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The development of inexpensive non-precious metal materials as high-efficiency stable oxygen reduction reaction (ORR) catalysts holds significant promise for application in metal-air batteries. Here, we synthesized a series of nanohybrids formed from MnO nanoparticles anchored on N-doped Ketjenblack carbon (MnO/NC) via a facile hydrothermal reaction and pyrolysis strategy. We systematically investigated the influence of pyrolysis temperature (600 to 900 °C) on the ORR activities of the MnO/NC samples. At the optimized pyrolysis temperature of 900 °C, the resulting MnO/NC (referred to as MnO/NC-900) exhibited superior ORR activity (onset potential = 0.85 V; half-wave potential = 0.74 V), surpassing other MnO/NC samples and nitrogen-doped Ketjenblack carbon (NC). Additionally, MnO/NC-900 demonstrated better stability than the Pt/C catalyst. The enhanced ORR activity of MnO/NC-900 was attributed to the synergy effect between MnO and NC, abundant surface carbon defects and surface-active components (N species and oxygen vacancies). Notably, the Zinc-air battery (ZAB) equipped MnO/NC-900 as the cathode catalyst delivered promising performance metrics, including a high peak power density of 146.5 mW cm-2, a large specific capacity of 795 mA h gZn -1, and an excellent cyclability up to 360 cycles. These results underscore the potential of this nanohybrid for applications in energy storage devices.
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Metal-organic frameworks (MOFs) based on tin (Sn) have shown great potential as materials for lithium storage, thanks to their ability to alleviate volume expansion due to the homogeneous distribution of Sn in a porous matrix framework. However, the weak mechanical strength of the porous Sn-MOF structure has been a major challenge, leading to pulverization during the discharging/charging process. To overcome this issue, we have developed a feasible strategy to strengthen the Sn-MOF mechanical properties by incorporating SiO2/GeO2 nanoparticles during the synthesis process. The resulting composites of Sn-Si and Sn-Ge exhibited high energy density and long-term cycle stability, thanks to their synergistic effect in alloying and conversion reactions. Our density functional theory (DFT) calculations have revealed that the rigid SiO2/GeO2 nanoparticles enhance the Sn-MOF mechanical properties, including Young's and shear moduli, which contribute to the long-term cycle stability of these composites.
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OBJECTIVE: To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia (TDT), and reveal the changes of metabolic pattern in children with TDT. METHODS: 23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected, and 11 healthy children who underwent physical examination during the same period were selected as the control group. The routine indexes between children with TDT and the control group were compared, and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry. An OPLS-DA model was established to perform differential analysis on the detected metabolites, and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites. RESULTS: The results of routine testing showed that the indexes of ferritin, bilirubin, total bile acid, glucose and triglycerides in children with TDT were significantly higher than those in healthy controls, while hemoglobin and total cholesterol were significantly lower (all P <0.05). However there was no significant difference in lactate dehydrogenase between the two groups (P >0.05). Compared with the control group, 190 differential metabolites (VIP>1) were identified in TDT children. Among them, 168 compounds such as arginine, proline and glycocholic acid were significantly increased, while the other 22 compounds such as myristic acid, eleostearic acid, palmitic acid and linoleic acid were significantly decreased. The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism. CONCLUSION: The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group. This finding is helpful to optimize the treatment choice for children with TDT, and provides a new idea for clinical treatment.
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Metaboloma , Talasemia , Humanos , Niño , Talasemia/terapia , Talasemia/sangre , Transfusión Sanguínea , Estudios de Casos y Controles , Plasma , Metabolómica , Triglicéridos/sangre , FemeninoRESUMEN
Breast cancer, as the most prevalent female malignancy, leads the cancer-related death in women worldwide. Local anesthetic chloroprocaine exhibits antitumor potential, but its specific functions and underlying molecular mechanisms in breast cancer remain unclear. Here, we demonstrated chloroprocaine significantly inhibited proliferation, invasion and induced apoptosis of breast cancer cells in vitro. Tumor growth and pulmonary metastasis were also suppressed in BABL/c nude mice model with chloroprocaine treatment. LINC00494 was identified as one of the most downregulated long noncoding RNAs in chloroprocaine-treated breast cancer cells by high-throughput sequencing. Futhermore, high level of LINC00494 was positively associated with poor outcome of breast cancer patients. LINC00494 acted as a "miRNAs sponge" to compete with MED19 for the biding of miR-3619-5p, led to the upregulation of MED19. LINC00494/miR-3619-5p/MED19 axis participated in chloroprocaine-mediated inhibition of proliferation, invasion and promotion of apoptosis of breast cancer cells. Consequently, our finding suggested local anesthetic chloroprocaine attenuated breast cancer aggressiveness through LINC00494-mediated signaling pathway, which detailly revealed the clinical value of chloroprocaine during breast cancer treatment.
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Neoplasias de la Mama , MicroARNs , Procaína/análogos & derivados , Animales , Ratones , Humanos , Femenino , Neoplasias de la Mama/metabolismo , Ratones Desnudos , Anestésicos Locales/farmacología , Línea Celular Tumoral , Proliferación Celular , MicroARNs/genética , MicroARNs/metabolismo , Apoptosis , Regulación Neoplásica de la Expresión Génica , Movimiento Celular , Complejo Mediador/genética , Complejo Mediador/metabolismoRESUMEN
We applied network pharmacology and molecular docking analyses to study the efficacy of Broussonin E (BRE) in acute respiratory distress syndrome (ARDS) treatment and to determine the core components, potential targets, and mechanism of action of BRE. The SwissTargetprediction and SEA databases were used to predict BRE targets, and the GeneCards and OMIM databases were used to predict ARDS-related genes. The drug targets and disease targets were mapped to obtain an intersecting drug target gene network, which was then uploaded into the String database for protein-protein interaction network analysis. The intersecting gene was also uploaded into the DAVID database for gene ontology enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis. Molecular docking analysis was performed to verify the interaction of BRE with the key targets. Finally, to validate the experiment in vivo, we established an oleic acid-induced ARDS rat model and evaluated the protective effect of BRE on ARDS by histological evaluation and enzyme-linked immunosorbent assay. Overall, 79 targets of BRE and 3974 targets of ARDS were predicted, and 79 targets were obtained after intersection. Key genes such as HSP90AA1, JUN, ESR1, MTOR, and PIK3CA play important roles in the nucleus and cytoplasm by regulating the tumor necrosis factor, nuclear factor-κB, and PI3K-Akt signaling pathways. Molecular docking results showed that small molecules of BRE could freely bind to the active site of the target proteins. In vivo experiments showed that BRE could reduce ARDS-related histopathological changes, release of inflammatory factors, and infiltration of macrophages and oxidative stress reaction. BRE exerts its therapeutic effect on ARDS through target and multiple pathways. This study also predicted the potential mechanism of BRE on ARDS, which provides the theoretical basis for in-depth and comprehensive studies of BRE treatment on ARDS.
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Lithium titanate is a promising anode material for lithium-ion batteries due to its high-rate capability and long-cycle duration. However, gas swelling during electrochemical reactions has hindered its industrial application. Here, we synthesize self-assembled (400)-orientation lithium titanate (SA-LTONF) with ultrafine nanoparticles using a feasible thermal method. The SA-LTONF with an organic carbon coating exhibited superior electrochemical performance. To understand such high-rate capability, we perform density functional theory (DFT) calculations which elucidate the orientation-dependent electrochemical mechanism of hydrogen evolution and the atomically dynamic mechanism of lithium-ion migration in Li4Ti5O12 and Li7Ti5O12. Our findings provide a unique insight into the gas generation and ultrafast lithium-ion transportation in lithium titanate and offer guidance for nanoarchitecture construction and materials design of lithium titanate for commercial applications.
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Objective: To investigate the chronic respiratory symptoms and pulmonary function of adult residents in 3 towns of Hongtong County, Shanxi Province, and to explore their risk factors. Methods: The investigation of chronic respiratory symptoms and lung function status of adult residents in Hongdong County is based on the regional population of the entire county in Hongdong County. The project was initiated by the Science and Technology Department of Linfen City and coordinated by the Hongdong County Government. The investigation will be conducted in 3 townships in Hongdong County, Linfen City, Shanxi Province from April to November 2021: Demographic characteristics, respiratory symptoms, smoking dust exposure and other personal history were collected through questionnaires. Physical examination, routine blood tests and lung function tests were also performed on each individual. SPSS 22.0 software was used to conduct t test, χ2 test, ANOVA or Kruskal-Wallis test for statistical analysis of the collected information. Results: 10 945 subjects aged 18-102 years were included in the analysis, of whom 3 754 (34.3%) were male, 1 222 (11.2%) had a history of dust exposure, 7 164 (65.5%) had used straw and firewood as cooking fuel, and 3 296 (30.1%) had a history of smoking. Among the participants, 394 (3.6%), 339 (3.1%), and 1 543 (14.1%) had respiratory symptoms such as chronic cough, sputum, and dyspnea. Statistics showed that the population with chronic respiratory symptoms was more elderly and had a smoking history, and the incidence of chronic respiratory symptoms was higher in those who smoked more than 40 packs a year (all P<0.05). Men with a history of dust exposure were more likely to suffer from chronic cough and expectoration, while emaciation and biofuel use for more than 40 years were more likely to suffer from chronic expectoration and dyspnea (all P<0.05). The median values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and FEV1/FVC in 1 second were 2.19 L/s, 3.24 L and 69.16%, respectively. Among them, the lung function of 5 801 (53.0%) respondents was lower than the expected value. The median FEV1/FVC decreased with the increase of age. The FEV1/FVC of people over 40 years old with smoking history was lower, the dust exposure history of people with decreased lung function was more than that of people with normal lung function, and the incidence of chronic expectoration and dyspnea was higher in people with decreased lung function (all P<0.05). The absolute value and ratio of eosinophils in patients with decreased ventilation function over 60 years old were significantly higher than those with normal ventilation function, but the level of body mass index (BMI) was lower (all P<0.05). Conclusion: In Hongdong County, Shanxi Province, grassroots residents have poor medical awareness, low lung function examination rate, chronic respiratory symptoms and lung function decline are associated with more risk factors. Primary medical institutions need to formulate prevention strategies and carry out lung function detection according to the actual situation, focusing on monitoring and follow-up of high-risk groups to achieve early and timely prevention, diagnosis and treatment of chronic obstructive pulmonary disease.
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Anciano , Adulto , Humanos , Masculino , Persona de Mediana Edad , Femenino , Tos/epidemiología , Pulmón , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Crónica , Enfermedades Pulmonares , Capacidad Vital , Disnea , Polvo/análisis , Volumen Espiratorio ForzadoRESUMEN
Objective: To investigate the chronic respiratory symptoms and pulmonary function of adult residents in 3 towns of Hongtong County, Shanxi Province, and to explore their risk factors. Methods: The investigation of chronic respiratory symptoms and lung function status of adult residents in Hongdong County is based on the regional population of the entire county in Hongdong County. The project was initiated by the Science and Technology Department of Linfen City and coordinated by the Hongdong County Government. The investigation will be conducted in 3 townships in Hongdong County, Linfen City, Shanxi Province from April to November 2021: Demographic characteristics, respiratory symptoms, smoking dust exposure and other personal history were collected through questionnaires. Physical examination, routine blood tests and lung function tests were also performed on each individual. SPSS 22.0 software was used to conduct t test, χ2 test, ANOVA or Kruskal-Wallis test for statistical analysis of the collected information. Results: 10 945 subjects aged 18-102 years were included in the analysis, of whom 3 754 (34.3%) were male, 1 222 (11.2%) had a history of dust exposure, 7 164 (65.5%) had used straw and firewood as cooking fuel, and 3 296 (30.1%) had a history of smoking. Among the participants, 394 (3.6%), 339 (3.1%), and 1 543 (14.1%) had respiratory symptoms such as chronic cough, sputum, and dyspnea. Statistics showed that the population with chronic respiratory symptoms was more elderly and had a smoking history, and the incidence of chronic respiratory symptoms was higher in those who smoked more than 40 packs a year (all P<0.05). Men with a history of dust exposure were more likely to suffer from chronic cough and expectoration, while emaciation and biofuel use for more than 40 years were more likely to suffer from chronic expectoration and dyspnea (all P<0.05). The median values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and FEV1/FVC in 1 second were 2.19 L/s, 3.24 L and 69.16%, respectively. Among them, the lung function of 5 801 (53.0%) respondents was lower than the expected value. The median FEV1/FVC decreased with the increase of age. The FEV1/FVC of people over 40 years old with smoking history was lower, the dust exposure history of people with decreased lung function was more than that of people with normal lung function, and the incidence of chronic expectoration and dyspnea was higher in people with decreased lung function (all P<0.05). The absolute value and ratio of eosinophils in patients with decreased ventilation function over 60 years old were significantly higher than those with normal ventilation function, but the level of body mass index (BMI) was lower (all P<0.05). Conclusion: In Hongdong County, Shanxi Province, grassroots residents have poor medical awareness, low lung function examination rate, chronic respiratory symptoms and lung function decline are associated with more risk factors. Primary medical institutions need to formulate prevention strategies and carry out lung function detection according to the actual situation, focusing on monitoring and follow-up of high-risk groups to achieve early and timely prevention, diagnosis and treatment of chronic obstructive pulmonary disease.
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Anciano , Adulto , Humanos , Masculino , Persona de Mediana Edad , Femenino , Tos/epidemiología , Pulmón , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Crónica , Enfermedades Pulmonares , Capacidad Vital , Disnea , Polvo/análisis , Volumen Espiratorio ForzadoRESUMEN
Combined with Network Analysis (NA) and in vivo experimental methods, we explored and verified the mechanism of Cepharanthine (CEP) involved in the treatment of acute respiratory distress syndrome (ARDS). Potential targets of CEP were searched using the SwissTargetPrediction database. The pathogenic genes related to ARDS were obtained using the DisGeNET database. A protein-protein interaction network of common target genes of disease-compound was subsequently built and visualised. Functional enrichment analysis was performed through the Enrichr database. Finally, for in vivo experimental verification, we established an oleic acid-induced ARDS rat model, mainly through histological evaluation and the ELISA method to evaluate both the protective effect of CEP on ARDS and its effect on inflammation. A total of 100 genes were found to be CEP targeted genes, while 153 genes were found to be associated with ARDS. The PPI network was used to illustrate the link and purpose of the genes associated with CEP and ARDS, which contained 238 nodes and 2,333 links. GO and KEGG analyses indicated that inflammatory response and its related signalling pathways were closely associated with CEP-mediated ARDS treatment. Thus, a key CEP-gene-pathway-ARDS network was constructed through network analysis, including 152 nodes (5 targets and 6 pathways) and 744 links. The results of in vivo experiments showed that CEP could alleviate histopathological changes and pulmonary edema related to ARDS, in addition to reducing neutrophil infiltration and secretion of inflammatory cytokines, whilst increasing serum contents of ResolvinD1 and ResolvinE1. Thus, these effects enhance the anti-inflammatory responses. Thus, our results show that CEP can treat oleic acid-induced ARDS in rats via ResolvinE1 and ResolvinD1 signalling pathways that promote inflammation resolution, providing a new avenue to explore for the clinical treatment of ARDS.
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Exploring high-efficiency and stable monolithic structured catalysts is vital for catalytic combustion of volatile organic compounds. Herein, we prepared a series of Pd/δ-MnO2 nanoflower arrays monolithic integrated catalysts (0.01-0.07 wt% theoretical Pd loading) via the hydrothermal growth of δ-MnO2 nanoflowers onto the honeycomb cordierite, which subsequently served as the carrier for loading the Pd nanoparticles (NPs) through the electroless plating route. Moreover, we characterized the resulting monolithic integrated catalysts in detail and evaluated their catalytic activities for toluene combustion, in comparison to the controlled samples including only Pd NPs loading and the δ-MnO2 nanoflower arrays. Amongst all the monolithic samples, the Pd/δ-MnO2 nanoflower arrays monolithic catalyst with 0.05 wt% theoretical Pd loading delivered the best catalytic performance, reaching 90% toluene conversion at 221°C at a gas hourly space velocity (GHSV) of 10,000 h-1. Moreover, this sample displayed superior catalytic activity for o-xylene combustion under a GHSV of 10,000 h-1. The monolithic sample with optimal catalytic activity also displayed excellent catalytic stability after 30 h constant reaction at 210 and 221°C.
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Manganese oxides have wide application in the ambient decomposition of ozone, although their activities are affected by many parameters. Morphology engineering and metal doping are, together, one of the most effective methods to enhance catalytic activity for O3 decomposition. Herein, a topochemical transformation route to Mn3O4 nanospheres composed of 2D nanosheets is first provided by using layered ß-MnOOH as the precursor. Then, silver nanoparticles are deposited over the Mn3O4 nanosheets via a redox reaction without any extra reducing agents. In comparison with Mn3O4 with a conventional octahedral morphology, the prepared Mn3O4 nanosphere (Mn3O4-NF), and its Ag-doped composite, Mn3O4@Ag (Mn3O4@Ag-NF), both retain the morphology of ß-MnOOH, and display better reducibility and higher oxygen vacancies. The best catalytic performance for O3 decomposition is found over Mn3O4@Ag-NF, which exhibits â¼88.5% removal efficiency within 24 h at a space velocity of 600 L g-1 h-1 and a relative humidity of 50% at room temperature. This work emphasizes the advantages of nanosheet morphology and metal doping in optimizing the catalytic activity for O3 elimination of manganese oxide.
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Mammalian studies have demonstrated that B cell immune responses are regulated by mechanistic target of rapamycin complex 1 (mTORC1) signaling. Teleost fish represent the oldest living bony vertebrates that contain bona fide B cells. So far, whether the regulatory mechanism of mTORC1 signaling in B cells occurred in teleost fish is still unknown. In this study, we developed a fish model by using rapamycin (RAPA) treatment to inhibit mTORC1 signaling and demonstrated the role of mTORC1 signaling in teleost B cells. In support, we found inhibition of mTORC1 signaling by RAPA decreased the phagocytic capacity, proliferation, and Ig production of B cells. Critically, Flavobacterium columnare induced specific IgM binding in serum, and these titers were significantly inhibited by RAPA treatment, thus decreasing Ab-mediated agglutination of F. columnare and significantly increasing the susceptibility of fish upon F. columnare reinfection. Collectively, our findings elucidated that the mTORC1 pathway is evolutionarily conserved in regulating B cell responses, thus providing a new point for understanding the B cells functions in teleost fish.
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Linfocitos B , Transducción de Señal , Animales , Peces , Inmunoglobulina M , Mamíferos , Diana Mecanicista del Complejo 1 de la Rapamicina , Sirolimus/farmacologíaRESUMEN
Cyprinid herpesvirus 2 (CyHV-2) causes herpesviral hematopoietic necrosis (HVHN) disease outbreaks in farmed Cyprinid fish, which leads to serious economic losses worldwide. Although oral vaccination is considered the most suitable strategy for preventing infectious diseases in farmed fish, so far there is no commercial oral vaccine available for controlling HVNN in gibel carp (C. auratus gibelio). In the present study, we developed for the first time an oral vaccine against CyHV-2 by using yeast cell surface display technology and then investigated the effect of this vaccine in gibel carp. Furthermore, the protective efficacy was evaluated by comparing the immune response of a single vaccination with that of a booster vaccination (booster-vaccinated once 2 weeks after the initial vaccination). Critically, the activities of immune-related enzymes and genes expression in vaccine group, especially in the booster vaccine group, were higher than those in the control group. Moreover, strong innate and adaptive immune responses could be elicited in both mucosal and systemic tissues after receipt of the oral yeast vaccine. To further understand the protective efficacy of this vaccine in gibel carp, we successfully developed the challenge model with CyHV-2. Our results showed the relative percent survival was 66.7% in the booster vaccine group, indicating this oral yeast vaccine is a promising vaccine for controlling CyHV-2 disease in gibel carp aquaculture.
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Enfermedades de los Peces , Infecciones por Herpesviridae , Vacunas , Animales , Carpa Dorada , Herpesviridae , Infecciones por Herpesviridae/prevención & control , Infecciones por Herpesviridae/veterinaria , Inmunidad Mucosa , Saccharomyces cerevisiaeRESUMEN
Myocardial ischemia/reperfusion injury (MI/RI) is a serious pathophysiological process relating to cardiovascular disease. Oroxin A (OA) is a natural flavonoid glycoside with various biological activities. However, its effect on the pathophysiological process of MI/RI has not yet been reported. The aim of this study was to determine whether OA could alleviate MI/RI induced inflammation and pyroptosis in vivo and in vitro, providing a novel therapeutic regimen for the treatment of MI/RI. A high-throughput drug screening strategy was employed to test 2,661 natural compound libraries that can alleviate MI/RI in vivo and in vitro. The rat model of MI/RI was established by ligating the left anterior descending (LAD) coronary artery. H9c2 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to simulate MI/RI. The results show that OA is able to significantly inhibit apoptosis, pyroptosis and the inflammation response (TNF-α, IL-6, IL-8, IL-10, IL-1ß, IL-18) in vivo and in vitro, and reduce the release of myocardial enzymes (cTnI, cTnT, CK-MB, LDH, AST). In the rat MI/RI model, OA can not only improve cardiac function and reduce inflammatory cell infiltration but also reduce myocardial infarct size. The results revealed that OA is an effective remedy against MI/RI as it reduces the inflammatory response and inhibits pyroptosis. This may provide a new therapeutic target for the clinical treatment of MI/RI.
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Introduction: Post-operative delirium (POD) is a serious complication which occurs after surgery, especially in the elderly undergoing abdominal surgery. Increasing evidence has revealed an association between the gut microbiota and psychological disorders involving the "brain-gut" axis. However, the association between the pathogenesis of POD after abdominal surgery in aging and composition of the gut microbiota remains unclear. Methods: Forty patients (≥65 years old) who underwent abdominal surgery were included in the study. Twenty patients had POD, whereas 20 patients did not. POD was diagnosed and assessed using the confusion assessment method (CAM) during the postoperative period. Total DNA fractions were extracted from all fecal samples of patients. 16S rRNA sequencing was performed to determine the composition of the gut microbiota. The quality of the samples was determined by calculating the α- and ß-diversities. Results: The α- and ß-diversities indicated that the samples were eligible for detection and comparison. We observed multiple differentially abundant bacteria in patients with and without POD. Generally, Proteobacteria, Enterbacteriaceae, Escherichia shigella, Klebsiella, Ruminococcus, Roseburia, Blautia, Holdemanella, Anaerostipes, Burkholderiaceae, Peptococcus, Lactobacillus, and Dorea were abundant in the POD cohort, whereas Streptococcus equinus and Blautia hominis were abundant in the control cohort. The results of receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of Escherichia shigella was 0.75. Phenotype prediction showed that the gut microbiota may influence POD by altering the tolerance to oxidative stress. Conclusion: There were significant associations between the pathogenesis of POD and composition of the gut microbiota. Escherichia shigella are promising diagnostic bacterial species for predicting POD onset after abdominal surgery in elderly people. Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, Chinese Clinical Trial Registry ChiCTR200030131.
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Chemical investigation of bioactive components from the whole plant of Euphorbia helioscopia resulted in the isolation and identification of 17 new jatrophane diterpenoids, namely, heliojatrone D (1) and helioscopids A-P (2-17), along with 11 known analogues (18-28). The structural elucidation of the new diterpenoids was achieved by the comprehensive analysis of HRESIMS, NMR, and X-ray crystallographic data, as well as using electronic circular dichroism. Structurally, heliojatone D (1) is the fourth natural diterpenoid with a rare bicyclo[8.3.0]tridecane skeleton. The inhibitory effect of the isolated diterpenoids against Kv1.3 ion channels was evaluated in a human embryonic kidney 293 cell model transfected with plasmid encoding Kv1.3, resulting in the identification of a series of potent Kv1.3 ion channel inhibitors, with the most active ones (2 and 15) showing IC50 values of 0.9 µM.
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Diterpenos , Euphorbia , Cristalografía por Rayos X , Diterpenos/química , Diterpenos/farmacología , Euphorbia/química , Humanos , Estructura MolecularRESUMEN
OBJECTIVE@#To clarify the clinical characteristics of influenza pneumonia in the elderly patients and the relationship between D-dimer and the severity of influenza pneumonia.@*METHODS@#In the study, 52 hospitalized patients older than 65 years with confirmed influenza pneumonia diagnosed in Peking University People's Hospital on 5 consecutive influenza seasons from 2014 were retrospectively analyzed. General information, clinical symptoms, laboratory data, treatment methods and prognosis of the patients were collected. The relationship between D-dimer and pneumonia severity was analyzed, and receiver operating characteristic (ROC) curve was used to evaluate the predictive value of D-dimer.@*RESULTS@#Among the 52 patients, 31 were male (31/52, 59.6%), the average age was (77.1±7.4) years, and 19 of them (36.5%) were diagnosed with severe pneumonia. About 70% patients presenting with fever. In the severe group, the patients were more likely to complain of dyspnea than in the non-severe group (14/19, 73.7% vs. 10/33, 30.3%, P=0.004), severe pneumonia group had higher level of CURB-65 (confusion, urea, respiratory rate, blood pressure, and age>65), pneumonia severity index (PSI), C-reactive protein, urea nitrogen, lactate dehydrogenase, fasting glucose, and D-dimer (P value was 0.004, < 0.001, < 0.001, 0.003, 0.038, 0.018, and < 0.001, respectively), albumin was lower than that in the non-severe group [(35.8±5.6) g/L vs. (38.9±3.5) g/L, t=-2.348, P=0.018]. There was a significant positive correlation between the D-dimer at the first admission and PSI score (r=0.540, 95%CI: 0.302 to 0.714, P < 0.001), while a significant negative correlation with PaO2/FiO2 (r=-0.559, 95%CI: -0.726 to -0.330, P < 0.001). Area under the curve of D-dimer was 0.765 (95%CI: 0.627 to 0.872). Area under the curve of PSI was 0.843 (95%CI: 0.716 to 0.929). There was no statistically significant difference in test efficacy between the two (Z=2.360, P=0.174). D-dimer level over 1 225 μg/L had a positive predict value for influenza pneumonia in hospital death with a sensitivity of 76.92% and a specificity of 74.36%.@*CONCLUSION@#Influenza pneumonia in the elderly always has atypical symptoms, dyspnea is a prominent feature in severe cases, D-dimer level is associated with the severity of influenza pneumonia, and greater than 1 200 μg/L has a good predictive value for in-hospital death in the elderly.
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Anciano , Anciano de 80 o más Años , Humanos , Masculino , Productos de Degradación de Fibrina-Fibrinógeno , Mortalidad Hospitalaria , Gripe Humana/diagnóstico , Neumonía/diagnóstico , Pronóstico , Curva ROC , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Hepatic ischaemia-reperfusion (I/R) injury constitutes a tough difficulty in liver surgery. Dexmedetomidine (Dex) plays a protective role in I/R injury. This study investigated protective mechanism of Dex in hepatic I/R injury. The human hepatocyte line L02 received hypoxia/reoxygenation (H/R) treatment to stimulate cell model of hepatic I/R. The levels of pyroptosis proteins and inflammatory factors were detected. Functional rescue experiments were performed to confirm the effects of miR-494 and JUND on hepatic I/R injury. The levels of JUND, PI3K/p-PI3K, AKT/p-AKT, Nrf2, and NLRP3 activation were detected. The rat model of hepatic I/R injury was established to confirm the effect of Dex in vivo. Dex reduced pyroptosis and inflammation in H/R cells. Dex increased miR-494 expression, and miR-494 targeted JUND. miR-494 inhibition or JUND upregulation reversed the protective effect of Dex. Dex repressed NLRP3 inflammasome by activating the PI3K/AKT/Nrf2 pathway. In vivo experiments confirmed the protective effect of Dex on hepatic I/R injury. Overall, Dex repressed NLRP3 inflammasome and alleviated hepatic I/R injury via the miR-494/JUND/PI3K/AKT/Nrf2 axis.
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Dexmedetomidina/farmacología , Hepatopatías/etiología , Hepatopatías/metabolismo , Daño por Reperfusión/etiología , Daño por Reperfusión/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Biomarcadores , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Hepatopatías/tratamiento farmacológico , Hepatopatías/patología , Factor 2 Relacionado con NF-E2/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Sustancias Protectoras/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/patologíaRESUMEN
The intercellular adhesion molecule-1 (ICAM-1), known as CD54, is a transmembrane cell surface glycoprotein that interacts with two integrins (i.e., LFA-1 and Mac-l) important for trans-endothelial migration of leukocytes. The level of ICAM-1 expression is upregulated in response to some inflammatory stimulations, including pathogen infection and proinflammatory cytokines. Yet, to date, our knowledge regarding the functional role of ICAM-1 in teleost fish remains largely unknown. In this study, we cloned and characterized the sequence of ICAM-1 in rainbow trout (Oncorhynchus mykiss) for the first time, which exhibited that the molecular features of ICAM-1 in fishes were relatively conserved compared with human ICAM-1. The transcriptional level of ICAM-1 was detected in 12 different tissues, and we found high expression of this gene in the head kidney, spleen, gills, skin, nose, and pharynx. Moreover, upon stimulation with infectious hematopoietic necrosis virus (IHNV), Flavobacterium columnare G4 (F. columnare), and Ichthyophthirius multifiliis (Ich) in rainbow trout, the morphological changes were observed in the skin and gills, and enhanced expression of ICAM-1 mRNA was detected both in the systemic and mucosal tissues. These results indicate that ICAM-1 may be implicated in the mucosal immune responses to viral, bacterial, and parasitic infections in teleost fish, meaning that ICAM-1 emerges as a master regulator of mucosal immune responses against pathogen infections in teleost fish.
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Infecciones por Cilióforos , Enfermedades de los Peces/inmunología , Proteínas de Peces/inmunología , Infecciones por Flavobacteriaceae , Regulación de la Expresión Génica/inmunología , Molécula 1 de Adhesión Intercelular/inmunología , Oncorhynchus mykiss , Infecciones por Rhabdoviridae , Animales , Infecciones por Cilióforos/inmunología , Infecciones por Cilióforos/veterinaria , Infecciones por Flavobacteriaceae/inmunología , Infecciones por Flavobacteriaceae/veterinaria , Flavobacterium/inmunología , Hymenostomatida/inmunología , Virus de la Necrosis Hematopoyética Infecciosa/inmunología , Oncorhynchus mykiss/inmunología , Oncorhynchus mykiss/microbiología , Oncorhynchus mykiss/parasitología , Oncorhynchus mykiss/virología , Infecciones por Rhabdoviridae/inmunología , Infecciones por Rhabdoviridae/veterinariaRESUMEN
CD79a and CD79b heterodimers are important components that consist of B cell receptor compound, which play a crucial role in transduction activation signal of the antigen binding BCR, and B cell development and antibody production. In order to investigate the characters and potential functions of CD79a and CD79b in rainbow trout (Oncorhynchus mykiss), we firstly cloned and analyzed the expression of CD79a and CD79b and found that the cDNA sequences of CD79a and CD79b both contained open reading frame of 711 and 645 bp in length for encoding the protein of 237 and 215 amino acid residues, respectively. The predicted amino acid sequences from trout were highly conserved with those of other teleost fishes in structure. Phylogenetic tree was constructed to analyze the evolutionary relationship between the trout and other known species, the result indicated that CD79a and CD79b of trout clustered at high bootstrap values with Salmo salar. Moreover, three trout infection models with F. columnare G4, I. multifiliis and infectious hematopoietic necrosis virus (IHNV) were constructed, which resulted in morphological changes and serious lesions in skin and gills. Importantly, the high expression of CD79a and CD79b occurred in skin, gills, and followed by head kidney in response to bacterial, parasitic, and viral infection, as its expression was closely related to that of Igs. Our findings indicated that CD79a and CD79b play vital roles in both systemic and mucosal immune responses of rainbow trout during bacterial, parasitic, and viral infection, which will contribute to explore the roles of CD79 subunits in B cell signaling during ontogeny and disease.