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1.
BMC Med Imaging ; 24(1): 86, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600525

RESUMEN

Medical imaging AI systems and big data analytics have attracted much attention from researchers of industry and academia. The application of medical imaging AI systems and big data analytics play an important role in the technology of content based remote sensing (CBRS) development. Environmental data, information, and analysis have been produced promptly using remote sensing (RS). The method for creating a useful digital map from an image data set is called image information extraction. Image information extraction depends on target recognition (shape and color). For low-level image attributes like texture, Classifier-based Retrieval(CR) techniques are ineffective since they categorize the input images and only return images from the determined classes of RS. The issues mentioned earlier cannot be handled by the existing expertise based on a keyword/metadata remote sensing data service model. To get over these restrictions, Fuzzy Class Membership-based Image Extraction (FCMIE), a technology developed for Content-Based Remote Sensing (CBRS), is suggested. The compensation fuzzy neural network (CFNN) is used to calculate the category label and fuzzy category membership of the query image. Use a basic and balanced weighted distance metric. Feature information extraction (FIE) enhances remote sensing image processing and autonomous information retrieval of visual content based on time-frequency meaning, such as color, texture and shape attributes of images. Hierarchical nested structure and cyclic similarity measure produce faster queries when searching. The experiment's findings indicate that applying the proposed model can have favorable outcomes for assessment measures, including Ratio of Coverage, average means precision, recall, and efficiency retrieval that are attained more effectively than the existing CR model. In the areas of feature tracking, climate forecasting, background noise reduction, and simulating nonlinear functional behaviors, CFNN has a wide range of RS applications. The proposed method CFNN-FCMIE achieves a minimum range of 4-5% for all three feature vectors, sample mean and comparison precision-recall ratio, which gives better results than the existing classifier-based retrieval model. This work provides an important reference for medical imaging artificial intelligence system and big data analysis.


Asunto(s)
Inteligencia Artificial , Tecnología de Sensores Remotos , Humanos , Ciencia de los Datos , Almacenamiento y Recuperación de la Información , Redes Neurales de la Computación
2.
Immunity ; 56(11): 2492-2507.e10, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37890481

RESUMEN

Lipid metabolism has been associated with the cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) stimulator of interferon genes (STING) DNA-sensing pathway, but our understanding of how these signals are integrated into a cohesive immunometabolic program is lacking. Here, we have identified liver X receptor (LXR) agonists as potent inhibitors of STING signaling. We show that stimulation of lipid metabolism by LXR agonists specifically suppressed cyclic GMP-AMP (cGAMP)-STING signaling. Moreover, we developed cyclic dinucleotide-conjugated beads to biochemically isolate host effectors for cGAMP inhibition, and we found that LXR ligands stimulated the expression of sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A), which is a 2'3'-cGAMP-degrading enzyme. Results of crystal structures suggest that cGAMP analog induces dimerization of SMPDL3A, and the dimerization is critical for cGAMP degradation. Additionally, we have provided evidence that SMPDL3A cleaves cGAMP to restrict STING signaling in cell culture and mouse models. Our results reveal SMPDL3A as a cGAMP-specific nuclease and demonstrate a mechanism for how LXR-associated lipid metabolism modulates STING-mediated innate immunity.


Asunto(s)
Metabolismo de los Lípidos , Nucleotidiltransferasas , Animales , Ratones , Receptores X del Hígado/metabolismo , Nucleotidiltransferasas/metabolismo , ADN , Nucleótidos Cíclicos/metabolismo , Inmunidad Innata
3.
Cancer Immunol Res ; 11(5): 583-599, 2023 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-36921097

RESUMEN

Cyclic GMP-AMP (cGAMP) is a second messenger that activates the stimulator of interferon genes (STING) innate immune pathway to induce the expression of type I IFNs and other cytokines. Pharmacologic activation of STING is considered a potent therapeutic strategy in cancer. In this study, we used a cell-based phenotypic screen and identified podophyllotoxin (podofilox), a microtubule destabilizer, as a robust enhancer of the cGAMP-STING signaling pathway. We found that podofilox enhanced the cGAMP-mediated immune response by increasing STING-containing membrane puncta and the extent of STING oligomerization. Furthermore, podofilox changed the trafficking pattern of STING and delayed trafficking-mediated STING degradation. Importantly, the combination of cGAMP and podofilox had profound antitumor effects on mice by activating the immune response through host STING signaling. Together, these data provide insights into the regulation of cGAMP-STING pathway activation and demonstrate what we believe to be a novel approach for modulating this pathway and thereby promoting antitumor immunity.


Asunto(s)
Neoplasias , Podofilotoxina , Animales , Ratones , Podofilotoxina/farmacología , Proteínas de la Membrana/metabolismo , Transducción de Señal , Inmunidad Innata
4.
Antioxidants (Basel) ; 12(2)2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36829913

RESUMEN

Influenza A virus infection induces the production of excessive reactive oxygen species (ROS). Overproduction of ROS can overwhelm the antioxidant defense system, leading to increasing intensive oxidative stress. However, antioxidant defense against oxidative damage induced by influenza A virus infection, and in particular the significance of the SOD3 response in the pathogenesis of influenza virus infection, has not been well characterized. Here, we investigated the potential role of SOD3 in resistance to influenza A virus infection. In this study, SOD3, as an important antioxidant enzyme, was shown to be highly elevated in A549 cells following influenza A virus infection. Furthermore, inhibition of SOD3 impacted viral replication and virulence. We found that SOD3 disrupts IAV replication by impairing the synthesis of vRNA, whereas it did not affect viral ribonucleoprotein nuclear export. In addition, overexpression of SOD3 greatly reduced the levels of ROS caused by influenza A virus infection, regulated the inflammatory response to virus infection by inhibiting the phosphorylation of p65 of the NF-κB signaling pathway, and inhibited virus-induced apoptosis to a certain extent. Taken together, these findings indicate that SOD3 is actively involved in influenza A virus replication. Pharmacological modulation or targeting of SOD3 may pave the way for a novel therapeutic approach to combating influenza A virus infection.

5.
Viruses ; 14(12)2022 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-36560742

RESUMEN

Influenza virus infections and the continuing spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are global public health concerns. As there are limited therapeutic options available in clinical practice, the rapid development of safe, effective and globally available antiviral drugs is crucial. Drug repurposing is a therapeutic strategy used in treatments for newly emerging and re-emerging infectious diseases. It has recently been shown that the voltage-dependent Ca2+ channel Cav1.2 is critical for influenza A virus entry, providing a potential target for antiviral strategies. Nisoldipine, a selective Ca2+ channel inhibitor, is commonly used in the treatment of hypertension. Here, we assessed the antiviral potential of nisoldipine against the influenza A virus and explored the mechanism of action of this compound. We found that nisoldipine treatment could potently inhibit infection with multiple influenza A virus strains. Mechanistic studies further revealed that nisoldipine impaired the internalization of the influenza virus into host cells. Overall, our findings demonstrate that nisoldipine exerts antiviral effects against influenza A virus infection and could serve as a lead compound in the design and development of new antivirals.


Asunto(s)
COVID-19 , Virus de la Influenza A , Gripe Humana , Humanos , Gripe Humana/tratamiento farmacológico , Internalización del Virus , SARS-CoV-2 , Nisoldipino/farmacología , Nisoldipino/uso terapéutico , Antivirales/farmacología , Antivirales/uso terapéutico
6.
PeerJ ; 7: e8172, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31844576

RESUMEN

BACKGROUND: This study was designed to explore the profile and potential influencers of the vaginal microbiome (VMB) among asymptomatic pregnant Chinese women and its possible association with pregnancy outcomes. METHODS: A prospective study was conducted among pregnant Chinese women receiving regular prenatal care at a hospital in Shanghai, China from March 2017 to March 2018. Vaginal swabs were obtained from 113 asymptomatic pregnant women in mid-pregnancy and sequenced by the V3-V4 region of 16S rRNA on an Ion S5™ XL platform. Demographic characteristics and major pregnancy outcomes were collected through questionnaires and electronic medical records. RESULTS: The predominant vaginal community state types (CSTs) were CST I (45.1%) and CST III (31.9%). Participants were divided into a lactobacilli-dominant group (LD, CST I/II/III/I-III/V, n = 100, 88.5%) and a less lactobacilli-dominant group (LLD, CST IV-A/B, n = 13, 11.5%). Women in the LLD group showed an increased alpha diversity [median (interquartile range, IQR): 2.41 (1.67, 2.49) vs. 0.30 (0.17, 0.59), P < 0.001], which was related to a lower pre-pregnancy body mass index (BMI) (P = 0.012), and a greater instance of passive smoking (P = 0.033). The relative abundance of Lactobacillus was correlated positively with the pre-pregnancy BMI (r = 0.177, P = 0.041), but negatively with passive smoking (r =  - 0.204, P = 0.030). CONCLUSION: The vaginal flora of asymptomatic pregnant Chinese women was mostly dominated by Lactobacillus crispatus and L. iners. A lower BMI and greater instance of passive smoking may contribute to a less lactobacilli-dominant VMB. However, a larger sample size is needed.

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