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1.
Crit Rev Biomed Eng ; 52(4): 1-15, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38780102

RESUMEN

Computer assisted diagnostic technology has been widely used in clinical practice, specifically focusing on medical image segmentation. Its purpose is to segment targets with certain special meanings in medical images and extract relevant features, providing reliable basis for subsequent clinical diagnosis and research. However, because of different shapes and complex structures of segmentation targets in different medical images, some imaging techniques have similar characteristics, such as intensity, color, or texture, for imaging different organs and tissues. The localization and segmentation of targets in medical images remains an urgent technical challenge to be solved. As such, an improved full scale skip connection network structure for the CT liver image segmentation task is proposed. This structure includes a biomimetic attention module between the shallow encoder and the deep decoder, and the feature fusion proportion coefficient between the two is learned to enhance the attention of the overall network to the segmented target area. In addition, based on the traditional point sampling mechanism, an improved point sampling strategy is proposed for characterizing medical images to further enhance the edge segmentation effect of CT liver targets. The experimental results on the commonly used combined (CT-MR) health absolute organ segmentation (CHAOS) dataset show that the average dice similarity coefficient (DSC) can reach 0.9467, the average intersection over union (IOU) can reach 0.9623, and the average F1 score can reach 0.9351. This indicates that the model can effectively learn image detail features and global structural features, leading to improved segmentation of liver images.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Hígado , Tomografía Computarizada por Rayos X , Humanos , Algoritmos , Diagnóstico por Imagen/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Hígado/diagnóstico por imagen , Redes Neurales de la Computación , Tomografía Computarizada por Rayos X/métodos
2.
J Psychiatr Res ; 175: 96-102, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38718445

RESUMEN

The aim of this study was to establish a multi-factor-induced depression model in mice within a relatively short period, specifically through the combination of intraperitoneal injection of lipopolysaccharide (LPS) and chronic restraint stress (CRS), and to evaluate the differences in depressive-like behaviors among three different strains of mice, seeking mouse strains more suitable for this combined model. The mice of each strain were randomly divided into the normal group and model group. The mice in the model group received a single intraperitoneal injection of LPS once daily (1 mg/kg/d for 7 days) and subsequent CRS for 6 h, to induce depression, while the mice in the normal group received no treatment. Behavioral tests: sucrose preference test (SPT), open field test (OFT), forced swim test (FST), and tail suspension test (TST) were conducted to assess depressive-like behaviors in the mice. Data analysis showed that there were significant intergroup differences in depressive-like behaviors in ICR and C57BL/6 J mice, while KM mice exhibited minor differences with relatively high deviation in individual behavioral score. This study indicated that the combined depression mouse model could successfully induce significant depressive-like behaviors in ICR and C57BL/6 J mice.

3.
J Phys Chem Lett ; 15(11): 3055-3060, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38466221

RESUMEN

Precise characterization of archetypal systems of aqueous hydrogen-bonding networks is essential for developing accurate potential functions and universal models of water. The structures of water clusters (H2O)n (n = 2-9) have been verified recently through size-specific infrared spectroscopy with a vacuum ultraviolet free electron laser (VUV-FEL) and quantum chemical studies. For (H2O)10, the pentagonal prism and butterfly motifs were proposed to be important building blocks and were observed in previous experiments. Here we report the size-specific infrared spectra of (H2O)10 via a joint experimental and theoretical study. Well-resolved spectra provide a unique signature for the coexistence of pentagonal prism and butterfly motifs. These (H2O)10 motifs develop from the dominant structures of (H2O)n (n = 8, 9) clusters. This work provides an intriguing prelude to the diverse structure of liquid water and opens avenues for size-dependent measurement of larger systems to understand the stepwise formation mechanism of hydrogen-bonding networks.

4.
Sci Rep ; 13(1): 13003, 2023 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-37563290

RESUMEN

The effect of double filtration plasma apheresis (DFPP) on improving the outcomes of patients with hypertriglyceridaemia-induced acute pancreatitis (HTG-AP) remains unclear. The aim of this study was to evaluate the relationship between the initiation time of DFPP and the risk of persistent organ failure (POF) in an HTG-AP cohort in China. We retrospectively evaluated data from HTG-AP patients treated with DFPP 48 h after diagnosis between January 2017 and January 2022. Comparisons across tertiles of the interval from diagnosis to completion of one DFPP session (DTD) were analysed. Logistic regression models and restricted cubic splines (RCS) were used to determine the correlation between the DTD time and risk of POF. Of the 89 patients enrolled, 46 patients (51.69%) suffered POF in the first week of HTG-AP. DFPP was initiated at a median of 17 h after the diagnosis was confirmed. The patients in the highest tertile of DTD time had a significantly increased prevalence of POF. After multivariate adjustment, the logistic regression models found a significant decrease in the odds ratios (OR) of POF from the highest to the lowest DTD tertile (P for trend = 0.006). Moreover, the RCS curves showed a nonlinear relationship in the adjusted OR of POF and DTD time, which remained relatively low and flat during the early DTD time but increased sharply afterwards. Early initiation of DFPP treatment correlates with a reduced risk of POF in HTG-AP patients.


Asunto(s)
Eliminación de Componentes Sanguíneos , Hiperlipidemias , Hipertrigliceridemia , Pancreatitis , Humanos , Pancreatitis/etiología , Pancreatitis/terapia , Estudios Retrospectivos , Enfermedad Aguda , Insuficiencia Multiorgánica/epidemiología , Hipertrigliceridemia/complicaciones , Hipertrigliceridemia/terapia
5.
Angew Chem Int Ed Engl ; 62(32): e202305490, 2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-37340827

RESUMEN

Spectroscopic characterization of neutral highly-coordinated compounds is essential in fundamental and applied research, but has been proven to be a challenging experimental target because of the difficulty in mass selection. Here, we report the preparation and size-specific infrared-vacuum ultraviolet (IR-VUV) spectroscopic identification of group-3 transition metal carbonyls Sc(CO)7 and TM(CO)8 (TM=Y, La) in the gas phase, which are the first confinement-free neutral heptacarbonyl and octacarbonyl complexes. The results indicate that Sc(CO)7 has a C2v structure and TM(CO)8 (TM=Y, La) have a D4h structure. Theoretical calculations predict that the formation of Sc(CO)7 and TM(CO)8 (TM=Y, La) is both thermodynamically exothermic and kinetically facile in the gas phase. These highly-coordinated carbonyls are 17-electron complexes when only those valence electrons that occupy metal-CO bonding orbitals are considered, in which the ligand-only 4b1u molecular orbital is ignored. This work opens new avenues toward the design and chemical control of a large variety of compounds with unique structures and properties.

6.
J Phys Chem Lett ; 14(16): 3878-3883, 2023 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-37068164

RESUMEN

Investigation of the reactions between water molecules and neutral metal clusters is important in water splitting but is very challenging due to the inherent difficulty of size selection. Here, we report a size-specific infrared-vacuum ultraviolet spectroscopic study on the reactions of water with neutral vanadium dimer. The V2O3H4 and V2O4H6 products were characterized to have unexpected V2(µ2-OH)(µ2-H)(η1-OH)2 and V2(µ2-OH)2(η1-H)2(η1-OH)2 structures, indicative of a water decomposition. A combination of theory and experiment reveals that the water splitting by V2 is both thermodynamically exothermic and kinetically facile in the gas phase. The present system serves as a model for clarifying the pivotal roles played by neutral metal clusters in water decomposition and also opens new avenues toward systematic understanding of water splitting by a large variety of single-cluster catalysts.

7.
Adv Mater ; 35(21): e2300227, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36870326

RESUMEN

The evolution of the physical properties of 2D material from monolayer limit to the bulk reveals unique consequences from dimension confinement and provides a distinct tuning knob for applications. Monolayer 1T'-phase transition metal dichalcogenides (1T'-TMDs) with ubiquitous quantum spin Hall (QSH) states are ideal 2D building blocks of various 3D topological phases. However, the stacking geometry has been previously limited to the bulk 1T'-WTe2 type. Here, the novel 2M-TMDs consisting of translationally stacked 1T'-monolayers are introduced as promising material platforms with tunable inverted bandgaps and interlayer coupling. By performing advanced polarization-dependent angle-resolved photoemission spectroscopy as well as first-principles calculations on the electronic structure of 2M-TMDs, a topology hierarchy is revealed: 2M-WSe2 , MoS2, and MoSe2 are weak topological insulators (WTIs), whereas 2M-WS2 is a strong topological insulator (STI). Further demonstration of topological phase transitions by tunning interlayer distance indicates that band inversion amplitude and interlayer coupling jointly determine different topological states in 2M-TMDs. It is proposed that 2M-TMDs are parent compounds of various exotic phases including topological superconductors and promise great application potentials in quantum electronics due to their flexibility in patterning with 2D materials.

8.
J Phys Chem Lett ; 14(10): 2481-2486, 2023 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-36867598

RESUMEN

Capturing the hydrogen radical is of central importance in various systems ranging from catalysis to biology to astronomy, but it has been proven to be challenging experimentally because of its high reactivity and short lifetime. Here, neutral MO3H4 (M = Sc, Y, La) complexes were characterized by size-specific infrared-vacuum ultraviolet spectroscopy. All these products were determined to be the hydrogen radical adducts in the form of H•M(OH)3. The results indicate that the addition of the hydrogen radical to the M(OH)3 complex is both thermodynamically exothermic and kinetically facile in the gas phase. Moreover, the soft collisions in the cluster growth channel with the helium expansion were found to be demanded for the formation of H•M(OH)3. This work highlights the pivotal roles played by the soft collisions in the formation of hydrogen radical adducts and also opens new avenues toward the design and chemical control of compounds.

9.
J Chem Phys ; 158(1): 014301, 2023 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-36610966

RESUMEN

Structural characterization of neutral water clusters is crucial to understanding the structures and properties of water, but it has been proven to be a challenging experimental target due to the difficulty in size selection. Here, we report the size-specific infrared spectra of confinement-free neutral water nonamer (H2O)9 based on threshold photoionization, using a tunable vacuum ultraviolet free-electron laser. Distinct OH stretch vibrational fundamentals in the 3200-3350 cm-1 region are observed, providing unique spectral signatures for the formation of an unprecedented (H2O)9 structure evolved by adding a ninth water molecule onto a hydrogen bond-unbroken edge of the (H2O)8 octamer with D2d symmetry. This nonamer structure coexists with the five previously identified structures that can be viewed as derived by inserting a ninth water molecule into a hydrogen bond-broken edge of the D2d/S4 octamer. These findings provide key microscopic information for systematic understanding of the formation and growth mechanism of dynamical hydrogen-bonding networks that are responsible for the structure and properties of condensed-phase water.

10.
Microbiol Spectr ; 10(6): e0385822, 2022 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-36445078

RESUMEN

In China, the duck industry has been severely impacted by the newly emerging duck Tembusu virus (DTMUV). For DTMUV to successfully infect host cells, it employs several strategies that subvert the host's innate immune response. It has been found that several viral proteins encoded by DTMUV have strategically targeted the crucial molecules of the RIG-I-like Receptor (RLR) signaling pathway to antagonize host antiviral responses. However, it is not well known how the host proteins manipulated by DTMUV contribute to innate immune evasion. The present study reports that duck TRIM35 (duTRIM35) antagonizes DTMUV-induced innate immune responses by targeting duck RIG-I (duRIG-I) in duck embryo fibroblasts. A significant increase in duTRIM35 expression occurred during DTMUV infection. DuTRIM35 overexpression suppressed DTMUV-triggered expression of interferon beta (IFN-ß) and interferon-stimulated genes (ISGs), promoting viral replication, whereas knockdown of duTRIM35 augments the innate immune response, reducing viral replication. Furthermore, duTRIM35 significantly impaired the IFN-ß expression mediated by duRIG-I but not by other RLR signaling molecules. Mechanistically, duTRIM35 interfered with duRIG-I-duTRIM25 interaction and impeded duTRIM25-mediated duRIG-I ubiquitination by interacting with both duRIG-I and duTRIM25. Our findings indicate that duTRIM35 expression induced by DTMUV infection interfered with the duRIG-I-mediated antiviral response, illustrating a novel strategy in which DTMUV can evade the host's innate immunity. IMPORTANCE Duck Tembusu virus (DTMUV), an emerging flavivirus pathogen causing a substantial drop in egg production and severe neurological disorders in duck populations, has led to massive economic losses in the global duck industry. DTMUV has employed various strategies to subvert the host's innate immune response to establish a productive infection in host cells. In this study, we report that duck TRIM35 (duTRIM35) expression was upregulated upon DTMUV infection in vitro and in vivo, and its expression antagonized DTMUV-induced innate immune responses by targeting duck RIG-I (duRIG-I) in duck embryo fibroblasts. Further studies suggest that duTRIM35 interfered with duRIG-I-duTRIM25 interaction and impeded duTRIM25-mediated duRIG-I ubiquitination by interacting with both duRIG-I and duTRIM25. Together, these results revealed that duTRIM35 expression induced by DTMUV infection downregulated duRIG-I-mediated host antiviral response, which elucidated a novel strategy of DTMUV for innate immune evasion.


Asunto(s)
Infecciones por Flavivirus , Flavivirus , Enfermedades de las Aves de Corral , Animales , Antivirales , Patos/metabolismo , Infecciones por Flavivirus/veterinaria , Proteína 58 DEAD Box/metabolismo , Flavivirus/genética , Interferón beta , Transducción de Señal , Inmunidad Innata , Replicación Viral , Fibroblastos/metabolismo
11.
Gut Microbes ; 14(1): 2127456, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36195972

RESUMEN

Severe acute pancreatitis (SAP) is a critical illness characterized by a severe systemic inflammatory response resulting in persistent multiple organ failure and sepsis. The intestinal microbiome is increasingly appreciated to play a crucial role in modulation of AP disease outcome, but limited information is available about the identity and mechanism of action for specific commensal bacteria involved in AP-associated inflammation. Here we show that Bifidobacteria, particularly B. animalis, can protect against AP by regulating pancreatic and systemic inflammation in germ-free (GF) and oral antibiotic-treated (Abx) mouse models. Colonization by B. animalis and administration of its metabolite lactate protected Abx and GF mice from AP by reducing serum amylase concentration, ameliorating pancreatic lesions and improving survival rate after retrograde injection of sodium taurocholate. B. animalis relieved macrophage-associated local and systemic inflammation of AP in a TLR4/MyD88- and NLRP3/Caspase1-dependent manner through its metabolite lactate. Supporting our findings from the mouse study, clinical AP patients exhibited a decreased fecal abundance of Bifidobacteria that was inversely correlated with the severity of systemic inflammatory responses. These results may shed light on the heterogeneity of clinical outcomes and drive the development of more efficacious therapeutic interventions for AP, and potentially for other inflammatory disorders.


Asunto(s)
Microbioma Gastrointestinal , Pancreatitis , Enfermedad Aguda , Amilasas/metabolismo , Amilasas/uso terapéutico , Animales , Antibacterianos/uso terapéutico , Bifidobacterium/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Ácido Láctico , Ratones , Factor 88 de Diferenciación Mieloide/metabolismo , Factor 88 de Diferenciación Mieloide/uso terapéutico , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Pancreatitis/metabolismo , Ácido Taurocólico , Receptor Toll-Like 4/metabolismo
12.
Materials (Basel) ; 15(18)2022 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-36143801

RESUMEN

The confinement of concrete enhances its strength and ductility by restraining lateral dilation. The accuracy of a confinement model depends on how well it captures the dilation of concrete. In the current paper, a mesoscale model is established to study the dilation properties of concrete in active confinement, where the heterogeneity of concrete is considered. The stress-strain and lateral-axial strain curves of concrete in active confinement were used to demonstrate the validity of the mesoscale model. Subsequently, the distribution of lateral strain and the influences of the strength grade and confinement ratio on the dilation of concrete were investigated in a simulation. The results show that the distribution of the lateral strain along the radial or longitudinal directions is not uniform on the specimen when compressive failure occurs. The confinement ratio has a more significant influence on the concrete's transverse dilation than the strength grade. Finally, an expression of the lateral-axial strain relationship of concrete in active confinement is proposed. The proposed formula can reflect the simulation results of the mesoscale model and is in good agreement with the prediction of existing formulas.

13.
J Phys Chem Lett ; 13(24): 5654-5659, 2022 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-35708351

RESUMEN

Experimental characterization of microscopic events and behaviors of SO2-H2O interactions is crucial to understanding SO2 atmospheric chemistry but has been proven to be very challenging due to the difficulty in size selection. Here, size-dependent development of SO2 hydrate structure and cluster growth in the SO2(H2O)n (n = 1-16) complexes was probed by infrared spectroscopy based on threshold photoionization using a tunable vacuum ultraviolet free electron laser. Spectral changes with cluster size demonstrate that the sandwich structure initially formed at n = 1 develops into cycle structures with the sulfur and oxygen atoms in a two-dimensional plane (n = 2 and 3) and then into three-dimensional cage structures (n ≥ 4). SO2 is favorably bound to the surface of larger water clusters. These stepwise features of SO2 hydration on various sized water clusters contribute to understanding the reactive sites and electrophilicity of SO2 on cloud droplets, which may have important atmospheric implications for studying the SO2-containing aerosol systems.

14.
Nano Lett ; 22(11): 4307-4314, 2022 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-35604392

RESUMEN

The topological electronic structure plays a central role in the nontrivial physical properties in topological quantum materials. A minimal, "hydrogen-atom-like" topological electronic structure is desired for research. In this work, we demonstrate an effort toward the realization of such a system in the intrinsic magnetic topological insulator MnBi2Te4, by manipulating the topological surface state (TSS) via surface modification. Using high resolution laser- and synchrotron-based angle-resolved photoemission spectroscopy (ARPES), we found the TSS in MnBi2Te4 is heavily hybridized with a trivial Rashba-type surface state (RSS), which could be efficiently removed by the in situ surface potassium (K) dosing. By employing multiple experimental methods to characterize K dosed surface, we attribute such a modification to the electrochemical reactions of K clusters on the surface. Our work not only gives a clear band assignment in MnBi2Te4 but also provides possible new routes in accentuating the topological behavior in the magnetic topological quantum materials.

15.
Chemphyschem ; 23(9): e202200060, 2022 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-35294798

RESUMEN

A neutral boron carbonyl complex B4 (CO)3 is generated in the gas phase and is characterized by infrared plus vacuum ultraviolet (IR+VUV) two-color ionization spectroscopy and quantum chemical calculations. The complex is identified to have a planar C2v structure with three CO ligands terminally coordinated to a rhombus B4 core. It has a closed-shell singlet ground state that correlates to an excited state of B4 . Bonding analyses on B4 (CO)3 as well as the previously reported B4 and B4 (CO)2 indicate that the electronic structure of rhombus tetraboron cluster changes from a close-shell singlet to an open-shell singlet in B4 (CO)2 and to a close-shell singlet in B4 (CO)3 , demonstrating that the electronic structures of boron clusters can be effectively tuned via sequential CO ligand coordination.

16.
Environ Pollut ; 302: 119055, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-35227849

RESUMEN

To elucidate the molecular composition and sources of organic aerosols in Central Asia, carbonaceous compounds, major ions, and 15 organic molecular tracers of total suspended particulates (TSP) were analyzed from September 2018 to August 2019 in Dushanbe, Tajikistan. Extremely high TSP concentrations (annual mean ± std: 211 ± 131 µg m-3) were observed, particularly during summer (seasonal mean ± std: 333 ± 183 µg m-3). Organic carbon (OC: 11.9 ± 7.0 µg m-3) and elemental carbon (EC: 5.1 ± 2.2 µg m-3) exhibited distinct seasonal variations from TSP, with the highest values occurring in winter. A high concentration of Ca2+ was observed (11.9 ± 9.2 µg m-3), accounting for 50.8% of the total ions and reflecting the considerable influence of dust on aerosols. Among the measured organic molecular tracers, levoglucosan was the predominant compound (632 ± 770 ng m-3), and its concentration correlated significantly with OC and EC during the study period. These findings highlight biomass burning (BB) as an important contributor to the particulate air pollution in Dushanbe. High ratios of levoglucosan to mannosan, and syringic acid to vanillic acid suggest that mixed hardwood and herbaceous plants were the main burning materials in the area, with softwood being a minor one. According to the diagnostic tracer ratio, OC derived from BB constituted a large fraction of the primary OC (POC) in ambient aerosols, accounting for an annual mean of nearly 30% and reaching 63% in winter. The annual contribution of fungal spores to POC was 10%, with a maximum of 16% in spring. Measurements of plant debris, accounting for 3% of POC, divulged that these have the same variation as fungal spores.


Asunto(s)
Contaminantes Atmosféricos , Material Particulado , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Carbono/análisis , Monitoreo del Ambiente , Material Particulado/análisis , Estaciones del Año , Tayikistán
18.
J Environ Sci (China) ; 112: 1-15, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34955192

RESUMEN

Much attention is drawn to polycyclic aromatic hydrocarbons (PAHs) as an air pollutant due to their toxic, mutagenic and carcinogenic properties. Therefore, to understand the levels, seasonality, sources and potential health risk of PAHs in two distinct geographical locations at Karachi and Mardan in Pakistan, total suspended particle (TSP) samples were collected for over one year period. The average total PAH concentrations were 31.5 ± 24.4 and 199 ± 229 ng/m3 in Karachi and Mardan, respectively. The significantly lower concentration in Karachi was attributed to diffusion and dilution of the PAHs by the influence of clean air mass from the Arabian sea and high temperature, enhancing the volatilization of the particle phase PAHs to the gas phase. Conversely, the higher concentration (~6 times) in Mardan was due to large influence from local and regional emission sources. A clear seasonality was observed at both the sites, with the higher values in winter and post-monsoon due to higher emissions and less scavenging, and lower values during monsoon season due to the dilution effect. Diagnostic ratios and principal component analysis indicated that PAHs in both sites originated from traffic and mixed combustion sources (fossil fuels and biomass). The average total BaP equivalent concentrations (BaPeq) in Karachi and Mardan were 3.26 and 34 ng/m3, respectively, which were much higher than the WHO guideline of 1 ng/m3. The average estimates of incremental lifetime cancer risk from exposure to airborne BaPeq via inhalation indicated a risk to human health from atmospheric PAHs at both sites.


Asunto(s)
Contaminantes Atmosféricos , Hidrocarburos Policíclicos Aromáticos , Compuestos Policíclicos , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente , Humanos , Pakistán , Material Particulado/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Compuestos Policíclicos/análisis , Medición de Riesgo , Estaciones del Año
19.
Virulence ; 12(1): 2400-2414, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34506259

RESUMEN

Duck Tembusu virus (DTMUV), an emergent flavivirus, causes domestic waterfowls to suffer from severe egg-drop syndrome and fatal encephalitis, greatly threatens duck production globally. Like other mosquito-borne flaviviruses, the envelope (E) protein of all DTMUV strains was N-glycosylated at the amino acid position 154. Thus far, the biological roles of DTMUV E glycosylation have remained largely unexplored. Herein, we demonstrated the key roles of E glycosylation in the replication and pathogenicity of DTMUV in ducks by characterizing the reverse-genetics-derived DTMUV wild-type MC strain and MC bearing mutations (N154Q and N154I) that abolish the E glycosylation. Our data showed that the disruption of E glycosylation could substantially impair virus attachment, entry, and infectivity in DEFs and C6/36 cells. Notably, ducks inoculated intracerebrally with the wild-type virus exhibited severe disease onset. In contrast, those inoculated with mutant viruses were mildly affected as manifested by minimal weight loss, no mortality, lower viral loads in the various tissues, and reduced brain lesions. Attenuated phenotypes of the mutant viruses might be partly associated with lower inflammatory cytokines expression in the brains of infected ducks. Our study offers the first evidence that E glycosylation is vital for DTMUV replication, pathogenicity, and neurovirulence in vivo.


Asunto(s)
Infecciones por Flavivirus , Flavivirus , Enfermedades de las Aves de Corral , Proteínas del Envoltorio Viral/química , Replicación Viral , Animales , Enfermedades de las Aves/virología , Patos/virología , Flavivirus/fisiología , Infecciones por Flavivirus/veterinaria , Glicosilación , Virulencia
20.
Viruses ; 13(9)2021 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-34578449

RESUMEN

Porcine epidemic diarrhea virus (PEDV) is the predominant cause of an acute, highly contagious enteric disease in neonatal piglets. There are currently no approved drugs against PEDV infection. Here, we report the development of a nanoluciferase (NLuc)-based high-throughput screening (HTS) platform to identify novel anti-PEDV compounds. We constructed a full-length cDNA clone for a cell-adapted PEDV strain YN150. Using reverse genetics, we replaced the open reading frame 3 (ORF3) in the viral genome with an NLuc gene to engineer a recombinant PEDV expressing NLuc (rPEDV-NLuc). rPEDV-NLuc produced similar plaque morphology and showed similar growth kinetics compared with the wild-type PEDV in vitro. Remarkably, the level of luciferase activity could be stably detected in rPEDV-NLuc-infected cells and exhibited a strong positive correlation with the viral titers. Given that NLuc expression represents a direct readout of PEDV replication, anti-PEDV compounds could be easily identified by quantifying the NLuc activity. Using this platform, we screened for the anti-PEDV compounds from a library of 803 natural products and identified 25 compounds that could significantly inhibit PEDV replication. Interestingly, 7 of the 25 identified compounds were natural antioxidants, including Betulonic acid, Ursonic acid, esculetin, lithocholic acid, nordihydroguaiaretic acid, caffeic acid phenethyl ester, and grape seed extract. As expected, all of the antioxidants could potently reduce PEDV-induced oxygen species production, which, in turn, inhibit PEDV replication in a dose-dependent manner. Collectively, our findings provide a powerful platform for the rapid screening of promising therapeutic compounds against PEDV infection.


Asunto(s)
Antivirales/farmacología , Productos Biológicos/farmacología , Ensayos Analíticos de Alto Rendimiento , Luciferasas/genética , Pruebas de Sensibilidad Microbiana , Virus de la Diarrea Epidémica Porcina/efectos de los fármacos , Virus de la Diarrea Epidémica Porcina/genética , Animales , Antioxidantes/farmacología , Chlorocebus aethiops , Ingeniería Genética , Genoma Viral , Luciferasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Genética Inversa , Células Vero
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