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Lung cancer, which is a leading cause of cancer-related deaths worldwide, frequently metastasizes to the bones, significantly diminishing patients' quality of life and complicating treatment strategies. This study aims to develop an advanced 3D Mask R-CNN model, enhanced with the ConvNeXt-V2 backbone, for the automatic segmentation of bone tumors and identification of lung cancer metastasis to support personalized treatment planning. Data were collected from two hospitals: Center A (106 patients) and Center B (265 patients). The data from Center B were used for training, while Center A's dataset served as an independent external validation set. High-resolution CT scans with 1 mm slice thickness and no inter-slice gaps were utilized, and the regions of interest (ROIs) were manually segmented and validated by two experienced radiologists. The 3D Mask R-CNN model achieved a Dice Similarity Coefficient (DSC) of 0.856, a sensitivity of 0.921, and a specificity of 0.961 on the training set. On the test set, it achieved a DSC of 0.849, a sensitivity of 0.911, and a specificity of 0.931. For the classification task, the model attained an AUC of 0.865, an accuracy of 0.866, a sensitivity of 0.875, and a specificity of 0.835 on the training set, while achieving an AUC of 0.842, an accuracy of 0.836, a sensitivity of 0.847, and a specificity of 0.819 on the test set. These results highlight the model's potential in improving the accuracy of bone tumor segmentation and lung cancer metastasis detection, paving the way for enhanced diagnostic workflows and personalized treatment strategies in clinical oncology.
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This study focused on exploring the Zn2+ chelating peptide GFLGSP: the characterization of structure/Zn2+ chelating mode and the potential mechanisms for promoting Zn2+ transport in Caco-2 cells. The findings revealed the bidentate chelating between Zn2+ and carboxyl oxygen atom in Pro6 residue. Thereafter, the secondary structure of GFLGSP remained unchanged, but there was an increase in zeta potential and particle size. Notably, the GFLGSP-Zn2+ complex enhanced the Zn2+ transport rate and modulated ZIP4 and ZNT1 expression in a Caco-2 cells monolayer model. As revealed by molecular docking analysis, GFLGSP interacted with ZIP4 through intermolecular hydrogen bonds as well as Van der Waals forces. The Zn2+ transport mechanisms of the GFLGSP-Zn2+ complex encompassed ZIP4 (vital channel), endocytosis (primary pathway) and paracellular transport (supplementary pathway). Based on these results, the tilapia skin collagen-derived GFLGSP hold promise as the potential dietary Zn2+ supplement.
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Proteínas de Transporte de Cátions , Quelantes , Simulação de Acoplamento Molecular , Peptídeos , Zinco , Humanos , Células CACO-2 , Zinco/metabolismo , Zinco/química , Quelantes/química , Quelantes/metabolismo , Quelantes/farmacologia , Proteínas de Transporte de Cátions/metabolismo , Peptídeos/química , Peptídeos/metabolismo , Transporte BiológicoRESUMO
Objective Biochemical remission rates of endoscopic endonasal transsphenoidal surgery (EETS) and its associated predictive factors were evaluated in patients with somatotrophin pituitary adenomas. Methods The patients who underwent EETS in Jinling Hospital were identified between 2011 and 2020. The surgeons' experience, preoperative insulin-like growth factor 1 (IGF-1), basal growth hormone (GH) levels, nadir GH levels, and the tumor characteristics were analyzed for their relationships with endocrine outcomes. Total 98 patients were included for single factor analysis and regression analysis. They were divided into three groups according to the admission chronologic order. Results The overall remission rate of the patients was 57% (56/98) for all the patients over 10 years. In the single factor analysis, we found that the tumor size, cavernous invasion, and sellar invasion were valuable to predict the endocrine outcome after surgery. As for the suprasellar invasion, no significant difference was found between the noninvasive group and the invasive group. The preoperative IGF-1 level ( p = 0.166), basal GH level ( p = 0.001), and nadir GH level ( p = 0.004) were also different between the remission group and the nonremission group in the single factor analysis. The logistic regression analysis indicated that the preoperative nadir GH (odds ratio = 0.930, 95% confidence interval = 0.891-0.972, p = 0.001) was a significant predictor for the endocrine outcomes after surgery. Conclusion The surgeons' experience is an important factor that can affect the patients' endocrine outcomes after surgery. The macroadenomas with lateral invasion are more difficult to cure. Patients with higher preoperative nadir GH levels are less likely to achieve remission.
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Crustacean shellfish are major allergens in East Asia. In the present study, a major allergic protein in crustaceans, tropomyosin, was detected accurately using multiple reaction monitoring mode-based mass spectrometry, with shared signature peptides identified through proteomic analysis. The peptides were deliberately screened through thermal stability and enzymatic digestion efficiency to improve the suitability and accuracy of the developed method. Finally, the proposed method demonstrated a linear range of 0.15 to 30 mgTM/kgfood (R2 > 0.99), with a limit of detection of 0.15 mgTM/kg food and a limit of quantification of 0.5mgTM/kgfood and successfully applied to commercially processed foods, such as potato chips, biscuits, surimi, and hot pot seasonings, which evidenced the applicability of proteomics-based methodology for food allergen analysis.
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Alérgenos , Peptídeos , Proteômica , Frutos do Mar , Tropomiosina , Animais , Alérgenos/química , Alérgenos/imunologia , Proteínas de Artrópodes/química , Proteínas de Artrópodes/imunologia , Crustáceos/química , Hipersensibilidade Alimentar/imunologia , Alimento Processado , Espectrometria de Massas/métodos , Peptídeos/química , Proteômica/métodos , Frutos do Mar/análise , Hipersensibilidade a Frutos do Mar/imunologia , Tropomiosina/química , Tropomiosina/imunologiaRESUMO
OBJECTIVES: To compare the efficacy of nadroparin and fondaparinux sodium for prevention of deep vein thromboembolism (DVT) in lower extremities after total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: A total of 592 patients were enrolled in the study. Clinical data of patients who underwent total hip arthroplasty (THA) and total knee arthroplasty (TKA) in our hospital from December 2021 to September 2022 were retrospectively collected, which mainly included patients' general information, surgery-related information, and DVT-related information. The patients were categorized into the nadroparin group(n = 278) and the fondaparinux sodium group(n = 314) according to the types of anticoagulants used. Anticoagulant therapy began 12-24 h after operation and continued until discharge. DVT prevalence between two groups was compared. The Statistical Package for Social Sciences (SPSS) software version 25 (SPSS, Armonk, NY, USA) was used for statistical analysis. RESULTS: The prevalence of DVT in the nadroparin group and the fondaparinux sodium group was 8.3% (23/278) and 15.0% (47/314), respectively(p = 0.012). Statistical analysis showed that nadroparin group showed a lower prevalence of thrombosis than fondaparinux group (OR = 1.952, P = 0.012). Subgroup analyses showed that nadroparin group had a lower prevalence of DVT than fondaparinux group in some special patients groups such as female patients (OR = 2.258, P = 0.007), patients who are 65-79 years old (OR = 2.796, P = 0.004), patients with hypertension (OR = 2.237, P = 0.042), patients who underwent TKA (OR = 2.091, P = 0.011), and patients who underwent combined spinal-epidural anesthesia (OR = 2.490, P = 0.003) (P < 0.05). CONCLUSION: Nadroparin may have an advantage over fondaparinux sodium in preventing DVT in lower extremities after THA and TKA.
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Anticoagulantes , Artroplastia de Quadril , Artroplastia do Joelho , Fondaparinux , Nadroparina , Complicações Pós-Operatórias , Tromboembolia Venosa , Humanos , Fondaparinux/uso terapêutico , Feminino , Masculino , Estudos Retrospectivos , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Nadroparina/uso terapêutico , Nadroparina/administração & dosagem , Pessoa de Meia-Idade , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/epidemiologia , Idoso , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/cirurgia , Resultado do TratamentoRESUMO
As a notorious phytopathogenic virus, the tobacco mosaic virus (TMV) severely reduced the quality of crops worldwide and caused critical constraints on agricultural production. The development of novel virucides is a persuasive strategy to address this predicament. Herein, a series of novel bisamide-decorated benzotriazole derivatives were elaborately prepared and screened. Biological tests implied that the optimized compound 7d possessed the most brilliant antiviral inactive profile (EC50 = 157.6 µg/mL) and apparently surpassed that of commercial ribavirin (EC50 = 442.1 µg/mL) 2.8-fold. The preliminary antiviral mechanism was elaborately investigated via transmission electron microscopy, microscale thermophoresis (MST) determination, RT-qPCR, and Western blot analysis. The results showed that compound 7d blocked the assembly of TMV by binding with coat protein (Kd = 0.7 µM) and suppressed TMV coat protein gene expression and biosynthesis process. Computational simulations indicated that 7d displayed strong H-bonds and pi interactions with TMV coat protein, affording a lower binding energy (ΔGbind = -17.8 kcal/mol) compared with Ribavirin (ΔGbind = -10.7 kcal/mol). Overall, current results present a valuable perception of bisamide decorated benzotriazole derivatives with appreciably virustatic competence and should be profoundly developed as virucidal candidates in agrochemical.
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Ribavirina , Vírus do Mosaico do Tabaco , Triazóis , Relação Estrutura-Atividade , Ribavirina/farmacologia , Antivirais/farmacologia , Antivirais/química , Desenho de FármacosRESUMO
BACKGROUND: Naturally occurring alkaloids are particularly suitable for use as pesticide precursors and further modifications due to their cost-effectiveness, unique mechanism of action, tolerable degradation, and environmental friendliness. The famous tobacco mosaic virus (TMV) is a persistent plant pathogenic virus that can parasitize many plants and severely reduce crop production. To treat TMV disease, TMV helicase acts as a crucial target by hydrolyzing adenosine triphosphate (ATP) to provide energy for double-stranded RNA unwinding. RESULTS: To seek novel framework alkaloid leads targeting TMV helicase, this work successfully established an efficient screening platform for TMV helicase inhibitors based on natural alkaloids. In vivo activity screening, enzyme activity detection, and binding assays showed that Rutaecarpine from Evodia rutaecarpa (Juss.) Benth exhibited excellent TMV helicase inhibitory properties [dissociation constant (Kd ) = 1.1 µm, half maximal inhibitory concentration (IC50 ) = 227.24 µm] and excellent anti-TMV ability. Molecular docking and dynamic simulations depicted that Rutaecarpine could stably bind in active pockets of helicase with low binding energy (ΔGbind = -17.8 kcal/mol) driven by hydrogen bonding and hydrophobic interactions. CONCLUSION: Given Rutaecarpine's laudable bioactivity and structural modifiability, it can serve as a privileged building block for further pesticide discovery.
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Alcaloides , Alcaloides Indólicos , Praguicidas , Quinazolinonas , Vírus do Mosaico do Tabaco , Viroses , Simulação de Acoplamento Molecular , Nicotiana , Doenças das Plantas/prevenção & controleRESUMO
Abstract Objective: This study mainly explores (2R,6R; 2S,6S)-HNK and its compounds whether there are antidepressant effects. Methods: Four HNK compounds were obtained from 2-(Chlorophenyl) Cyclopentylmethanone. Forced swimming test, locomotor sensitization test, and conditioned location preference test were used to screen the antidepressant activity of the synthesized target compounds. Results: In the case of 10 mg HNK treatment, compared with saline, the immobile time of mice in the HNK group, I5 group and I6 group at 1 h and 7 days had statistical significance. In the case of 10 mg HNK treatment, compared with saline, the immobile time of compound C and D groups in the glass cylinder area was significantly different. In the locomotor sensitization test, the movement distance of compound C and D groups on day 15 and day 7 mice increased significantly compared with the first day. In the conditioned place preference experiment, compound C and compound D induced conditioned place preference in mice compared with the Veh group. Conclusion: The results of the forced swimming test, locomotor sensitization test, and conditioned location preference test showed that compounds C and D may have certain anti-depressant activity. However, HNK exerts a rapid and significant antidepressant effect within 1 week, but the duration is short.
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Highly effective and selective noble metal-free catalysts attract significant attention. Here, a single-atom iron catalyst is fabricated by saturated adsorption of trace iron onto zeolitic imidazolate framework-8 (ZIF-8) followed by pyrolysis. Its performance toward catalytic transfer hydrogenation of furfural is comparable to state-of-the-art catalysts and up to four orders higher than other Fe catalysts. Isotopic labeling experiments demonstrate an intermolecular hydride transfer mechanism. First principles simulations, spectroscopic calculations and experiments, and kinetic correlations reveal that the synthesis creates pyrrolic Fe(II)-plN3 as the active center whose flexibility manifested by being pulled out of the plane, enabled by defects, is crucial for collocating the reagents and allowing the chemistry to proceed. The catalyst catalyzes chemoselectively several substrates and possesses a unique trait whereby the chemistry is hindered for more acidic substrates than the hydrogen donors. This work paves the way toward noble-metal free single-atom catalysts for important chemical reactions.
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Objective. In brain tumor segmentation tasks, the convolutional neural network (CNN) or transformer is usually acted as the encoder since the encoder is necessary to be used. On one hand, the convolution operation of CNN has advantages of extracting local information although its performance of obtaining global expressions is bad. On the other hand, the attention mechanism of the transformer is good at establishing remote dependencies while it is lacking in the ability to extract high-precision local information. Either high precision local information or global contextual information is crucial in brain tumor segmentation tasks. The aim of this paper is to propose a brain tumor segmentation model that can simultaneously extract and fuse high-precision local and global contextual information.Approach. We propose a network model DE-Uformer with dual encoders to obtain local features and global representations using both CNN encoder and Transformer encoder. On the basis of this, we further propose the nested encoder-aware feature fusion (NEaFF) module for effective deep fusion of the information under each dimension. It may establishe remote dependencies of features under a single encoder via the spatial attention Transformer. Meanwhile ,it also investigates how features extracted from two encoders are related with the cross-encoder attention transformer.Main results. The proposed algorithm segmentation have been performed on BraTS2020 dataset and private meningioma dataset. Results show that it is significantly better than current state-of-the-art brain tumor segmentation methods.Significance. The method proposed in this paper greatly improves the accuracy of brain tumor segmentation. This advancement helps healthcare professionals perform a more comprehensive analysis and assessment of brain tumors, thereby improving diagnostic accuracy and reliability. This fully automated brain model segmentation model with high accuracy is of great significance for critical decisions made by physicians in selecting treatment strategies and preoperative planning.
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Neoplasias Encefálicas , Neoplasias Meníngeas , Meningioma , Humanos , Reprodutibilidade dos Testes , Neoplasias Encefálicas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , EncéfaloRESUMO
Plant diseases caused by malignant and refractory phytopathogenic viruses have considerably restricted crop yields and quality. To date, drug design targeting functional proteins or enzymes of viruses is an efficient and viable strategy to guide the development of new pesticides. Herein, a series of novel eugenol derivatives targeting the tobacco mosaic virus (TMV) helicase have been designed using structure-based virtual screening (SBVS). Structure-activity relationship indicated that 2 t displayed the most powerful bonding capability (Kd = 0.2 µM) along with brilliant TMV helicase ATPase inhibitory potency (IC50 = 141.9 µM) and applausive anti-TMV capability (EC50 = 315.7 µg/mL), ostentatiously outperforming that of commercial Acyclovir (Kd = 23.0 µM, IC50 = 183.7 µM) and Ribavirin (EC50 = 624.3 µg/mL). Molecular dynamics simulations and docking suggested ligand 2 t was stable and bound in the active pocket of the TMV helicase by multiple interactions. Given these superior properties, eugenol-based derivatives could be considered as the novel potential plant viral helicase inhibitors. Furthermore, this effective and feasible SBVS strategy established a valuable screening platform for helicase-targeted drug development.
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Vírus do Mosaico do Tabaco , Eugenol/farmacologia , Antivirais/farmacologia , Relação Estrutura-Atividade , DNA Helicases , Desenho de FármacosRESUMO
The active substances derived from plants have received increasing attention owing to their wide range of pharmacological applications, including anti-tumor, anti-allergic, anti-viral, and anti-oxidative activities. The allergy epidemic is a growing global public health problem that threatens human health and safety. Polyphenols from plants have significant anti-allergic effects and are an important source of anti-allergic drug research and development. Here, we describe recent advances in the anti-allergic efficacy of plant polyphenols, including their comprehensive effects on cellular or animal models. The current issues and directions for future development in this field are discussed to provide a theoretical basis for the development and utilization of these active substances as anti-allergic products.
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Fermentation techniques may induce alterations in fish allergen immunoreactivity. In this study, the influence of fermentation with three different strains of Lactobacillus helveticus (Lh187926, Lh191404, and Lh187926) on the immunoreactivity of Atlantic cod allergens was investigated via several methods. Gradually reduced protein composition and band intensity due to the fermentation by strain Lh191404 were found in SDS-PAGE analysis, and decreased immunoreactivity of fish allergens was confirmed by Western blotting and ELISA analysis due to the fermentation of strain Lh191404. Additionally, results from nLC-MS/MS and immunoinformatics tools analysis demonstrated that the protein polypeptide and allergen composition of Atlantic cod showed evident alterations after fermentation, with the epitopes of the main fish allergens being heavily exposed and destroyed. These results indicated that the fermentation of L. helveticus Lh191404 could destroy the structure and linear epitopes of the allergens from Atlantic cod and may have considerable potential in mitigating the allergenicity of fish.
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Gadus morhua , Lactobacillus helveticus , Animais , Alérgenos/química , Gadus morhua/metabolismo , Fermentação , Espectrometria de Massas em Tandem , Epitopos/química , Peixes/metabolismoRESUMO
BACKGROUND: The discovery and identification of targets is of far-reaching significance for developing novel pesticide candidates and increasing the probability of success. To explore and identify highly effective tobacco mosaic virus (TMV) helicase-targeted lead structures, a series of novel phosphonate derivatives containing a 1,2,3-triazole motif were rationally engineered and their antiviral activity was assessed. RESULTS: Bioassay results showed that the optimized B17 exhibited more potent curative activity (EC50 = 271.5 µg mL-1 ) against TMV in vivo, which was superior to that of commercial Ribavirin (EC50 = 689.3 µg mL-1 ). B17 presented a stronger binding capacity through binding analysis with helicase, affording a corresponding value of 12.7 µM. Enzyme activity assay showed B17 exhibited excellent inhibitory activity on TMV helicase (39.2% at 300 µM). Furthermore, molecular docking simulations demonstrated that B17 displayed strong hydrogen-bond interactions (2.1, 2.1, 2.2, and 3.2 Å) with Ala-33, Gly-10, Gly-8, and Glu-217 of TMV helicase. Encouragingly, transmission electron microscopy analysis revealed that B17 could remarkably disrupt surface morphology and inhibit TMV proliferation. Additionally, these compounds also displayed potential anti-CMV (cucumber mosaic virus) and antipathogens (Xanthomonas oryzae pv. oryzae and Xanthomonas axonopodis pv. citri) by expanding their applications in agriculture. CONCLUSION: Current research demonstrated that B17 could be considered as a potential antiviral agent alternative though targeting TMV helicase. © 2023 Society of Chemical Industry.
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Vírus do Mosaico do Tabaco , Viroses , Humanos , Simulação de Acoplamento Molecular , Testes de Sensibilidade Microbiana , Antivirais/farmacologia , Antivirais/química , Relação Estrutura-Atividade , Desenho de FármacosRESUMO
Tropomyosin (TM) is the main allergen in shrimp food. Algae polyphenol reportedly could affect the structures and allergenicity of shrimp TM. In this study, the alterations of conformational structures and allergenicity of TM induced by Sargassum fusiforme polyphenol (SFP) were investigated. Compared to TM, the conjugation of SFP to TM induced conformational structure instability, the IgG-binding capacity and IgE-binding capacity of TM gradually decreased with more conjugation of SFP to TM, and the conjugation of SFP to TM could significantly reduce degranulation, histamine secretion and release of IL-4 and IL-13 from RBL-2H3 mast cells. Therefore, the conjugation of SFP to TM led to conformational instability, significantly decreased the IgG-binding capacity and IgE-binding capacity, weakened the allergic responses of TM-stimulated mast cell, and performed in vivo anti-allergic properties in BALB/c mouse model. Therefore, SFP could serve as candidate natural anti-allergic substances to reduce shrimp TM-induced food allergy.
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Antialérgicos , Sargassum , Animais , Camundongos , Alérgenos , Tropomiosina , Alimentos Marinhos , Crustáceos , Camundongos Endogâmicos BALB C , Polifenóis , Imunoglobulina E , Imunoglobulina GRESUMO
BACKGROUND: Plant pathogens have led to large yield and quality losses in crops worldwide. The discovery and study of novel agrochemical alternatives based on the chemical modification of bioactive natural products is a highly efficient approach. Here, two series of novel cinnamic acid derivatives incorporating diverse building blocks with alternative linking patterns were designed and synthesized to identify their antiviral capacity and antibacterial activity. RESULTS: The bioassay results demonstrated that most cinnamic acid derivatives had excellent antiviral competence toward tobacco mosaic virus (TMV) in vivo, especially compound A5 (median effective concentration [EC50 ] = 287.7 µg mL-1 ), which had a notable protective effect against TMV when compared with the commercial virucide ribavirin (EC50 = 622.0 µg mL-1 ). In addition, compound A17 had a protective efficiency of 84.3% at 200 µg mL-1 against Xac in plants. Given these outstanding results, the engineered title compounds could be regarded as promising leads for controlling plant virus and bacterial diseases. Preliminary mechanistic studies suggest that compound A5 could enhance the host's defense responses by increasing the activity of defense enzymes and upregulating defense genes, thereby suppressing phytopathogen invasion. CONCLUSION: This research lays a foundation for the practical application of cinnamic acid derivatives containing diverse building blocks with alternative linking patterns in pesticide exploration. © 2023 Society of Chemical Industry.
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Infecções Bacterianas , Vírus de Plantas , Vírus do Mosaico do Tabaco , Humanos , Agroquímicos/farmacologia , Antivirais/farmacologia , Antivirais/química , Relação Estrutura-Atividade , Desenho de Fármacos , Doenças das Plantas/prevenção & controleRESUMO
The evaluation of energy security offers a standard for policy research and highlights the problems of securing the energy supply. A composite index for analyzing the risk of Southeast Asian nations' oil supply is developed in this study. Indicators used to calculate the index include the import-to-LGE ratio, GPR, market liquidity, gross domestic product, the import-to-consumption ratio, heterogeneity, oil price volatility, US$ volatility, and transportation risk. The index is based on these and other factors. According to the findings, Nepal and Sri Lanka are the most susceptible to oil supply interruptions. This indicates that India is more likely to shift its oil suppliers. At the same time, Maldives, Nepal, and Sri Lanka have the lowest supply risk scores, indicating that they are the most vulnerable to supply disruptions. Reduce the effect of oil supply risk by enacting policies such as the adoption of renewable technologies, nuclear power generation, diversification of exporting supplies, and reducing fossil fuel subsidies.
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Fontes Geradoras de Energia , Combustíveis Fósseis , Sri Lanka , Índia , Produto Interno BrutoRESUMO
Target-based drug design, a high-efficiency strategy used to guide the development of novel pesticide candidates, has attracted widespread attention. Herein, various natural-derived ferulic acid derivatives incorporating substituted isopropanolamine moieties were designed to target the tobacco mosaic virus (TMV) helicase. Bioassays demonstrating the optimized A19, A20, A29, and A31 displayed excellent in vivo antiviral curative abilities, affording corresponding EC50 values of 251.1, 336.2, 347.1, and 385.5 µg/mL, which visibly surpassed those of commercial ribavirin (655.0 µg/mL). Moreover, configurational analysis shows that the R-forms of target compounds were more beneficial to aggrandize antiviral profiles. Mechanism studies indicate that R-A19 had a strong affinity (Kd = 5.4 µM) to the TMV helicase and inhibited its ability to hydrolyze ATP (50.61% at 200 µM). Meanwhile, A19 could down-regulate the expression of the TMV helicase gene in the host to attenuate viral replication. These results illustrate the excellent inhibitory activity of A19 towards the TMV helicase. Additionally, docking simulations uncovered that R-A19 formed more hydrogen bonds with the TMV helicase in the binding pocket. Recent studies have unambiguously manifested that these designed derivatives could be considered as promising potential helicase-based inhibitors for plant disease control.
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Vírus do Mosaico do Tabaco , Relação Estrutura-Atividade , Antivirais/farmacologia , Antivirais/química , DNA HelicasesRESUMO
Hypoxia is a major regulator of tumor aggressiveness and metastasis in cancer progression. Exosomes (exos) play an important role in the communication between lung cancer and hypoxic microenvironment. However, the underlying mechanisms are largely undefined. Exos were isolated from A549 cells under hypoxia conditions. Transmission electron microscopy and nanoparticle tracking analysis were carried out to characterize exos. CCK-8 assay, flow cytometry, Western blot, wound healing, and transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of A549 cells, respectively. The M2 polarization of macrophages was evaluated by RT-qPCR and Western blot analysis. In vivo nude mice model was established to determine the regulatory effect of hypoxia/exos on the progression of lung cancer. Hypoxic A549 cell-derived exos (hypoxia/exos) promoted the proliferation and migration, and inhibited the apoptosis in A549 cells. The expression of PKM2 was significantly upregulated in hypoxia/exos. Hypoxic exosomal PKM2 induced M2 polarization of macrophages by activating AMPK pathway. Co-culture with hypoxia/exos-treated macrophages enhanced the migration, invasion, and epithelial-mesenchymal transition (EMT) in A549 cells. Moreover, treatment with hypoxia/exos facilitated the tumor growth and lung metastasis of A549 cells. Our findings reveal that hypoxic exosomal PKM2 induces M2 macrophage polarization via AMPK pathway, and thus exerts a simulative effect on the growth and metastasis of lung carcinoma.
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Proteínas Quinases Ativadas por AMP , Exossomos , Neoplasias Pulmonares , Macrófagos , Piruvato Quinase , Células A549 , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Exossomos/metabolismo , Humanos , Hipóxia/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/patologia , Ativação de Macrófagos , Macrófagos/metabolismo , Camundongos , Camundongos Nus , Piruvato Quinase/metabolismo , Microambiente TumoralRESUMO
Aquatic food allergy has become a key food safety problem and therefore it is urgent to study the mechanism of aquatic food allergy. Turbot parvalbumin (PV) is a major marine food allergen that could cause allergic reactions but the cellular and molecular mechanisms remain to be defined. In this study, we used flow cytometry and ELISA, a coupled co-culture system of dendritic cells and T cells, and revealed that PV could promote the maturation of dendritic cells, mainly by inducing bone marrow-derived dendritic cells (BMDCs) to express MHC II and CD86, and promote the cytokines/chemokines IL-6, IFN-γ, IL-23, and IL-12p70, whereas inhibiting TNF-α expression. Our results suggested that murine BMDCs play a crucial role in the effect of PV on the induction of Th2 responses.