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Filter cloth brush-coating (FCBC), using soft filter cloth as a brush-coating medium, in conjunction with viscous silver nanowire (AgNW) conductive solution, is used to prepare AgNW conductive films. The density and uniformity of AgNWs deposited on the substrate are controlled by the interplay between the filter cloth aperture, the conductive solution viscosity, and the brush-coating speed. Further, with appropriate AgNW concentration and flow rate, uniform AgNW transparent conductive film with sheet resistance of 18 Ω sq-1and transmittance of 94% at 550 nm is acquired by FCBC. Due to the precise control of the coating process in FCBC, large-area uniform AgNW conductive film fabricated on printing paper has a low non-uniformity factor of 1.2% at a sheet resistance of 19.0 Ω sq-1. The resultant paper-based AgNW film heater shows sensitive and stable heating performance. FCBC shows great potential in producing large-area uniform AgNW films on various substrates.
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Persistent chronic inflammation of the lungs and airway remodeling are important pathological features that cannot be ignored in patients with chronic asthma. Apigenin (API) is a natural small molecule compound with good anti-inflammatory and antioxidant activity that has been widely reported in recent years, but its role in chronic asthma is not well defined. Our study began with oral gavage intervention using API (10, 20 mg/kg) or dexamethasone (DEX, 2 mg/kg) in a BALB/c mouse model of ovalbumin (OVA) sensitization. Different doses of API intervention effectively reduced airway resistance in the administered group. Additionally, inflammation was downregulated, mucus secretion was reduced, and airway remodeling was inhibited in the API intervention group compared with the model group. Asthma-related inflammatory cytokines, such as IgE, IL-4, IL-5, IL-13, and IL-17, were downregulated in alveolar lavage fluid. Moreover, the apoptosis level of the administered group was found to be lower than that of the model group in the Tunel staining experiment. By analyzing transcriptome sequencing results, we found that API may exert anti-inflammatory and anti-apoptotic effects by inhibiting the MAPK pathway. Our subsequent results supported this conclusion, showing that the phosphorylation levels of ERKs, JNKs, and p38 MAPKs were inhibited in the administered group relative to the model group. Downstream expression of the apoptosis-related protein B-cell lymphoma-2 (Bcl-2) was upregulated, and the expression of Bcl-2-associated × protein (Bax) and cleaved caspase-3 was downregulated. To further investigate the specific mechanism by which API acted, we established an in vitro model with house dust mite (HDM) stimulation, using API (10, 20 µM) for administration intervention. The results showed that API was able to improve cell viability, inhibit ROS production, and reverse HDM-induced decreases in mitochondrial membrane potential (MMP) and apoptosis in airway epithelial cells via the MAPK pathway.
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Apigenina , Asma , Animales , Ratones , Apigenina/farmacología , Remodelación de las Vías Aéreas (Respiratorias) , Transcriptoma , Asma/tratamiento farmacológico , Inflamación/metabolismo , Antiinflamatorios/farmacología , Apoptosis , Células Epiteliales/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismoRESUMEN
Sensory processing issues are one of the most common issues observed in autism spectrum disorders (ASD). Technologies that could address the issue serve a more and more important role in interventions for ASD individuals nowadays. In this study, a sensory management recommendation system was developed and tested to help ASD children deal with atypical sensory responses in class. The system employed sensor fusion and machine learning techniques to identify distractions, anxious situations, and the potential causes of these in the surroundings. Another novelty of the system included a sensory management strategy making a module based on fuzzy logic, which generated alerts to inform teachers and caregivers about children's states and risky environmental factors. Sensory management strategies were recommended to help improve children's attention or calm children down. The evaluation results suggested that the use of the system had a positive impact on children's performance and its design was user-friendly. The sensory management recommendation system could work as an intelligent companion for ASD children that helps with their in-class performance by recommending management strategies in relation to the real-time information about the children's environment.
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Trastorno del Espectro Autista , Trastorno del Espectro Autista/terapia , Cuidadores , Niño , Humanos , Aprendizaje AutomáticoRESUMEN
OBJECTIVES: Prediabetes is associated with an increased risk of cognitive impairment and neurodegenerative diseases. However, the exact mechanism of prediabetes-related brain diseases has not been fully elucidated. The brain structure of patients with prediabetes has been damaged to varying degrees, and these changes may affect the topological characteristics of large-scale brain networks. The structural covariance of connected gray matter has been demonstrated valuable in inferring large-scale structural brain networks. The alterations of gray matter structural covariance networks in prediabetes remain unclear. This study aims to examine the topological features and robustness of gray matter structural covariance networks in prediabetes. METHODS: A total of 48 subjects were enrolled in this study, including 23 patients with prediabetes (the PD group) and 25 age-and sex-matched healthy controls (the Ctr group). All subjects' high-resolution 3D T1 images of the brain were collected by a 3.0 Tesla MR machine. Mini-mental state examination was used to evaluate the cognitive status of each subject. We calculated the gray matter volume of 116 brain regions with automated anatomical labeling (AAL) template, and constructed gray matter structural covariance networks by thresholding interregional structural correlation matrices as well as graph theoretical analysis. The area under the curve (AUC) in conjunction with permutation testing was employed for testing the differences in network measures, which included small world parameter (Sigma), normalized clustering coefficient (Gamma), normalized path length (Lambda), global efficiency, characteristic path length, local efficiency, mean clustering coefficient, and network robustness parameters. RESULTS: The network in both groups followed small-world characteristics, showing that Sigma was greater than 1, the Lambda was much higher than 1, and Gamma was close to 1. Compared with the Ctr group, the network of the PD group showed increased Sigma, Lambda, and Gamma across a range of network sparsity. The Gamma of the PD group was significantly higher than that in the Ctr group in the network sparsity range of 0.12-0.16, but there was no difference between the 2 groups (all P>0.05). The grey matter network showed an increased characteristic path length and a decreased global efficiency in the PD group, but AUC analysis showed that there was no significant difference between groups (all P>0.05). For the network separation measures, the local efficiency and mean clustering coefficient of the gray matter network in the PD group were significantly increased and AUC analysis also confirmed it (P=0.001 and P=0.004, respectively). In addition, network robustness analysis showed that the grey matter network of the PD group was more vulnerable to random damage (P=0.001). CONCLUSIONS: The prediabetic gray matter network shows an increased average clustering coefficient and local efficiency, and is more vulnerable to random damage than the healthy control, suggesting that the topological characteristics of the prediabetes grey matter covariant network have changed (network separation enhanced and network robustness reduced), which may provide new insights into the brain damage relevant to the disease.
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Sustancia Gris , Estado Prediabético , Humanos , Sustancia Gris/diagnóstico por imagen , Imagen por Resonancia Magnética , Corteza Cerebral , EncéfaloRESUMEN
Solution-processed white organic light-emitting diodes (WOLEDs) with silica-coated silver nanocubes (Ag@SiO2 NCs) incorporated at the interface of a hole transporting layer and emission layer are studied. The concentration of Ag@SiO2 NCs is varied to investigate the effect of Ag@SiO2 NCs on the performances of WOLEDs. Owing to the sharp edges and corners, Ag NCs greatly improve the radiative rate and emission intensity of nearby blue excitons. The blue emission at different Ag@SiO2 NC concentrations determines the performance of the WOLEDs. The emission of the orange excitons is strengthened by the high concentration of Ag@SiO2 NCs, which slightly influences the device performance. On the other hand, the SiO2 shell and some SiO2 nanospheres coexisting with Ag NCs reduce the hole transporting, improving the carrier balance in the WOLEDs. The experimental and simulated results also show that excessive Ag@SiO2 NCs may cause a rough film surface, unbalanced carrier injection, and fluorescence quenching, which decreases the device performance. The optimized WOLED with a proper concentration of Ag@SiO2 NCs has a peak current efficiency of 53.9 cd/A, acquiring a significant enhancement factor of 77.3% compared to the control device without Ag@SiO2 NCs.
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An eco-friendly and efficient method for the synthesis of organophosphinates via an electrochemical cross-dehydrogenative-coupling reaction between alcohols and secondary phosphine oxides has been developed. This electrochemical reaction was conducted at room temperature without the addition of any oxidant, metal catalyst, or additive, which provides a new strategy for the synthesis of organophosphinates.
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A blue organic light-emitting diode (OLED) with silica-coated silver nanocubes (Ag@SiO2 NCs) inserted at the hole transporting layer/emission layer interface is reported. The localized surface plasmon resonance (LSPR) properties of the Ag@SiO2 NCs were characterized by the measured absorption spectra, stable-stated and transient photoluminescence, and calculated dipole radiation power. The results suggest that the Ag NCs significantly improved the radiation intensity of the nearby excitons due to their sharp corners and edges, but had less impact on the radiation rate of the excitons. The exciton recombination zone in the blue OLED was confirmed by a group of devices with an ultra-thin yellow emission layer located at different places, which helped to figure out the distribution of the excitons around the Ag@SiO2 NCs and deeply understand the coupling between the excitons and the Ag@SiO2 NCs. In our blue OLED, an appropriate distance between the Ag NCs and the excitons was realized by the SiO2 coating layer and the exciton distribution, which greatly improved the energy transfer between the excitons and the Ag NCs. In addition, the LSPR enhanced electric field around the Ag@SiO2 NCs improved the carrier injection at the hole transporting layer/emission layer interface and increased the current density of the blue OLED. Finally, the blue OLED with a simple triple layer structure achieved a high current efficiency of 51.1 cd A-1.
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OBJECTIVE: To investigate the value of the total liver CT perfusion imaging in the evaluation of rabbit VX2 liver tumors treated with TACE and apatinib.â© Methods: Thirty-six rabbit VX2 liver cancer models were established and randomly divided into 4 groups. Group A: simple TACE group; Group B: simple oral administration of apatinib mesylate; Group C: TACE + oral apatinib mesylate; Group D: control group, administration of saline. CT perfusion imaging (CTPI) was performed before treatment and on the 7 and 14 days after the treatment to acquire perfusion parameters including blood flow (BF), blood volume (BV), MTT (mean transit time), surface permeability (PS), and hepatic artery fraction (HAF). One tumor rabbit was sacrificed in each group after the first perfusion scan, and the remaining tumor rabbits were sacrificed after the last perfusion scan on the 14th day of the treatment. The borders of the tumors were stained immunohistochemically, and microvascular density (MVD) was measured by anti-CD34. The differences of perfusion parameters were compared to evaluate the liver hemodynamic changes, and statistical repeated measurement variance analysist correlation analysis were performed.â© Results: There were no significant differences in CTPI parameters of BF, BV, MTT, HAF and PS between the 4 groups before treatment (P>0.05). After the treatment, HB, HAF and PS were decreased significantly in Group A, B, and C and slightly increased in the Group D. The value of MVD after 14 d treatment was 80.1±16.4 in Group A, 50.2±11.2 in Group B, 27.4±9.7 in Group C, 68.7±12.7 in Group D, respectively. The value of MVD in the Group C were significantly lower than that in Group A, B, and D. It showed positive correlation between BF, HAF, PS and MVD in Group B, C, and D, and there was no significant correlation between BV, MTT and MVD. It showed no significant correlation between MVD and each CTPI parameter in Group A.â© Conclusion: Total liver CT perfusion can quantitatively evaluate the blood perfusion information of rabbit liver VX2 tumor after TACE. TACE combined with oral apatinib can effectively inhibit tumor growth and improve the therapeutic effect of VX2 tumor.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Animales , Neovascularización Patológica , Imagen de Perfusión , Piridinas , Conejos , Tomografía Computarizada por Rayos XRESUMEN
A Cu-catalyzed multicomponent cascade reaction of DABCO·(SO2)2 (DABSO), alcohol, and aryl diazonium tetrafluoroborate was developed which afforded sulfonic esters in moderate to good chemical yields. In this reaction, the SO2 surrogate DABSO was used for the first time in the synthesis of sulfonic aliphatic esters. This multicomponent reaction was carried out under mild conditions and tolerated a wide range of substrates, which provides a new and efficient strategy for the synthesis of sulfonic esters.
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OBJECTIVE: To explore the possibility of using peritoneal alternatively activated M2 macrophages to prevent rejection after islet allotransplantation in a murine model.â© Methods: Peritoneal monocytes from C57BL/6 mice were induced and modulated to M2 and M0 macrophages in vitro, then the phenotype of macrophage was assessed by flow cytometry. C57BL/6 mice were induced diabetic by streptozotocin (STZ) injection and transplanted with islets isolated from BALB/c mice under the left kidney capsule. The recipients were randomly divided to 3 groups (n=8). A total of 2.5×106 M2 macrophages were injected intravenously at 0, 3, 7 d after transplantation in islet+M2 group; 2.5×106 M0 macrophages were injected intravenously at 0, 3, 7 d after transplantation in islet+M0 group; the mice in islet+PBS group were injected with PBS. Blood glucose was monitored after transplantation. On day 10 after transplantation, 2 recipients in each group were randomly selected and sacrificed, and the left kidneys were resected for pathological examination.â© Results: Achievement of euglycemia was significantly prolonged after islet transplantation in the islet+M2 group than that in the other two groups (P<0.01). The median survival time of islet allografts in the islet+PBS group, the islet+M0 group, and the islet+M2 group were 6.5 (4-10), 7.5 (4-10), and 24(ï¹¥15) d, respectively. Pathological examination also showed that the grafts in islet+M2 group remained an intact structure with positive insulin stain and no apparent lymphocytes infiltration, while the graft was rejected in other 2 groups with negative insulin stain and massive lymphocytes infiltration.â© Conclusion: Peritoneal alternatively activated M2 macrophages can prevent rejection after islet allotransplantation, prolong the survival time of islet allografts and enhance the tolerance of the recipient to blood glucose in mice.
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Diabetes Mellitus Experimental , Supervivencia de Injerto , Trasplante de Islotes Pancreáticos , Macrófagos/metabolismo , Aloinjertos , Animales , Rechazo de Injerto , Macrófagos/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BLRESUMEN
OBJECTIVE: To evaluate the feasibility and therapeutic efficacy of transhepatic arterial embolization with superparamagnetic iron oxide (SPIO) and lipiodol (LIP) for the treatment of VX2 tumor in rabbits.â© Methods: Twenty-four rabbits with hepatic VX2 tumors by surgical implantation were randomly divided into 4 groups and treated with transhepatic arterial embolization of 4 different agents as follows (n=6 each): doxorubicin (DOX) group, DOX-LIP group, SPIO-DOX group, and SPIO-DOX-LIP group. Liver function (AST and ALT) was measured at 0, 1, 3, 5 and 7 d after transhepatic arterial embolization. The serum DOX level was measured at 0, 5, 15, 30, 60, and 120 minutes after transhepatic arterial embolization. MRI was performed at 7 d after the treatment to assess the distribution of SPIO in the SPIO-DOX group and SPIO-DOX-LIP group, while CT was performed to assess the distribution of LIP in the DOX-LIP group and SPIO-DOX-LIP group. All the rabbits were sacrificed and their livers were removed at 7 d after treatment for the detection of tissue DOX level. The histopathologic examinations were performed including HE staining, Prussian blue staining and TUNEL assay, and then the tumor necrosis percentage and apoptosis index were calculated.â© Results: Compared to the DOX group, the levels of AST and ALT in other 3 groups were significantly elevated at 1 and 3 d after embolization (P<0.05). The levels of ALT and AST in the DOX group, DOX-LIP group or SPIO-DOX-LIP group returned to the baseline at day 7, there were no significant differences (P>0.05). The SPIO-DOX-LIP group exhibited the lowest serum DOX level at all time points up to 120 minutes after embolization (P<0.05). However, the tissue DOX level in the SPIO-DOX-LIP group was the highest among all groups at day 7 (P<0.05). The SPIO-DOX group and SPIO-DOX-LIP group showed significantly lower MRI signal intensity of tumors in T2 weighted imaging (T2WI) at day 7. Meanwhile DOX-LIP group and SPIO-DOX-LIP group showed that high-density lipiodol was deposited in the tumors in CT images. Histopathologic findings showed an almost complete central necrosis coagulation of tumors in the SPIO-DOX-LIP group, and the tumor necrosis percentage and tumor apoptosis index were significantly increased in the SPIO-DOX-LIP group compared to those in other 3 groups (P<0.05).â© Conclusion: This novel drug-delivery system of SPIO nano-drug carrier together with LIP is safe and feasible when it is used for transhepatic arterial embolization for liver tumor. It provides an excellent MR and CT visualization and improves the therapeutic efficacy for the treatment of rabbit VX2 liver tumor.
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Antineoplásicos/administración & dosificación , Quimioembolización Terapéutica/métodos , Aceite Etiodizado/administración & dosificación , Compuestos Férricos/administración & dosificación , Arteria Hepática , Neoplasias Hepáticas/terapia , Nanopartículas de Magnetita/administración & dosificación , Alanina Transaminasa/sangre , Animales , Antineoplásicos/sangre , Aspartato Aminotransferasas/sangre , Doxorrubicina/administración & dosificación , Doxorrubicina/sangre , Estudios de Factibilidad , Compuestos Férricos/sangre , Etiquetado Corte-Fin in Situ , Neoplasias Hepáticas/sangre , Conejos , Distribución AleatoriaRESUMEN
Wnt signaling is a key pathway involving the regulation of cell development and growth in metazoa. An analysis of Wnt signaling in Schistosoma japonicum might provide information regarding the molecular mechanisms underlying parasite development, which might be useful for vaccine screening and identification of pharmaceutical targets. The SjWnt5 gene, a member of the Wnt gene family, contained an 1149-bp open reading frame that encoded a 382-aa protein. Analysis of the SjWnt5 amino acid sequence revealed a domain that was conserved among members of the Wnt protein family. Expression of SjWnt5 was observed at all of the developmental stages in definitive hosts, and the highest level of SjWnt5 messenger RNA (mRNA) was detected at the schistosomula stage. Higher levels of SjWnt5 mRNA and protein were observed in mature male worms, compared with those in mature females. SjWnt5 mRNA was expressed at higher levels in maldeveloped worms from nonpermissive host or single-sex infection than in normal worms from permissive host and mixed-sex infection. The immunohistochemical analysis showed that SjWnt5 protein was expressed in the subtegumental musculature and acetabulum musculature of schistosomulum and adult worms, suggesting that SjWnt5 may play a role in regulation of parasite muscle development. Furthermore, SjWnt5 was found prominently expressed in the testes of the male and the ovary as well as the vitellarium of the female, suggesting that SjWnt5 may involve in the development of the reproductive organs of both sexes.
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Regulación del Desarrollo de la Expresión Génica/fisiología , Proteínas del Helminto/metabolismo , Schistosoma japonicum/metabolismo , Proteínas Wnt/metabolismo , Secuencia de Aminoácidos , Animales , ADN Complementario/genética , Femenino , Proteínas del Helminto/genética , Humanos , Masculino , ARN Mensajero/metabolismo , Schistosoma japonicum/crecimiento & desarrollo , Proteínas Wnt/genéticaRESUMEN
Herein, the spatial evolution characteristics of high-level Grade A tourist attractions in the Yangtze River Delta (YRD) urban agglomeration, from 2001 to 2021, are studied by comprehensively applying the nearest neighbor index, kernel density analysis, standard deviation ellipse, and spatial autocorrelation. High-level Grade A tourist attractions are investigated using the random forest model as the driving mechanism of the spatial pattern. Results show that 1) the spatial distribution of high-level Class A tourist attractions in the YRD city cluster has grown to be an agglomeration, and the high-density areas have evolved from "point-like dispersion to regiment-like combination," gradually forming a B-shaped core density structure. 2) The spatial distribution comprises an overall "northwest-southeast" direction, a small counterclockwise rotation, the distribution of the center of gravity to the southwest migration, and the center of gravity from the territory of Suzhou City to the territory of Huzhou City. 3) The high-level Class A tourist attractions in the YRD city cluster as a whole show a strong positive spatial correlation, and the significantly clustered areas include three types: high-high (H-H), low-low (L-L), and low-high (L-H). 4) The spatial distribution of high, A-level tourist attractions in the YRD city cluster results from the combined action of the natural environment, resource endowment, socioeconomy, and policy background. Each element has a nonlinear and complex influence on the distribution of scenic spots.
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Ciudades , Ríos , China , Humanos , Turismo , Análisis Espacio-TemporalRESUMEN
Colorectal cancer (CRC) is one of the most prevalent and deadly malignancies that can be influenced by Fusobacterium nucleatum (Fn), a bacterium that promotes tumor development and chemoresistance, resulting in limited therapeutic efficacy. Traditional antibiotics cannot effectively eliminate Fn at tumor site due to issues like biofilm formation, while chemotherapy alone fails to suppress tumor progression. Therefore, the development of new methods to eliminate Fn and promote antitumor efficacy is of great significance for improving the outcome of CRC treatment. Herein, we developed a nanodrug (OPPL) that integrates oleic acid-modified superparamagnetic iron oxide nanoparticles (O-SPIONs) and an amphiphilic polymer (PPL) to deliver the platinum prodrug and antimicrobial lauric acid (LA) for enhancing the treatment of CRC. We demonstrated that OPPL can synergistically enhance antibacterial and biofilm disruption activities against Fn along with the antimicrobial LA by producing reactive oxygen species (ROS) through its peroxidase-like activity. Furthermore, the OPPL nanodrug can increase intracellular ROS, promote lipid peroxides and deplete glutathione, leading to ferroptosis. By combining chemotherapy and induced ferroptosis, the OPPL nanodrug exhibited high cytotoxicity against CRC cells. In vivo studies showed that the OPPL nanodrug could enhance tumor accumulation, enable magnetic resonance imaging, suppresse tumor growth, and inhibit growth of intratumor Fn. These results suggest that OPPL is an effective and promising candidate for the treatment of Fn-infected CRC. STATEMENT OF SIGNIFICANCE: The enrichment of Fusobacterium nucleatum (Fn) in colorectal cancer is reported to exacerbate tumor malignancy and is particularly responsible for chemoresistance. To this respect, we strategically elaborated multifaceted therapeutics, namely OPPL nanodrug, combining oleic acid-modified superparamagnetic iron oxide nanoparticles (O-SPIONs) with a polymer containing a platinum prodrug and antimicrobial lauric acid. The O-SPION components exert distinctive peroxidase-like activity, capable of stimulating Fenton reactions selectively in the tumor microenvironment, consequently accounting for the progressive production of reactive oxygen species. Hence, O-SPIONs have been demonstrated to not only supplement the antimicrobial activities of lauric acid in overcoming Fn-induced chemoresistance but also stimulate potent tumor ferroptosis. Our proposed dual antimicrobial and chemotherapeutic nanodrug provides an appreciable strategy for managing challenging Fn-infected colorectal cancer.
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Antiinfecciosos , Neoplasias Colorrectales , Profármacos , Humanos , Especies Reactivas de Oxígeno , Ácido Oléico , Platino (Metal) , Fusobacterium nucleatum , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Polímeros , Nanopartículas Magnéticas de Óxido de Hierro , Antibacterianos/farmacología , Peroxidasas , Línea Celular Tumoral , Microambiente TumoralRESUMEN
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a debilitating interstitial lung disorder characterized by its limited therapeutic interventions. Macrophages, particularly the alternatively activated macrophages (M2 subtype), have been acknowledged for their substantial involvement in the development of pulmonary fibrosis. Hence, targeting macrophages emerges as a plausible therapeutic avenue for IPF. Icariside II (ISE II) is a natural flavonoid glycoside molecule known for its excellent anti-tumor and anti-fibrotic activities. Nevertheless, the impact of ISE II on pulmonary fibrosis and the intricate mechanisms through which it operates have yet to be elucidated. OBJECTIVE: To scrutinize the impact of ISE II on the regulation of M2 macrophage polarization and its inhibitory effect on pulmonary fibrosis, as well as to delve deeper into the underlying mechanisms of its actions. METHODS: The effect of ISE II on proliferation and apoptosis in RAW264.7 cells was assessed through the use of EdU-488 labeling and the Annexin V/PI assay. Flow cytometry, western blot, and qPCR were employed to detect markers associated with the M2 polarization phenotype. The anti-fibrotic effects of ISE II in NIH-3T3 cells were investigated in a co-culture with M2 macrophages. Si-Ctnnb1 and pcDNA3.1(+)-Ctnnb1 plasmid were used to investigate the mechanism of targeted intervention. The murine model of pulmonary fibrosis was induced by intratracheal administration of bleomycin (BLM). Pulmonary function, histopathological manifestations, lung M2 macrophage infiltration, and markers associated with pulmonary fibrosis were evaluated. Furthermore, in vivo transcriptomics analysis was employed to elucidate differentially regulated genes in lung tissues. Immunofluorescence, western blot, and immunohistochemistry were conducted for corresponding validation. RESULTS: Our investigation demonstrated that ISE II effectively inhibited the proliferation of RAW264.7 cells and mitigated the pro-fibrotic characteristics of M2 macrophages, exemplified by the downregulation of CD206, Arg-1, and YM-1, Fizz1, through the inhibition of the PI3K/Akt/ß-catenin signaling pathway. This impact led to the amelioration of myofibroblast activation and the suppression of nuclear translocation of ß-catenin of NIH-3T3 cells in a co-culture. Consequently, it resulted in decreased collagen deposition, reduced infiltration of profibrotic macrophages, and a concurrent restoration of pulmonary function in mice IPF models. Furthermore, our RNA sequencing results showed that ISE II could suppress the expression of genes related to M2 polarization, primarily by inhibiting the PI3K/Akt and ß-catenin signaling pathway. In essence, our findings suggest that ISE II holds potential as an anti-fibrotic agent by orchestrating macrophage polarization. This may have significant implications in clinical practice. CONCLUSION: This study has provided evidence that ISE II exerts a significant anti-fibrotic effect by inhibiting macrophage M2 polarization through the suppression of the PI3K/Akt/ß-catenin signaling pathway. These findings underscore the potential of ISE II as a promising candidate for the development of anti-fibrotic pharmaceuticals in the future.
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Flavonoides , Macrófagos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , beta Catenina , Animales , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Flavonoides/farmacología , Células RAW 264.7 , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , beta Catenina/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Células 3T3 NIH , Proliferación Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Bleomicina , Ratones Endogámicos C57BL , Apoptosis/efectos de los fármacos , Masculino , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar/tratamiento farmacológicoRESUMEN
The matrilineal Mosuo of southwest China live in large communal houses where brothers and sisters of three generations live together, and adult males walk to visit their wives only at night; hence males do not reside with their own offspring. This duolocal residence with 'walking' or 'visiting' marriage is described in only a handful of matrilineal peasant societies. Benefits to women of living with matrilineal kin, who cooperate with child-care, are clear. But why any kinship system can evolve where males invest more in their sister's offspring than their own is a puzzle for evolutionary anthropologists. Here, we present a new hypothesis for a matrilineal bias in male investment. We argue that, when household resources are communal, relatedness to the whole household matters more than relatedness to individual offspring. We use an inclusive fitness model to show that the more sisters (and other closely related females) co-reside, the more effort males should spend working on their sister's farm and less on their wife's farm. The model shows that paternity uncertainty may be a cause of lower overall work rates in males, but it is not likely to be the cause of a matrilineal bias. The bias in work effort towards working on their natal farm, and thus the duolocal residence and 'visiting marriage' system, can be understood as maximizing inclusive fitness in circumstances where female kin breed communally.
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Relaciones Familiares , Aptitud Genética , Relaciones Interpersonales , Reproducción , Agricultura , Evolución Biológica , China , Composición Familiar , Femenino , Humanos , Masculino , Matrimonio , Modelos Biológicos , Relaciones entre Hermanos , Conducta SocialRESUMEN
A replication-defective, recombinant Sindbis virus vector was utilized in a novel immunization strategy to induce humoral and cellular responses against hepatitis C virus (HCV). The recombinant vector, pVaXJ-E1E2, expressing the gene for HCV glycoproteins E2 and E1, was constructed by inserting the E1E2 gene into the replicon pVaXJ, a DNA vector derived from Sindbis-like virus XJ-160. The defective replicon particles, XJ-E1E2, were produced by transfecting BHK-21(E+Capsid) cells, the packaging cell lines for the vector from XJ-160 virus, with pVaXJ-E1E2. Both glycoproteins, E2 and E1, were stably expressed, as indicated by immunofluorescence assay (IFA) and Western blotting. Mice were vaccinated using a prime-boost strategy with XJ-E1E2 particles combined with Freund's incomplete adjuvant via intramuscular injection at 0 and 2 weeks. HCV-specific IgG antibody levels and cellular immune responses were evaluated by IFA and IFN-γ ELISPOT, respectively. The results showed that the defective XJ-E1E2 particles in combination with Freund's incomplete adjuvant induced effective humoral and cellular immune responses against HCV glycoprotein E1 or E2, suggesting that a defective Sindbis particle vaccine is capable of eliciting an effective immune response. These findings have important implications for the development of HCV vaccine candidates.
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Portadores de Fármacos , Vectores Genéticos , Hepacivirus/inmunología , Virus Sindbis/genética , Proteínas del Envoltorio Viral/inmunología , Vacunas Virales/inmunología , Animales , Femenino , Adyuvante de Freund/administración & dosificación , Hepacivirus/genética , Anticuerpos contra la Hepatitis C/sangre , Inmunidad Celular , Inmunoglobulina G/sangre , Inyecciones Intramusculares , Leucocitos Mononucleares/inmunología , Ratones , Ratones Endogámicos BALB C , Vacunación/métodos , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología , Proteínas del Envoltorio Viral/genética , Vacunas Virales/administración & dosificación , Vacunas Virales/genéticaRESUMEN
BACKGROUND: Many studies have reported Xp 11.2 translocation renal cancer in radioimaging,but there is little literature on the evaluation of Xp11.2 translocation renal cell carcinoma by ultrasound. OBJECTIVE: To investigate the ultrasonographic features and diagnostic value of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion in children and adolescents. MATERIALS AND METHODS: The clinical and ultrasonographic data of 10 patients with renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion confirmed by pathology in our hospital were analyzed retrospectively. The age ranged from 3 to 18 years old, including 7 males and 3 females. The tumor location, size, boundary, echo, hemorrhage, cystic change, calcification, blood flow, lymph node status and metastasis were mainly observed, and the results were compared with the pathological results. RESULTS: There were 10 masses in 10 cases of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion, including 4 in the right kidney and 6 in the left kidney; the maximum diameter line is 5-23cm; 9 cases had clear mass boundary (90%); 9 masses (90%) showed mixed cystic and solid masses with high echo of solid components, and 1 mass (10%) showed huge multilocular cystic mass with multiple septations; necrosis and cystic changes were seen in all 10 masses (100%); calcification in 5 masses (50%); blood flow signals were seen in the solid components of the mass (100%). CONCLUSION: Renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion in children and adolescents are mostly large cystic and solid mixed echo masses, with high echo of solid components, and often accompanied by cystic changes and calcification. Its ultrasonic manifestations have certain characteristics. Color Doppler ultrasound has a certain diagnostic value for this disease.
RESUMEN
BACKGROUND: Astragaloside III (AS III), a saponin-like metabolite derived from the traditional Chinese medicine Astragali Radix, has been shown to be effective in the treatment of cancer and heart failure, and a variety of digestive disorders. However, its molecular mechanism in the treatment of non-small cell lung cancer (NSCLC) is unknown. METHODS: Human lung cancer A549 cells and NCI-H460 cells and a normal human lung epithelial cell BEAS-2B were treated with different concentrations of AS III. CCK-8 and EdU staining were used to determine the anti-proliferative effects of AS III in vitro. Quantitative proteomic analysis was performed on A549 cells treated with the indicated concentrations of AS III, and the expression levels of apoptosis-related proteins were examined by Western blotting. RESULTS: AS III treatment significantly inhibited proliferation and increased apoptosis in A549 and H460 cells and modulated functional signaling pathways associated with apoptosis and metabolism. At the molecular level, AS III promoted a reduction in the expression of ANXA1 (p < 0.01), with increased levels of cleaved Caspase 3 and PARP 1. In addition, AS III treatment significantly decreased the LC3-I/LC3-II ratio. The results of experiment in vitro showed that AS III promoted NSCLC apoptosis by down-regulating the phosphorylation levels of P38, JNK, and AKT (p < 0.01), inhibiting the expression of Bcl-2 (p < 0.01), and up-regulating the expression of Bax (p < 0.01). CONCLUSION: These findings provide a mechanism whereby AS III treatment induces apoptosis in NSCLC cells, which may be achieved in part via modulation of the P38, ERK and mTOR signaling pathways.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Proteómica , Línea Celular Tumoral , ApoptosisRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Jia-Wei-Bu-Shen-Yi-Qi formula (JWBSYQF), a classical traditional Chinese herbal formula consisting of five herbs, is used clinically in China to treat inflammatory lung diseases, including asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Its mechanism for treating asthma and COPD has been reported, however, how it works against IPF remains unclear. RESEARCH PURPOSE: Our study aims to observe the therapeutic effect of JWBSYQF on pulmonary fibrosis and further identify the potential active ingredients and molecular pathways. RESEARCH METHODS: In this study, we used a bleomycin-induced mouse model to investigate the therapeutic effect of JWBSYQF on pulmonary fibrosis. To further explore the potential effective ingredients and molecular pathways, we used the network pharmacology approach to construct a drug-ingredient-target network of JWBSYQF. Then, the common target set was established for JWBSYQF, fibroblast, and lung fibrosis. Analyses of the KEGG pathway, GO enrichment, and network topology were performed to identify key biological processes and molecular pathways for the common targets. Finally, a TGF-ß-induced NIH/3T3 proliferation and activation model was used to validate the possible active ingredients and signaling pathways. RESEARCH RESULTS: JWBSYQF reversed BLM-induced balf leukocyte levels, pulmonary inflammatory lesions and fibrotic collagen deposition in mice and reduced the levels of a-SMA, Col1a1 and TGF-ß. A total of 86 active ingredients were identified, 12 of which were considered as potential effective ingredients, while only baicalein effectively improved TGF-ß-induced proliferation and activation of NIH/3T3. KEGG results showed that PI3K/Akt signaling pathway may be the potential action mechanism, and Western Blot demonstrated that both JWBSYQF and baicalein downregulated the protein levels of p-PI3K and p-Akt. The molecular docking results suggest that baicalein may have a direct effect on the catalytic and regulatory subunits of P13K, which is stronger than direct binding to Aktl. CONCLUSIONS: Our study revealed that baicalein may be the material basis for JWBSYQF in the treatment of pulmonary fibrosis, and the PI3K/Akt signaling pathway may be a common pathway of action for JWBSYQF and baicalein.