinas Meningocócicas/imunologia , Polissacarídeos Bacterianos/imunologia , Vacinas Combinadas/imunologia , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Anticorpos Antivirais/imunologia , Enterovirus/imunologia , Infecções por Enterovirus/imunologia , Feminino , Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Humanos , Lactente , Masculino , Infecções Meningocócicas/imunologia , Neisseria meningitidis/imunologia , Vacinação/efeitos adversos
7.
J Virol ; 92(12)2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29618645

RESUMO

As a prevalent agent in cats, feline herpesvirus 1 (FHV-1) infection contributes to feline respiratory disease and acute and chronic conjunctivitis. FHV-1 can successfully evade the host innate immune response and persist for the lifetime of the cat. Several mechanisms of immune evasion by human herpesviruses have been elucidated, but the mechanism of immune evasion by FHV-1 remains unknown. In this study, we screened for FHV-1 open reading frames (ORFs) responsible for inhibiting the type I interferon (IFN) pathway with an IFN-ß promoter reporter and analysis of IFN-ß mRNA levels in HEK 293T cells and the Crandell-Reese feline kidney (CRFK) cell line, and we identified the Ser/Thr kinase US3 as the most powerful inhibitor. Furthermore, we found that the anti-IFN activity of US3 depended on its N terminus (amino acids 1 to 75) and was independent of its kinase activity. Mechanistically, the ectopic expression of US3 selectively inhibited IFN regulatory factor 3 (IRF3) promoter activation. Furthermore, US3 bound to the IRF association domain (IAD) of IRF3 and prevented IRF3 dimerization. Finally, US3-deleted recombinant FHV-1 and US3-repaired recombinant FHV-1 (rFHV-dUS3 and rFHV-rUS3, respectively) were constructed. Compared with wild-type FHV-1 and rFHV-rUS3, infection with rFHV-dUS3 induced large amounts of IFN-ß in vitro and in vivo More importantly, US3 deletion significantly attenuated virulence, reduced virus shedding, and blocked the invasion of trigeminal ganglia. These results indicate that FHV-1 US3 efficiently inhibits IFN induction by using a novel immune evasion mechanism and that FHV-1 US3 is a potential regulator of neurovirulence.IMPORTANCE Despite widespread vaccination, the prevalence of FHV-1 remains high, suggesting that it can successfully evade the host innate immune response and infect cats. In this study, we screened viral proteins for inhibiting the IFN pathway and identified the Ser/Thr kinase US3 as the most powerful inhibitor. In contrast to other members of the alphaherpesviruses, FHV-1 US3 blocked the host type I IFN pathway in a kinase-independent manner and via binding to the IRF3 IAD and preventing IRF3 dimerization. More importantly, the depletion of US3 attenuated the anti-IFN activity of FHV-1 and prevented efficient viral replication in vitro and in vivo Also, US3 deletion significantly attenuated virulence and blocked the invasion of trigeminal ganglia. We believe that these findings not only will help us to better understand the mechanism of how FHV-1 manipulates the host IFN response but also highlight the potential role of US3 in the establishment of latent infection in vivo.


Assuntos
Alphaherpesvirinae/patogenicidade , Fator Regulador 3 de Interferon/antagonistas & inibidores , Interferon beta/antagonistas & inibidores , Nucleotidiltransferases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Virais/metabolismo , Alphaherpesvirinae/genética , Animais , Doenças do Gato/virologia , Gatos , Dimerização , Células HEK293 , Humanos , Fator Regulador 3 de Interferon/metabolismo , Interferon beta/genética , Interferon beta/metabolismo , Proteínas de Membrana/genética , Ligação Proteica/fisiologia , Proteínas Serina-Treonina Quinases/genética , Interferência de RNA , RNA Interferente Pequeno/genética , Transdução de Sinais/fisiologia , Proteínas Virais/genética
8.
Arch Virol ; 161(10): 2807-11, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27379971

RESUMO

Bluetongue virus (BTV) has been found to trigger autophagy to favor its replication, but the underlying mechanisms have not been clarified. Here, we show that cellular energy metabolism is involved in BTV-induced autophagy. Cellular ATP synthesis was impaired by BTV1 infection, causing metabolic stress, which was responsible for activation of autophagy, since the conversion of LC3 and aggregation of GFP-LC3 (autophagy markers) were suppressed when infection-caused energy depletion was reversed via MP (metabolic substrate) treatment. The reduced virus yields with MP further supported this view. Overall, our findings suggest that BTV1-induced disruption of cellular energy metabolism contributes to autophagy, and this provides new insights into BTV-host interactions.


Assuntos
Autofagia , Vírus Bluetongue/fisiologia , Metabolismo Energético , Replicação Viral , Animais , Vírus Bluetongue/patogenicidade , Células Cultivadas , Cricetinae
9.
J Gen Virol ; 96(9): 2714-2720, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25998915

RESUMO

Epizootic haemorrhagic disease is a non-contagious infectious viral disease of wild and domestic ruminants caused by epizootic hemorrhagic disease virus (EHDV). EHDV belongs to the genus Orbivirus within the family Reoviridae and is transmitted by insects of the genus Culicoides. The impact of epizootic haemorrhagic disease is underscored by its designation as a notifiable disease by the Office International des Epizooties. The EHDV genome consists of 10 linear dsRNA segments (Seg1-Seg10). Until now, no reverse genetics system (RGS) has been developed to generate replication-competent EHDV entirely from cloned cDNA, hampering detailed functional analyses of EHDV biology. Here, we report the generation of viable EHDV entirely from cloned cDNAs. A replication-competent EHDV-2 (Ibaraki BK13 strain) virus incorporating a marker mutation was rescued by transfection of BHK-21 cells with expression plasmids and in vitro synthesized RNA transcripts. Using this RGS, two additional modified EHDV-2 viruses were also generated: one that contained a duplex concatemeric Seg9 gene and another that contained a duplex concatemeric Seg10 gene. The modified EHDV-2 with a duplex Seg9 gene was genetically stable during serial passage in BHK-21 cells. In contrast, the modified EHDV-2 with a duplex Seg10 gene was unstable during serial passage, but displayed enhanced replication kinetics in vitro when compared with the WT virus. This RGS provides a new platform for the investigation of EHDV replication, pathogenesis and novel EHDV vaccines.


Assuntos
Doenças dos Bovinos/virologia , Duplicação Gênica , Rearranjo Gênico , Vírus da Doença Hemorrágica Epizoótica/genética , Infecções por Reoviridae/veterinária , Genética Reversa/métodos , Animais , Bovinos , Vírus da Doença Hemorrágica Epizoótica/isolamento & purificação , Vírus da Doença Hemorrágica Epizoótica/fisiologia , Filogenia , Infecções por Reoviridae/virologia , Replicação Viral
10.
Biochem Biophys Res Commun ; 466(3): 406-12, 2015 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-26363458

RESUMO

Bluetongue virus (BTV) is an important pathogen of wild and domestic ruminants. We have previously reported that BTV1 infection induced autophagy for its own benefit, but how this occurs remains unclear. Here, the classical autophagy features including autophagsomes formation, GFP-LC3 dots and LC3-II conversation were shown in BTV1-infected cells, we also found the endoplasmic reticulum (ER) stress was triggered by BTV1 infection, which was demonstrated by the increased transcription level of the ER stress marker GRP78 and the expanded morphology of ER. During ER stress, PERK and eIF2α phosphorylation increased along with BTV1 infection, consistent with the elevated LC3 level, indicating that the PERK pathway of the unfolded protein response (UPR) was activated. In addition, both the blockage of PERK by GSK2656157 or knockdown of eIF2α by siRNA reduced the level of LC3, which suggested that the PERK-eIF2α pathway contributed to autophagy induced by BTV1. Furthermore, inactivation of PERK or silencing of eIF2α both significantly reduced the expression of VP2 protein and the viral yields in the supernatants. In sum, these data suggest that ER stress mediates autophagy via the PERK-eIF2α pathway and contributes to BTV1 replication, thus offering new insight into the molecular mechanisms of the BTV-host interaction.


Assuntos
Vírus Bluetongue/patogenicidade , Fator de Iniciação 2 em Eucariotos/metabolismo , eIF-2 Quinase/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Autofagia , Vírus Bluetongue/genética , Vírus Bluetongue/fisiologia , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/fisiologia , Células Cultivadas , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Fator de Iniciação 2 em Eucariotos/antagonistas & inibidores , Fator de Iniciação 2 em Eucariotos/genética , Técnicas de Silenciamento de Genes , Proteínas de Choque Térmico/metabolismo , Indóis/farmacologia , Modelos Biológicos , Transdução de Sinais , Resposta a Proteínas não Dobradas , Replicação Viral , eIF-2 Quinase/antagonistas & inibidores
11.
Arch Virol ; 160(9): 2249-58, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26115692

RESUMO

Bluetongue virus (BTV) is the etiological agent of bluetongue (BT) disease, a noncontagious insect-transmitted disease of international importance. To date, 26 BTV serotypes have been recognized worldwide. Methods to discriminate BTV serotypes in clinical samples are essential to epidemiological surveillance efforts and BTV vaccination programs. The BTV VP2 major outer capsid protein, encoded by genomic segment 2 (Seg-2), is the most highly variable BTV protein and is the primary determinant of the virus serotype. Here, we report the development of rapid and reliable real-time RT-PCR assays to detect and discriminate 22 BTV serotypes on the basis of VP2-encoding genomic sequences. Serotype-specific primers and probes detected only the targeted BTV serotype and displayed no cross-amplification of off-target BTV serotypes or other closely related Reoviridae and Bunyaviridae family members. The real-time RT-PCR assays developed were highly sensitive, and the majority of serotype-specific reactions could detect template when present at ≥10 copies. These BTV serotype-specific real-time RT-PCR assays represent a rapid, sensitive, and reliable method for the identification, differentiation and quantification of 22 BTV serotypes.


Assuntos
Vírus Bluetongue/classificação , Bluetongue/virologia , Genótipo , Técnicas de Genotipagem/métodos , Sondas de Oligonucleotídeos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Animais , Vírus Bluetongue/genética , Sensibilidade e Especificidade , Sorogrupo , Ovinos
12.
Foods ; 13(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38338569

RESUMO

In this paper, the effects on drying time (Y1), the color difference (Y2), unit energy consumption (Y3), polysaccharide content (Y4), rehydration ratio (Y5), and allantoin content (Y6) of yam slices were investigated under different drying temperatures (50-70 °C), slice thicknesses (2-10 mm), and radiation distances (80-160 mm). The optimal drying conditions were determined by applying the BP neural network wolf algorithm (GWO) model based on response surface methodology (RMS). All the above indices were significantly affected by drying conditions (p < 0.05). The drying rate and effective water diffusion coefficient of yam slices accelerated with increasing temperature and decreasing slice thickness and radiation distance. The selection of lower temperature and slice thickness helped reduce the energy consumption and color difference. The polysaccharide content increased and then decreased with drying temperature, slice thickness, and radiation distance, and it was highest at 60 °C, 6 mm, and 120 mm. At 60 °C, lower slice thickness and radiation distance favored the retention of allantoin content. Under the given constraints (minimization of drying time, unit energy consumption, color difference, and maximization of rehydration ratio, polysaccharide content, and allantoin content), BP-GWO was found to have higher coefficients of determination (R2 = 0.9919 to 0.9983) and lower RMSEs (reduced by 61.34% to 80.03%) than RMS. Multi-objective optimization of BP-GWO was carried out to obtain the optimal drying conditions, as follows: temperature 63.57 °C, slice thickness 4.27 mm, radiation distance 91.39 mm, corresponding to the optimal indices, as follows: Y1 = 133.71 min, Y2 = 7.26, Y3 = 8.54 kJ·h·kg-1, Y4 = 20.73 mg/g, Y5 = 2.84 kg/kg, and Y6 = 3.69 µg/g. In the experimental verification of the prediction results, the relative error between the actual and predicted values was less than 5%, proving the model's reliability for other materials in the drying technology process research to provide a reference.

13.
Front Plant Sci ; 15: 1289783, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38501134

RESUMO

To monitor the moisture content of agricultural products in the drying process in real time, this study applied a model combining multi-sensor fusion and convolutional neural network (CNN) to moisture content online detection. This study built a multi-sensor data acquisition platform and established a CNN prediction model with the raw monitoring data of load sensor, air velocity sensor, temperature sensor, and the tray position as input and the weight of the material as output. The model's predictive performance was compared with that of the linear partial least squares regression (PLSR) and nonlinear support vector machine (SVM) models. A moisture content online detection system was established based on this model. Results of the model performance comparison showed that the CNN prediction model had the optimal prediction effect, with the determination coefficient (R2) and root mean square error (RMSE) of 0.9989 and 6.9, respectively, which were significantly better than those of the other two models. Results of validation experiments showed that the detection system met the requirements of moisture content online detection in the drying process of agricultural products. The R2 and RMSE were 0.9901 and 1.47, respectively, indicating the good performance of the model combining multi-sensor fusion and CNN in moisture content online detection for agricultural products in the drying process. The moisture content online detection system established in this study is of great significance for researching new drying processes and realizing the intelligent development of drying equipment. It also provides a reference for online detection of other indexes in the drying process of agricultural products.

14.
Microbiol Spectr ; 12(1): e0312423, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38019020

RESUMO

IMPORTANCE: miR-26a serves as a potent positive regulator of type I interferon (IFN) responses. By inhibiting USP15 expression, miR-26a promotes RIG-I K63-ubiquitination to enhance type I IFN responses, resulting in an active antiviral state against viruses. Being an intricate regulatory network, the activation of type I IFN responses could in turn suppress miR-26a expression to avoid the disordered activation that might result in the so-called "type I interferonopathy." The knowledge gained would be essential for the development of novel antiviral strategies against viral infection.


Assuntos
Interferon Tipo I , MicroRNAs , Proteína DEAD-box 58/metabolismo , Transdução de Sinais , MicroRNAs/genética , Antivirais/farmacologia , Imunidade Inata
15.
Micromachines (Basel) ; 15(5)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38793128

RESUMO

Continuous monitoring of vital signs based on advanced sensing technologies has attracted extensive attention due to the ravages of COVID-19. A maintenance-free and low-cost passive wireless sensing system based on surface acoustic wave (SAW) device can be used to continuously monitor temperature. However, the current SAW-based passive sensing system is mostly designed at a low frequency around 433 MHz, which leads to the relatively large size of SAW devices and antenna, hindering their application in wearable devices. In this paper, SAW devices with a resonant frequency distributed in the 870 MHz to 960 MHz range are rationally designed and fabricated. Based on the finite-element method (FEM) and coupling-of-modes (COM) model, the device parameters, including interdigital transducer (IDT) pairs, aperture size, and reflector pairs, are systematically optimized, and the theoretical and experimental results show high consistency. Finally, SAW temperature sensors with a quality factor greater than 2200 are obtained for real-time temperature monitoring ranging from 20 to 50 °C. Benefitting from the higher operating frequency, the size of the sensing system can be reduced for human body temperature monitoring, showing its potential to be used as a wearable monitoring device in the future.

16.
Virol Sin ; 39(1): 123-133, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37984761

RESUMO

Hepatitis E virus (HEV) infection can cause severe complications and high mortality, particularly in pregnant women, organ transplant recipients, individuals with pre-existing liver disease and immunosuppressed patients. However, there are still unmet needs for treating chronic HEV infections. Herein, we screened a best-in-class drug repurposing library consisting of 262 drugs/compounds. Upon screening, we identified vidofludimus calcium and pyrazofurin as novel anti-HEV entities. Vidofludimus calcium is the next-generation dihydroorotate dehydrogenase (DHODH) inhibitor in the phase 3 pipeline to treat autoimmune diseases or SARS-CoV-2 infection. Pyrazofurin selectively targets uridine monophosphate synthetase (UMPS). Their anti-HEV effects were further investigated in a range of cell culture models and human liver organoids models with wild type HEV strains and ribavirin treatment failure-associated HEV strains. Encouragingly, both drugs exhibited a sizeable therapeutic window against HEV. For instance, the IC50 value of vidofludimus calcium is 4.6-7.6-fold lower than the current therapeutic doses in patients. Mechanistically, their anti-HEV mode of action depends on the blockage of pyrimidine synthesis. Notably, two drugs robustly inhibited ribavirin treatment failure-associated HEV mutants (Y1320H, G1634R). Their combination with IFN-α resulted in synergistic antiviral activity. In conclusion, we identified vidofludimus calcium and pyrazofurin as potent candidates for the treatment of HEV infections. Based on their antiviral potency, and also the favorable safety profile identified in clinical studies, our study supports the initiation of clinical studies to repurpose these drugs for treating chronic hepatitis E.


Assuntos
Amidas , Compostos de Bifenilo , Ácidos Dicarboxílicos , Vírus da Hepatite E , Hepatite E , Pirazóis , Ribose , Gravidez , Humanos , Feminino , Hepatite E/tratamento farmacológico , Ribavirina/farmacologia , Ribavirina/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Cálcio/farmacologia , Cálcio/uso terapêutico , Reposicionamento de Medicamentos
17.
Hum Vaccin Immunother ; 20(1): 2324538, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38509699

RESUMO

This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three doses of an oral, live, pentavalent rotavirus vaccine (RV5) and three doses of an intramuscular, inactivated poliomyelitis vaccine (IPV) in 400 healthy infants. The primary objective was the non-inferiority of neutralizing antibody (nAb) responses in the concomitant- versus the staggered-use groups. Antibody responses were measured at baseline and 1-month post-dose 3 (PD3). Parents/legal guardians recorded adverse events for 30 or 15 d after study vaccinations in the concomitant-use or staggered-use groups, respectively. At PD3, >98% of participants seroconverted to all three poliovirus types, and the primary objective was met as lower bounds of the two-sided 95% CI for between-group difference in nAb seroconversion percentages ranged from - 4.3% to - 1.6%, for all poliovirus types, p < .001. At PD3, geometric mean titers (GMTs) of nAb responses to poliovirus types 1, 2, and 3 in the concomitant-use group and the staggered-use group were comparable; 100% of participants had nAb titers ≥1:8 and ≥1:64 for all poliovirus types. Anti-rotavirus serotype-specific IgA GMTs and participants with ≥3-fold rise in postvaccination titers from baseline were comparable between groups. Administration of RV5 and IPV was well tolerated with comparable safety profiles in both groups. The immunogenicity of IPV in the concomitant-use group was non-inferior to the staggered-use group and RV5 was immunogenic in both groups. No safety concerns were identified. These data support the concomitant use of RV5 and IPV in healthy Chinese infants.


Assuntos
Poliomielite , Poliovirus , Vacinas contra Rotavirus , Humanos , Lactente , Anticorpos Neutralizantes , Anticorpos Antivirais , China , Imunogenicidade da Vacina , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado , Vacina Antipólio Oral , Vacinas Atenuadas
18.
Eur J Radiol ; 166: 110979, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37473618

RESUMO

PURPOSE: Tools to predict a screening mammogram recall at the time of scheduling could improve patient care. We extracted patient demographic and breast care history information within the electronic medical record (EMR) for women undergoing digital breast tomosynthesis (DBT) to identify which factors were associated with a screening recall recommendation. METHOD: In 2018, 21,543 women aged 40 years or greater who underwent screening DBT at our institution were identified. Demographic information and breast care factors were extracted automatically from the EMR. The primary outcome was a screening recall recommendation of BI-RADS 0. A multivariable logistic regression model was built and included age, race, ethnicity groups, family breast cancer history, personal breast cancer history, surgical breast cancer history, recall history, and days since last available screening mammogram. RESULTS: Multiple factors were associated with a recall on the multivariable model: history of breast cancer surgery (OR: 2.298, 95% CI: 1.854, 2.836); prior recall within the last five years (vs no prior, OR: 0.768, 95% CI: 0.687, 0.858); prior screening mammogram within 0-18 months (vs no prior, OR: 0.601, 95% CI: 0.520, 0.691), prior screening mammogram within 18-30 months (vs no prior, OR: 0.676, 95% CI: 0.520, 0.691); and age (normalized OR: 0.723, 95% CI: 0.690, 0.758). CONCLUSIONS: It is feasible to predict a DBT screening recall recommendation using patient demographics and breast care factors that can be extracted automatically from the EMR.


Assuntos
Neoplasias da Mama , Registros Eletrônicos de Saúde , Feminino , Humanos , Estudos de Viabilidade , Mamografia , Neoplasias da Mama/diagnóstico por imagem , Densidade da Mama , Mama , Detecção Precoce de Câncer , Programas de Rastreamento , Estudos Retrospectivos
19.
Foods ; 12(16)2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37628048

RESUMO

Using hot air drying (HAD) and combined infrared hot air drying (IR-HAD) test devices, the drying kinetics, unit energy consumption, color difference values, rehydration rate, microstructure, and changes in polysaccharide and allantoin contents of yam slices were examined at various temperatures (50 °C, 55 °C, 60 °C, 65 °C, and 70 °C). The findings demonstrated that each of the aforementioned parameters was significantly impacted by the drying temperature. IR-HAD dries quicker and takes less time to dry than HAD. The Deff of IR-HAD is higher than that of HAD at the same temperature and increases with the increase in temperature. The activation energy required for IR-HAD (26.35 kJ/mol) is lower than that required for HAD (32.53 kJ/mol). HAD uses more energy per unit than IR-HAD by a factor of greater than 1.3. Yam slices treated with IR-HAD had higher microscopic porosity, better rehydration, lower color difference values, and higher polysaccharide and allantoin levels than HAD-treated yam slices. The IR-HAD at 60 °C had the greatest comprehensive rating after a thorough analysis of the dried yam slices using the coefficient of variation method. Three statistical indicators were used to evaluate six thin-layer drying models, and the Weibull model was most applicable to describe the variation of drying characteristics of yam slices.

20.
Artif Intell Med ; 141: 102553, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37295897

RESUMO

Machine learning (ML) for diagnosis of thyroid nodules on ultrasound is an active area of research. However, ML tools require large, well-labeled datasets, the curation of which is time-consuming and labor-intensive. The purpose of our study was to develop and test a deep-learning-based tool to facilitate and automate the data annotation process for thyroid nodules; we named our tool Multistep Automated Data Labelling Procedure (MADLaP). MADLaP was designed to take multiple inputs including pathology reports, ultrasound images, and radiology reports. Using multiple step-wise 'modules' including rule-based natural language processing, deep-learning-based imaging segmentation, and optical character recognition, MADLaP automatically identified images of a specific thyroid nodule and correctly assigned a pathology label. The model was developed using a training set of 378 patients across our health system and tested on a separate set of 93 patients. Ground truths for both sets were selected by an experienced radiologist. Performance metrics including yield (how many labeled images the model produced) and accuracy (percentage correct) were measured using the test set. MADLaP achieved a yield of 63 % and an accuracy of 83 %. The yield progressively increased as the input data moved through each module, while accuracy peaked part way through. Error analysis showed that inputs from certain examination sites had lower accuracy (40 %) than the other sites (90 %, 100 %). MADLaP successfully created curated datasets of labeled ultrasound images of thyroid nodules. While accurate, the relatively suboptimal yield of MADLaP exposed some challenges when trying to automatically label radiology images from heterogeneous sources. The complex task of image curation and annotation could be automated, allowing for enrichment of larger datasets for use in machine learning development.


Assuntos
Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Inteligência Artificial , Curadoria de Dados , Ultrassonografia/métodos , Redes Neurais de Computação
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