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Age-related macular degeneration (AMD) is a progressive, degenerative disease of the macula. The formation of macular neovascularization (MNV) and subretinal fibrosis of AMD is the most classic cause of the loss of vision in older adults worldwide. While the underlying causes of MNV and subretinal fibrosis remain elusive, the common feature of many common retinal diseases is changes the proportions of protein deposition in extracellular matrix (ECM) when compared to normal tissue. In ECM, fibronectin (FN) is a crucial component and plays a pivotal part not only in fibrotic diseases but also in the process of angiogenesis. The study aims to understand the role of ligand FN and its common integrin receptor α5ß1 on MNV, and to understand the molecular mechanism involved. To study this, the laser-induced MNV mouse model and the rhesus macaque choroid-retinal endothelial cell line (RF/6A) chemical hypoxia mode were established, and the FN-α5ß1 expression levels were detected by immunohistochemistry (IHC) and quantitative real-time PCR analysis (qRT-PCR). Fibronectin expression was silenced using small interfering RNA (siRNA) targeting FN. The tube formation and vitro scratch assays were used to assess the ability to form blood vessels and cell migration. To measure the formation of MNV, immunofluorescence, and Western blot assays were used. These results revealed that the expressions of FN and integrin α5ß1 were distinctly increased in the laser-induced MNV mouse model and in the RF/6A cytochemically induced hypoxia model, and the expression tendency was identical. After the use of FN siRNA, the tube formation and migration abilities of the RF/6A cells were lower, the ability of endothelial cells to proliferate was confined and the scope of damage caused by the laser in animal models was significantly cut down. In addition, FN gene knockdown dramatically inhibited the expression of Wnt/ß-catenin signal. The interaction of FN with the integrin receptor α5ß1 in the constructed model, which may act through the Wnt/ß-catenin signaling pathway, was confirmed in this study. In conclusion, FN may be a potential new molecular target for the prevention and treatment of subretinal fibrosis and MNV.
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Modelos Animales de Enfermedad , Fibronectinas , Integrina alfa5beta1 , Ratones Endogámicos C57BL , Vía de Señalización Wnt , Animales , Fibronectinas/metabolismo , Integrina alfa5beta1/metabolismo , Integrina alfa5beta1/genética , Ratones , Vía de Señalización Wnt/fisiología , Movimiento Celular/fisiología , Western Blotting , Macaca mulatta , Neovascularización Retiniana/metabolismo , Neovascularización Retiniana/patología , beta Catenina/metabolismo , Inmunohistoquímica , Reacción en Cadena en Tiempo Real de la Polimerasa , Masculino , Células CultivadasRESUMEN
Age-related macular degeneration (AMD) is a leading blinding disease worldwide, and macular neovascularization (MNV) is a common complication encountered in the advanced stages of AMD. While the underlying causes of MNV remain elusive, aberrant multiplication of choroidal endothelial cells (CECs) and increased vascular endothelial growth factor (VEGF) are thought to play significant roles in the occurrence and development of MNV. Allograft inflammatory factor-1(AIF-1) is a crucial regulatory factor of vascular tubular structure formation and growth, involving the proliferation and migration of vascular endothelial cells and various tumor cells. This study aimed to understand how AIF-1 effects the proliferation of CECs and the subsequent progression of MNV. To study this, a mouse MNV model was established through laser injury, and the AIF-1 expression levels were then measured using western blot and immunohistochemistry. AIF-1 siRNA was intravitreally injected to silence AIF-1 gene expression. Western blot and choroidal flat mount were performed to measure the progression of MNV and proliferation of the CECs. These results showed that the protein expression of AIF-1 was significantly elevated in the laser-induced mouse MNV model, and the expression trend was consistent with VEGF. The protein level of AIF-1 was significantly decreased after the intravitreal injection of AIF-1 siRNA, the damage range of laser lesions was significantly reduced, and the proliferation of endothelial cells was inhibited. Knockdown of the AIF-1 gene significantly inhibited the expression of mitogen-activated protein kinase p44/42 in MNV lesions. In summary, this research demonstrates that AIF-1 promoted MNV progression by promoting the proliferation of CECs and that silencing AIF-1 significantly ameliorates MNV progression in mouse models, which may act through the p44/42 MAPK signaling pathway. AIF-1 could be a new potential molecular target for MNV.
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Neovascularización Coroidal , Degeneración Macular , Ratones , Animales , Factor A de Crecimiento Endotelial Vascular/metabolismo , Células Endoteliales/metabolismo , Neovascularización Coroidal/metabolismo , Transducción de Señal/fisiología , ARN Interferente Pequeño/genética , Degeneración Macular/metabolismo , Proliferación Celular , Rayos LáserRESUMEN
Underwater video object detection is a challenging task due to the poor quality of underwater videos, including blurriness and low contrast. In recent years, Yolo series models have been widely applied to underwater video object detection. However, these models perform poorly for blurry and low-contrast underwater videos. Additionally, they fail to account for the contextual relationships between the frame-level results. To address these challenges, we propose a video object detection model named UWV-Yolox. First, the Contrast Limited Adaptive Histogram Equalization method is used to augment the underwater videos. Then, a new CSP_CA module is proposed by adding Coordinate Attention to the backbone of the model to augment the representations of objects of interest. Next, a new loss function is proposed, including regression and jitter loss. Finally, a frame-level optimization module is proposed to optimize the detection results by utilizing the relationship between neighboring frames in videos, improving the video detection performance. To evaluate the performance of our model, We construct experiments on the UVODD dataset built in the paper, and select mAP@0.5 as the evaluation metric. The mAP@0.5 of the UWV-Yolox model reaches 89.0%, which is 3.2% better than the original Yolox model. Furthermore, compared with other object detection models, the UWV-Yolox model has more stable predictions for objects, and our improvements can be flexibly applied to other models.
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A severe disease occurred in farmed Eriocheir sinensis characterized by milky liquid accumulation in the pectoral cavity, in the province of Liaoning, China, during October 2018-April 2019. Diseased crabs moved sluggishly, exhibited appetite loss and readily lost legs. Under the microscopic analysis, it was observed that the milky liquid contained a large number of yeastlike microorganisms (0.8-1.2 µm × 1.5-1.9 µm), which were also present in the muscle, hepatopancreas and gills. A dominant strain was isolated from the milky liquid and other tissues of diseased crabs. It grew on nutrient agar and formed 1- to 3-mm white opaque colonies, each with a protuberance in the centre. Besides, the results of TEM and SEM also demonstrate a typical multilateral budding model of the yeast clearly. We identified the strain, which we named 2EJM001, as Metschnikowia bicuspidata based on 18S rDNA, ITS and 26S rDNA sequence analyses and on its morphological, physiological and biochemical characteristics. Phylogenetic analysis revealed that 26S rDNA of 2EJM001 was clustered with M. bicuspidata (LNES0119) as reported by Bao et al. In addition, unlike Bao et al., two challenge experiments (injection and immersion) were used in this study. The results of challenge experiments show that 2EJM001 was pathogenic to E. sinensis and caused signs similar to those found in the naturally infected crabs. At the same time, the minimum inhibitory concentrations (MIC80 and MIC90 ) were determined. This study further confirms that M. bicuspidata 2EJM001 was the pathogen responsible for 'milky disease' in E. sinensis from Liaoning Province.
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Braquiuros , Enfermedades de los Peces , Animales , Antifúngicos , Metschnikowia , FilogeniaRESUMEN
The quality of the root bark of Morus alba L. (SBP) herbs currently circulating in the market is variable. In order to ensure clinical effectiveness, a high-performance liquid chromatography (HPLC) fingerprinting method combined with chemical pattern recognition should be established to control the quality of SBP herbs. The differences of 23 batches of SBP were analyzed by exploratory cluster analysis based on shared fingerprint peak data, and the results indicated that the processing method to remove the cork layer from SBP materials is an important influencing factor on SBP quality. Principal component analysis indicated that SBP samples with the cork layer removed can be clearly distinguished from samples without cork layer removal. The potential chemical markers (kuwanon G, morusin and oxyresveratrol) were screened by partial least squares discriminant analysis. Finally, the contents of the main components were determined, indicating that the processing method of SBP materials can affect content of bioactive ingredients and that cork layer removal leads to a more uniform chemometric profile. The HPLC-based chemometrics approach described here will support the development of quality standards in SBP products.
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Medicamentos Herbarios Chinos , Morus , Quimiometría , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Morus/química , Corteza de la Planta/químicaRESUMEN
INTRODUCTION: The characteristics of chemical components or groups of chemical components in traditional Chinese medicines (TCMs) determine their clinical efficacy. Quality markers (Q-markers) is of great significance for standardizing the quality control system of TCM. OBJECTIVES: We aimed to develop a new strategy to discover potential Q-markers of TCM by integrating chemometrics, network pharmacology, and molecular docking, using Centipeda minima (also known as ebushicao [EBSC]) as an example. MATERIALS AND METHODS: First, fingerprints of different batches of EBSC and its counterfeit Arenaria oreophila (also known as zaozhui [ZZ]) were established. Second, chemometric analysis was conducted to determine the influence of varying authenticity/batches of herbs on quality and the chemical markers were screened out. Third, network pharmacology and molecular docking simulations were used to verify the relationship between active ingredients and targets. Lastly, potential Q-markers were selected based on TCM theory. RESULTS: The chemical profiles of EBSC and ZZ were investigated. It was found that different batches of EBSC have differences in chemical composition. Based on our chemometric analysis, chlorogenic acid, rutin, isochlorogenic acid A, quercetin, arnicolide D, and brevilin A were selected as candidate active ingredients. ATIL6, EGFR, CASP3, MYC, HIF1A, and VEGFA were the main targets. Molecular docking was used to verify the binding ability. Based on the concept of Q-marker, arnicolide D and brevilin A were identified as potential Q-markers for EBSC. CONCLUSIONS: Our strategy could be used as a practical approach to discover Q-markers of TCM to evaluate overall chemical consistency.
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Asteraceae , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Farmacología en Red , Quimiometría , Asteraceae/química , Biomarcadores/análisisRESUMEN
A pathogen was isolated from diseased pink-tailed chalceus Chalceus macrolepidotus during a high-mortality outbreak in a freshwater culture farm in Liaoyang, China. The diseased fish were characterized by disoriented behaviors, exophthalmos, and redness and swelling of the top of the head. A Gram-negative, pure strain of bacteria (CM0428) was isolated from the brain, kidney, and liver. The isolate was identified as Vibrio cholerae based on ompW gene amplification and 16S rRNA and gyrB gene sequence analysis. Serogroup testing indicated that CM0428 was a non-O1/O139 strain of V. cholerae. The challenge test showed that CM0428 exhibited strong virulence to pink-tailed chalceus, and hlyA and toxR virulence-related genes were detected. The isolate was sensitive to multi-class antibiotics, but resistant to tetracycline. Histological examination revealed that V. cholerae CM0428 infection caused multiple organ and tissue lesions, and typical pathological features were cell degeneration and necrosis.
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Cólera , Vibrio cholerae , Animales , China , Cólera/veterinaria , ARN Ribosómico 16S , Vibrio cholerae/genética , VirulenciaRESUMEN
Modified polyethyleneimine (PEI) has been widely used as siRNA delivery agents. Here, a new Triton X-100-modified low-molecular-weight PEI siRNA delivery agent is developed together with the coupling of 4-carboxyphenylboronic acid (PBA) and dopamine grafted vitamin E (VEDA). Triton X-100, a nonionic detergent, greatly improves the cellular uptake of siRNA as well as the siRNA escape from endosome/lysosome because of its high transmembrane ability. In addition, the boronate bond between PBA and VEDA of the transfection agent can be triggered to release its entrapped siRNA because of the high level of adenosine triphosphate (ATP) in cancer cells. The transfection agent is successfully applied to deliver siRNAs targeting endogenous genes of epidermal growth factor receptor (EGFR) and kinesin-5 (Eg5) to cancer cells, showing good results on Eg5 and EGFR silencing ability and inhibition of cancer cell migration. Further in vivo study indicates that the Triton X-100-modified transfection agent is also efficient to deliver siRNA to cancer cells and shows significant tumor growth inhibition on mice tumor models. These results indicate that the Triton X-100-modified ATP-responsive transfection agent is a promising gene delivery vector for target gene silencing in vitro and in vivo.
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Portadores de Fármacos/química , Neoplasias/tratamiento farmacológico , ARN Interferente Pequeño/administración & dosificación , Transfección/métodos , Adenosina Trifosfato/metabolismo , Animales , Línea Celular Tumoral , Liberación de Fármacos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Femenino , Técnicas de Silenciamiento del Gen , Silenciador del Gen , Humanos , Inyecciones Intralesiones , Cinesinas/antagonistas & inhibidores , Cinesinas/genética , Ratones , Neoplasias/genética , Neoplasias/patología , Octoxinol/química , Polietileneimina/química , ARN Interferente Pequeño/farmacocinética , Microambiente Tumoral/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The power generation performance of a microbial fuel cell (MFC) greatly depends on the relative amount of electricigens in the anodic microbial community. Running the MFC multiple times can practically enrich the electricigens, and thus improve its power generation efficiency. However, Gram-positive electricigens cannot be enriched well because of their thick non-conductive peptidoglycan layer. Herein, we report a new Gram-positive electricigen enrichment method by regulating the peptidoglycan layer of the bacteria using lysozyme. Lysozyme can partially hydrolyze the peptidoglycans layer of Gram-positive Firmicutes to improve the permeability of cell wall, and thus enhance its electricity generation activity. The stimulation of Gram-positive electricigen endows MFCs a high power generation community structure, which results in the power density 42% higher than that of the control sample. Our work has provided a new and simple method for optimizing the anode community structure by regulating weak electricigens in the community with lysozyme.
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Fuentes de Energía Bioeléctrica , Peptidoglicano , Pared Celular , Electricidad , MuramidasaRESUMEN
In fluid machineries, the flow energy dissipates by transforming into internal energy which performs as the temperature changes. The flow-induced noise is another form that flow energy turns into. These energy dissipations are related to the local flow regime but this is not quantitatively clear. In turbomachineries, the flow regime becomes pulsating and much more complex due to rotor-stator interaction. To quantitatively understand the energy dissipations during rotor-stator interaction, the centrifugal air pump with a vaned diffuser is studied based on total energy modeling, turbulence modeling and acoustic analogy method. The numerical method is verified based on experimental data and applied to further simulation and analysis. The diffuser blade leading-edge site is under the influence of impeller trailing-edge wake. The diffuser channel flow is found periodically fluctuating with separations from the blade convex side. Stall vortex is found on the diffuser blade trailing-edge near outlet. High energy loss coefficient sites are found in the undesirable flow regions above. Flow-induced noise is also high in these sites except in the stall vortex. Frequency analyses show that the impeller blade frequency dominates in the diffuser channel flow except in the outlet stall vortexes. These stall vortices keep their own stall frequency which is about 1/5 impeller frequency with high energy loss coefficient but low noise level. Results comparatively prove the energy dissipation mechanism in the centrifugal air pump under rotor-stator interaction. Results also provide the quantitative basis for turbomachinery's loss reduction design.
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Pneumolysin (PLY) is a devastating bacterial protein toxin of Streptococcus pneumoniae that punctures the cytomembrane, leading to pathological reactions, such as cell disruption and inflammation. Drugs capable of closely impacting the toxin are considered advantageous in the treatment of bacterial infections. Amentoflavone (AMF) is a chemical substance extracted from traditional Chinese herbs. Previous studies have demonstrated that AMF has multiple pharmacological effects and mentioned without attenuating pneumolysin-mediated cytotoxicity. This work focuses on the influence of AMF on inhibitory hemolytic mechanisms. AMF interacts with the toxin at Ser254, Glu277, Arg359, and effectively weakens the oligomerization of wild-type PLY and provides considerable protection against pneumolysin-mediated human alveolar epithelial (A549) cell damage. The results of our study demonstrate that AMF could be a candidate against pneumolysin-related injury.
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Lesión Pulmonar Aguda/tratamiento farmacológico , Biflavonoides/farmacología , Biflavonoides/uso terapéutico , Infecciones Neumocócicas/tratamiento farmacológico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Estreptolisinas , Lesión Pulmonar Aguda/patología , Animales , Proteínas Bacterianas/genética , Línea Celular Tumoral , Citoprotección/efectos de los fármacos , Hemólisis/efectos de los fármacos , Humanos , L-Lactato Deshidrogenasa/metabolismo , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Ratones Endogámicos C57BL , Infecciones Neumocócicas/patología , Infecciones del Sistema Respiratorio/patología , Streptococcus pneumoniae , Estreptolisinas/genéticaRESUMEN
Streptococcus pneumoniae (pneumococcus) is an important causative agent of acute invasive and non-invasive infections. Pneumolysin is one of a considerable number of virulence traits produced by pneumococcus that exhibits a variety of biological activities, thus making it a target of small molecule drug development. In this study, we aimed to evaluate the effect of morin, a natural compound that has no antimicrobial activity against S. pneumonia, is a potent neutralizer of pneumolysin-mediated cytotoxicity and genotoxicity by impairing oligomer formation, and possesses the capability of mitigating tissue damage caused by pneumococcus. These findings indicate that morin could be a potent candidate for a novel therapeutic or auxiliary substance to treat infections for which there are inadequate vaccines and that are resistant to traditional antibiotics.
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Biopolímeros/metabolismo , Flavonoides/farmacología , Streptococcus pneumoniae/metabolismo , Estreptolisinas/toxicidad , Células A549 , Animales , Proteínas Bacterianas/toxicidad , Femenino , Hemólisis/efectos de los fármacos , Humanos , Ratones , Ratones Endogámicos C57BL , Pruebas de Sensibilidad Microbiana , Streptococcus pneumoniae/efectos de los fármacosRESUMEN
Pneumolysin (PLY), an essential virulence factor of Streptococcus pneumoniae (pneumococcus), can penetrate the physical defenses of the host and possesses inflammatory properties. The vital role PLY plays in pneumococcus pathogenesis makes this virulence factor one of the most promising targets for the treatment of pneumococcal infection. Verbascoside (VBS) is an agent that does not exhibit bacteriostatic activity but has been shown to inhibit PLY-mediated cytotoxicity. The results from molecular dynamics simulations and mutational analysis indicated that VBS binds to the cleft between domains 3 and 4 of PLY, thereby blocking PLY's oligomerization and counteracting its hemolytic activity. Moreover, VBS can effectively alleviate PLY-mediated human alveolar epithelial (A549) cell injury, and treatment with VBS provides significant protection against lung damage and reduces mortality in a pneumococcal pneumonia murine model. Our results demonstrate that VBS is a strong candidate as a novel therapeutic in the treatment of Streptococcus pneumoniae infection.
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Glucósidos/metabolismo , Glucósidos/uso terapéutico , Fenoles/metabolismo , Fenoles/uso terapéutico , Neumonía Neumocócica/tratamiento farmacológico , Estreptolisinas/antagonistas & inhibidores , Estreptolisinas/metabolismo , Animales , Antiinfecciosos/metabolismo , Antiinfecciosos/farmacología , Antiinfecciosos/uso terapéutico , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/metabolismo , Sitios de Unión/efectos de los fármacos , Sitios de Unión/fisiología , Femenino , Glucósidos/farmacología , Humanos , Ratones , Ratones Endogámicos C57BL , Fenoles/farmacología , Neumonía Neumocócica/metabolismo , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Ovinos , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/metabolismoRESUMEN
Introduction: Scutellariae Radix (SR), derived from the root of Scutellaria baicalensis Georgi, is a traditional Chinese medicine (TCM) for clearing heat and cooling blood. It has been used as a traditional herbal medicine and is popular as a functional food in Asian countries today. Methods: In this study, UPLC-Q-TOF-MS was first employed to identify the chemical components in the ethanol extract of SR. Then, the extraction process was optimized using star point design-response surface methodology. Fingerprints of different batches and processed products were established, and chemical markers were screened through a combination of various artificial neural network models. Finally, network pharmacology and molecular simulation techniques were utilized for verification to determine the quality markers. Results: A total of 35 chemical components in SR were identified, and the optimal extraction process was determined as follows: ultrasonic extraction with 80% methanol at a ratio of 120:1 for 70 minutes, with a soaking time of 30 minutes. Through discriminant analysis using various artificial neural network models, the samples of SR could be classified into two categories based on their growth years: Kuqin (dried roots of older plants) and Ziqin (roots of younger plants). Moreover, the samples within each category could be further clustered according to their origins. The four different processed products of SR could also be distinguished separately. Finally, through the integration of network pharmacology and molecular simulation techniques, it was determined that baicalin, baicalein, wogonin, norwogonin, norwogonin-8-O-glucuronide, skullcapflavone II, hispidulin, 8, 8"-bibaicalein, and oroxylin A-7-O-beta-D-glucuronide could serve as quality markers for SR. Discussion: The primary factors affecting the quality of SR were its growth years. The geographic origin of SR was identified as a secondary factor affecting its quality. Processing also had a significant impact on its quality. The selected quality markers have laid the foundation for the quality control of SR, and this research strategy also provides a research paradigm for improving the quality of TCM.
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Avian leukosis virus subgroup K (ALV-K) is composed of newly emerging isolates, which cluster separately from the well-characterized subgroups A, B, C, D, E, and J in sequence analysis, and exhibits a specific host range and a unique pattern of superinfection interference. Avian leukosis virus subgroup K replicate more slowly in avian cells than other ALV strains, leading to escaped detection during ALV eradication, but the underlying mechanism are largely unknown. In our previous study, we have reported that JS11C1 and most of other suspected ALV-K strains possessed unique mutations in the U3 region. Here, we selected 5 mutations in some important transcriptional regulation elements to explore the possible factor contributing for the lower activity of LTR, including CA-TG mutation in the CAAT box, 21 nt deletion in the CAAT box, A-G and A-T mutations in the CArG boxes, 11 nt insertion in the PRE boxes, and C-T mutation in the TATA box. On the basis of infectious clone of JS11C1, we demonstrated that the 11 nt fragment in the PRE boxes was associated with the transcription activity of LTR, the enhancer ability of U3, and the replication capacity of the virus. Notably, we determined the differential U3-protein interaction profile of ALVs and found that the 11 nt fragment specifically binds to cellular SERPINE1 mRNA binding protein 1 (SERBP1) to increase the LTR activity and enhance virus replication. Collectively, these findings reveal that a 11 nt fragment in the U3 gene contributed to its binding ability to the cellular SERBP1 to enhance its transcription and the infectious virus productions in avian cells. This study highlighted the vital role of host factor in retrovirus replication and thus provides a new perspective to elucidate the interaction between retrovirus and its host and a molecular basis to develop efficient strategies against retroviruses.
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Virus de la Leucosis Aviar , Leucosis Aviar , Pollos , Virus de la Leucosis Aviar/fisiología , Virus de la Leucosis Aviar/genética , Animales , Leucosis Aviar/virología , Enfermedades de las Aves de Corral/virología , Transcripción Genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Replicación Viral , Línea Celular , MutaciónRESUMEN
Avian influenza virus (AIV) infection and vaccination against live attenuated infectious bronchitis virus (aIBV) are frequent in poultry worldwide. Here, we evaluated the clinical effect of H9N2 subtype AIV and QX genotype aIBV co-infection in specific-pathogen-free (SPF) white leghorn chickens and explored the potential mechanisms underlying the observed effects using by 4D-FastDIA-based proteomics. The results showed that co-infection of H9N2 AIV and QX aIBV increased mortality and suppressed the growth of SPF chickens. In particular, severe lesions in the kidneys and slight respiratory signs similar to the symptoms of virulent QX IBV infection were observed in some co-infected chickens, with no such clinical signs observed in single-infected chickens. The replication of H9N2 AIV was significantly enhanced in both the trachea and kidneys, whereas there was only a slight effect on the replication of the QX aIBV. Proteomics analysis showed that the IL-17 signaling pathway was one of the unique pathways enriched in co-infected chickens compared to single infected-chickens. A series of metabolism and immune response-related pathways linked with co-infection were also significantly enriched. Moreover, co-infection of the two pathogens resulted in the enrichment of the negative regulation of telomerase activity. Collectively, our study supports the synergistic effect of the two pathogens, and pointed out that aIBV vaccines might increased IBV-associated lesions due to pathogenic co-infections. Exacerbation of the pathogenicity and mortality in H9N2 AIV and QX aIBV co-infected chickens possibly occurred because of an increase in H9N2 AIV replication, the regulation of telomerase activity, and the disturbance of cell metabolism and the immune system.
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Pollos , Coinfección , Infecciones por Coronavirus , Virus de la Bronquitis Infecciosa , Subtipo H9N2 del Virus de la Influenza A , Gripe Aviar , Enfermedades de las Aves de Corral , Animales , Pollos/virología , Subtipo H9N2 del Virus de la Influenza A/patogenicidad , Subtipo H9N2 del Virus de la Influenza A/genética , Virus de la Bronquitis Infecciosa/patogenicidad , Virus de la Bronquitis Infecciosa/genética , Coinfección/virología , Coinfección/veterinaria , Gripe Aviar/virología , Enfermedades de las Aves de Corral/virología , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/virología , Organismos Libres de Patógenos Específicos , Replicación Viral , Vacunas Atenuadas/inmunología , Genotipo , Virulencia , Proteómica , Riñón/virología , Riñón/patologíaRESUMEN
Gene therapy has been one of potential strategies for the treatment of different diseases, where efficient and safe gene delivery systems are also extremely in need. Current lipid nanoparticles (LNP) technology highly depends on the packing and condensation of nucleic acids with amine moieties. Here, an attempt to covalently link two natural compounds, spermine and vitamin E, is made to develop self-assembled nucleic acid delivery systems. Among them, the spermine moieties specifically interact with the major groove of siRNA helix through salt bridge interaction, while vitamin E moieties are located around siRNA duplex. Such amphiphilic vitamin E-spermine/siRNA complexes can further self-assemble into nanocomplexes like multiblade wheels. Further studies indicate that these siRNA nanocomplexes with the neutrally charged surface of vitamin E can enter cells via caveolin/lipid raft mediated endocytosis pathway and bypass lysosome trapping. With these self-assembled delivery systems, efficient siRNA delivery is successfully achieved for Eg5 and Survivin gene silencing as well as DNA plasmid delivery. Further in vivo study indicates that VE-Su-Sper/DSPE-PEG2000/siSurvivin self-assembled nanocomplexes can accumulate in cancer cells and gradually release siRNA in tumor tissues and show significant antitumor effect in vivo. The self-assembled delivery system provides a novel strategy for highly efficient siRNA delivery.
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Nanopartículas , ARN Interferente Pequeño , Espermina , Vitamina E , ARN Interferente Pequeño/química , Espermina/química , Animales , Humanos , Vitamina E/química , Nanopartículas/química , Ratones , Línea Celular Tumoral , Ratones Desnudos , Técnicas de Transferencia de Gen , Ratones Endogámicos BALB C , Survivin/genética , Survivin/metabolismo , Neoplasias/terapiaRESUMEN
Medical image segmentation algorithms based on deep learning have achieved good segmentation results in recent years, but they require a large amount of labeled data. When performing pixel-level labeling on medical images, labeling a target requires marking ten or even hundreds of points along its edge, which requires a lot of time and labor costs. To reduce the labeling cost, we utilize a click-based interactive segmentation method to generate high-quality segmentation labels. However, in current interactive segmentation algorithms, only the interaction information clicked by the user and the image features are fused as the input of the backbone network (so-called early fusion). The early fusion method has the problem that the interactive information is much sparse at this time. Furthermore, the interactive segmentation algorithms do not take into account the boundary problem, resulting in poor model performance. So we propose early fusion and late fusion strategy to prevent the interaction information from being diluted prematurely and make better use of the interaction information. At the same time, we propose a decoupled head structure, by extracting the image boundary information, and combining the boundary loss function to establish the boundary constraint term, so that the network can pay more attention to the boundary information and further improve the performance of the network. Finally, we conduct experiments on three medical datasets (Chaos, VerSe and Uterine Myoma MRI) to verify the effectiveness of our network. The experimental results show that our network greatly improved compared with the baseline, and NoC@80(the number of interactive clicks over 80% of the IoU threshold) improved by 0.1, 0.1, and 0.2. In particular, we have achieved a NoC@80 score of 1.69 on Chaos. According to statistics, manual annotation takes 25 min to label a case(Uterine Myoma MRI). Annotating a medical image with our method can be done in only 2 or 3 clicks, which can save more than 50% of the cost.
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Aprendizaje Profundo , Mioma , Humanos , Algoritmos , Tiempo , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Uterine myomas are the most common pelvic tumors in women, which can lead to abnormal uterine bleeding, abdominal pain, pelvic compression symptoms, infertility, or adverse pregnancy. In this article, we provide a dataset named uterine myoma MRI dataset (UMD), which can be used for clinical research on uterine myoma imaging. The UMD is the largest publicly available uterine MRI dataset to date including 300 cases of uterine myoma T2-weighted imaging (T2WI) sagittal patient images and their corresponding annotation files. The UMD covers 9 types of uterine myomas classified by the International Federation of Obstetrics and Gynecology (FIGO), which were annotated and reviewed by 11 experienced doctors to ensure the authority of the annotated data. The UMD is helpful for uterine myomas classification and uterine 3D reconstruction tasks, which has important implications for clinical research on uterine myomas.
Asunto(s)
Leiomioma , Imagen por Resonancia Magnética , Neoplasias Uterinas , Femenino , Humanos , Neoplasias Uterinas/diagnóstico por imagen , Leiomioma/diagnóstico por imagen , Útero/diagnóstico por imagenRESUMEN
With the awakening of health awareness, people are raising a series of health-related requirements for the buildings they live in, with a view to improving their living conditions. In this context, BIM (Building Information Modeling) makes full use of cutting-edge theories and technologies in many domains such as health, environment, and information technology to provide a new way for engineers to design and build various healthy and green buildings. Specifically, sensors are playing an important role in achieving smart building goals by monitoring the surroundings of buildings, objects and people with the help of cloud computing technology. In addition, it is necessary to quickly determine the optimal sensor placement to save energy and minimize the number of sensors for a building, which is a de-trial task for the cloud platform due to the limited number of sensors available and massive candidate locations for each sensor. In this paper, we propose a Fast Sensor Placement Location Optimization approach (FSPLO) to solve the BIM problem in cloud-aided smart buildings. In particular, we quickly filter out the repeated candidate locations of sensors in FSPLO using Locality Sensitive Hashing (LSH) techniques to maintain only a small number of optimized locations for deploying sensors around buildings. In this way, we can significantly reduce the number of sensors used for health and green buildings. Finally, a set of simulation experiments demonstrates the excellent performance of our proposed FSPLO method.