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Ssu72 is a component of the yeast cleavage/polyadenylation factor (CPF) complex, which catalyzes the dephosphorylation of the C-terminal domain (CTD) of RNA polymerase II at S5-P and S7-P. It has been shown that Ssu72 phosphatase is involved in regulating chromosome cohesion during mitosis. To further clarify whether Ssu72 phosphatase affects chromosome separation during meiotic division in Schizosaccharomyces pombe, we utilized green fluorescent protein (GFP) to label centromeres and red fluorescent protein to label microtubule protein Atb2. The entire meiotic chromosome separation process of ssu72∆ cells was observed in real-time under fluorescence microscope. It was found that two spindles of ssu72∆ cells crossed during the metaphase and anaphase of the second meiotic division, and this spindle crossing led to a new type of spore defect distribution pattern. The results of this study can provide important reference significance for studying the roles of phosphatase Ssu72 in higher organisms.
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Meiosis , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Huso Acromático , Schizosaccharomyces/genética , Schizosaccharomyces/enzimología , Huso Acromático/genética , Huso Acromático/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Segregación CromosómicaRESUMEN
During meiosis, defects in cohesin localization within the centromere region can result in various diseases. Accurate cohesin localization depends on the Mis4-Ssl3 loading complex. Although it is known that cohesin completes the loading process with the help of the loading complex, the mechanisms underlying its localization in the centromere region remain unclear. Previous studies suggest cohesin localization in the centromere is mediated by phosphorylation of centromeric proteins. In this study, we focused on the Fta2 protein, a component of the Sim4 centromere protein complex. Using bioinformatics methods, potential phosphorylation sites were identified, and fta2-9A and fta2-9D mutants were constructed in Schizosaccharomyces pombe. The phenotypes of these mutants were characterized through testing thiabendazole (TBZ) sensitivity and fluorescent microscopy localization. Results indicated that Fta2 phosphorylation did not impact mitosis but affected chromosome segregation during meiosis. This study suggests that Fta2 phosphorylation is vital for meiosis and may be related to the specific localization of cohesin during this process.
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Meiosis , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Centrómero/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Proteínas Cromosómicas no Histona/genética , Segregación Cromosómica/efectos de los fármacos , Cohesinas , Meiosis/efectos de los fármacos , Fosforilación , Schizosaccharomyces/citología , Schizosaccharomyces/efectos de los fármacos , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteínas de Schizosaccharomyces pombe/genéticaRESUMEN
The localization of the meiotic specific regulatory molecule Moa1 to the centromere is regulated by the kinetochore protein CENP-C, and participates in the cohesion of sister chromatids in the centromere region mediated by the cohesin Rec8. To examine the interaction of these proteins, we analyzed the interactions between Moa1 and Rec8, CENP-C by yeast two-hybrid assays and identified several amino acid residues in Moa1 required for the interaction with CENP-C and Rec8. The results revealed that the interaction between Moa1 and CENP-C is crucial for the Moa1 to participate in the regulation of monopolar attachment of sister kinetochores. However, mutation at S143 and T150 of Moa1, which are required for interaction with Rec8 in the two-hybrid assay, did not show significant defects. Mutations in amino acid residues may not be sufficient to interfere with the interaction between Moa1 and Rec8 in vivo. Further research is needed to determine the interaction domain between Moa1 and Rec8. This study revealed specific amino acid sites at which Moa1 affects the meiotic homologous chromosome segregation, providing a deeper understanding of the mechanism of meiotic chromosome segregation.
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Proteínas Cromosómicas no Histona , Meiosis , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Proteínas Cromosómicas no Histona/genética , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Unión Proteica , Cinetocoros/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Técnicas del Sistema de Dos Híbridos , Segregación Cromosómica , Cohesinas , FosfoproteínasRESUMEN
BACKGROUND: Requirements of blood transfusions rise rapidly in China. Improving the efficiency of blood donation could help maintaining sufficient blood supplement. We conducted a pilot research to investigate the reliability and safety of collecting more units of red blood cell by apheresis. METHODS: Thirty-two healthy male volunteers were randomized into two groups: red blood cell apheresis (RA) (n = 16) and whole blood (WB) donation (n = 16). RA group donated individualized RBC volumes by apheresis according to the volunteers' basal total blood volumes and haematocrit levels, WB group donated 400 mL whole blood. All volunteers were scheduled seven visit times in 8 weeks' study period. The cardiovascular functions were assessed by laboratory examinations, echocardiography and cardiopulmonary functional tests. All results were compared between groups at the same visit time and compared between visit 1(before donation) and other visit times within the same group. RESULTS: The average donated RBC volume in RA group and in WB group was 627.25 ± 109.74 mL and 175.28 ± 8.85 mL, respectively(p < 0.05); the RBC, haemoglobin and haematocrit levels changed significantly between times and between groups (p < 0.05). Cardiac biomarker levels such as NT-proBNP, hs-TnT and CK-MB did not change significantly between times or between groups (p > 0.05). The echocardiographic and cardiopulmonary results did not change significantly between times or between groups during the whole study period(p > 0.05). CONCLUSIONS: We provided an efficient and secure method for RBC apheresis. By harvesting more RBC volumes at one single-time, the cardiovascular functions did not change significantly compared with traditional whole blood donation.
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Background: While sarcopenia is an important clinical finding in individuals diagnosed with chronic heart failure (CHF), efforts to identify a reliable biomarker capable of predicting the overall muscular and functional decline in CHF patients have been unsuccessful to date. Objectives: The objectives of this study were to study the diagnostic utility of MicroRNA (miRNA)-1-3p as a predictor of sarcopenia status in individuals diagnosed with CHF. Methods: In total, 80 individuals with heart failure exhibiting a left ventricular ejection fraction < 50% were enrolled in this study. All patients were analyzed to assess miR-1-3p expression levels, with body composition being evaluated through dual-energy X-ray absorptiometry and sarcopenia being defined based on the sum of appendicular lean muscle mass (ALM) divided by height in meters squared and handgrip strength (HGS). In addition, the activation of the Akt/mTOR signaling pathway was evaluated in these individuals. Results: In total, 40 of the enrolled patients (50%) exhibited sarcopenia. Sarcopenic patients presented with increased miR-1-3p expression levels as compared to non-sarcopenic individuals (1.69 ± 0.132 vs. 1.22 ± 0.106; p < 0.05). With respect to sarcopenic indices, appendicular skeletal mass index was most strongly correlated with miR-1-3p expression, which was also strongly correlated with HGS. High levels of Akt/mTOR signaling pathway components were expressed in sarcopenic individuals, highlighting a significant relationship between miR-1-3p activity and signaling through this pathway. Moreover, miR-1-3p was identified as a specific marker for sarcopenia in individuals with CHF. Conclusions: These results suggest that circulating miR-1-3p levels are related to Akt/mTOR pathway activation and can offer valuable insight into the overall physical capacity and muscular integrity of CHF patients as a predictor of sarcopenia. (Rev Invest Clin. 2022;74(5):276-83).
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MicroARN Circulante , Insuficiencia Cardíaca , Sarcopenia , Humanos , Sarcopenia/diagnóstico , Fuerza de la Mano/fisiología , Volumen Sistólico , Proteínas Proto-Oncogénicas c-akt , Función Ventricular Izquierda , Biomarcadores , Serina-Treonina Quinasas TORRESUMEN
On-orbit radiometric calibration of the optical sensors on-board SuperView-1 satellites is the foundation for further quantitative applications. A field calibration campaign was orchestrated to radiometrically calibrate the SuperView-1 optical sensors at the Baotou calibration site in China during September 2018. Based on the collected datasets, three independent methods (reflectance-based, radiance-based, and cross-calibration) were used to determine the radiometric calibration coefficients of the SuperView-1 optical sensors with multiple permanent artificial calibration targets. Comparisons of the desert top-of-atmosphere radiance calculated based on the coefficients determined with independent methods were analyzed. Comparison results show that the minimum and maximum relative differences of the radiometrically-calibrated desert TOA radiance between the reflectance-based and radiance-based methods are 1.26% and 4.23% for SV0102 and SV0104, respectively. While, the minimum and maximum relative differences of the radiometrically-calibrated desert TOA radiance between the reflectance-based and radiance-based methods are 0.82% and 6.83% for SV0101 and SV0103, respectively. The reasonably good agreement of the radiometrically calibrated coefficients of the SuperView-1 on-board sensors between these independent methods is encouraging. An uncertainty analysis was also discussed, and the results suggest that the overall uncertainties of the predicted TOA radiance are less than 4.5%, 4.0%, and 5.15% for the reflectance-based, radiance-based, and cross-calibration methods, respectively.
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We present a physical-based atmospheric correction algorithm for land surface reflectance retrieval based on radiative transfer model MODTRAN 5, with which the aerosol optical thickness @550 nm (AOT@550nm), columnar water vapor (CWV) could also be estimated from the hyperspectral data collected over UAV platform. Then, the method was tested on both the synthetic and field campaign-collected hyperspectral data by an UAV-VNIRIS (UAV visible/near-infrared imaging hyperspectrometer) with the spectral range covering from 400 to 1000 nm. The retrieval results were validated with theoretical values from synthetic data and truth values from field campaign measurements. The results show that the averaged MAE (mean absolute error) and RMSE (root mean squared error) of measured and retrieved surface reflectance based on estimated AOT@550nm and CWV is 0.0134 and 0.0130. Meanwhile, the averaged MAE and RMSE of measured and retrieved surface reflectance based on ground measured AOT@550nm and CWV is 0.0101 and 0.0112. The results show that our introduced method has good agreement with the method based on ground-measured AOT@550nm and CWV. These encouraging results also indicate that the introduced physical-based atmospheric approach provides a quick and reliable way to acquire the land surface reflectance from UAV platform-observed hyperspectral data for further quantitative remote sensing applications.
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BACKGROUND: Osteoporosis (OP) is common in patients with chronic obstructive pulmonary disease (COPD). The relationship between OP and COPD has been primarily studied in male patients, and few reports are available in postmenopausal women. OBJECTIVE: The purpose of this study was to investigate the association between bone mineral density (BMD) and COPD in postmenopausal women. METHODS: This cross-sectional study included 133 clinically stable female ex-smokers with confirmed COPD, and 31 age-matched "ex-smoker" female controls. We analyzed groups according to their airway obstruction category. BMD was measured on dual-energy X-ray absorptiometry images of the left femoral neck. RESULTS: Patients with COPD had lower T-scores and higher prevalence of osteopenia/OP than the control group. In the COPD group, the airway obstruction category was significantly associated with the T-score after adjustment for confounders. Multivariate logistic regression analysis showed COPD was an independent marker for increased risk of osteopenia/OP in postmenopausal women. CONCLUSIONS: COPD and airway obstruction category were strongly related to BMD. Postmenopausal women with COPD, especially those with severe airway obstruction, had a higher prevalence rate and a higher risk of osteopenia and OP than female controls without COPD.
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Densidad Ósea/fisiología , Osteoporosis Posmenopáusica/epidemiología , Posmenopausia , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Absorciometría de Fotón , Anciano , Obstrucción de las Vías Aéreas/etiología , Obstrucción de las Vías Aéreas/fisiopatología , Enfermedades Óseas Metabólicas/epidemiología , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Factores de RiesgoRESUMEN
Land surface temperature (LST) is one of the key parameters in the physics of land surface processes at local/global scales. In this paper, a LST retrieval method was proposed from airborne multispectral scanner data comparing one mid-infrared (MIR) channel and one thermal infrared (TIR) channel with the land surface emissivity given as a priori knowledge. To remove the influence of the direct solar radiance efficiently, a relationship between the direct solar radiance and water vapor content and the view zenith angle and solar zenith angle was established. Then, LST could be retrieved with a split-window algorithm from MIR/TIR data. Finally, the proposed algorithm was applied to the actual airborne flight data and validated with in situ measurements of land surface types in the Baotou site in China on 17 October 2014. The results demonstrate that the difference between the retrieved and in situ LST was less than 1.5 K. The bais, RMSE, and standard deviation of the retrieved LST were 0.156 K, 0.883 K, and 0.869 K, respectively, for samples.
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Due to the lack of enough spectral bands for multi-spectral sensor, it is difficult to reconstruct surface retlectance spectrum from finite spectral information acquired by multi-spectral instrument. Here, taking into full account of the heterogeneity of pixel from remote sensing image, a method is proposed to simulate hyperspectral data from multispectral data based on canopy radiation transfer model. This method first assumes the mixed pixels contain two types of land cover, i.e., vegetation and soil. The sensitive parameters of Soil-Leaf-Canopy (SLC) model and a soil ratio factor were retrieved from multi-spectral data based on Look-Up Table (LUT) technology. Then, by combined with a soil ratio factor, all the parameters were input into the SLC model to simulate the surface reflectance spectrum from 400 to 2 400 nm. Taking Landsat Enhanced Thematic Mapper Plus (ETM+) image as reference image, the surface reflectance spectrum was simulated. The simulated reflectance spectrum revealed different feature information of different surface types. To test the performance of this method, the simulated reflectance spectrum was convolved with the Landsat ETM + spectral response curves and Moderate Resolution Imaging Spectrometer (MODIS) spectral response curves to obtain the simulated Landsat ETM+ and MODIS image. Finally, the simulated Landsat ETM+ and MODIS images were compared with the observed Landsat ETM+ and MODIS images. The results generally showed high correction coefficients (Landsat: 0.90-0.99, MODIS: 0.74-0.85) between most simulated bands and observed bands and indicated that the simulated reflectance spectrum was well simulated and reliable.
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Monitoreo del Ambiente/métodos , Hojas de la Planta , Imágenes Satelitales , Análisis Espectral/métodosRESUMEN
Purpose: Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG2000-HA and DSPE-PEG2000-TK-PEG5000, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration. Methods and Results: PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects. Conclusion: The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.
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Apoptosis , Diosgenina , Ácido Hialurónico , Liposomas , Neoplasias Ováricas , Paclitaxel , Polietilenglicoles , Especies Reactivas de Oxígeno , Femenino , Liposomas/química , Liposomas/farmacocinética , Paclitaxel/farmacología , Paclitaxel/química , Paclitaxel/farmacocinética , Paclitaxel/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Diosgenina/farmacología , Diosgenina/química , Diosgenina/farmacocinética , Diosgenina/administración & dosificación , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Línea Celular Tumoral , Polietilenglicoles/química , Animales , Especies Reactivas de Oxígeno/metabolismo , Humanos , Apoptosis/efectos de los fármacos , Sinergismo Farmacológico , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , FosfatidiletanolaminasRESUMEN
Immunotherapy has shown clinical benefit in patients with non-small-cell lung cancer (NSCLC). Due to the limited response of monotherapy, combining immune checkpoint inhibitors (ICIs) and chemotherapy is considered a treatment option for advanced NSCLC. However, the mechanism of combined therapy and the potential patient population that could benefit from combined therapy remain undetermined. Here, we developed an NSCLC model based on the published quantitative systems pharmacology (QSP)-immuno-oncology platform by making necessary adjustments. After calibration and validation, the established QSP model could adequately characterise the biological mechanisms of action of the triple combination of atezolizumab, nab-paclitaxel, and carboplatin in patients with NSCLC, and identify predictive biomarkers for precision dosing. The established model could efficiently characterise the objective response rate and duration of response of the IMpower131 trial, reproducing the efficacy of alternative dosing. Furthermore, CD8+ and CD4+ T cell densities in tumours were found to be significantly related to the response status. This significant extension of the QSP model not only broadens its applicability but also more accurately reflects real-world clinical settings. Importantly, it positions the model as a critical foundation for model-informed drug development and the customisation of treatment plans, especially in the context of combining single-agent ICIs with platinum-doublet chemotherapy.
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BACKGROUND: Difficulty in obtaining tetracycline, increased adverse reactions, and relatively complicated medication methods have limited the clinical application of the classic bismuth quadruple therapy. Therefore, the search for new alternative drugs has become one of the research hotspots. In recent years, minocycline, as a semisynthetic tetracycline, has demonstrated good potential for eradicating Helicobacter pylori (H. pylori) infection, but the systematic evaluation of its role remains lacking. AIM: To explore the efficacy, safety, and compliance of minocycline in eradicating H. pylori infection. METHODS: We comprehensively retrieved the electronic databases of PubMed, Embase, Web of Science, China National Knowledge Infrastructure, SinoMed, and Wanfang database as of October 30, 2023, and finally included 22 research reports on H. pylori eradication with minocycline-containing regimens as per the inclusion and exclusion criteria. The eradication rates of H. pylori were calculated using a fixed or a random effect model, and the heterogeneity and publication bias of the studies were measured. RESULTS: The single-arm meta-analysis revealed that the minocycline-containing regimens achieved good overall H. pylori eradication rates, reaching 82.3% [95% confidence interval (CI): 79.7%-85.1%] in the intention-to-treat analysis and 90.0% (95%CI: 87.7%-92.4%) in the per-protocol analysis. The overall safety and compliance of the minocycline-containing regimens were good, demonstrating an overall incidence of adverse reactions of 36.5% (95%CI: 31.5%-42.2%). Further by traditional meta-analysis, the results showed that the minocycline-containing regimens were not statistically different from other commonly used eradication regimens in eradication rate and incidence of adverse effects. Most of the adverse reactions were mild to moderate and well-tolerated, and dizziness was relatively prominent in the minocycline-containing regimens (16%). CONCLUSION: The minocycline-containing regimens demonstrated good efficacy, safety, and compliance in H. pylori eradication. Minocycline has good potential to replace tetracycline for eradicating H. pylori infection.
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Antibacterianos , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Minociclina , Humanos , Minociclina/efectos adversos , Minociclina/administración & dosificación , Minociclina/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Quimioterapia Combinada/métodos , Resultado del Tratamiento , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Cumplimiento de la MedicaciónRESUMEN
Simultaneous manipulation of multiple degrees of freedom of light lies at the heart of photonics. Nonlinear wavefront shaping offers an exceptional way to achieve this goal by converting incident light into beams of new frequencies with spatially varied phase, amplitude, and angular momenta. Nevertheless, the reconfigurable control over structured light fields for advanced multimode nonlinear photonics remains a grand challenge. Here, we propose the concept of nonlinear geometric phase in an emerging ferroelectric nematic fluid, of which the second-order nonlinear susceptibility carries spin-dependent nonlinearity phase. A case study with photopatterned q-plates demonstrates the generation of second-harmonic optical vortices with spin-locked topological charges by using cascaded linear and nonlinear optical spin-orbit interactions. Furthermore, we present the dynamic tunability of second-harmonic structured light through temperature, electric field, and twisted elastic force. The proposed strategy opens new avenues for reconfigurable nonlinear photonics, with potential applications in optical communications, quantum computing, high-resolution imaging, etc.
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Natural killer (NK) cells directly recognize and kill fungi, such as the pathogenic fungus Cryptococcus neoformans, via cytolytic mechanisms. However, the precise signaling pathways governing this NK cell microbicidal activity and the implications for fungal recognition are still unknown. Previously, it was reported that NK cell anticryptococcal activity is mediated through a conserved phosphatidylinositol 3-kinase-extracellular signal-regulated kinase 1/2 (PI3K-ERK1/2) pathway. Using YT (a human NK-like cell line) and primary human NK cells, we sought to identify the upstream, receptor-proximal signaling elements that led to fungal cytolysis. We demonstrate that Src family kinases were activated in response to C. neoformans. Furthermore, pharmacologic inhibition with an Src kinase inhibitor blocked C. neoformans-induced downstream activation of PI3K and ERK1/2 and abrogated cryptococcal killing. At the same time, the inhibitor disrupted the polarization of perforin-containing granules toward the NK cell-cryptococcal synapse but had no effect on conjugate formation between the organism and the NK cell. Finally, small interfering RNA (siRNA) double (but not single) knockdown of two Src family kinases, Fyn and Lyn, blocked cryptococcal killing. Together these data demonstrate a mechanism whereby the Src family kinases, Fyn and Lyn, redundantly mediate anticryptococcal activity through the activation of PI3K and ERK1/2, which in turn facilitates killing by inducing the polarization of perforin-containing granules to the NK cell-cryptococcal synapse.
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Cryptococcus neoformans/fisiología , Células Asesinas Naturales/metabolismo , Perforina/metabolismo , Proteínas Proto-Oncogénicas c-fyn/metabolismo , Familia-src Quinasas/metabolismo , Línea Celular Tumoral , Quinasas MAP Reguladas por Señal Extracelular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación de la Expresión Génica/inmunología , Humanos , Microdominios de Membrana , Perforina/genética , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-fyn/genética , Interferencia de ARN , ARN Interferente Pequeño , Tirosina , Familia-src Quinasas/genéticaRESUMEN
Despite increasing evidence that patients with heart failure (HF) are susceptible to sarcopenia, the reason for the association is not well understood. The purpose of this study is to explore further the molecular mechanism of the occurrence of this complication. Gene expression datasets for HF (GSE57345) and Sarcopenia (GSE1428) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using 'edgeR' and "limma" packages of R, and their functions were analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-protein interaction (PPI) networks were constructed and visualized using Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. Hub genes were selected using the plugin cytoHubba and validation with GSE76701 for HF and GSE136344 for Sarcopenia. The related pathways and molecular mechanisms of the hub genes were performed by Gene set enrichment analysis (GSEA). The statistical analyses were performed using R software. P < 0.05 was considered statistically significant. A total of 114 common DEGs were found. Pathways related to growth factor, Insulin secretion and cGMP-PKG were enriched in both HF and Sarcopenia. CYP27A1, KCNJ8, PIK3R5, TIMP2, CXCL12, KIT, and VCAM1 were found to be significant hub genes after validation, with GSEA emphasizing the importance of the hub genes in the regulation of the inflammatory response. Our study reveals that HF and Sarcopenia share common pathways and pathogenic mechanisms. These findings may suggest new directions for future research into the underlying pathogenesis.
Apesar das evidências crescentes de que pacientes com insuficiência cardíaca (IC) são suscetíveis à sarcopenia, o motivo da associação não é bem compreendido. O objetivo deste estudo é explorar ainda mais o mecanismo molecular de ocorrência desta complicação. Conjuntos de dados de expressão gênica para HF (GSE57345) e Sarcopenia (GSE1428) foram obtidos do banco de dados Gene Expression Omnibus (GEO). Genes diferencialmente expressos (DEGs) foram identificados usando pacotes 'edgeR' e "limma" de R, e suas funções foram analisadas usando Gene Ontology (GO) e a Enciclopédia de Genes e Genomas de Kyoto (KEGG). Redes de interação proteína-proteína (PPI) foram construídas e visualizadas usando Search Tool for the Retrieval of Interacting Genes (STRING) e Cytoscape. Os genes hub foram selecionados usando o plugin cytoHubba e validados com GSE76701 para IC e GSE136344 para Sarcopenia. As vias relacionadas e os mecanismos moleculares dos genes hub foram realizados pela análise de enriquecimento de genes (GSEA). As análises estatísticas foram realizadas no software R. P < 0,05 foi considerado estatisticamente significativo. Foram encontrados 114 DEGs comuns. As vias relacionadas ao fator de crescimento, secreção de insulina e cGMP-PKG estavam enriquecidas tanto na IC quanto na sarcopenia. Descobriu-se que CYP27A1, KCNJ8, PIK3R5, TIMP2, CXCL12, KIT e VCAM1 são genes hub significativos após validação com GSEA enfatizando a importância dos genes hub na regulação da resposta inflamatória. Nosso estudo revela que a IC e a Sarcopenia compartilham vias e mecanismos patogênicos comuns. Estes achados podem sugerir novas direções para pesquisas futuras sobre a patogênese subjacente.
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Insuficiencia Cardíaca , Sarcopenia , Humanos , Biología de Sistemas , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Sarcopenia/genética , Biología Computacional , Insuficiencia Cardíaca/genéticaRESUMEN
BACKGROUND: The incidence of ingestion of magnetic foreign bodies in the gastrointestinal tract has been increasing year by year. Due to their strong magnetic attraction, if multiple gastrointestinal foreign bodies enter the small intestine, it can lead to serious complications such as intestinal perforation, necrosis, torsion, and bleeding. Severe cases require surgical intervention. CASE SUMMARY: We report a 6-year-old child who accidentally swallowed multiple magnetic balls. Under timely and safe anesthesia, the magnetic balls were quickly removed through gastroscopy before entering the small intestine. CONCLUSION: General anesthesia with endotracheal intubation can ensure full anesthesia under the condition of fasting for less than 6 h. In order to prevent magnetic foreign bodies from entering the small intestine, timely and effective measures must be taken to remove the foreign bodies.
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Quantum interference and traditional domain wall effects are two common ways to manipulate the magnetism in magnetic materials. Here, we report both effects emerge in the designed graphene nanodisks simultaneously, and thus providing an accessible way to engineer the magnetism in graphene nanostructures. By adjusting the length of the armchair edges at the corners of hexagonal disk, connecting the adjacent zigzag edges, we show that the quantum interference among the zigzag edges remains robust and consequently determines the magnetic structure in the small-size systems, in analogy with the nanoribbons. More importantly, a domain-wall-like magnetic mechanism is numerically identified to dominate the larger-size disks. In particular, a magnetic state with fully spin-polarized edges achieved in a wide parameter region promises the future applications for spintronics.
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Objective: The aim of this study is to evaluate the associations between admission hyperglycemia and the risk of all-cause mortality in patients with acute myocardial infarction (AMI) with or without diabetes, to find optimal admission glucose intervention cut-offs, and to clarify the shape of the dose-response relations. Methods: Medline/PubMed and EMBASE were searched from inception to 1 April 2022. Cohort studies reporting estimates of all-cause mortality risk in patients with admission hyperglycemia with AMI were included. The outcomes of interest include mortality and major adverse cardiac events (MACEs). A random effect dose-response meta-analysis was conducted to access linear trend estimations. A one-stage linear mixed effect meta-analysis was used for estimating dose-response curves. Relative risks and 95% confidence intervals were pooled using a random-effects model. Results: Of 1,222 studies screened, 47 full texts were fully reviewed for eligibility. The final analyses consisted of 23 cohort studies with 47,177 participants. In short-term follow-up, admission hyperglycemia was associated with an increased risk of all-cause mortality (relative risk: 3.12, 95% confidence interval 2.42-4.02) and MACEs (2.34, 1.77-3.09). In long-term follow-up, admission hyperglycemia was associated with an increased risk of all-cause mortality (1.97, 1.61-2.41) and MACEs (1.95, 1.21-3.14). A linear dose-response association was found between admission hyperglycemia and the risk of all-cause mortality in patients with or without diabetes. Conclusion: Admission hyperglycemia was significantly associated with higher all-cause mortality risk and rates of MACEs. However, the association between admission hyperglycemia and long-term mortality risk needs to be determined with caution. Compared with current guidelines recommendations, a lower intervention cut-off and more stringent targets for admission hyperglycemia may be appropriate. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022317280], identifier [CRD42022317280].
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Background: Allergic respiratory diseases have increased dramatically due to air pollution over the past few decades. However, studies are limited on the effects of inorganic components and particulate matter with different particle sizes in smog on allergic diseases, and the possible molecular mechanism of inducing allergies has not been thoroughly studied. Methods: Four common mineral elements with different particle sizes in smog particles were selected, including Al2O3, TiO2, Fe2O3, and SiO2. We studied the relationship and molecular mechanism of smog particle composition, particle size, and allergic reactions using mast cells, immunoglobulin E (IgE)-mediated passive cutaneous anaphylaxis (PCA) model, and an ovalbumin (OVA)-induced asthmatic mouse model in vitro and in vivo, combined with transmission electron microscopy, scanning transmission X-ray microscopy analysis, and transcriptome sequencing. Results: Only 20 nm SiO2 particles significantly increased ß-hexosaminidase release, based on dinitrophenol (DNP)-human serum albumin (HSA) stimulation, from IgE-sensitized mast cells, while other particles did not. Meanwhile, the PCA model showed that Evan's blue extravasation in mice was increased after treatment with nano-SiO2 particles. Nano-SiO2 particles exposure in the asthmatic mouse model caused an enhancement of allergic airway inflammation as manifested by OVA-specific serum IgE, airway hyperresponsiveness, lung inflammation injury, mucous cell metaplasia, cytokine expression, mast cell activation, and histamine secretion, which were significantly increased. Nano-SiO2 particles exposure did not affect the expression of FcϵRI or the ability of mast cells to bind IgE but synergistically activated mast cells by enhancing the mitogen-activated protein kinase (MAPK) signaling pathway, especially the phosphorylation levels of the extracellular signal-regulated kinase (ERK)1/2. The ERK inhibitors showed a significant inhibitory effect in reducing ß-hexosaminidase release. Conclusion: Our results indicated that nano-SiO2 particles stimulation might synergistically activate IgE-sensitized mast cells by enhancing the MAPK signaling pathway and that nano-SiO2 particles exposure could exacerbate allergic inflammation. Our experimental results provide useful information for preventing and treating allergic diseases.