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A TMSOTf-catalyzed C2-sulfenylation of indole alkaloids with N-sulfenylsuccinimides has been developed. This straightforward, metal-free, and cost-effective catalytic system produces valuable 2-thioindole derivatives with yields ranging from moderate to excellent. The synthetic applicability demonstrated includes the total syntheses of isatindigotindolosides I-IV.
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Traumatic brain injury (TBI), a significant global health issue, is affecting â¼69 million annually. To better understand TBI's impact on brain function and assess the efficacy of treatments, this study uses a novel temporal-spatial cross-group approach with a porcine model, integrating resting-state functional magnetic resonance imaging (rs-fMRI) for temporal and arterial spin labeling for spatial information. Our research used 18 four-week-old pigs divided into three groups: TBI treated with saline (SLN, n = 6), TBI treated with fecal microbial transplant (FMT, n = 6), and a sham group (sham, n = 6) with only craniectomy surgery as the baseline. By applying machine learning techniques-specifically, independent component analysis and sparse dictionary learning-across seven identified resting-state networks, we assessed the temporal and spatial correlations indicative of treatment efficacy. Both temporal and spatial analyses revealed a consistent increase of correlation between the FMT and sham groups in the executive control and salience networks. Our results are further evidenced by a simulation study designed to mimic the progression of TBI severity through the introduction of variable Gaussian noise to an independent rs-fMRI dataset. The results demonstrate a decreasing temporal correlation between the sham and TBI groups with increasing injury severity, consistent with the experimental results. This study underscores the effectiveness of the methodology in evaluating post-TBI treatments such as the FMT. By presenting comprehensive experimental and simulated data, our research contributes significantly to the field and opens new paths for future investigations into TBI treatment evaluations.
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PURPOSE AND METHOD: Necrotizing tracheobronchitis is a rare clinical entity presented as a necrotic inflammation involving the mainstem trachea and distal bronchi. We reported a case of severe necrotizing tracheobronchitis caused by influenza B and methicillin-resistant Staphylococcus aureus (MRSA) co-infection in an immunocompetent patient. CASE PRESENTATION: We described a 36-year-old man with initial symptoms of cough, rigors, muscle soreness and fever. His status rapidly deteriorated two days later and he was intubated. Bronchoscopy demonstrated severe necrotizing tracheobronchitis, and CT imaging demonstrated multiple patchy and cavitation formation in both lungs. Next-generation sequencing (NGS) and bronchoalveolar lavage fluid (BALF) culture supported the co-infection of influenza B and MRSA. We also found T lymphocyte and NK lymphocyte functions were extremely suppressed during illness exacerbation. The patient was treated with antivirals and antibiotics including vancomycin. Subsequent bronchoscopy and CT scans revealed significant improvement of the airway and pulmonary lesions, and the lymphocyte functions were restored. Finally, this patient was discharged successfully. CONCLUSION: Necrotizing tracheobronchitis should be suspected in patients with rapid deterioration after influenza B infection. The timely diagnosis of co-infection and accurate antibiotics are important to effective treatment.
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Bronquitis , Coinfección , Gripe Humana , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Coinfección/microbiología , Gripe Humana/complicaciones , Adulto , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/complicaciones , Bronquitis/microbiología , Bronquitis/tratamiento farmacológico , Bronquitis/complicaciones , Bronquitis/diagnóstico , Bronquitis/virología , Antibacterianos/uso terapéutico , Traqueítis/microbiología , Traqueítis/tratamiento farmacológico , Traqueítis/complicaciones , Traqueítis/virología , Virus de la Influenza B/aislamiento & purificación , Broncoscopía , Necrosis , Tomografía Computarizada por Rayos X , Líquido del Lavado Bronquioalveolar/microbiología , Antivirales/uso terapéuticoRESUMEN
BACKGROUND: The piglet brain has been increasingly used as an excellent surrogate for investigation of pediatric neurodevelopment, nutrition, and traumatic brain injuries. This study intends to establish a piglet brain's structural connectivity model and compare it with the adult pig, enhancing its application for structurally guided functional analysis. METHODS: In this study, diffusion-weighted (DW)-MRI data from piglets (n=11, 3-week-old) was used to establish piglet model and compare with adult pigs. We employed a data-driven independent component analysis (ICA) method to derive piglet-specific tracts. Pearson correlations and Kullback-Leibler (KL) divergences was employed to identify common tracts and unique tracts for piglet. Common tracts were then used in a blueprint connectome study to highlight differences in regions of interest (ROI). RESULTS: The data-driven approach applied to piglet brains revealed 17 common tracts, showing high similarity with adult pigs' white matter (WM) tracts, and identified 3 tracts unique to piglets and 10 negative marker tracts. Additionally, the study highlighted notable differences in 3 ROIs associated with blueprint connectome. COMPARING WITH EXISTING METHODS: This study marks a significant shift from surface-based to voxel-based methodologies in analyzing pig brain structural connectivity and generating connectome blueprints. Additionally, it sheds light on the use of the piglet model for developmental studies, offering new perspectives in this area. CONCLUSION: This study established a piglet brain tract model and conducts a comparative analysis of adult pig's and piglet's structural connectivity. These findings underscore the potential use of the piglet brain model in employing piglet model for developmental studies.
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Conectoma , Sustancia Blanca , Animales , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/crecimiento & desarrollo , Sustancia Blanca/anatomía & histología , Porcinos , Conectoma/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Encéfalo/crecimiento & desarrollo , Encéfalo/diagnóstico por imagen , Encéfalo/anatomía & histología , Animales Recién Nacidos , Vías Nerviosas/crecimiento & desarrollo , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/anatomía & histología , Masculino , Femenino , Procesamiento de Imagen Asistido por Computador/métodos , Imagen de Difusión Tensora/métodosRESUMEN
Pediatric traumatic brain injury (TBI) often induces significant disability in patients, including long-term motor deficits. Early detection of injury severity is key in determining a prognosis and creating appropriate intervention and rehabilitation plans. However, conventional magnetic resonance imaging (MRI) scans, such as T2 Weighted (T2W) sequences, do not reliably assess the extent of microstructural white matter injury. Diffusion tensor imaging (DTI) tractography enables three-dimensional reconstruction of specific white matter tracts throughout the brain in order to detect white matter injury based on anisotropic diffusion. The objective of this study was to employ DTI tractography to detect acute changes to white matter integrity within the intersecting fibers of key motor-related brain regions following TBI. Piglets were assigned to either the sham craniectomy group (sham; n = 6) or the controlled cortical impact TBI group (TBI; n = 6). Gait and MRI were collected at seven days post-surgery (DPS). T2W sequences confirmed a localized injury predominately in the ipsilateral hemisphere in TBI animals. TBI animals, relative to sham animals, showed an increased apparent diffusion coefficient (ADC) and decreased fractional anisotropy (FA) in fiber bundles associated with key brain regions involved in motor function. TBI animals exhibited gait deficits, including stride and step length, compared to sham animals. Together these data demonstrate acute reductions in the white matter integrity, measured by DTI tractography, of fibers intersecting key brain regions that strongly corresponded with acute motor deficits in a pediatric piglet TBI model. These results provide the foundation for the further development of DTI-based biomarkers to evaluate motor outcomes following TBI.
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Purpose: Both nonthyroidal illness syndrome (NTIS) and disseminated intravascular coagulation (DIC) are commonly occurred in sepsis. The objective of this study is to evaluate the association between NTIS and DIC, as well as their impacts on the mortality in adults with sepsis. Patients and methods: A total of 1219 septic patients in two Chinese academic centers from October 2012 and October 2022 were enrolled in analysis. We conduct logistic regression models to analyze the independent risk factors for DIC. Modified Poisson regression models are used to estimate the relative risk (RR) of NTIS on the 28 days mortality in septic patients with DIC. Correlation analysis between thyroid function parameters and coagulation parameters is performed with Pearson coefficient be reported. Results: DIC is diagnosed on 388 (31.8%) of all the 1219 enrolled septic patients within 72 hours after admission. In multivariate logistic regression models, NTIS (OR 3.19; CI 2.31-4.46; p<0.001) is a statistically significant independent risk factor for DIC after adjustment for potential confounders. Twenty-eight days mortality is significantly higher in DIC patients complicated with NTIS compared with the other DIC patients (23.2% vs 14.0%, p=0.024). This result is also robust in different modified Poisson regression models (Model 1: RR 1.46; CI 1.25-1.70; p<0.001; Model 2: RR 1.35; CI 1.14-1.60; p<0.001; Model 3: RR 1.18; CI 1.02-1.37; p=0.026). Correlation analysis reveals that the thyroid function parameters of FT3, FT4 and TSH only have weak correlations with coagulation parameters of platelet count, fibrinogen, FDP, D-dimers, PT, APTT and INR in sepsis. Conclusion: NTIS is an independent risk factor for DIC in adults with sepsis. DIC patients complicated with NTIS have significantly higher severity and higher rate of mortality.
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BACKGROUND: To identify the factors influencing the early encapsulation of peripancreatic fluid/necrosis collections via contrast-enhanced computed tomography (CECT) and to determine the clinical significance of early encapsulation for determining the prognosis of acute pancreatitis (AP) patients. METHODS: AP patients who underwent CECT between 4 and 10 days after disease onset were enrolled in this study. Early encapsulation was defined as a continuous enhancing wall around peripancreatic fluid/necrosis collections on CECT. Univariate and multivariate logistic regression analyses were performed to assess the associations between the variables and early encapsulation. Clinical outcomes were compared between the non-encapsulation and early encapsulation groups with 1:1 propensity score matching. RESULTS: A total of 289 AP patients were enrolled. The intra-observer and inter-observer agreement were considered good (kappa statistics of 0.729 and 0.614, respectively) for identifying early encapsulation on CECT. The ratio of encapsulation increased with time, with a ratio of 12.5% on day 5 to 48.7% on day 9. Multivariate logistic regression analysis revealed that the longer time from onset to CECT examination (OR 1.55, 95% CI 1.23-1.97), high alanine aminotransferase level (OR 0.98, 95% CI 0.97-0.99), and high APACHE II score (OR 0.89, 95% CI 0.81-0.98) were found to be independent factors associated with delayed encapsulation. The incidence of persistent organ failure was significantly lower in the early encapsulation group after matching (22.4% vs 6.1%, p = 0.043). However, there was no difference in the incidence of infected pancreatic necrosis, surgical intervention, or in-hospital mortality. CONCLUSIONS: AP patients without early encapsulation of peripancreatic fluid/necrosis collections have a greater risk of persistent organ failure. In addition to longer time, the high APACHE II score and elevated alanine aminotransferase level are factors associated with delayed encapsulation.
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Pancreatitis , Humanos , Pancreatitis/diagnóstico por imagen , Pancreatitis/cirugía , Enfermedad Aguda , Relevancia Clínica , Alanina Transaminasa , Pronóstico , Necrosis/diagnóstico por imagenRESUMEN
Sodium manganese hexacyanoferrate (NaMnHCF) has emerged as a research hotspot among Prussian blue analogs for sodium-ion battery cathode materials due to its advantages of high voltage, high specific capacity, and abundant raw materials. However, its practical application is limited by its poor electronic conductivity. In this study, we aim to solve this problem through the in situ growth of NaMnHCF on carbon nanotubes (CNTs) using a simple coprecipitation method. The results show that the overall electronic conductivity of NaMnHCF is significantly improved after the introduction of CNTs. The NaMnHCF@10%CNT sample presents a specific capacity of 90 mA h g-1, even at a current density of 20 C (2400 mA g-1). The study shows that the optimized composite exhibits a superior electrochemical performance at different mass loadings (from low to high), which is attributed to the enhanced electron transport and shortened electron pathway. Surprisingly, the cycling performance of the composites was also improved, resulting from decreased polarization and the subsequent reduction in the side reactions at the cathode/electrolyte interface. Furthermore, we revealed the evolution of potential plateau roots from the extraction of crystal water during the charge-discharge process of NaMnHCF based on the experimental results. This study is instructive not only for the practical application of NaMnHCF materials but also for advancing our scientific understanding of the behavior of crystal water during the charge-discharge process.
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BACKGROUND: Functional connectivity (FC) measures statistical dependence between cortical brain regions. Studies of FC facilitate understanding of the brain's function and architecture that underpin normal cognition, behavior, and changes associated with various factors (e.g. nutritional supplements) at a large scale. OBJECTIVE: We aimed to identify modifications in FC patterns and targeted brain anatomies in piglets following perinatal intake of different nutritional diets using a graph theory based approach. METHODS: Forty-four piglets from four groups of pregnant sows, who were treated with nutritional supplements, including control diet, docosahexaenoic acid (DHA), egg yolk (EGG), and DHA + EGG, went through resting-state functional magnetic resonance imaging (rs-fMRI). We introduced the use of differential degree test (DDT) to identify differentially connected edges (DCEs). Simulation studies were first conducted to compare the DDT with permutation test, using three network structures at different noise levels. DDT was then applied to rs-fMRI data acquired from piglets. RESULTS: In simulations, the DDT showed a greater accuracy in detecting DCEs when compared with the permutation test. For empirical data, we found that the strength of internodal connectivity is significantly increased for more than 6% of edges in the EGG group and more than 8% of edges in the DHA and DHA + EGG groups, all compared to the control group. Moreover, differential wiring diagrams between group comparisons provided means to pinpoint brain hubs affected by nutritional supplements. CONCLUSION: DDT showed a greater accuracy of detection of DCEs and demonstrated EGG, DHA, and DHA + EGG supplemented diets lead to an improved internodal connectivity in the developing piglet brain.
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Encéfalo , Suplementos Dietéticos , Embarazo , Animales , Porcinos , Femenino , Dieta/veterinaria , Ácidos Docosahexaenoicos , Cognición , Imagen por Resonancia Magnética/métodosRESUMEN
We herein report the copper-catalyzed C-S bond coupling reaction of indoles with N-thiosuccinimides, resulting in moderate to excellent yields of mono- and bis-sulfenylated compounds such as arylthioindoles, alkylthioindoles, selenylated indoles, and cysteine-substituted indoles. Thioarylation and thioglycosylation at the C2 position of indole alkaloids in the Radix Isatidis were achieved via structural modification. The first total syntheses of isatindigotindolosides III and IV have been successfully carried out. The electrophilic sulfenyl bromides generated in situ can play an important role in the catalytic cycle.
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BACKGROUND: Antibiotic use in the early stages of acute pancreatitis is controversial. The purpose of this study was to investigate the effect of early antibiotic application on the prognosis of acute pancreatitis (AP). MATERIALS AND METHODS: Clinical data of patients with primary AP admitted to our emergency ward within 72 hours of onset were retrospectively collected from January 2016 to December 2020. We classified patients with acute pancreatitis according to etiology and disease severity, and compared the differences in hospital stay, laparotomy rate, and in-hospital mortality among AP patients who received different antibiotic treatment strategies within 72 hours of onset. RESULTS: A total of 1134 cases were included, with 681 (60.1%) receiving early antibiotic treatment and 453 (39.9%) not receiving it. There were no significant differences in baseline values and outcomes between the two groups. In subgroup analysis, patients with biliary severe acute pancreatitis (SAP) who received early antibiotics had lower rates of laparotomy and invasive mechanical ventilation, as well as shorter hospital stays compared to those who did not receive antibiotics. In logistic regression analysis, the early administration of carbapenem antibiotics in biliary SAP patients was associated with a lower in-hospital mortality rate. Early antibiotic use in biliary moderate-severe acute pancreatitis (MSAP) reduced hospital stays and in-hospital mortality. Quinolone combined with metronidazole treatment in biliary mild acute pancreatitis (MAP) shortened hospital stays. Early antibiotic use does not benefit patients with non-biliary AP. CONCLUSION: Strategies for antibiotic use in the early stages of AP need to be stratified according to cause and disease severity.
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Pancreatitis , Humanos , Pancreatitis/tratamiento farmacológico , Enfermedad Aguda , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Pronóstico , Antibacterianos/uso terapéuticoRESUMEN
Introduction: Acute pancreatitis is a common gastrointestinal disease. The mortality of patients affected by severe acute pancreatitis (SAP) remains high. It is unclear whether high-dose intravenous vitamin C (HDIVC) therapy could improve the prognosis of these patients. The current prospective, randomized, double-blinded, placebo-controlled study will explore the effect of high-dose intravenous vitamin C therapy on the prognosis in patients with moderately severe and severe acute pancreatitis. Methods and design: A total of 418 participants with moderately severe and severe acute pancreatitis who meet the eligible criteria will be randomly assigned in a 1:1 ratio to receive treatment with HDIVC (200 mg/kg/24 h) or placebo (saline) for a period of 7 days. The primary outcome is 28-day mortality in these patients. The secondary outcomes include organ functions and interventions, laboratory tests, healthcare, and 90-day mortality. Ethics and dissemination: This protocol was approved by the institutional ethics board of the Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Registration Number: 2019-90). The report of the study will be published in peer-reviewed journals and presented at conferences, both nationally and internationally. Clinical trial registration: Chinese Clinical Trial Registry (ChiCTR1900022022). Version 1.5.
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Background: Nonthyroidal illness syndrome (NTIS) is a common endocrine dysfunction predicting unfavorable outcomes in critical illness. The objective of the study is to evaluate the association between different NTIS subtypes with outcomes in septic patients. Methods: Septic patients in two Chinese academic centers from October 2012 and October 2022 are enrolled in analysis. Multivariable regressions are used to assess associations between NTIS and outcomes. Outcomes include in-hospital mortality, length of stay in hospital (LOS), non-invasive ventilation failure and weaning failure. Patients with NTIS are categorized into 4 types according to the different levels of FT4 and TSH. The association between different NTIS subtypes and mortality are further analyzed. Survival curve is plotted using the Kaplan-Meier method. Results: After screening, a total of 1226 septic patients with complete thyroid hormones result are eventually enrolled. Among them, 520 (42.4%) patients are diagnosed as NTIS. In multivariable regression analysis, NTIS is independently associated with increased 30-days mortality (OR=1.759, CI 1.009-3.104, p=0.047), but has no association with 60-days mortality (OR=1.524, CI 0.893-2.618, p=0.123), 90-days mortality (OR=1.411, CI 0.831-2.408, p=0.203), LOS, non-invasive ventilation failure or weaning failure. In NTIS subtypes, NTIS patients with low FT3 and TSH levels, regardless of the FT4 values, have significantly higher mortality than euthyroid patients (30-days mortality, OR= 6.488, CI 1.546-27.808, p=0.01; 60-days mortality, OR=3.973, CI 1.006-15.579, p=0.046; 90-days mortality, OR=3.849, CI 0.977-15.088, p=0.051). This result is consistent in patients with low FT3 and FT4 levels, regardless of the TSH values (30-days mortality, OR=3.349, CI 1.402-7.957, p=0.006; 60-days mortality, OR= 2.594, CI 1.122-5.930, p=0.024; 90-days mortality, OR=2.55, CI 1.110-5.804, p=0.025). There is no survival difference between NTIS patients with low FT3 only and euthyroid patients. Survival plot shows the worst prognosis is in NTIS patients with low FT3, FT4 and TSH level. Conclusions: NTIS is frequent in sepsis. A reduction of FT3 together with FT4 or TSH, but not FT3 only, is associated with an increased risk of mortality.
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Sepsis , Hormonas Tiroideas , Humanos , Estudios Retrospectivos , Pronóstico , Tirotropina , Sepsis/complicacionesRESUMEN
Sodium manganese hexacyanoferrate (NaMnHCF) is an attractive candidate as a cathode material for sodium-ion batteries due to its low cost and high energy density. However, its practical application is hindered by poor electrochemical stability caused by the Jahn-Teller effect of Mn and the unstable structure of NaMnHCF. Here, this paper aims to address this issue by introducing highly stable AMnHCF (where A = K, Rb, or Cs) through a facile method to composite with NaMnHCF. The findings reveal that all AMnHCFs have a "pillar effect" on the crystal structure of NaMnHCF. It is observed that the degree of pillar effect varies depending on the specific AMnHCF used. The less electrochemically inactive the alkaline ion is and the greater the degree of compositing with NaMnHCF, the more dramatic the pillar effect. KMnHCF shows limited pillar effect due to its rough composition with NaMnHCF and the loss of K+ upon (de)intercalation. RbMnHCF has lower electrochemical activity and can be better composited with NaMnHCF. On the other hand, CsMnHCF exhibits the strongest pillar effect due to the inactivation of Cs+ and the excellent coherent structure formed by CsMnHCF and NaMnHCF. This research provides a new perspective on stabilizing NaMnHCF with other alkaline elements.
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Introduction: Hypertension affects over a billion people worldwide, and the application of neuroimaging may elucidate changes brought about by the disease. We have applied a graph theory approach to examine the organizational differences in resting-state functional magnetic resonance imaging (rs-fMRI) data between hypertensive and normotensive participants. To detect these groupwise differences, we performed statistical testing using a modified difference degree test (DDT). Methods: Structural and rs-fMRI data were collected from a cohort of 52 total (29 hypertensive and 23 normotensive) participants. Functional connectivity maps were obtained by partial correlation analysis of participant rs-fMRI data. We modified the DDT null generation algorithm and validated the change through different simulation schemes and then applied this modified DDT to our experimental data. Results: Through a comparative analysis, the modified DDT showed higher true positivity rates (TPR) when compared with the base DDT while also maintaining false positivity rates below the nominal value of 5% in nearly all analytically thresholded trials. Applying the modified DDT to our rs-fMRI data showed differential organization in the hypertension group in the regions throughout the brain including the default mode network. These experimental findings agree with previous studies. Conclusions: While our findings agree with previous studies, the experimental results presented require more investigation to prove their link to hypertension. Meanwhile, our modification to the DDT results in higher accuracy and an increased ability to discern groupwise differences in rs-fMRI data. We expect this to be useful in studying groupwise organizational differences in future studies.
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Encéfalo , Hipertensión , Humanos , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Imagen por Resonancia Magnética/métodos , Descanso , Hipertensión/diagnóstico por imagenRESUMEN
Smoking or occupational exposure leads to low concentrations of acrolein on the surface of the airways. Acrolein is involved in the pathophysiological processes of various respiratory diseases. Reports showed that acrolein induced an increase in mitochondrial reactive oxygen species (mROS). Furthermore, exogenous H2O2 was found to increase intracellular Zn2⺠concentration ([Zn2âº]áµ¢). However, the specific impact of acrolein on changes in intracellular Zn2⺠levels has not been fully investigated. Therefore, this study aimed to investigate the effects of acrolein on mROS and [Zn2âº]áµ¢ in A549 cells. We used Mito Tracker Red CM-H2Xros (MitoROS) and Fluozin-3 fluorescent probes to observe changes in mROS and intracellular Zn2âº. The results revealed that acrolein increased [Zn2âº]áµ¢ in a time- and dose-dependent manner. Additionally, the production of mROS was observed in response to acrolein treatment. Subsequent experiments showed that the intracellular Zn2⺠chelator TPEN could inhibit the acrolein-induced elevation of [Zn2âº]áµ¢ but did not affect the acrolein-induced mROS production. Conversely, the acrolein-induced elevation of mROS and [Zn2âº]áµ¢ were significantly decreased by the inhibitors of ROS formation (NaHSO3, NAC). Furthermore, external oxygen free radicals increased both [Zn2âº]áµ¢ levels and mROS production. These results demonstrated that acrolein-induced elevation of [Zn2âº]áµ¢ in A549 cells was mediated by mROS generation, rather than through a pathway where [Zn2âº]áµ¢ elevation leads to mROS production.
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Acroleína , Estrés Oxidativo , Humanos , Especies Reactivas de Oxígeno/metabolismo , Acroleína/toxicidad , Células A549 , Peróxido de Hidrógeno , Zinc/farmacologíaRESUMEN
Background: Platelet activation in the early stage of pancreatitis is the key step developing into pancreatic necrosis. Studies suggested that vitamin C (Vit C) can inhibit platelet activity by targeting CXCL12/CXCR4 pathway. High-dose Vit C were showed to reduce pancreatic necrosis in severe acute pancreatitis (SAP) but the mechanism remains unclear. Here we speculate high-dose Vit C reduce pancreatic necrosis by inhibiting platelet activation through downregulating CXCL12/CXCR4 pathway. Methods: The pancreatic microcirculation of rats was observed by intravital microscopy. The platelet activity of SAP rats treated with or without high-dose Vit C was analyzed by platelet function test. Besides, the activity of platelets preincubated with high-dose Vit C or vehicle from SAP patients was also evaluated. Then, the TFA (CXCR4 agonist) and rCXCL12 were used to neutralize the effect of high-dose Vit C in SAP rats treated with high-dose Vit C. Meanwhile, the levels of enzymes and inflammatory cytokines in rat plasma, and rats' pancreatic histopathology and mortality were assessed. Results: Platelets from animals and patients with SAP are more sensitive to agonists and are more easily activated. Administration of high-dose Vit C significantly ameliorated excessive activation of platelets in SAP rats, ultimately increasing the microvessel density and inducing microthrombus and blood stasis; these results were consistent with clinical sample analysis. Moreover, high-dose Vit C significantly inhibited the release of amylase, lipase, TNF-α, and IL-6 in SAP rat plasma, reducing pancreatic damage and the mortality of SAP rats. However, using TFA and rCXCL12 significantly reversed the effect of high-dose Vit C on excessive activation of platelets, aggravating microcirculation impairment and pancreatic damage. Conclusion: The present study suggests that high-dose Vit C can ameliorate pancreatic necrosis by improving microcirculation disorders of SAP. For the first time, the underlying mechanism is related with inhibiting platelet activation through the CXCL12/CXCR4 pathway.
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In this study, oxygen-doped graphitic carbon nitride (g-C3N4), named O-g-C3N4, was successfully fabricated and characterized, and its performance in activating peroxymonosulfate (PMS, HSO5-) for the removal of phenol, 2,4-dichlorophenol (2,4-DCP), bisphenol A (BPA), rhodamine B (RhB), reactive brilliant blue (RBB) and acid orange 7 (AO7) was evaluated. The catalytic performance of O-g-C3N4 for AO7 removal increased by 14 times compared to g-C3N4. In the presence of 0.2 g L-1 O-g-C3N4, 3.5 mM PMS at natural pH 5.8, 96.4% of AO7 could be removed in 60 min, reduced toxicity of the treated AO7 solution was obtained, and the mineralization efficiency was 47.2% within 120 min. Density functional theory (DFT) calculations showed that the charge distribution changed after oxygen doping, and PMS was more readily adsorbed by O-g-C3N4 with the adsorption energy (Eads) of -0.855 kcal/mol than that of the pristine g-C3N4 (Eads: -0.305 kcal/mol). Mechanism investigation implied that AO7 was primarily removed by the sulfate radicals (SO4â¢-) and hydroxyl radicals (â¢OH) on the surface of O-g-C3N4, but the role of singlet oxygen (1O2) to AO7 elimination was negligible. The results of cyclic experiments and catalyst characterization after reaction confirmed the favorable catalytic activity and structural stability of O-g-C3N4 particles. Furthermore, the O-g-C3N4/PMS system was very resistant to most of the environmental impacts, and AO7 removal was still acceptable in natural water environment. This study may provide an efficient metal-free carbonaceous activator with low dosage for PMS activation to remove recalcitrant organic pollutants (ROPs).
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Grafito , Grafito/química , Oxígeno , Peróxidos/química , MetalesRESUMEN
Despite the importance of nucleosides and nucleotides for drug discovery, only a few practical methods to prepare tricyclic nucleosides have been reported. Here, we describe a synthetic strategy for late-stage functionalization of nucleosides and nucleotides via chemo- and site-selective acid-promoted intermolecular cyclization. The nucleoside analogs with an additional ring were obtained in moderate-to-high yields, including some antiviral drugs (acyclovir, ganciclovir, and penciclovir) derivatives, endogenous fused ring nucleoside (M1 dG) and its derivatives, and nucleotide derivatives. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Synthesis of tricyclic acyclovir analogs (3a-3c) Basic Protocol 2: Synthesis of tricyclic nucleosides M1 dG (6) and M1 G (9) Basic Protocol 3: Synthesis of tricyclic nucleotide (12).
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Aciclovir , Nucleósidos , Ciclización , Guanina , NucleótidosRESUMEN
The cycloaddition reaction of N-hydroxysuccinimide ester and isocyanatoacetate catalyzed by copper was described. A series of 4,5-disubstituted oxazole compounds, including ones derived from natural fatty acids, drugs, amino acids, and peptides, were obtained in moderate to high yields. The derivatization reaction was explored. The reaction mechanism was discussed.