RESUMO
The problem of poisoning on the surface of catalysts used in CO oxidation reactions, such as Pt, needs to be solved. In this work, we constructed lattice-matched C2N/Pt(111) catalysts with different configurations (top/fcc/hcp) and found that, within the confined space between the cover and the substrate, the adsorption energy of CO is reduced by 0.35 eV to 0.43 eV, while the adsorption of other reactants O/O2 is strengthened and the adsorption energy of the product CO2 is positive, indicating that the constraint effect produced by C2N and Pt(111) is beneficial to CO oxidation, when compared to the pure Pt(111). Our work suggests that the C2N cover not only protects the Pt surface under harsh conditions but also allows gaseous molecules CO and O2 to approach the Pt surface through a facile intercalation process, with enhanced surface reactivity for CO oxidation and reduced catalyst poisoning.
RESUMO
Delay discounting (DD) refers to a phenomenon that humans tend to choose small-sooner over large-later rewards during intertemporal choices. Steep discounting of delayed outcome is related to a variety of maladaptive behaviors and is considered as a transdiagnostic process across psychiatric disorders. Previous studies have investigated the association between brain structure (e.g. gray matter volume) and DD; however, it is unclear whether the intracortical myelin (ICM) influences DD. Here, based on a sample of 951 healthy young adults drawn from the Human Connectome Project, we examined the relationship between ICM, which was measured by the contrast of T1w and T2w images, and DD and further tested whether the identified associations were mediated by the regional homogeneity (ReHo) of brain spontaneous activity. Vertex-wise regression analyses revealed that steeper DD was significantly associated with lower ICM in the left temporoparietal junction (TPJ) and right middle-posterior cingulate cortex. Region-of-interest analysis revealed that the ReHo values in the left TPJ partially mediated the association of its myelin content with DD. Our findings provide the first evidence that cortical myelination is linked with individual differences in decision impulsivity and suggest that the myelin content affects cognitive performances partially through altered local brain synchrony.
Assuntos
Imageamento por Ressonância Magnética , Bainha de Mielina , Adulto Jovem , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Comportamento Impulsivo , Substância Cinzenta/diagnóstico por imagemRESUMO
The technique of CO2 capture and separation using charge-modulated sorbent materials holds promise for reducing CO2 emissions. Density functional theory with long-range dispersion correction has been used to study the adsorption of CO2, H2, CH4, and N2 on BC3 nanosheets with/without charge injections. We find that CO2 is weakly adsorbed on pristine BC3, but injection of 3 negative charges (3 e) can change the adsorption to chemical adsorption. Removing the charge results in the release of CO2 without any energy barrier. A high capacity of 4.30 × 1014 cm-2 can be achieved with 5 e charge injection, and CO2 molecules could automatically desorb after charge removal. Additionally, negatively charged BC3 exhibits high selectivity for separating CO2 from other industrial gases such as CH4, H2, and N2. Our findings provide useful guidance for the development of switchable CO2 capture and storage materials.
RESUMO
BACKGROUND: Severe influenza, especially influenza pneumonia, causes large numbers of deaths each year. Some patients who develop severe influenza have no known risk factors. In this study we investigated risk factors for mortality of patients with influenza A-related pneumonia who have different basic conditions. We also evaluated the power of pneumonia severity assessment tools in Chinese patients hospitalized with influenza A-related pneumonia. Together, these results could provide a basis for a screening method that has improved ability for the early identification of critical patients who will have poor prognoses in clinical practice. METHODS: This single-center, retrospective case-control study included 152 adult patients with severe influenza over six influenza seasons. Data for diagnoses and demographics, as well clinical data, laboratory findings, treatment methods, 30-day and 60-day outcomes of the patients were collected. Patients who had any of the risk factors for severe influenza were included in the high-risk group, and those that had no known risk factors were included in the low-risk group. RESULTS: The PSI, CURB-65 and PIRO-CAP tools all underestimated the mortality rate of patients hospitalized with influenza A-related pneumonia, and this underestimate was more pronounced for low-risk patients. D-dimer (Odds ratio [OR] = 1.052, 95% confidence interval [CI] 1.001-1.106, p = 0.045) and direct bilirubin (OR = 1.143, 95%CI 1.049-1.246, p = 0.002) were independent risk factors for mortality of patients with influenza A-related pneumonia. When used in combination with ferritin and D-dimer, the area under receiver operator characteristic curve (AUCROC) was 0.851 (95%CI 0.780-0.922, p < 0.001), 0.840 (95%CI 0.763-0.916, p < 0.001) and 0.829 (95%CI 0.748-0.911, p < 0.001) for PSI, CURB-65 and PIRO-CAP, respectively, which was higher than that obtained using PSI, CURB-65 and PIRO-CAP alone. CONCLUSIONS: The findings demonstrate that currently used community-acquired pneumonia (CAP) scoring systems could underestimate the risk of influenza A-related pneumonia mortality. D-dimer was shown to be an independent risk factor of mortality for influenza A-related pneumonia in hospitalized patients, and a combination of D-dimer with ferritin could improve the predictive value of PSI, CURB-65 and PIRO-CAP for adverse prognoses of patients with influenza A-related pneumonia.
Assuntos
Infecções Comunitárias Adquiridas , Influenza Humana , Pneumonia , Adulto , Humanos , Estudos Retrospectivos , Influenza Humana/complicações , Estudos de Casos e Controles , Índice de Gravidade de Doença , Pneumonia/diagnóstico , Fatores de Risco , PrognósticoRESUMO
Sludge is the by-product of wastewater treatment process. Multisource sludge can be defined as sludge from different sources. Based on the sludge properties of five typical cities in the Yangtze River basin, including Jiujiang, Wuhu, Lu'an, Zhenjiang and Wuhan, this study investigated and summarized the characteristic variations and distribution differences of multiple indicators and substances from municipal sludge, dredged sludge, and river and lake sediments. The results demonstrated pH of multisource sludge was relatively stable in the neutral range. Organic matter and water content among municipal sludge were high and varied considerably between different wastewater treatment plants. Dredged sludge had an obviously higher sand content and wider particle distribution, which could be considered for graded utilization depending on its size. The nutrients composition of river and lake sediments was usually stable and special, with lower nitrogen and phosphorus content but higher potassium levels. The sources of heavy metals and persistent organic pollutants in multisource sludge were correlated, generally much higher among municipal sludge than dredged sludge and river and lake sediments, which were the most important limitation for final land utilization. Despite various properties of multisource sludge, the final fate and destination have some overall similarities, which need to be supplemented and improved by standards and laws. The study provided a preliminary analysis of suitable technical routes for municipal sludge, dredged sludge, river and lake sediments based on their different characteristics respectively, which was of great significance for multisource sludge co-treatment and disposal in the future of China.
Assuntos
Rios , Esgotos , Lagos , Cidades , FósforoRESUMO
Dysfunction of late endothelial progenitor cells (EPCs) has been suggested to be associated with hypertension. ß2-Adrenergic receptor (ß2AR) is a novel and key target for EPC homing. Here, we proposed that attenuated ß2AR signaling contributes to EPCs dysfunction, whereas enhanced ß2AR signaling restores EPCs' functions in hypertension. EPCs derived from hypertensive patients exhibited reduced cell number, impaired in vitro migratory and adhesion abilities, and impaired re-endothelialization after transplantation in nude mice with carotid artery injury. ß2AR expression of EPCs from hypertensive patients was markedly downregulated, whereas the phosphorylation of the p38 mitogen-activated protein kinase (p38-MAPK) was elevated. The cleaved caspase-3 levels were elevated in EPCs. The overexpression of ß2AR in EPCs from hypertensive patients inhibited p38-MAPK signaling, whereas it enhanced in vitro EPC proliferation, migration, and adhesion and in vivo re-endothelialization. The ß2AR-mediated effects were attenuated by treating the EPCs with a neutralizing monoclonal antibody against ß2AR, which could be partially antagonized by the p38-MAPK inhibitor SB203580. Moreover, shear stress stimulation, a classic nonpharmacological intervention, increased the phosphorylation levels of ß2AR and enhanced the in vitro and in vivo functions of EPCs from hypertensive patients. Collectively, the current investigation demonstrated that impaired ß2AR/p38-MAPK/caspase-3 signaling at least partially reduced the re-endothelialization capacity of EPCs from hypertensive patients. Restoration of ß2AR expression and shear stress treatment could improve their endothelial repair capacity by regulating the p38-MAPK/caspase-3 signaling pathway. The clinical significance of ß2AR in endothelium repair still requires further investigation.NEW & NOTEWORTHY Impaired ß2-adrenergic receptor (ß2AR) expression with an elevation of p38-MAPK/caspase-3 signaling at least partially contributes to the decline of re-endothelialization capacity of late endothelial progenitor cells (EPCs) from hypertensive patients. ß2AR gene transfer and shear stress treatment improve the late EPC-mediated enhancement of the re-endothelialization capacity in hypertensive patients through activating ß2AR/p38-MAPK/caspase-3 signaling. The present study is the first to reveal the potential molecular mechanism of the impaired endothelium-reparative capacity of late EPCs in hypertension after vascular injury and strongly suggests that ß2AR is a novel and crucial therapeutic target for increasing EPC-mediated re-endothelialization capacity in hypertension.
Assuntos
Lesões das Artérias Carótidas/prevenção & controle , Proliferação de Células , Células Progenitoras Endoteliais/metabolismo , Hipertensão/metabolismo , Reepitelização , Receptores Adrenérgicos beta 2/metabolismo , Animais , Apoptose , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/patologia , Estudos de Casos e Controles , Caspase 3/metabolismo , Adesão Celular , Movimento Celular , Células Cultivadas , Técnicas de Cocultura , Modelos Animais de Doenças , Células Progenitoras Endoteliais/patologia , Células Progenitoras Endoteliais/transplante , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Hipertensão/patologia , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Painful burn injuries are among the most debilitating form of trauma, globally ranking in the top 15 leading causes of chronic disease burden. Despite its prevalence, however, chronic pain after burn injury is under-studied. We previously demonstrated the contribution of the Rac1-signaling pathway in several models of neuropathic pain, including burn injury. However, Rac1 belongs to a class of GTPases with low therapeutic utility due to their complex intracellular dynamics. To further understand the mechanistic underpinnings of burn-induced neuropathic pain, we performed a longitudinal study to address the hypothesis that inhibition of the downstream effector of Rac1, Pak1, will improve pain outcome following a second-degree burn injury. Substantial evidence has identified Pak1 as promising a clinical target in cognitive dysfunction and is required for dendritic spine dysgenesis associated with many neurological diseases. In our burn injury model, mice exhibited significant tactile allodynia and heat hyperalgesia and dendritic spine dysgenesis in the dorsal horn. Activity-dependent expression of c-fos also increased in dorsal horn neurons, an indicator of elevated central nociceptive activity. To inhibit Pak1, we repurposed an FDA-approved inhibitor, romidepsin. Treatment with romidepsin decreased dendritic spine dysgenesis, reduced c-fos expression, and rescued pain thresholds. Drug discontinuation resulted in a relapse of cellular correlates of pain and in lower pain thresholds in behavioral tests. Taken together, our findings identify Pak1 signaling as a potential molecular target for therapeutic intervention in traumatic burn-induced neuropathic pain.
Assuntos
Queimaduras/complicações , Espinhas Dendríticas/patologia , Neuralgia/etiologia , Neuralgia/metabolismo , Pele/inervação , Quinases Ativadas por p21/metabolismo , Animais , Antibióticos Antineoplásicos/uso terapêutico , Peso Corporal/efeitos dos fármacos , Espinhas Dendríticas/efeitos dos fármacos , Depsipeptídeos/uso terapêutico , Modelos Animais de Doenças , Feminino , Estudos Longitudinais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/metabolismo , Neuralgia/tratamento farmacológico , Limiar da Dor/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Medula Espinal/patologia , Proteínas rac1 de Ligação ao GTP/metabolismoRESUMO
Procrastination is a pervasive phenomenon across different cultures and brings about lots of serious consequences, including performance, subjective well-being, and even public policy. However, little is known about the neural substrates of procrastination. In order to shed light upon this question, we investigated the neuroanatomical substrates of procrastination across two independent samples using voxel-based morphometry (VBM) method. The whole-brain analysis showed procrastination was positively correlated with the graymatter (GM) volume of clusters in the parahippocampal gyrus (PHG) and the orbital frontal cortex (OFC), while negatively correlated with the GM volume of clusters in the inferior frontal gyrus (IFG) and the middle frontal gyrus (MFG) in sample one (151 participants). We further conducted a verification procedure on another sample (108 participants) using region-of-interest analysis to examine the reliability of these results. Results showed procrastination can be predicted by the GM volume of the OFC and the MFG. The present findings suggest that the MFG and OFC, which are the key regions of self-control and emotion regulation, may play an important role in procrastination.
Assuntos
Substância Cinzenta/diagnóstico por imagem , Giro Para-Hipocampal/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Procrastinação , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Mapeamento Encefálico/métodos , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Substância Cinzenta/patologia , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Tamanho do Órgão , Giro Para-Hipocampal/patologia , Córtex Pré-Frontal/patologia , Reprodutibilidade dos Testes , Autocontrole , Adulto JovemRESUMO
Therapeutic benefits offered by common chemotherapy drugs, such as oxaliplatin, are limited due to the development of resistance, which contributes to treatment failure and metastasis. The epithelial-mesenchymal transition (EMT) is a key event contributing to the development of resistance to chemotherapeutics. Although the relationship between oxaliplatin and chemotherapy resistance has been described for decades, the molecular mechanisms have remained elusive. The aim of the present study was to investigate the underlying mechanisms of oxaliplatin-mediated metastasis. Here, we identify reactive oxygen species (ROS) as mediators that promote the oxaliplatin-induced EMT. Following oxaliplatin treatment, the messenger RNA (mRNA) levels of most peroxiredoxin family genes, except for peroxiredoxin 1 (prdx1) gene, were constant or even decreased, resulting in ROS abundance. And the antioxidant guardian Nrf2 was unconspicuously raised both transcriptionally and translationally with oxaliplatin treatment as compared to those induced by topotecan treatment, which has been proved with no induced metastasis. In addition, the study evaluated high levels of ROS leading to EMT via activation of the known oncogenes Akt and Snail. Using the Akt inhibitor LY294002 or knocking down Snail expression via RNA interference (RNAi) reversed the effects of oxaliplatin on the EMT and metastasis. Our studies establish a role for the ROS-Akt-Snail axis as a mechanism by which chemotherapeutics induce EMT and cancer metastasis.
Assuntos
Antineoplásicos/farmacologia , Neoplasias do Colo/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Compostos Organoplatínicos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Cromonas/farmacologia , Neoplasias do Colo/metabolismo , Imunofluorescência , Humanos , Imuno-Histoquímica , Morfolinas/farmacologia , Oxaliplatina , Peroxirredoxinas/genética , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Interferência de RNA , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição da Família Snail/genéticaRESUMO
Aggressive behavior can have serious physical, psychological, and social consequences. However, little is known about the personality and neurological antecedents underlying aggressive behavior in children. The objective of this study was to investigate the relationship between self-esteem, aggression, and brain structure (i.e., cortical thickness and surface area) in a population of healthy children (N = 78; 9-12 years; mean age: 9.95 ± 0.90 years). The results revealed that self-esteem showed a negative association with aggression and significantly predicted aggressive behavior. No gender differences were found in aggression and its neural correlates. We performed the cortical parcellation method to further explore the neural foundations underlying the association of self-esteem with aggression. Children with higher aggression had increased cortical thickness in four clusters after multiple comparison correction: right medial orbitofrontal cortex, right lateral orbitofrontal cortex, right superior frontal gyrus, and left insula. In a mediation analysis, cortical thickness in the right medial orbitofrontal cortex contributed to the effect of self-esteem on aggression. These findings extend our understanding of morphological correlates of aggression in children, suggesting that an increased cortical thickness in childhood is a potential mechanism linking low self-esteem to aggression.
Assuntos
Agressão , Córtex Pré-Frontal , Humanos , Criança , Autoimagem , Personalidade , Encéfalo/anatomia & histologia , Imageamento por Ressonância MagnéticaRESUMO
Objectives: This study aimed to analyze the risk factors for mortality of idiopathic inflammatory myopathy (IIM) patients admitted with interstitial lung disease (ILD) to guide rapid and accurate judgment of clinical prognosis. Patients and methods: This retrospective, single-center cohort study was conducted with 135 participants (37 males, 98 females; mean age: 54.8±11.1 years; range, 24 to 85 years) between June 1, 2016, and June 30, 2021. The participants were categorized into the survival group (n=111) and nonsurvivors (n=24) according to whether they survived during the one-year follow-up. The independent risk factors for mortality in one year after discharge were analyzed. Receiver operating characteristic curve analysis was used to determine the accuracy of oxygenation index at baseline combined with pulmonary infection (PI) at follow-up to indicate death in IIM-ILD patients. Results: Compared to the survival group, nonsurvivors were older (p=0.006) and had a higher proportion of anti-MDA5 (melanoma differentiation-associated protein 5) positivity (p<0.001). The ILD duration was shorter (p=0.006), the oxygenation index was lower (p<0.001), and the intensive care unit occupancy rate (p<0.001) and ventilator utilization rate (p<0.001) were elevated in nonsurvivors compared to the survival group. Oxygenation index at baseline (odds ratio [OR]=1.021, 95% confidence interval [CI]: 1.001-1.023, p=0.040) and PI (clinical judgment) at follow-up (OR=16.471, 95% CI: 1.565-173.365, p=0.020) were found as independent risk factors for death in the year after discharge in IIM inpatients with ILD. An oxygenation index ≤279 mmHg at baseline combined with PI at follow-up exhibited a promising predictive value for all-cause death in IIM-ILD patients within one year. Conclusion: Oxygenation index at baseline and PI during follow-up were independent risk factors for death of IIM-ILD patients within one year after discharge. Patients with an oxygenation index ≤279 mmHg at baseline had an increased risk of death once they developed PI during the one-year follow-up.
RESUMO
The reward system has been proven to be contributed to the vulnerability of obesity. Previous fMRI studies have shown abnormal functional connectivity of the reward system in obesity. However, most studies were based on static index such as resting-state functional connectivity (FC), ignoring the dynamic changes over time. To investigate the dynamic neural correlates of obesity susceptibility, we used a large, demographically well-characterized sample from the Human Connectome Project (HCP) to determine the relationship of body mass index (BMI) with the temporal variability of FC from integrated multilevel perspectives, i.e., regional and within- and between-network levels. Linear regression analysis was used to investigate the association between BMI and temporal variability of FC, adjusting for covariates of no interest. We found that BMI was positively associated with regional FC variability in reward regions, such as the ventral orbitofrontal cortex and visual regions. At the intra-network level, BMI was positively related to the variability of FC within the limbic network (LN) and default mode network (DMN). At the inter-network level, variability of connectivity of LN with DMN, frontoparietal, sensorimotor, and ventral attention networks showed positive correlations with BMI. These findings provided novel evidence for abnormal dynamic functional interaction between the reward network and the rest of the brain in obesity, suggesting a more unstable state and over-frequent interaction of the reward network and other attention and cognitive networks. These findings, thus, provide novel insight into obesity interventions that need to decrease the dynamic interaction between reward networks and other brain networks through behavioral treatment and neural modulation.
RESUMO
Perceived stress, which refers to people's evaluation of a stressful event and their ability to cope with it, has emerged as a stable predictor for physical and mental health outcomes. Increasing evidence has suggested the buffering effect of social support on perceived stress. Although previous studies have investigated the brain structural features (e.g., gray matter volume) associated with perceived stress, less is known about the association between perceived chronic stress and intra-cortical myelin (ICM), which is an important microstructure of brain and is essential for healthy brain functions, and the role of social support in this association. Using a sample of 1076 healthy young adults drawn from the Human Connectome Project, we quantified the ICMby the contrast of T1w and T2w images and examined its association with perceived chronic stress during the last month and social support. Behavioral results showed that perceived chronic stress was negatively associated with both emotional support and instrumental support. Vertex-wise multiple regression analyses revealed that higher level of perceived chronic stress was significantly associated with lower ICM content of a cluster in the right supramarginal gyrus (rSMG). Interestingly, the emotional support, but not the instrumental support, significantly mediated the association of perceived chronic stress with ICM in the rSMG. Overall, the present study provides novel evidence for the cortical myelination of perceived chronic stress in humans and highlights the essential role of the rSMG in perceived chronic stress and emotional support.
RESUMO
Academic self-concept, which can be defined as one's beliefs about their academic ability, plays an important role in students' future academic achievement. Here, we examined the neuroanatomical substrates underlying academic self-concept in 92 school-aged children (9.90 ± 0.85 years, 41 girls) using voxel-based morphometry of images obtained by structural magnetic resonance imaging. Our results revealed a significant positive correlation between academic self-concept and achievement 1 year after assessment. Whole-brain regression analyses found that gray matter volume in the right dorsolateral prefrontal cortex (DLPFC) and dorsomedial prefrontal cortex (DMPFC) was negatively associated with academic self-concept. Region of interest analyses further showed that regional gray matter volume in the right DLPFC could significantly predict achievement 1 year after assessment. Notably, mediation analyses suggested that regional gray matter volume in the right DLPFC mediated the effect of academic self-concept on students' future academic achievement.
Assuntos
Sucesso Acadêmico , Encéfalo/patologia , Criança , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/diagnóstico por imagemRESUMO
A growing body of evidence suggests that engagement in episodic future thinking (EFT) could reduce delay discounting rates. However, little is known about whether individual differences in the ability of EFT are associated with differences in delay discounting in young adults. In the present study, this association was tested in healthy college students (n = 106, 19.98 ± 1.56 years), and the neural basis underlying this association was also examined using voxel-based morphometry (VBM) method. Behavioral analysis indicated that individual differences in EFT ability can significantly negatively predict discounting rates. VBM analysis first revealed that the EFT score positively correlated with gray matter volume (GMV) of a cluster in hippocampus, while negatively correlated with GMV of a cluster in rostral anterior cingulate cortex. We also found the GMV of a cluster in the mPFC was positively correlated with delay discounting. ROI analysis further revealed that individual differences in delay discounting could be reliably predicted by the GMV in the hippocampus and mPFC. The final mediation analysis showed that the GMV of the hippocampus plays a significant mediating role in the association between EFT and delay discounting, and the indirect effect of the hippocampal GMV accounts for 33.2% of the total effect. Our results suggest that individuals' EFT ability may be an important determinant of differences in delay discounting, and highlight the hippocampal structure as a neural biomarker for explaining the association between EFT ability and delay discounting.
RESUMO
Retinoblastoma is a most frequently occurring primary intraocular tumor in infancy and children, highlighting the requirement to find and develop novel and more effective therapeutic approaches. Wedelolactone (WDL), a nature compound isolated from E. prostrata, exhibits multiple biological activities through regulating various signaling pathways; however, its potential influences on retinoblastoma progression are still unknown, and thus was investigated in our study, as well as the underlying mechanisms. Here, we found that WDL treatments significantly reduced the proliferation of retinoblastoma cells by inducing apoptosis and pyroptosis through increasing Caspase-3, Caspase-1, gasdermin E (GSDME) and gasdermin D (GSDMD) activation. Mitochondrial impairment and reactive oxygen species (ROS) generation were considerably up-regulated in WDL-incubated retinoblastoma cells through a dose-dependent manner. Notably, we found that ROS scavenge significantly abolished the function of WDL to provoke apoptosis and pyroptosis in retinoblastoma cell lines, revealing that ROS was required for WDL to perform its anti-cancer role in retinoblastoma. Moreover, our in vivo experiments indicated that WDL administration significantly reduced the tumor growth in the established retinoblastoma mouse models with undetectable toxicity. Collectively, these findings highlighted the potential of WDL to inhibit the growth and induce cell death of retinoblastoma in vitro and in vivo, and thereby showed promise as a therapeutic agent for the treatment of retinoblastoma.
Assuntos
Neoplasias da Retina , Retinoblastoma , Animais , Apoptose , Cumarínicos , Camundongos , Piroptose , Espécies Reativas de Oxigênio/metabolismo , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológicoRESUMO
Background: Most deaths from coronary artery disease (CAD) are due to acute myocardial infarction (AMI). There is an urgent need for early AMI detection, particularly in patients with stable CAD. 5-methylcytosine (5mC) regulatory genes have been demonstrated to involve in the progression and prognosis of cardiovascular diseases, while little research examined 5mC regulators in CAD to AMI progression. Method: Two datasets (GSE59867 and GSE62646) were downloaded from Gene Expression Omnibus (GEO) database, and 21 m5C regulators were extracted from previous literature. Dysregulated 5mC regulators were screened out by "limma." The least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) algorithm were employed to identify hub 5mC regulators in CAD to AMI progression, and 43 clinical samples (Quantitative real-time PCR) were performed for expression validation. Then a logistic model was built to construct 5mC regulator signatures, and a series of bioinformatics algorithms were performed for model validation. Besides, 5mC-associated molecular clusters were studied via unsupervised clustering analysis, and correlation analysis between immunocyte and 5mC regulators in each cluster was conducted. Results: Nine hub 5mC regulators were identified. A robust model was constructed, and its prominent classification accuracy was verified via ROC curve analysis (area under the curve [AUC] = 0.936 in the training cohort and AUC = 0.888 in the external validation cohort). Besides, the clinical effect of the model was validated by decision curve analysis. Then, 5mC modification clusters in AMI patients were identified, along with the immunocyte infiltration levels of each cluster. The correlation analysis found the strongest correlations were TET3-Mast cell in cluster-1 and TET3-MDSC in cluster-2. Conclusion: Nine hub 5mC regulators (DNMT3B, MBD3, UHRF1, UHRF2, NTHL1, SMUG1, ZBTB33, TET1, and TET3) formed a diagnostic model, and concomitant results unraveled the critical impact of 5mC regulators, providing interesting epigenetics findings in AMI population vs. stable CAD.
RESUMO
Oseltamivir phosphate is widely used to treat and prevent influenza, and is available in the form of capsules, powder for oral suspension, pediatric solutions, and granules. Because of the amino group, oseltamivir is easy to react with the excipients of the formulation to generate drug-excipient interaction impurities. In this research, two degradation products in a commercial oseltamivir phosphate powder for oral suspension due to interaction between API and citrate were investigated. They were characterized to be 3-((-6-acetamido-3-(ethoxycarbonyl)-5-(pentan-3-yloxy)cyclohex-3-en-1-yl)carbamoyl)-3-hydroxypentanedioic acid and 2-(2-((-6-acetamido-3-(ethoxycarbonyl)-5-(pentan-3-yloxy)cyclohex-3-en-1-yl)amino)-2-oxoethyl)-2-hydroxysuccinic acid by MS and NMR, respectively. Furthermore, the formation mechanisms of these impurities were verified, and the method of analysis of covariance was used to assess the rate of impurities' degradation. HIGHLIGHTS: Two excipient interaction degradation products in commercial oseltamivir phosphate powder for oral suspension were studied and elucidated in detail via LC-MS/MS and NMR. The incompatibility risk of pH conditioners such as citrate and citric acid with formulations that contain an amino group was disclosed in this article. Analysis of covariance was demonstrated to assess the impact of various formulations and preparation techniques on the rate of impurity degradation.
Assuntos
Excipientes , Oseltamivir , Humanos , Criança , Oseltamivir/química , Excipientes/química , Pós , Cromatografia Líquida , Espectrometria de Massas em Tandem , Contaminação de Medicamentos , Fosfatos , CitratosRESUMO
INTRODUCTION: Intra-arterial chemotherapy (IAC) has been used successfully for unilateral and bilateral eye disease with advanced or less advanced intraocular disease and of children as young as 3âmonths of age. In this study, we expanded the use of IAC to eyes of two infants with very low birthweight (birth weight of 1000-1500âg) and retinoblastoma. PATIENT CONCERNS: The ophthalmologists refused to give patients intravenous chemotherapy (IVC), considering the risk of IVC because of the low body weight. DIAGNOSIS: Two patients were diagnosed unilateral eye retinoblastoma at 31âdays old and 27âdays old respectively when newborn fundus screening. INTERVENTIONS: Chemotherapeutic agents were injected into the ophthalmic artery during the four IAC session. The two patients' oculars were preserved due to calcification during follow-up periods to the final IAC. OUTCOMES: Complications included eyelid edema in the patient #1 and neutropenia in both patients. No fever, sepsis and other systemic toxic effects were observed. After two successful IAC treatment for each patient, their oculars were all preserved without serious complications. LESSONS: Our center for the first time reported the management of retinoblastoma in very low birthweight infants with especially challenging and we recommend this to be useful to the patient community.
Assuntos
Antineoplásicos/uso terapêutico , Recém-Nascido de muito Baixo Peso , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Infusões Intra-Arteriais , Artéria OftálmicaRESUMO
Sewage sludge was rich in pollutants such as heavy metals, nutrients and persistent organic pollutants. Anaerobic digestion can effectively degrade the pollutants while achieving sludge stabilization and reduction. This study took a sludge treatment plant located in Anhui Province, China as a case study, investigating the variations of multiple substances and particle size distribution during sludge anaerobic digestion-solar drying-land utilization process. The results demonstrated anaerobic digestion had a positive effect on the removal of heavy metals, nutrients and persistent organic pollutants, for polycyclic aromatic hydrocarbons, antibiotics and disinfection by-products with 41.38%, 62.26% and 68.68%, respectively, which were related to their molecular weight and structure. Large amounts of heavy metals would flow away with liquid digestate, in which Cr and Hg were the most and least, 90.44% and 41.95% respectively. The degradation of extracellular polymers in this process led to a decrease in particle size distribution, which caused the deterioration of sludge dewatering performance. Nutrients and water content increased and decreased respectively during solar drying along with the volatilization of organic matter under high temperature, which was beneficial for the final sludge product to subsequent land utilization. No significant correlation was demonstrated between heavy metals and sludge properties besides electrical conductivity. The study provided a new thinking on the variations of different substances and the way of actual treatment and disposal from the perspective of sludge anaerobic digestion-solar drying-land utilization process, which had a considerable significance for the further promotion and application of anaerobic digestion process in China's engineering community.