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1.
Front Cell Dev Biol ; 12: 1466491, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39355120

RESUMEN

As one of the key components of the immune system, mast cells are well known for their role in allergic reactions. However, they are also involved in inflammatory and fibrotic processes. Mast cells participate in all the stages of acute inflammatory responses, playing an immunomodulatory role in both innate and adaptive immunity. Mast cell-derived histamine, TNF-α, and IL-6 contribute to the inflammatory processes, while IL-10 mediates the suppression of inflammation. Crosstalk between mast cells and other immune cells is also involved in the development of inflammation. The cell-cell adhesion of mast cells and fibroblasts is crucial for fibrosis. Mast cell mediators, including cytokines and proteases, play contradictory roles in the fibrotic process. Here, we review the double-edged role of mast cells in inflammation and fibrosis.

2.
Polymers (Basel) ; 16(17)2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39274035

RESUMEN

Gellan gum (GG) is a natural polysaccharide with a wide range of industrial applications. This review aims to investigate the potential of GG-based films and coatings to act as environmentally friendly substitutes for traditional petrochemical plastics in food packaging. GG-based films and coatings exhibit versatile properties that can be tailored through the incorporation of various substances, such as plant extracts, microorganisms, and nanoparticles. These functional additives enhance properties like the light barrier, antioxidant activity, and antimicrobial capabilities, all of which are essential for extending the shelf-life of perishable food items. The ability to control the release of active compounds, along with the adaptability of GG-based films and coatings to different food products, highlights their effectiveness in preserving quality and inhibiting microbial growth. Furthermore, GG-based composites that incorporate natural pigments can serve as visual indicators for monitoring food freshness. Overall, GG-based composites present a promising avenue for the development of sustainable and innovative food packaging solutions.

4.
Int J Biol Macromol ; 280(Pt 1): 135719, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39293612

RESUMEN

The diverse active hydroxyl groups of lignin pose challenges in the preparation of lignin-based polyurethane coatings with exceptional long-term anticorrosive properties. Here, the dense and defect-free lignin-based polyurethane coating with a thickness of 25 ± 5 µm was successfully synthesized using a mild hydroxypropyl lignin modification approach, exhibiting outstanding barrier properties (|Z| > 109 Ω cm2) and long-term anti-corrosion performance exceeding 120 d. Under ambient conditions (i.e., 25 °C and atmospheric pressure), propylene oxide was directly blended with the alkali solution of lignin to effectively convert phenolic hydroxyl groups into more reactive aliphatic hydroxyl groups, while also minimizing the significant increase in molecular weight caused by lignin condensation. As a result, the high crosslinking density of lignin polyurethane coatings effectively prevented the penetration of corrosive media and enhanced the long-term corrosion resistance of the coatings. Overall, the results demonstrate that a mild hydroxypropyl modification process is an effective and facile strategy to prepare highly reactive lignin-based polyols, which is crucial for the development of high-performance bio-based polyurethane anticorrosive coatings.

5.
BMC Pulm Med ; 24(1): 473, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39334033

RESUMEN

BACKGROUND: The expression of 2'-5'-oligoadenylate synthetase 1 (OAS1) in lung cancer has been validated in numerous studies. However, the prognostic value of OAS1 expression in lung adenocarcinoma (LUAD) still remains unclear. This study aimed to reveal the prognostic value and associated molecular mechanisms of OAS1 expression in LUAD. METHODS: Gene expression data of LUAD were extracted from online databases. Gene and protein expression levels of OAS1 in LUAD and normal samples were revealed, followed by prognostic analysis of OAS1. Next, we conducted a thorough bioinformatics analysis to examine the enrichment of key functional and biological signaling pathways and their correlation with the abundance of immune cells. The independent prognoses, drug responses, and PPI networks associated with OAS1 were analyzed. OAS1 expression was evaluated in LUAD tissues and cell lines. OAS1 was knocked down by siRNA transfection, followed by CCK8, colony formation, and wound-healing assays. RESULTS: Gene and protein expression levels of OAS1 in LUAD samples were significantly higher than those in normal samples (all P < 0.05). OAS1 stimulation were correlated with poor prognosis, lymph node metastasis, advanced tumor stage, immune cells, and immunomodulators. The prognostic value of OAS1 in LUAD was determined via univariate regression analysis. In total, 10 OAS1-associated genes were revealed via PPI analysis of OAS1, which were primarily enriched in functions, such as the negative regulation of viral genome replication. Transcriptional analysis revealed several OAS1-related interactions, including STAT3-miR-21-OAS1. STAT3 was overexpressed and miR-21 was expressed in LUAD cells. Upregulation of OAS1 protein was determined in LUAD tissues and cell lines. OAS1 knockdown significantly reduced proliferation and migration of LUAD cells. CONCLUSIONS: OAS1 overexpression influenced survival and immune cell infiltration in patients with LUAD, which might be a potential prognostic gene for LUAD. Moreover, OAS1 contributed to LUAD progression by participating in STAT3-miR-21-OAS1 axis.


Asunto(s)
2',5'-Oligoadenilato Sintetasa , Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , 2',5'-Oligoadenilato Sintetasa/genética , 2',5'-Oligoadenilato Sintetasa/metabolismo , Pronóstico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Femenino , Masculino , Proliferación Celular/genética , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Biología Computacional , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Persona de Mediana Edad
6.
ACS Appl Mater Interfaces ; 16(37): 49371-49379, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39230483

RESUMEN

Photocatalytic reforming of ethanol provides an effective way to produce hydrogen energy using natural and nontoxic ethanol as raw material. Developing highly efficient catalysts is central to this field. Although traditional semiconductor/metal heterostructures (e.g., Rh/TiO2) can result in relatively high catalyst performance by promoting the separation of photoinduced hot carriers, it will still be highly promising to further improve the catalytic performance via a cost-effective and convenient method. In this study, we developed a highly efficient photocatalyst for ethanol reformation by preparing a ternary composite structure of Rh/TiO2/g-C3N4. Hydrogen is the main product, and the reaction rate could reach up to 27.5 mmol g-1 h-1, which is ∼1.41-fold higher than that of Rh/TiO2. The catalytic performance here is highly dependent on the wavelength of the light illumination. Moreover, the photocatalytic reforming of ethanol and production of hydrogen were also dependent on the Rh loading and g-C3N4:TiO2 ratio in Rh/TiO2/g-C3N4 composites as well as the ethanol content in the reaction system. The mechanism of the enhanced hydrogen production in Rh/TiO2/g-C3N4 is determined as the improvement in the separation of photoinduced hot carriers. This work provides an effective photocatalyst for ethanol reforming, largely expanding its application in the field of renewable energy and interface science.

7.
Oral Oncol ; 159: 107028, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39298831

RESUMEN

BACKGROUND: Immune-related biomarkers are linked to the outcomes of cancer immunotherapy. This study evaluates the baseline and longitudinal association between the lung immune prognostic index (LIPI) and immune checkpoint inhibitor outcomes in previously treated recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC) patients. METHODS: Data from 153 R/M NPC patients (median age = 49.00 years old) enrolled in a multicenter, single-arm, phase 2 study (NCT03848286) were analyzed. Pretreatment LIPI was classified into good and intermediate/poor (inter/poor) groups. Longitudinal LIPI variations were categorized into "Stable good", "Trend to increase", "Trend to decrease", and "Stable inter/poor". Primary and secondary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). RESULTS: Pretreatment LIPI was significantly associated with OS (inter/poor vs. good: HR = 2.54, 95 % CI: 1.60-4.04, P < 0.001), PFS [inter/poor vs. good: hazard ratio (HR) = 2.18, 95 % CI: 1.47-3.23, P < 0.001], and DCR [inter/poor vs. good: odd ratio (OR) = 0.26, 95 % CI: 0.12-0.58, P < 0.001)]. Patients with persistently inter/poor LIPI status showed worse OS (HR = 3.25, 95 % CI: 1.84-5.74, P < 0.001), PFS (HR = 2.96, 95 % CI: 1.85-4.74, P < 0.001), and ORR (OR = 0.21, 95 % CI: 0.08-0.56, P < 0.001) compared to the persistently good subgroup. CONCLUSION: Pretreatment LIPI and its longitudinal variations may serve as potential biomarkers for predicting immune checkpoint inhibitor outcomes in R/M NPC patients.

8.
Chem Biodivers ; : e202401460, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39152549

RESUMEN

Cardenolides are a class of steroidal glycoside compounds that are mainly distributed in plants, have significant physiological activity in the heart, and have been used clinically for over 200 years. To provide a reference for further research and development of these compounds, the phytochemical and biological properties of natural cardenolides (295 compounds in total) isolated between 2010 and 2023 from 17 families and hundreds of species belonging to 70-80 genera were reviewed. In vitro and in vivo studies have indicated that antitumor, antibacterial, and antiviral activities are the most commonly reported pharmacological properties of cardenolides. Antitumor activities have been thoroughly studied to understand their structure-activity relationships, revealing numerous potential anticancer molecules that lay the theoretical foundation for further development of traditional Chinese medicinal herbs and the creation of new drugs.

9.
Heliyon ; 10(15): e35085, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39170187

RESUMEN

The series-parallel hybrid system has attracted much attention from scholars for its effective integration of the power advantages and operating characteristics of different power sources, which is influenced by international emission regulations, energy-saving and emission reduction policies. As such, a series-parallel hybrid powertrain is introduced to the amphibious vehicle, and an innovative powertrain topology architecture is proposed. Meanwhile, the operation mode and energy efficiency characteristics are investigated during the working process. Firstly, the energy flow simulation model of a series-parallel gas-electric hybrid propulsion system is constructed using a modular modeling approach. Secondly, four operating modes, namely mechanical propulsion, electric propulsion, hybrid propulsion and charging mode, were formulated due to the fact that the propulsion system has multiple forms of power sources in the form of natural gas engine and reversible motor. Meanwhile, the energy flow states were investigated under different operating modes. Meanwhile, a comprehensive investigation of the energy efficiency associated with propulsion, storage and start-up energy was conducted for each specific mode. The results of the research indicated that the energy efficiency of the electric propulsion mode can reach up to 35.15 %, which is the gain from the wide operating range of the motor's high efficiency. The hybrid propulsion mode can obtain the highest energy efficiency of 35.88 %, which fully demonstrates the advantages of coordinating and complementing the two power sources, the natural gas engine and the reversible electric motor. This investigation also provides theoretical and empirical support for optimizing energy matching and formulating energy management strategies.

10.
Saudi Pharm J ; 32(9): 102139, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39139718

RESUMEN

Lung cancer ranks as the 2nd most common cancer globally. It's the most prevalent cancer in men and the 2nd most common in women. The prominent events in EGFR-mutated non-small-cell lung cancer (NSCLC) include the emergence of the L858R mutation within EGFR exon 21. Despite the promising efficacy of EGFR inhibitors in managing lung cancer, the development of acquired resistance poses a significant hurdle. In the current investigation, we focused on the screening of two phytochemicals, namely Dehydrocostus lactone and Mokkolactone, derived from the Saussurea lappa plant, as potential inhibitors targeting EGFR L858R mutant lung cancer. The chloroform and ethanol extract of the plant demonstrated anti-proliferative activity through the Resazurin chemosensitivity assay, exhibiting an IC50 value of 37.90 ± 0.29 µg/ml with selectivity index 2.4. Through a GC-MS study, we identified 11 phytochemicals for further insilico analysis. These compounds underwent ADMET assessment followed by drug likeliness analysis before being subjected to molecular docking against EGFR L858R, identified through protein-protein interaction network analysis. All phytochemicals exhibited binding energy scores ranging from -6.9 to -8.1 kcal/mol. Dehydrocostus lactone and Mokkolactone were specifically identified for their binding profile. Findings from 100 ns molecular dynamics simulations demonstrated their enhanced stability compared to the reference ligand DJK. This was evident in the root mean square deviation (RMSD) values, ranging from 0.23 ± 0.01 nm to 0.30 ± 0.05 nm, the radius of gyration values, from 1.71 ± 0.01 nm to 1.72 ± 0.01 nm, and the solvent accessible surface area values, from 155.39 ± 2.40 nm2 to 159.32 ± 2.14 nm2. Additionally, favourable characteristics were observed in terms of hydrogen bonding, principal component analysis, and free energy landscape analysis. Examination of their electronic structure via density functional theory revealed efficient properties, with the highest occupied molecular orbital-least unoccupied molecular orbital energy gap values ranging from -3.984 eV to -6.547 eV. Further, in vivo analysis is required to gain a more comprehensive understanding and efficacy of these identified phytochemicals against lung cancer.

12.
Bioorg Chem ; 151: 107619, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39024806

RESUMEN

Two rare 8-hydroxysteroid glycosides (6-7), and their downstream metabolites (1-5) with an unprecedented 6/6/5/5/5-pentacyclic scaffold, together with seven known analogues (8-14) were isolated from the twigs and leaves of Strophanthus divaricatus. Their structures were fully assigned by analysis of the spectroscopic and ECD data, NMR calculations, X-ray crystallographic study, and chemical methods. In addition, the inhibitory effects of 1-14 on liver and lung cancer cell lines were evaluated, and preliminary structure-activity relationship was discussed. Data-independent acquisition (DIA)-based quantitative proteomic analysis and biological verification of H1299 cells suggested that this family of compounds may play an anticancer role by suppressing both DNA damage response (DDR) and mTOR/S6K signaling pathways.


Asunto(s)
Daño del ADN , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Glicósidos , Transducción de Señal , Serina-Treonina Quinasas TOR , Humanos , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Relación Estructura-Actividad , Glicósidos/química , Glicósidos/farmacología , Glicósidos/aislamiento & purificación , Daño del ADN/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Estructura Molecular , Proliferación Celular/efectos de los fármacos , Esteroides/química , Esteroides/farmacología , Esteroides/aislamiento & purificación , Proteínas Quinasas S6 Ribosómicas/metabolismo , Proteínas Quinasas S6 Ribosómicas/antagonistas & inhibidores , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/química
13.
Heliyon ; 10(12): e33277, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-39021997

RESUMEN

Background: Cervical cancer is among the most prevalent malignancies worldwide. This study explores the relationships between angiogenesis-related genes (ARGs) and immune infiltration, and assesses their implications for the prognosis and treatment of cervical cancer. Additionally, it develops a diagnostic model based on angiogenesis-related differentially expressed genes (ARDEGs). Methods: We systematically evaluated 15 ARDEGs using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA). Immune cell infiltration was assessed using a single-sample gene-set enrichment analysis (ssGSEA) algorithm. We then constructed a diagnostic model for ARDEGs using Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and evaluated the diagnostic value of this model and the hub genes in predicting clinical outcomes and immunotherapy responses in cervical cancer. Results: A set of ARDEGs was identified from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and UCSC Xena database. We performed KEGG, GO, and GSEA analyses on these genes, revealing significant involvement in cell proliferation, differentiation, and apoptosis. The ARDEGs diagnostic model, constructed using LASSO regression analysis, showed high predictive accuracy in cervical cancer patients. We developed a reliable nomogram and decision curve analysis to evaluate the clinical utility of the ARDEG diagnostic model. The 15 ARDEGs in the model were associated with clinicopathological features, prognosis, and immune cell infiltration. Notably, ITGA5 expression and the abundance of immune cell infiltration (specifically mast cell activation) were highly correlated. Conclusion: This study identifies the prognostic characteristics of ARGs in cervical cancer patients, elucidating aspects of the tumor microenvironment. It enhances the predictive accuracy of immunotherapy outcomes and establishes new strategies for immunotherapeutic interventions.

15.
Heliyon ; 10(11): e32090, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38933933

RESUMEN

As a paradigm shift in tandem with the expansion of ICT, smart electronic health systems hold great promise for enhancing healthcare delivery and illness prevention efforts. These systems acquire an in-depth understanding of patient health states through the real-time collection and analysis of medical data enabled by the Internet of Things (IoT) and machine learning. With the widespread use of cutting-edge artificial intelligence and machine learning techniques, predictive analytics in medicine can assist in making the shift from a reactive to a proactive healthcare strategy. With the ability to rapidly and precisely evaluate massive amounts of data, draw intelligent conclusions, and solve difficult issues, artificial neural networks could revolutionize several industries. Two cardiac illnesses were assessed in this study using a multilayer perceptron artificial neural network that incorporated a genetic algorithm and an error-back propagation mechanism. The ability of artificial neural networks to handle consecutive time series data is crucial for optimizing resources in smart electronic health systems, especially with the increasing volume of patient information and the broad use of electronic clinical records. This requires the creation of more accurate predictive models. Through the use of Internet of Things (IoT) sensors, the proposed system gathers data, which is then used to do predictive analytics on patient history-related electronic clinical data saved in the cloud. A smart healthcare system that uses Mu-LTM (multidirectional long-term memory) to accurately monitor and predict the risk of heart disease has a coverage error of 97.94 %, an accuracy of 97.89 %, a sensitivity of 97.96 %, and a specificity of 97.99 %. In comparison to other smart heart disease prediction systems, the F1-score of 97.95 % and precision of 97.71 % is very good.

16.
J Am Chem Soc ; 146(28): 19108-19117, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38847788

RESUMEN

Previous findings have suggested a close association between oxygen vacancies in SnO2 and charge carrier recombination as well as perovskite decomposition at the perovskite/SnO2 interface. Underlying the fundamental mechanism holds great significance in achieving a more favorable balance between the efficiency and stability. In this study, we prepared three SnO2 samples with different oxygen vacancy concentrations and observed that a low oxygen vacancy concentration is conducive to long-term device stability. Iodide ions were observed to easily diffuse into regions with high oxygen vacancies, thereby speeding up the deprotonation of FAI, as made evident by the detection of the decomposition product formamide. In contrast, a high oxygen vacancy concentration in SnO2 could prevent hole injection, leading to a decrease in interfacial recombination losses. To suppress this decomposition reaction and address the trade-off, we designed a bilayer SnO2 structure to ensure highly efficient carrier transport still while maintaining a chemically inert surface. As a result, an enhanced efficiency of 25.06% (certified at 24.55% with an active area of 0.09 cm2 under fast scan) was achieved, and the extended operational stability maintained 90% of their original efficiency (24.52%) after continuous operation for nearly 2000 h. Additionally, perovskite submodules with an active area of 14 cm2 were successfully assembled with a PCE of up to 22.96% (20.09% with an aperture area).

17.
Int J Mol Sci ; 25(11)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38891899

RESUMEN

In aquaculture, viral diseases pose a significant threat and can lead to substantial economic losses. The primary defense against viral invasion is the innate immune system, with interferons (IFNs) playing a crucial role in mediating the immune response. With advancements in molecular biology, the role of non-coding RNA (ncRNA), particularly microRNAs (miRNAs), in gene expression has gained increasing attention. While the function of miRNAs in regulating the host immune response has been extensively studied, research on their immunomodulatory effects in teleost fish, including silver carp (Hyphthalmichthys molitrix), is limited. Therefore, this research aimed to investigate the immunomodulatory role of microRNA-30b-5p (miR-30b-5p) in the antiviral immune response of silver carp (Hypophthalmichthys molitrix) by targeting cytokine receptor family B5 (CRFB5) via the JAK/STAT signaling pathway. In this study, silver carp were stimulated with polyinosinic-polycytidylic acid (poly (I:C)), resulting in the identification of an up-regulated miRNA (miR-30b-5p). Through a dual luciferase assay, it was demonstrated that CRFB5, a receptor shared by fish type I interferon, is a novel target of miR-30b-5p. Furthermore, it was found that miR-30b-5p can suppress post-transcriptional CRFB5 expression. Importantly, this study revealed for the first time that miR-30b-5p negatively regulates the JAK/STAT signaling pathway, thereby mediating the antiviral immune response in silver carp by targeting CRFB5 and maintaining immune system stability. These findings not only contribute to the understanding of how miRNAs act as negative feedback regulators in teleost fish antiviral immunity but also suggest their potential therapeutic measures to prevent an excessive immune response.


Asunto(s)
Carpas , Proteínas de Peces , MicroARNs , Poli I-C , Transducción de Señal , Animales , Carpas/genética , Carpas/inmunología , Carpas/virología , Carpas/metabolismo , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/virología , Enfermedades de los Peces/genética , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Inmunidad Innata/genética , Quinasas Janus/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Poli I-C/farmacología , Factores de Transcripción STAT/metabolismo , Factores de Transcripción STAT/genética
18.
Biomolecules ; 14(6)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38927097

RESUMEN

MicroRNAs (miRNAs) are highly conserved endogenous single-stranded non-coding RNA molecules that play a crucial role in regulating gene expression to maintain normal physiological functions in fish. Nevertheless, the specific physiological role of miRNAs in lower vertebrates, particularly in comparison to mammals, remains elusive. Additionally, the mechanisms underlying the control of antiviral responses triggered by viral stimulation in fish are still not fully understood. In this study, we investigated the regulatory impact of miR-1388 on the signaling pathway mediated by IFN regulatory factor 3 (IRF3). Our findings revealed that following stimulation with the viral analog poly(I:C), the expression of miR-1388 was significantly upregulated in primary immune tissues and macrophages. Through a dual luciferase reporter assay, we corroborated a direct targeting relationship between miR-1388 and tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3). Furthermore, our study demonstrated a distinct negative post-transcriptional correlation between miR-1388 and TRAF3. We observed a significant negative post-transcriptional regulatory association between miR-1388 and the levels of antiviral genes following poly(I:C) stimulation. Utilizing reporter plasmids, we elucidated the role of miR-1388 in the antiviral signaling pathway activated by TRAF3. By intervening with siRNA-TRAF3, we validated that miR-1388 regulates the expression of antiviral genes and the production of type I interferons (IFN-Is) through its interaction with TRAF3. Collectively, our experiments highlight the regulatory influence of miR-1388 on the IRF3-mediated signaling pathway by targeting TRAF3 post poly(I:C) stimulation. These findings provide compelling evidence for enhancing our understanding of the mechanisms through which fish miRNAs participate in immune responses.


Asunto(s)
Carpas , MicroARNs , Poli I-C , Factor 3 Asociado a Receptor de TNF , Animales , MicroARNs/genética , MicroARNs/metabolismo , Poli I-C/farmacología , Carpas/genética , Carpas/metabolismo , Carpas/virología , Factor 3 Asociado a Receptor de TNF/genética , Factor 3 Asociado a Receptor de TNF/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Factor 3 Regulador del Interferón/metabolismo , Factor 3 Regulador del Interferón/genética , Regulación de la Expresión Génica/efectos de los fármacos , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Transducción de Señal
19.
Acta Pharm Sin B ; 14(6): 2773-2785, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38828142

RESUMEN

Although sulfonation plays crucial roles in various biological processes and is frequently utilized in medicinal chemistry to improve water solubility and chemical diversity of drug leads, it is rare and underexplored in ribosomally synthesized and post-translationally modified peptides (RiPPs). Biosynthesis of RiPPs typically entails modification of hydrophilic residues, which substantially increases their chemical stability and bioactivity, albeit at the expense of reducing water solubility. To explore sulfonated RiPPs that may have improved solubility, we conducted co-occurrence analysis of RiPP class-defining enzymes and sulfotransferase (ST), and discovered two distinctive biosynthetic gene clusters (BGCs) encoding both lanthipeptide synthetase (LanM) and ST. Upon expressing these BGCs, we characterized the structures of novel sulfonated lanthipeptides and determined the catalytic details of LanM and ST. We demonstrate that SslST-catalyzed sulfonation is leader-independent but relies on the presence of A ring formed by LanM. Both LanM and ST are promiscuous towards residues in the A ring, but ST displays strict regioselectivity toward Tyr5. The recognition of cyclic peptide by ST was further discussed. Bioactivity evaluation underscores the significance of the ST-catalyzed sulfonation. This study sets up the starting point to engineering the novel lanthipeptide STs as biocatalysts for hydrophobic lanthipeptides improvement.

20.
Artículo en Chino | MEDLINE | ID: mdl-38858123

RESUMEN

Objective:To evaluate the diagnostic efficacy of traditional radiomics, deep learning, and deep learning radiomics in differentiating normal and inner ear malformations on temporal bone computed tomography(CT). Methods:A total of 572 temporal bone CT data were retrospectively collected, including 201 cases of inner ear malformation and 371 cases of normal inner ear, and randomly divided into a training cohort(n=458) and a test cohort(n=114) in a ratio of 4∶1. Deep transfer learning features and radiomics features were extracted from the CT images and feature fusion was performed to establish the least absolute shrinkage and selection operator. The CT results interpretated by two chief otologists from the National Clinical Research Center for Otorhinolaryngological Diseases served as the gold standard for diagnosis. The model performance was evaluated using receiver operating characteristic(ROC), and the accuracy, sensitivity, specificity, and other indicators of the models were calculated. The predictive power of each model was compared using the Delong test. Results:1 179 radiomics features were obtained from traditional radiomics, 2 048 deep learning features were obtained from deep learning, and 137 features fusion were obtained after feature screening and fusion of the two. The area under the curve(AUC) of the deep learning radiomics model on the test cohort was 0.964 0(95%CI 0.931 4-0.996 8), with an accuracy of 0.922, sensitivity of 0.881, and specificity of 0.945. The AUC of the radiomics features alone on the test cohort was 0.929 0(95%CI 0.882 2-0.974 9), with an accuracy of 0.878, sensitivity of 0.881, and specificity of 0.877. The AUC of the deep learning features alone on the test cohort was 0.947 0(95%CI 0.898 2-0.994 8), with an accuracy of 0.913, sensitivity of 0.810, and specificity of 0.973. The results indicated that the prediction accuracy and AUC of the deep learning radiomics model are the highest. The Delong test showed that the differences between any two models did not reach statistical significance. Conclusion:The feature fusion model can be used for the differential diagnosis of normal and inner ear malformations, and its diagnostic performance is superior to radiomics or deep learning models alone.


Asunto(s)
Aprendizaje Profundo , Oído Interno , Hueso Temporal , Tomografía Computarizada por Rayos X , Humanos , Hueso Temporal/diagnóstico por imagen , Hueso Temporal/anomalías , Oído Interno/diagnóstico por imagen , Oído Interno/anomalías , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Masculino , Femenino , Sensibilidad y Especificidad , Curva ROC , Radiómica
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