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Colorectal cancer is caused by a sequence of somatic genomic alterations affecting driver genes in core cancer pathways1. Here, to understand the functional and prognostic impact of cancer-causing somatic mutations, we analysed the whole genomes and transcriptomes of 1,063 primary colorectal cancers in a population-based cohort with long-term follow-up. From the 96 mutated driver genes, 9 were not previously implicated in colorectal cancer and 24 had not been linked to any cancer. Two distinct patterns of pathway co-mutations were observed, timing analyses identified nine early and three late driver gene mutations, and several signatures of colorectal-cancer-specific mutational processes were identified. Mutations in WNT, EGFR and TGFß pathway genes, the mitochondrial CYB gene and 3 regulatory elements along with 21 copy-number variations and the COSMIC SBS44 signature correlated with survival. Gene expression classification yielded five prognostic subtypes with distinct molecular features, in part explained by underlying genomic alterations. Microsatellite-instable tumours divided into two classes with different levels of hypoxia and infiltration of immune and stromal cells. To our knowledge, this study constitutes the largest integrated genome and transcriptome analysis of colorectal cancer, and interlinks mutations, gene expression and patient outcomes. The identification of prognostic mutations and expression subtypes can guide future efforts to individualize colorectal cancer therapy.
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OBJECTIVES: Photoangiolytic lasers have yielded significant innovation in laryngeal surgery in the last 25 years. After the discontinuation of the potassium titanyl phosphate (KTP) laser, a novel 445-nm blue laser was developed. The optimal balance between a laser's desired tissue effects and collateral tissue damage is a major determinant of laser selection in microlaryngeal surgery. The shell-less incubation system for the chick chorioallantoic membrane (CAM) simulates the microvasculature of the human vocal fold and is useful for testing effects of laser settings and in simulated surgery. The aim of this study is to compare the tissue effects of the KTP and blue lasers using the shell-less CAM model. METHODS: The shell-less incubation system contains: polymethylpentene film (used as a culture vessel), calcium lactate and distilled water supplementations. By using this system, the chick chorioallantoic membrane (CAM) can be fully exposed with a good field for surgery simulation. The effects of the 2 lasers (532 nm KTP and 445 nm blue) were quantified at clinically relevant energy settings and laser distances from target. Measures included imaging real-time vascular reactions in the CAM model, post-procedure histologic analysis of CAM tissue and temperature changes. RESULTS: Vessel coagulation and rupture rates were less common with the blue laser compared with the KTP laser. Histologic analysis demonstrated less tissue disruption with the blue laser. Temperature changes were less with the blue laser. CONCLUSION: In this CAM model with specific conditions, the blue laser reveals less tissue damage than the KTP laser. Suitable working distance and power setting of the laser are necessary for desired tissue effects.Level of Evidence: Level 3.
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Psychoactive substances, including morphine and methamphetamine, have been shown to interact with the classic innate immune receptor Toll-like receptor 4 (TLR4) and its partner protein myeloid differentiation protein 2 (MD2) in a nonenantioselective manner. (-)-Nicotine, the primary alkaloid in tobacco and a key component of highly addictive cigarettes, targets the TLR4/MD2, influencing TLR4 signaling pathways. Existing as two enantiomers, the stereoselective recognition of nicotine by TLR4/MD2 in the context of the innate immune response remains unclear. In this study, we synthesized (+)-nicotine and investigated its effects alongside (-)-nicotine on lipopolysaccharide (LPS)-induced TLR4 signaling. (-)-Nicotine dose-dependently inhibited proinflammatory factors such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and cyclooxygenase-2 (COX-2). In contrast, (+)-nicotine showed no such inhibitory effects. Molecular dynamics simulations revealed that (-)-nicotine exhibited a stronger affinity with the TLR4 coreceptor MD2 than (+)-nicotine. Additionally, in silico simulations revealed that both nicotine enantiomers initially attach to the entrance of the MD2 cavity, creating a metastable state before they fully enter the cavity. In the metastable state, (-)-nicotine established more stable interactions with the surrounding residues at the entrance of the MD2 cavity compared to those of (+)-nicotine. This highlights the crucial role of the MD2 cavity entrance in the chiral recognition of nicotine. These findings provide valuable insights into the distinct interactions between nicotine enantiomers and the TLR4 coreceptor MD2, underscoring the enantioselective effect of nicotine on modulating TLR4 signaling.
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Antígeno 96 de Linfócito , Simulação de Dinâmica Molecular , Nicotina , Transdução de Sinais , Receptor 4 Toll-Like , Receptor 4 Toll-Like/metabolismo , Nicotina/farmacologia , Nicotina/química , Nicotina/análogos & derivados , Nicotina/metabolismo , Antígeno 96 de Linfócito/metabolismo , Antígeno 96 de Linfócito/química , Transdução de Sinais/efeitos dos fármacos , Estereoisomerismo , Humanos , Lipopolissacarídeos/farmacologia , Simulação de Acoplamento Molecular , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 2/químicaRESUMO
Coupling hydrazine oxidation reaction (HzOR) with hydrogen evolution reaction (HER) has been widely concerned for high efficiency of green hydrogen preparation with low energy consumption. However, the lacking of bifunctional electrodes with ampere-level performance severely limits its industrialization. Herein, we put forward an efficient active site anchored strategy for MnCo2O4 nanosheet arrays on nickel foam (NF) by introducing Pt species (denoted as Pt-MnCo2O4/NF), which is standing for excellent bifunctional electrodes. The Pt-MnCo2O4/NF delivers ultralow potentials of -195 mV and 350 mV at 1000 mA cm-2 as well as robust stability for HzOR and HER, respectively. The study of in-situ Raman and reaction kinetics reveal that the formation of key adsorbed *NH2 and *N2H4 intermediates and the rapidly oxidization of intermediates with a fast interfacial charge transfer on Pt-MnCo2O4/NF. Remarkably, the Pt-MnCo2O4/NF assembled two-electrode hydrazine assisted water electrolyzer realizes current density of 100 mA cm-2 and 1000 mA cm-2 at 0.16 V and 0.62 V with over 80 h stability. This work provides a promising way to design efficient electrodes for energy-saving H2 generation under ampere-level current density.
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Surface sediment samples were collected from the surrounding sea areas of the two largest tourist islands in Sanya City, China, to compare and assess the sources, distribution, and ecological risks of 16 polycyclic aromatic hydrocarbons (PAHs). The total PAHs concentrations ranged from 31.16 to 163.3 ng/g, with an average concentration of 102.46 ng/g, which is still lower than the levels detected in most other sediment studies worldwide. PAHs from coal combustion (Flu, Pyr, Fl, Phe) showed positive correlations with TOC, Silt, and Clay, indicating that these PAHs are easily adsorbed in muddy and silty sediments. Sanya Bay is primarily composed of mud and silt, whereas Haitang Bay is mainly sandy. This corresponds to the significantly higher concentrations of Fl, Phe, and Pyr in Sanya Bay compared to Haitang Bay. The main industrial activities in the study area are related to power and heat production and supply. The results indicate that the primary sources of sediment PAHs are high-temperature combustion during heavy industrial production, followed by maritime transportation and petroleum sources. Overall, the PAHs pollution levels in the study area range from slight to moderate. Sediment quality assessments show that only Ace and Phe have higher individual risk values. Six stations in Sanya Bay have higher adverse impact risks, while in Haitang Bay, only HT07 poses a high risk to biological impact. These two areas require enhanced monitoring and pollution source control.
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Monitoramento Ambiental , Sedimentos Geológicos , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Hidrocarbonetos Policíclicos Aromáticos/análise , Sedimentos Geológicos/química , Medição de Risco , Poluentes Químicos da Água/análise , China , IlhasRESUMO
Medical imaging is indispensable for accurate diagnosis and effective treatment, with modalities like MRI and CT providing diverse yet complementary information. Traditional image fusion methods, while essential in consolidating information from multiple modalities, often suffer from poor image quality and loss of crucial details due to inadequate handling of semantic information and limited feature extraction capabilities. This paper introduces a novel medical image fusion technique leveraging unsupervised image segmentation to enhance the semantic understanding of the fusion process. The proposed method, named DUSMIF, employs a multi-branch, multi-scale deep learning architecture that integrates advanced attention mechanisms to refine the feature extraction and fusion processes. An innovative approach that utilizes unsupervised image segmentation to extract semantic information is introduced, which is then integrated into the fusion process. This not only enhances the semantic relevance of the fused images but also improves the overall fusion quality. The paper proposes a sophisticated network structure that extracts and fuses features at multiple scales and across multiple branches. This structure is designed to capture a comprehensive range of image details and contextual information, significantly improving the fusion outcomes. Multiple attention mechanisms are incorporated to selectively emphasize important features and integrate them effectively across different modalities and scales. This approach ensures that the fused images maintain high quality and detail fidelity. A joint loss function combining content loss, structural similarity loss, and semantic loss is formulated. This function not only guides the network in preserving image brightness and texture but also ensures that the fused image closely resembles the source images in both content and structure. The proposed method demonstrates superior performance over existing fusion techniques in objective assessments and subjective evaluations, confirming its effectiveness in enhancing the diagnostic utility of fused medical images.
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Imageamento por Ressonância Magnética , Imagem Multimodal , Redes Neurais de Computação , Semântica , Humanos , Imagem Multimodal/métodos , Imageamento por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Aprendizado Profundo , AlgoritmosRESUMO
Antisense oligonucleotides (ASOs) are molecules used to regulate RNA expression by targeting specific RNA sequences. One specific type of ASO, known as neutralized DNA (nDNA), contains site-specific methyl phosphotriester (MPTE) linkages on the phosphate backbone, changing the negatively charged DNA phosphodiester into a neutralized MPTE with designed locations. While nDNA has previously been employed as a sensitive nucleotide sequencing probe for the PCR, the potential of nDNA in intracellular RNA regulation and gene therapy remains underexplored. Our study aims to evaluate the regulatory capacity of nDNA as an ASO probe in cellular gene expression. We demonstrated that by tuning MPTE locations, partially and intermediately methylated nDNA loaded onto mesoporous silica nanoparticles (MSNs) can effectively knock down the intracellular miRNA, subsequently resulting in downstream mRNA regulation in colorectal cancer cell HCT116. Additionally, the nDNA ASO-loaded MSNs exhibit superior efficacy in reducing miR-21 levels over 72 hours compared to the efficacy of canonical DNA ASO-loaded MSNs. The reduction in the miR-21 level subsequently resulted in the enhanced mRNA levels of tumour-suppressing genes PTEN and PDCD4. Our findings underscore the potential of nDNA in gene therapies, especially in cancer treatment via a fine-tuned methylation location.
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DNA , MicroRNAs , Nanopartículas , Dióxido de Silício , Dióxido de Silício/química , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Nanopartículas/química , DNA/química , Porosidade , Células HCT116 , Fosfatos/química , Tamanho da Partícula , Oligonucleotídeos Antissenso/química , Oligonucleotídeos Antissenso/farmacologia , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genética , Propriedades de Superfície , Proteínas de Ligação a RNA/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Reguladoras de Apoptose/genéticaRESUMO
Objective: The aim was to systematically review the association between depression and frailty in the elderly. Methods: Databases such as PubMed, Web of Science, Embase, and Scopus were searched for articles on the link between the risk of depression and frailty since the creation of the databases to September 1, 2023. A pair of investigators collaboratively conducted the screening, collected data, and evaluated the potential for bias in the included studies. R software was utilized for meta-synthesis. Results: Eight cohort studies comprising 13 043 participants and 14 854 senior individuals with depression were included. The meta-analysis showed that there was a significant connection regarding frailty and the incidence of depression among the elderly (Risk Ratio [RR] = 3.26, 95% Confidence Interval [CI]: 1.68-6.32). Subgroup evaluations showed that there was no association between frailty and depression in the community-dwelling elderly (RR = 2.28, 95% CI: 0.644-8.102) and in the elderly patients with depression assessed by Center for Epidemiological Studies Depression Scale (CES-D) (RR = 5.82, 95% CI: 0.481-70.526). Conclusion: Frailty is correlated with the risk of depression in the elderly. Frailty is a contributing factor to depression in the elderly.
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BACKGROUND: Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been administered as the first-line therapy for patients with EGFR mutations in LUAD, but it is almost inevitable that resistance to EGFR-TKIs therapy eventually arises. Polyphyllin I (PPI), derived from Paris polyphylla rhizomes, has been shown to have potent anti-cancer properties in a range of human cancer types including LUAD. However, the role of PPI in gefitinib resistance and the underlying mechanism remain elusive. PURPOSE: To evaluate the antitumor impacts of PPI on gefitinib resistance cells and investigate its molecular mechanism. METHODS: CCK-8, wound healing, transwell assay, and xenograft model were performed to determine the anti-cancer effects of PPI as well as its ability to overcome gefitinib resistance. Immunoblotting, co-immunoprecipitation, phospho-RTK antibody array, qRT-PCR, and immunofluorescence were utilized to explore the mechanism by which PPI overrides gefitinib resistance. RESULTS: PPI inhibited cell survival, growth, and migration/invasion in both gefitinib-sensitive (PC9) and -resistant (PC9/GR) LUAD cells (IC50 at 2.0 µM). Significantly, treatment with PPI at 1.0 µM resensitized the resistant cells to gefitinib. Moreover, cell-derived xenograft experiments revealed that the combination of PPI and gefitinib overcame gefitinib resistance. The phospho-RTK array and immunoblotting analyses showed PPI significant inhibition of the VEGFR2/p38 pathway. In addition, molecular docking suggested the interaction between PPI and HIF-1α. Mechanistically, PPI reduced the protein expression of HIF-1α in both normoxia and hypoxia conditions by triggering HIF-1α degradation. Moreover, HIF-1α protein but not mRNA level was elevated in gefitinib-resistant LUAD. We further demonstrated that PPI considerably facilitated the binding of HIF-1α to VHL. CONCLUSIONS: We present a novel discovery demonstrating that PPI effectively counteracts gefitinib resistance in LUAD by modulating the VEGF/VEGFR2/p38 pathway. Mechanistic investigations unveil that PPI facilitates the formation of the HIF-1α /VHL complex, leading to the degradation of HIF-1α and subsequent inhibition of angiogenesis. These findings uncover a previously unidentified mechanism governing HIF-1α expression in reaction to PPI, providing a promising method for therapeutic interventions targeting EGFR-TKI resistance in LUAD.
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Adenocarcinoma de Pulmão , Diosgenina , Resistencia a Medicamentos Antineoplásicos , Gefitinibe , Subunidade alfa do Fator 1 Induzível por Hipóxia , Neoplasias Pulmonares , Camundongos Nus , Fator A de Crescimento do Endotélio Vascular , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Gefitinibe/farmacologia , Humanos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Diosgenina/farmacologia , Diosgenina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Animais , Linhagem Celular Tumoral , Adenocarcinoma de Pulmão/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , FemininoRESUMO
Although the use of Doxorubicin (Dox) is extensive in the treatment of malignant tumor, the toxic effects of Dox on the heart can cause myocardial injury. Therefore, it is necessary to find an alternative drug to alleviate the Dox-induced cardiotoxicity. Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin, which is an active ingredient of Artemisia annua. The study investigates the effects of DHA on doxorubicin-induced cardiotoxicity and ferroptosis, which are related to the activation of Nrf2 and the regulation of autophagy. Different concentrations of DHA were administered by gavage for 4 weeks in mice. H9c2 cells were pretreated with different concentrations of DHA for 24 h in vitro. The mechanism of DHA treatment was explored through echocardiography, biochemical analysis, real-time quantitative PCR, western blotting analysis, ROS/DHE staining, immunohistochemistry, and immunofluorescence. In vivo, DHA markedly relieved Dox-induced cardiac dysfunction, attenuated oxidative stress, alleviated cardiomyocyte ferroptosis, activated Nrf2, promoted autophagy, and improved the function of lysosomes. In vitro, DHA attenuated oxidative stress and cardiomyocyte ferroptosis, activated Nrf2, promoted clearance of autophagosomes, and reduced lysosomal destruction. The changes of ferroptosis and Nrf2 depend on selective degradation of keap1 and recovery of lysosome. We found for the first time that DHA could protect the heart from the toxic effects of Dox-induced cardiotoxicity. In addition, DHA significantly alleviates Dox-induced ferroptosis through the clearance of autophagosomes, including the selective degradation of keap1 and the recovery of lysosomes.
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Artemisininas , Autofagia , Cardiotoxicidade , Doxorrubicina , Ferroptose , Miócitos Cardíacos , Fator 2 Relacionado a NF-E2 , Artemisininas/farmacologia , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Autofagia/efeitos dos fármacos , Doxorrubicina/efeitos adversos , Doxorrubicina/toxicidade , Camundongos , Ferroptose/efeitos dos fármacos , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Cardiotoxicidade/metabolismo , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Linhagem Celular , RatosRESUMO
Background: Mechanical thrombectomy (MT) is one of the effective treatment methods for acute ischemic stroke (AIS), which requires a period of dual antiplatelet therapy (DAPT) after endovascular treatment. This study aimed to compare the efficacy and safety of 3-month DAPT and 1-month DAPT in AIS patients receiving MT through a retrospective study. Methods: AIS patients who received MT from May 2018 to March 2023 were grouped into a 1-month group (1-M group) and a 3-month group (3-M group) according to the duration of DAPT after MT. The primary outcome was the mRS score at 90 days. Secondary outcomes included a good prognosis (mRS score of 0-2) at 90 days post-surgery, 6-month mortality, recurrence of cerebral infarction, Barthel's index, Montreal Cognitive Assessment (MoCA) score, and incidence of symptomatic intracranial hemorrhage (sICH) during hospitalization. Result: A total of 147 patients with AIS were included in the final analysis, with 78 patients in the 1-M group and 69 patients in the 3-M group. The baseline and neurological characteristics were comparable between both groups. At 3-month follow-up, a total of 61 patients had an mRS of 0-2 at 90 days, with an average mRS of 3.3 ± 0.9 for all patients. There was no statistically significant difference in the mRS between the two groups of patients at 90 days (P > 0.05). There was no statistically significant difference in the mortality rate and incidence of sICH between the two groups of patients during the 6-month follow-up period (P > 0.05), but the recurrence rate of AIS in the 3-M group was lower than that in the 1-M group (P < 0.05). The improvement of Barthel index and MoCA in patients in the 3-M group was higher than those in the 1-M group at 6 months but not statistically different (P > 0.05). Conclusion: For AIS patients undergoing mechanical thrombectomy, compared to 1-month DAPT, 3-month DAPT can reduce the recurrence rate of IS during a 6-month follow-up period, without increasing the mortality and risk of cerebral hemorrhage.
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Cortical surface registration plays a crucial role in aligning cortical functional and anatomical features across individuals. However, conventional registration algorithms are computationally inefficient. Recently, learning-based registration algorithms have emerged as a promising solution, significantly improving processing efficiency. Nonetheless, there remains a gap in the development of a learning-based method that exceeds the state-of-the-art conventional methods simultaneously in computational efficiency, registration accuracy, and distortion control, despite the theoretically greater representational capabilities of deep learning approaches. To address the challenge, we present SUGAR, a unified unsupervised deep-learning framework for both rigid and non-rigid registration. SUGAR incorporates a U-Net-based spherical graph attention network and leverages the Euler angle representation for deformation. In addition to the similarity loss, we introduce fold and multiple distortion losses to preserve topology and minimize various types of distortions. Furthermore, we propose a data augmentation strategy specifically tailored for spherical surface registration to enhance the registration performance. Through extensive evaluation involving over 10,000 scans from 7 diverse datasets, we showed that our framework exhibits comparable or superior registration performance in accuracy, distortion, and test-retest reliability compared to conventional and learning-based methods. Additionally, SUGAR achieves remarkable sub-second processing times, offering a notable speed-up of approximately 12,000 times in registering 9,000 subjects from the UK Biobank dataset in just 32 min. This combination of high registration performance and accelerated processing time may greatly benefit large-scale neuroimaging studies.
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Processamento de Imagem Assistida por Computador , Neuroimagem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Reprodutibilidade dos Testes , Neuroimagem/métodos , AlgoritmosRESUMO
As industrial technology continues to advance through integration, society's demand for electricity is rapidly increasing. To meet the requirements of refined grid management and address the elevated challenges arising from the increased electrical load, this paper delves into the investigation of distribution vehicle scheduling for the practical scenario of batch rotation of smart meters. Initially, based on the practical distribution task requirements of a provincial metrology verification center, a multi-level optimization model is constructed for the batch rotation and distribution vehicle scheduling of smart meters. The primary objective is to maximize the enhancement of smart meter distribution efficiency while minimizing the overall distribution cost. Moreover, this paper introduces a refined Grey Wolf Optimization algorithm (OLC-GWO) based on Opposition-based Learning, Levy flight strategy, and Cauchy mutation to solve the model. By generating an opposite population to improve the quality of initial feasible solutions and further harnessing the global search capabilities of Levy flight and Cauchy mutation operators, the algorithm's effectiveness is enhanced. The algorithm is subjected to testing using multiple benchmark functions and its performance is compared with variants of GWO, as well as several cutting-edge intelligent optimization algorithms including Particle Swarm Optimization (PSO), Harris Hawks Optimization (HHO), and Honey Bee Algorithm (HBA). The results indicate that OLC-GWO exhibits excellent performance in terms of convergence speed and optimization capability. Finally, the improved algorithm is subjected to simulation experiments by incorporating order data from the practical distribution operations of a provincial metrology verification center. The outcomes verify the efficiency of the proposed algorithm, reinforcing the practical significance of the established model in addressing the real-world challenge of batch rotation and distribution vehicle scheduling for smart meters.
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Disruptions in the toll-like receptor 4 (TLR4) signaling pathway are linked to chronic inflammation, neuropathic pain, and drug addiction. (+)-Naltrexone, an opioid-derived TLR4 antagonist with a (+)-isomer configuration, does not interact with classical opioid receptors and has moderate blood-brain barrier permeability. Herein, we developed a concise 10-step synthesis for (+)-naltrexone and explored its precursors, (+)-14-hydroxycodeinone (1) and (+)-14-hydroxymorphinone (3). These precursors exhibited TLR4 antagonistic activities 100 times stronger than (+)-naltrexone, particularly inhibiting the TLR4-TRIF pathway. In vivo studies showed that these precursors effectively reduced behavioral effects of morphine, like sensitization and conditioned place preference by suppressing microglial activation and TNF-α expression in the medial prefrontal cortex and ventral tegmental area. Additionally, 3 displayed a longer half-life and higher oral bioavailability than 1. Overall, this research optimized (+)-naltrexone synthesis and identified its precursors as potent TLR4 antagonists, offering potential treatments for morphine addiction.
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Dependência de Morfina , Naltrexona , Ratos , Animais , Humanos , Naltrexona/farmacologia , Receptor 4 Toll-Like , Dependência de Morfina/tratamento farmacológico , Ratos Sprague-Dawley , Antagonistas de Entorpecentes/farmacologia , Antagonistas de Entorpecentes/uso terapêutico , Morfina/farmacologia , Analgésicos Opioides/uso terapêuticoRESUMO
Understanding how bacteria evolve resistance to phages has implications for phage-based therapies and microbial evolution. In this study, the susceptibility of 335 Salmonella isolates to the wide host range Salmonella phage BPSELC-1 was tested. Potentially significant gene sets that could confer resistance were identified using bioinformatics approaches based on phage susceptibility phenotypes; more than 90 potential antiphage defense gene sets, including those involved in lipopolysaccharide (LPS) biosynthesis, DNA replication, secretion systems, and respiratory chain, were found. The evolutionary dynamics of Salmonella resistance to phage were assessed through laboratory evolution experiments, which showed that phage-resistant mutants rapidly developed and exhibited genetic heterogeneity. Most representative Salmonella hosts (58.1% of 62) rapidly developed phage resistance within 24 h. All phage-resistant mutant clones exhibited genetic heterogeneity and observed mutations in LPS-related genes (rfaJ and rfaK) as well as other genes such as cellular respiration, transport, and cell replication-related genes. The study also identified potential trade-offs, indicating that bacteria tend to escape fitness trade-offs through multi-site mutations, all tested mutants increased sensitivity to polymyxin B, but this does not always affect their relative fitness or biofilm-forming capacity. Furthermore, complementing the rfaJ mutant gene could partially restore the phage sensitivity of phage-resistant mutants. These results provide insight into the phage resistance mechanisms of Salmonella and the complexity of bacterial evolution resulting from phage predation, which can inform future strategies for phage-based therapies and microbial evolution.
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Bacteriófagos , Bacteriófagos/genética , Lipopolissacarídeos , Salmonella , Mutação , Fenótipo , BactériasRESUMO
Transparent dielectric ceramics are splendid candidates for transparent pulse capacitors (TPCs) due to splendid cycle stability and large power density. However, the performance and service life of TPCs at present are threatened by overheating damage caused by dielectric loss. Here, a cooperative optimization strategy of microstructure control and superparaelectric regional regulation is proposed to simultaneously achieve excellent energy storage performance and real-time temperature monitoring function in NaNbO3-based ceramics. By introducing aliovalent ions and oxides with large bandgap energy, the size of polar nanoregions is continuously reduced. Due to the combined effect of increased relaxor behavior and fine grains, excellent comprehensive performances are obtained through doping appropriate amounts of Bi, Yb, Tm, and Zr, Ta, Hf in A- and B-sites of the NaNbO3 matrix, including recoverable energy storage density (5.39 J cm-3), extremely high energy storage efficiency (91.97%), ultra-fast discharge time (29 ns), and superior optical transmittance (≈47.5% at 736 nm). Additionally, the phenomenon of abnormal fluorescent negative thermal expansion is realized due to activation mechanism of surface phonon at high temperatures that can promote the formation of [Yb···O]-Tm3+ pairs, showing great potential in real-time temperature monitoring of TPCs. This research provides ideas for developing electronic devices with multiple functionalities.
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Previous bismuth-based photocatalysts usually employ a strong acid solution (e.g., HNO3 solution) to obtain an ultrathin structure toward high photocatalytic activity. In this work, the ultrathin layered BiOIO3 nanosheets are successfully synthesized using just the glucose hydrothermal solution. The high-concentration glucose solution shows the obvious acidity after the hydrothermal process, which leads to the quick decrease in thickness of BiOIO3 nanosheets from â¼45.58 to â¼5.74 nm. The ultrathin structure can greatly improve charge carriers' separation and transfer efficiency. The generation of reductive iodide ions brings about oxygen vacancies in the ultrathin nanosheets, then the defect energy level is formed, causing the decreased band gap and improving the visible light absorption. Compared to thick BiOIO3 nanosheet with little oxygen vacancies, much higher carrier separation efficiency and visible light absorption are achieved in the ultrathin nanosheets with oxygen vacancies, resulting in an excellent photocatalytic performance (0.1980 min-1 for RhB degradation), which is much higher than most other bismuth-based photocatalysts. The superoxide radicals (â¢O2-) and holes (h+) are the major active species responsible for high photocatalytic activity. This work affords an environmentally friendly strategy to synthesize ultrathin photocatalysts with superior photocatalytic properties.
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In 2023, Baishideng Publishing Group (Baishideng) routinely published 47 open-access journals, including 46 English-language journals and 1 Chinese-language journal. Our successes were accomplished through the collective dedicated efforts of Baishideng staffs, Editorial Board Members, and Peer Reviewers. Among these 47 Baishideng journals, 7 are included in the Science Citation Index Expanded (SCIE) and 6 in the Emerging Sources Citation Index (ESCI). With the support of Baishideng authors, company staffs, Editorial Board Members, and Peer Reviewers, the publication work of 2023 is about to be successfully completed. This editorial summarizes the 2023 activities and accomplishments of the 13 SCIE- and ESCI-indexed Baishideng journals, outlines the Baishideng publishing policy changes and additions made this year, and highlights the unique advantages of Baishideng journals.
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Publicações Periódicas como Assunto , Editoração , Humanos , IdiomaRESUMO
Antimicrobial resistance in the laying hen production industry has become a serious public health problem. The antimicrobial resistance and phylogenetic relationships of the common conditional pathogen Enterococcus along the laying hen production chain have not been systematically clarified. 105 Enterococcus isolates were obtained from 115 environmental samples (air, dust, feces, flies, sewage, and soil) collected along the laying hen production chain (breeding chicken, chick, young chicken, and commercial laying hen). These Enterococcus isolates exhibited resistance to some clinically relevant antibiotics, such as tetracycline (92.4%), streptomycin (92.4%), and erythromycin (91.4%), and all strains had multidrug resistance phenotypes. Whole genome sequencing characterized 29 acquired antibiotic resistance genes (ARGs) that conferred resistance to 11 classes of antibiotics in 51 pleuromutilin-resistant Enterococcus isolates, and lsa(E), which mediates resistance to pleuromutilins, always co-occurred with lnu(B). Alignments with the Mobile Genetic Elements database identified four transposons (Tn554, Tn558, Tn6261, and Tn6674) with several ARGs (erm(A), ant(9)-la, fex(A), and optrA) that mediated resistance to many clinically important antibiotics. Moreover, we identified two new transposons that carried ARGs in the Tn554 family designated as Tn7508 and Tn7492. A complementary approach based on conventional multi-locus sequence typing and whole genome single nucleotide polymorphism analysis showed that phylogenetically related pleuromutilin-resistant Enterococcus isolates were widely distributed in various environments on different production farms. Our results indicate that environmental contamination by antimicrobial-resistant Enterococcus requires greater attention, and they highlight the risk of pleuromutilin-resistant Enterococcus and ARGs disseminating along the laying hen production chain, thereby warranting effective disinfection.