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Aqueous zinc metal batteries are regarded as a promising energy storage solution for a green and sustainable society in the future. However, the practical application of metallic zinc anode is plagued by the thermodynamic instability issue of water molecules in conventional electrolytes, which leads to severe dendrite growth and side reactions. In this work, an ultra-thin and high areal capacity metallic zinc anode is achieved by utilizing crystalline water with a stable stoichiometric ratio. Unlike conventional electrolytes, the designed electrolyte can effectively suppress the reactivity of water molecules and diminish the detrimental corrosion on the metallic zinc anode, while preserving the inherent advantages of water molecules, including great kinetic performance in electrolytes and H+ capacity contribution in cathodes. Based on the comprehensive performance of the designed electrolyte, the 10 µm Zn||10 µm Zn symmetric cell stably ran for 1000 h at the current density of 1 mA cm-2, and the areal capacity of 1 mAh cm-2, whose depth-of-discharge is over 17.1%. The electrochemical performance of the 10 µm Zn||9.3 mg cm-2 polyaniline (PANI) full-cell demonstrates the feasibility of the designed electrolyte. This work provides a crucial understanding of balancing activity of water molecules in aqueous zinc metal batteries.
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Pseudorabies virus (PRV) can infect multiple hosts and lead to fatal encephalitis. There is a significant increase in the number of microglia in the brain of animals infected with PRV. However, whether and how microglia contribute to central nervous system damage in PRV infection remain unknown. In the present study, we elucidated that PRV infection can cause more severe inflammatory cell infiltration, thicker and more numerous vessel sleeve walls, and more severe inflammatory responses in the brains of natural hosts (pigs) than in those of nonnatural hosts (mice). In a mice infection model, activated microglia restricted viral replication in the early stage of infection. Acute neuroinflammation caused by microglia hyperactivation at late-stage of infection. Furthermore, in vitro experiments revealed that microglia restricted viral replication and decreased viral infectivity. This may be associated with the phagocytic ability of microglia because we observed a significant increase in the expression of the membrane receptor TREM2 in microglia, which is closely related to phagocytosis, we observed that depletion of microglia exacerbated neurological symptoms, blood-brain barrier breakdown, and peripheral lymphocyte infiltration. Taken together, we revealed the dual role of microglia in protecting the host and neurons from PRV infection.
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Herpesvirus Suido 1 , Seudorrabia , Ratones , Animales , Porcinos , Microglía , Encéfalo , InmunidadRESUMEN
Tumor budding (TB) is considered a histomorphological marker of poor prognosis in patients with breast cancer (BC). Tumor vasculature is disordered and unstable in BC, which causes restricted drug delivery, hypoxia, and tumor metastasis. Traditional anti-angiogenic treatments cause extreme hypoxia, increased invasion, metastasis, and drug resistance due to blood vessel rarefaction or regression. Therefore, the application of anti-angiogenic strategies for vascular normalization in tumors is crucial to improve therapeutic efficacy in BC. In the present study, we found that transgelin (TAGLN) promoted the normalization of tumor vessels by regulating the structure and function of endothelial cells, and knockout of TAGLN in tumor-bearing mice resulted in tumor vessel abnormalization, an increase in epithelial-mesenchymal transition characteristics of tumor cells, and promotion of TB. Moreover, BC cells secrete exosomal miR-22-3p that mediates tumor vessel abnormalization by inhibiting TAGLN. We demonstrated for the first time that TAGLN plays an essential role in tumor vessel normalization, and thus it impairs TB and metastasis. Additionally, the findings of this study indicate that exosomal miR-22-3p is a potential therapeutic target for BC.
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Exosomas/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Proteínas de Microfilamentos/genética , Proteínas Musculares/genética , Neovascularización Patológica/genética , Interferencia de ARN , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular , Citoesqueleto/metabolismo , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Femenino , Xenoinjertos , Humanos , Ratones , PronósticoRESUMEN
BACKGROUND: Selenium supplementation can be used to treat tumors. However, inorganic selenium is highly toxic, and natural organic selenium is extremely rare. Polysaccharides can improve drug bioavailability and targeting. Lentinan is a polysaccharide that has been approved as an anti-cancer drug in Japan and China. METHODS: Lentinan, an antitumor polysaccharide extracted from Lentinus edodes, was conjugated with seleninic acid to be transformed into ester (Se-lentinan) and utilized as drug carrier. The enhancement of the anti-tumor effects of Se-lentinan was evaluated by cell viability, cell cycle, migration, and transwell assays and animal xenograft models. The effects of Se-lentinan on the expression levels of epithelial-mesenchymal transition (EMT) markers were determined through immunofluorescence, Western blot, and immunohistochemistry analyses. RESULTS: Se-lentinan inhibited the invasiveness of B16-BL6 and HCT-8 cells by suppressing EMT. In vivo, Se-lentinan significantly inhibited tumor growth and metastasis of the transplanted melanoma and colon cancer cells and showed less toxicity than sodium selenite. Moreover, Se-lentinan reduced the accumulation of selenium in the liver and kidney tissues of mice and exhibited low organ toxicity. CONCLUSION: The antitumor activity of selenium was enhanced greatly, and its side effects were reduced with the use of lentinan as drug carrier.
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Antineoplásicos/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Lentinano/farmacología , Selenio/farmacología , Células A549 , Animales , Ciclo Celular/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Progresión de la Enfermedad , Células HEK293 , Humanos , Células MCF-7 , Melanoma Experimental/tratamiento farmacológico , Ratones , Células 3T3 NIH , Metástasis de la Neoplasia/tratamiento farmacológico , Polisacáridos/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
As global demand for offshore wind energy continues to rise, the imperative to enhance the profitability of wind power projects and reduce their operational costs becomes increasingly urgent. This study proposes an innovative approach to optimize the inspection routes of offshore wind farms, which integrates the K-means clustering algorithm and genetic algorithm (GA). In this paper, the inspection route planning problem is formulated as a multiple traveling salesman problem (mTSP), and the advantages of the K-means clustering algorithm in distance similarity are utilized to effectively group the positions of wind turbines, thereby optimizing the inspection schedule for vessels. Subsequently, by harnessing the powerful optimization capability and robustness of genetic algorithms, further refinement is conducted to search for the optimal inspection routes, aiming to achieve cost reduction objectives. The results of simulation experiments demonstrate the effectiveness of this integrated approach. Compared to traditional genetic algorithms, the inspection route length has been significantly reduced, from 93 kilometers to 79.36 kilometers. Simultaneously, operational costs have also experienced a notable decrease, dropping from 141,500 Chinese Yuan to 125,600 Chinese Yuan.
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Algoritmos , Viento , Centrales Eléctricas , Análisis por Conglomerados , Simulación por ComputadorRESUMEN
Ulcerative colitis (UC) is one of the primary inflammatory bowel diseases (IBDs) and causes a serious threat to human public health around the world. Currently, there are no proven safe and effective treatment options to treat UC. Fraxetin (Fxt) is a widely recognized antioxidant and anti-inflammatory legume derived from ash bark. In the present study, we investigated the protective effect and mechanism of Fxt on UC. Our results showed that Fxt significantly attenuated the body weight, colon length reduction, tissue damage, and disease activity index induced by dextran sodium sulphate (DSS). Moreover, the DSS-induced activation of the NF-κB pathway and NLRP3 inflammasomes was inhibited, and the inflammatory response was reduced. Fxt restored gut barrier function by increasing the number of goblet cells and the levels of tight junction proteins (ZO-1 and occludin). In addition, Fxt can alter the intestinal microbiota by enhancing the diversity of the microbiota, increasing the relative abundance of beneficial bacteria and inhibiting the growth of harmful bacteria. These results revealed that Fxt alleviates DSS-induced colitis by modulating the inflammatory response, enhancing epithelial barrier integrity and regulating the gut microbiota. This study may provide a scientific basis for the potential therapeutic effect of Fxt in the prevention of colitis and other related diseases.
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[This corrects the article DOI: 10.3389/fphar.2023.1260288.].
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Electrochromic (EC) devices represent an emerging energy-saving technology, exhibiting the capability to dynamically modulate light and heat transmittance. Despite their promising potential, the commercialization of EC devices faces substantial impediments such as high cost, intricate fabrication process, and low optical contrast inherent in conventional EC materials relying on the ion insertion/extraction mechanism. In this study, we introduce an innovative "electrode-free" electrochromic (EC) device, termed the EECD, which lacks an EC-layer on the electrodes during device assembling and in the bleached state. This device features a simplified fabrication process and delivers superior optical modulation. It achieves a high optical contrast ranging from 68-85% across the visible spectrum and boasts a rapid response time, reaching 90% coloring in just 17 seconds. In addition, EECD exhibits stable cycling for over 10,000 cycles without noticeable degradation and maintains functionality across a broad temperature range (0 °C to 50 °C). Furthermore, the fabricated large-area devices (40 cm × 40 cm) demonstrate excellent tinting uniformity, suggesting excellent scalability of this approach. Our study establishes a paradigmatic breakthrough for EC smart windows.
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Waterway transportation is a crucial mode of transportation, but ensuring navigational safety in waterways requires effective guidance of ships by the Water Resources Bureau. However, supervisors may only be interested in the ship portion of a complex image and need to quickly obtain relevant ship information. Therefore, this paper proposes a two-dimensional OTSU inland ships multi-threshold image segmentation algorithm based on the improved genetic algorithm. The improved algorithm enhances search accuracy and efficiency, improving image thresholding accuracy and reducing algorithm time complexity. Experimental verification shows the algorithm has excellent evaluation indexes and can achieve real-time segmentation of complex images. This method can not only address the challenges of complex inland navigation environments and difficult acquisition of target data sets, but also be applied to optimization problems in other fields by combining various metaheuristic algorithms.
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Navíos , Transportes , Humanos , Algoritmos , Investigadores , Recursos HídricosRESUMEN
Introduction: Mulberry leaf (ML) is known for its antibacterial and anti-inflammatory properties, historically documented in "Shen Nong's Materia Medica". This study aimed to investigate the effects of ML on enterovirus 71 (EV71) using network pharmacology, molecular docking, and in vitro experiments. Methods: We successfully pinpointed shared targets between mulberry leaves (ML) and the EV71 virus by leveraging online databases. Our investigation delved into the interaction among these identified targets, leading to the identification of pivotal components within ML that possess potent anti-EV71 properties. The ability of these components to bind to the targets was verified by molecular docking. Moreover, bioinformatics predictions were used to identify the signaling pathways involved. Finally, the mechanism behind its anti-EV71 action was confirmed through in vitro experiments. Results: Our investigation uncovered 25 active components in ML that targeted 231 specific genes. Of these genes, 29 correlated with the targets of EV71. Quercetin, a major ingredient in ML, was associated with 25 of these genes. According to the molecular docking results, Quercetin has a high binding affinity to the targets of ML and EV71. According to the KEGG pathway analysis, the antiviral effect of Quercetin against EV71 was found to be closely related to the NF-κB signaling pathway. The results of immunofluorescence and Western blotting showed that Quercetin significantly reduced the expression levels of VP1, TNF-α, and IL-1ß in EV71-infected human rhabdomyosarcoma cells. The phosphorylation level of NF-κB p65 was reduced, and the activation of NF-κB signaling pathway was suppressed by Quercetin. Furthermore, our results showed that Quercetin downregulated the expression of JNK, ERK, and p38 and their phosphorylation levels due to EV71 infection. Conclusion: With these findings in mind, we can conclude that inhibiting the NF-κB signaling pathway is a critical mechanism through which Quercetin exerts its anti-EV71 effectiveness.
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Adopting a configurational perspective, this study explored the pathways for small and medium-sized enterprises (SMEs) to achieve high levels of radical innovation. On the basis of dynamic capabilities theory, six causal conditions for radical innovation were identified at both external and internal levels-that is, environmental turbulence (i.e., technological and market turbulence) and absorptive capacity (i.e., knowledge base, explorative, transformative, and exploitative learning processes). The results of a fuzzy-set qualitative comparative analysis (fsQCA) of 82 Chinese SMEs identified four solutions for high radical innovation. The six causal conditions interacted interdependently and different combinations of these conditions were equally effective pathways for SMEs to achieve radical innovation. Hence, SMEs could generate radical innovation through flexibly allocating resources and capabilities based on the environmental circumstances. By using the fsQCA method, this study contributes to the related literature with an investigation of the complex causal relationship between environmental turbulence, absorptive capacity, and SMEs' radical innovation. The results resolve some prior contradictory findings and provide new insights for future research. Other theoretical contributions, practical implications, and directions for future research are also discussed.
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The original version of this Article contained an error in the author affiliations. Affiliation number 4 incorrectly read "Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Disease, Tianjin Institute of Digestive Disease". It should be "Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300052, China".
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Colorectal cancer (CRC) is a common cancer type and a threat to human health. Tumor budding (TB) is the presence of a single cancer cell or clusters of up to five cancer cells prior to the invasive front of an aggressive carcinoma and is an independent prognosis factor for CRC. The molecular mechanism of TB is still unclear, and drugs that inhibit this process are still in the blank stage. This study found that TBs exhibit characteristics of partial EMT with a decreased expression of E-cadherin and no substantial differences in the expression of N-cadherin and vimentin. We also observed the interaction of integrin with extracellular matrix components, laminin-5γ2 (LN-5γ2), play essential roles in the TB of CRC. We then verified that the interaction between LN-5γ2 and integrin ß1 promotes the TB of CRC via the activation of FAK and Yes-associated proteins (YAP). A natural drug monomer, cucurbitacin B, was screened using virtual screening methods for the interaction interface of proteins. We found that this monomer could block the interaction interface between LN-5γ2 and integrin ß1 and substantially inhibit the TB of CRC cells via inactivation of YAP. This study provides new insights into the mechanism of TB mechanism and the development of drugs targeting the TB of CRC.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Carcinogénesis , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Integrina beta1/metabolismo , Laminina/metabolismo , Factores de Transcripción/metabolismo , Transporte Activo de Núcleo Celular , Adulto , Anciano , Anciano de 80 o más Años , Núcleo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Femenino , Células HCT116 , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Unión Proteica , Triterpenos/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas Señalizadoras YAPRESUMEN
BACKGROUND: Tumor cells transfer into endothelial cells by epithelial-endothelial transition (EET), which is characterized by vasculagenic mimicry (VM) in morphology. VM can change tumor microcirculation, progression, and metastasis. However, the molecular mechanisms of endothelial-like transition remain unclear. EET is a subtype of epithelial-mesenchymal transition (EMT). Twist1, a transcriptional regulatory factor of EMT, is an important factor that induces EET in hepatocellular carcinoma(HCC), but the upstream signal of Twist1 is unclear. METHODS: Expression plasmids, Ca mobilization, and three-dimensional cultures were evaluated. Western blot assay, reporter gene assay, and immunofluorescence staining were conducted. A murine xenograft model was established. Analyses of immunohistochemistry, patient samples, and complementary DNA (cDNA) microarrays were also performed. RESULTS: This study demonstrated that protease-activated receptor-1 (PAR1) can increase the expression of endothelial markers and enhance VM formation by upregulating Twist1 both in vitro and in vivo through thrombin binding. Thrombin not only activates PAR1 but also promotes PAR1 internalization in a time-dependent manner. Clinical pathological analysis further confirms that PAR1 expression is directly correlated with the endothelial marker expression, VM formation, and metastasis and indicates poor survival rate of patients with tumors. CONCLUSION: PAR1 promotes EET through Twist1 in HCC.