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Objective: This study aimed to isolate and analyze the components in cedar pine needles (needle leaves of Cedrus deodara (Roxb.) G. Don) that exhibit anti-obesity effects, as determined through animal experiments. Methods: The extract of cedar pine needles was separated into four fractions of different polarities using a macroporous resin column. The fraction that retained anti-obesity activity was evaluated based on the results of animal experiments. Monomeric compounds were structurally characterized and isolated from the active fraction using a preparative liquid chromatography system. Combined with subsequent glucose gel chromatographic separation. The content of the separated components was determined using ultrahigh performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-QQQ-MS/MS). Results: The water-washed fraction retained anti-obesity activity of the cedar pine needles more effectively. A total of 16 compounds were separated from this fraction, and the contents of 14 of these compounds were determined to be present in cedar pine needles. Conclusion: Nine components, namely p-hydroxy benzyl alcohol, chlorogenic acid, vanillic acid, syringic acid, P-coumaric acid, sinapic acid, benzoic acid, phenylacetic acid, salicylic acid, were characterized and determined for the first time in cedar pine needles. The components with anti-obesity activity in the pine needles of Cedrus are mainly derived from phenolic acids.
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The current status of clinical trials utilizing nanoparticle drug delivery system (NDDS) for brain tumors was summarized.Image 1.
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Nutrient reduction is an essential environmental policy for water quality remediation, but climate change can offset the ecological benefits of nutrient reduction and lead to the difficulty of environmental evaluation. Here, based on the records of three lipid microalgal biomarkers and stable isotopes of carbon and nitrogen in two sediment cores from the embayment of Perth, Australia, we reconstructed the microalgal biomasses (diatoms, dinoflagellates and coccolithophores) over the past century and evaluated the ecological effects of nutrient reduction on them, using Change Point Modeling (CPM) and redundancy analysis (RDA). The CPM result showed that total microalgal biomarkers increased by 25% and 51% in deep and shallow areas, respectively, due to nutrient enrichment caused by industrial wastewater in the 1950s and the causeway construction in the 1970s, and dinoflagellates were beneficiaries of eutrophication. The nutrient reduction policy since the 1980s had not decreased total microalgal biomass, and diatoms were beneficiaries of this period. RDA based on time series of sediment cores and water monitoring data revealed that the increase of sea-surface temperature and the decrease of rainfall since the 1980s may be important factors sustaining the high total microalgal biomass and increasing the degree of diatom dominance. The result also indicated that the variations of microalgal assemblages may better explain the effect of nutrient reduction rather than total microalgal biomass.
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Recuperação e Remediação Ambiental , Eutrofização , Microalgas , Qualidade da Água , Recuperação e Remediação Ambiental/métodos , Austrália , Monitoramento Ambiental/métodos , Diatomáceas , Biomassa , Dinoflagellida , Água do Mar/química , Mudança Climática , Nitrogênio/análise , Sedimentos Geológicos/química , Poluentes Químicos da Água/análiseRESUMO
We theoretically study the crossed Andreev reflection (CAR) of the normal metal-superconductor-normal metal (NSN) heterojunction based on Kekulé-Y patterned graphene with two doping types, i.e.nSnandnSpconfigurations. It is found that the enhanced CAR is more likely to occur in thenSpjunction rather than thenSnjunction. To be concrete, the almost perfect CAR occurs in a large range of incident angle in the single Dirac cone phase when the incident energy is inside the gap of the nonlinear band. Furthermore, the roles of the length of superconductor and pseudospin-valley coupling on conductance are also evaluated.
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CD93 is expressed in progenitor B (pro-B) cells, precursor B (pre-B) cells and various immature B cells. It can interact with moesin, MMRN2 and other molecules to participate in cell migration, adhesion and phagocytosis, so it plays an important role in inflammation and angiogenesis. Detection of CD93+ B cell subsets has a crucial role in the diagnosis, treatment and prognosis monitoring of inflammation and inflammation-related diseases, such as Helicobacter pylori-related gastritis, sepsis, non-obese diabetes and periodontitis.
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Subpopulações de Linfócitos B , Sepse , Humanos , Inflamação , Fagocitose , Movimento CelularRESUMO
The construction of attractive dual-functional lanthanide-based metal-organic frameworks (Ln-MOFs) with ratiometric fluorescent detection and proton conductivity is significant and challenging. Herein, a three-dimensional (3D) Eu-MOF, namely, [Eu4(HL)2(SBA)4(H2O)6]·9H2O, has been hydrothermally synthesized with a dual-ligand strategy, using (4-carboxypiperidyl)-N-methylenephosphonic acid (H3L = H2O3PCH2-NC5H9-COOH) and 4-sulfobenzoic acid monopotassium salt (KHSBA = KO3SC6H4COOH) as organic linkers. Eu-MOF showed ratiometric fluorescent broad-spectrum sensing of benzophenone-like ultraviolet filters (BP-like UVFs) with satisfactory sensitivity, selectivity, and low limits of detection in water/ethanol (1:1, v/v) solutions and real urine systems. A portable test paper was prepared for the convenience of actual detection. The potential sensing mechanisms were thoroughly analyzed by diversified experiments. The synergistic effect of the forbidden energy transfer from the ligand to Eu3+, the internal filtration effect (IFE), the formation of a complex, and weak interactions between the KHSBA ligand and BP-like UVFs is responsible for the ratiometric sensing effect. Meanwhile, Eu-MOF displayed relatively high proton conductivity of 2.60 × 10-4 S cm-1 at 368 K and 95% relative humidity (RH), making it a potential material for proton conduction. This work provides valuable guidance for the facile and effective design and construction of multifunctional Ln-MOFs with promising performance.
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BACKGROUND: Exacerbation of chronic obstructive pulmonary disease (ECOPD) is a complex phenomenon, with marked heterogeneity in the aetiology, pathophysiology and clinical manifestations. This study aimed to evaluate the clinical characteristics and long-term outcomes of patients with 30-day exacerbation among those hospitalised with ECOPD in China. METHODS: Data from the Acute Exacerbations of Chronic Obstructive Pulmonary Disease Inpatient Registry were used in this study. The patients were divided into re-event and non-event groups based on the incidence of re-exacerbation within 30 days of discharge. Exacerbation, severe exacerbation and all-cause readmissions in the following 12 months were the outcomes of interest. The cumulative incidence rates and incidence densities were calculated. Multivariate hazard function models were used to determine the association between 30-day re-exacerbation and the long-term outcomes after accounting for the competing risk of death. RESULTS: Re-exacerbation within 30 days of discharge was observed in 4.9% (n=242) of the patients (n=4963). The cumulative incidence rates and incidence densities of exacerbation, severe exacerbation and all-cause readmissions in the event group were significantly higher than those in the non-event group. After adjustment, re-exacerbation within 30 days of discharge was associated with increased risks of exacerbation, severe exacerbation and all-cause readmissions in the following 12 months (adjusted HR: 3.85 (95% CI: 3.09 to 4.80), 3.46 (2.66 to 4.50) and 3.28 (2.52 to 4.25) accordingly). CONCLUSION: Re-exacerbation of COPD within 30 days of discharge is a significant predictor of long-term prognosis. In clinical practice, short-term re-exacerbation is a significant clinical phenotype of ECOPD that requires careful management at the earliest.
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Alta do Paciente , Doença Pulmonar Obstrutiva Crônica , Humanos , Estudos de Coortes , Pacientes Internados , Fenótipo , Doença Pulmonar Obstrutiva Crônica/epidemiologiaRESUMO
Dynamic of chlorophyll-a (Chl-a) concentration is essential information to understand the status and trends of marine ecosystems. In this study, a Self-Organizing Map (SOM) was applied to delineate space-in-time patterns of Chl-a from satellite dataset during 2002-2022 over the Bohai and Yellow Seas of China (BYS). Six typical Chl-a spatial patterns were discerned through a 2 × 3 nodes SOM, while temporal evolutions of dominant spatial patterns were analyzed. The Chl-a spatial patterns were characterized by different concentrations and gradients, and obviously changed over time. The Chl-a spatial patterns and their temporal evolutions were mainly shaped by joint effects of nutrient level, light availability, water column stability, and other factors. Our findings provide first glimpse of space-in-time Chl-a dynamics in the BYS, and complement to the traditional time-in-space Chl-a pattern studies. The accurate identification and classification of the Chl-a spatial patterns are of great significance to marine regionalization and management.
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Ecossistema , Monitoramento Ambiental , Clorofila A , Clorofila/análise , Oceanos e Mares , ChinaRESUMO
Interleukin-12 (IL-12) is involved in the occurrence and development of many diseases, such as preeclampsia, intrauterine growth restriction, preterm labor, and recurrent pregnancy losses. This study aimed to determine whether a high serum level of IL-12 was associated with adverse in vitro fertilization (IVF) outcomes. Included infertile women with high serum IL-12 levels who underwent IVF cycles and infertile controls with pure tubal etiology. The impact of serum IL-12 on baseline and clinical characteristics, immune-related indicators, IVF laboratory, and pregnancy outcomes were compared. In addition, the correlation of follicular fluid IL-12 and serum IL-12 level and the role of IL-12 in apoptosis of granulosa cells (GCs) was investigated. Women with high serum IL-12 levels had lower numbers of retrieved oocytes, embryos, perfect and available embryos, lower rates of perfect and available embryos, and blastocyst formation. Additionally, significantly higher levels of serum Th1, Th2, and Th17-related cytokines were observed in women with high serum IL-12 levels than in the controls. Meanwhile, the follicular fluid IL-12 levels were positively correlated with serum IL-12 levels, and IL-12 promoted apoptosis of GCs in vitro. We concluded that women with serum high IL-12 levels may have adverse IVF outcomes, partly by promoting apoptosis of GCs. Therefore, early screening for cytokines, especially IL-12, and appropriate consultation for couples receiving IVF-ET should be considered. In addition, specific immune and inflammatory mechanisms associated with high serum IL-12 levels should be further explored.
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Infertilidade Feminina , Interleucina-12 , Feminino , Humanos , Recém-Nascido , Gravidez , Fertilização in vitro/efeitos adversos , Líquido Folicular , Infertilidade Feminina/terapia , Infertilidade Feminina/etiologia , Interleucina-12/sangueRESUMO
By selecting a bisphosphonic ligand H4L (H4L = 4-F-C6H4CH2N(CH2PO3H2)2) and a coligand oxalate (H2C2O4), three isostructural lanthanide metal-organic frameworks (Ln-MOFs) with a 2D layer structure, [Ln(H3L)(C2O4)]·2H2O (Ln = Eu (1), Gd (2), or Tb (3)), were hydrothermally prepared. By tuning the molar ratio of Eu3+, Gd3+, and Tb3+ in the above reactions, six bimetallic or trimetallic doped Ln-MOFs (EuxTb1-x (x = 0.02 (4), 0.04 (5), and 0.06 (6)), Gd0.94Eu0.06 (7), Gd0.96Tb0.04 (8) and Gd0.95Tb0.03Eu0.02 (9)) were obtained. The powder X-ray diffraction (PXRD) patterns of doped Ln-MOFs 4-9 show that they are isomorphous with 1-3. The bimetallic doped Ln-MOFs show a gradual variation of luminous colors between yellow-green, yellow, orange, pink, and light blue. Meanwhile, the trimetallic doped Gd0.95Tb0.03Eu0.02 Ln-MOF (9) displays near white-light emission with a quantum yield of 11.39%. Interestingly, the luminous inks of 1-9 are invisible and color tunable, which makes it possible to promote their anti-counterfeiting applications. Additionally, 3 displays good thermal, water, and pH stabilities, which provides the feasibility for its sensing application. The luminescence sensing experiments show that 3 can serve as a highly selective, reusable, and ratiometric luminescent sensor of sulfamethazine (SMZ). Moreover, 3 shows an excellent SMZ detection performance in real samples, such as mariculture water and real urine. Owing to the visible variation of the response signal under a UV lamp, portable SMZ test paper was prepared.
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OBJECTIVE: To compare the clinical features and outcomes in patients with pre-chronic obstructive pulmonary disease (COPD) and COPD hospitalised for confirmed or suspected acute exacerbation of COPD (AECOPD). DESIGN: A multicentre, longitudinal observational cohort study. SETTING: Data were obtained from the AECOPD Inpatient Registry Study in China. PARTICIPANTS: 5896 patients hospitalised for AECOPD between 2017 and 2021. OUTCOMES: Patients were divided into the COPD (n=5201) and pre-COPD (n=695) groups according to the lung function test results. The outcomes of interest included all-cause, respiratory disease-related and cardiovascular disease-related deaths as well as readmissions within 30 days and 12 months after discharge. Cumulative incidence functions were used to estimate the risk of cause-specific mortality and readmission. Multivariate hazard function models were used to determine the association between lung function and outcomes. RESULTS: There were significant between-group differences in the symptoms at admission and medication use during hospitalisation. However, there was no significant between-group difference in the 30-day all-cause mortality (0.00 vs 2.23/1000 person-month (pm), p=0.6110) and readmission (33.52 vs 30.64/1000 pm, p=0.7175). Likewise, the 30-day and 12-month cause-specific outcomes were not significantly different between groups (30-day readmission with acute exacerbation (AE): 26.07 vs 25.11/1000 pm; 12-month all-cause mortality: 0.20 vs 0.93/1000 pm; all-cause readmission: 11.49 vs 13.75/1000 pm; readmission with AE: 9.15 vs 11.64/1000 pm, p>0.05 for all comparisons). Cumulative incidence curves revealed no significant between-group differences in the 30-day and 12-month prognosis (p>0.05). Multivariate analysis revealed no significant association of lung function categories with 30-day and 12-month mortality or readmission (p>0.05 for all effect estimations). CONCLUSIONS: Patients with pre-COPD have mild symptoms and similar risks for mortality and readmission during follow-up as patients with COPD. Patients with pre-COPD should receive optimal therapies before the occurrence of irreversible damage.
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Readmissão do Paciente , Doença Pulmonar Obstrutiva Crônica , Humanos , Progressão da Doença , Hospitalização , Prognóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos RetrospectivosRESUMO
The recycling of cathode materials for spent NCM has always been a major concern for the energy industry. However, among the current processing methods, the general leaching efficiency of Li is between 85% and 93%, with much room for improvement. The recovery of Ni, Co and Mn requires a high cost of secondary purification. In this study, to recycle the NCM cathode material, a route of sulphated reduction roasting - selective Li water leaching - efficiency acid leaching of Ni, Co, Mn - extraction separation - crystallisation was adopted. The results showed that after roasting (a temperature of 800â °C, a reaction time of 90â min, a carbon content of 26%, and a sulphuric acid addition of nH2SO4:nLi = 0.85), Li water leaching efficiency was 98.6%, followed by acid leaching of Ni, Co and Mn at around 99%. Mn, Co were extracted with Di-(2-ethylhexyl) phosphoric acid and 2-Ethylhexyl phosphonic acid mono-2-ethylhexyl ester respectively to obtain Ni, Co, Mn solutions, which eventually were crystallized for manganese sulphate, cobalt sulphate, lithium carbonate and nickel sulphate products, with high purity of 99.40%, 98.95%, 99.10%, and 99.95%. The results of this study improved the leaching efficiency of Li and were closely linked to the actual industrial preparation of Ni, Co and Mn sulphates, providing a feasible and promising basis for spent NCM cathode materials industrial recovery.
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The fabrication of uniform and strong graphene-based conductive paper is challenging due to easy aggregation and poor film formability of graphene. Herein, on the basis of good dispersing effect of nanocellulose, high content graphene (50 wt%) composite paper with micro/nanocellulose fibers and silk fibroin (SF) was manufactured via simple casting method. The synergistic effects of cellulose microfibers (CMFs), cellulose nanofibers (CNFs) and SF result in the paper with ideal combination of flexibility, electrical conductivity and mechanical strength, where CNFs, CMFs and SF act as dispersing and film forming for GNPs, dimensional stability, and interfacial binding agents, respectively. Extraordinarily, by adding SF, graphene nanosheets are tightly coated on the surface of CMFs. The composite paper shows a tensile strength of 49.29 MPa, surface resistance of 39.0-42.1 Ω and good joints bend sensing performance. Additionally, it is found that CMFs can hinder the micro-cracks from propagating during the cyclic elbow bending test. The graphene-based conductive paper is helpful for the development of smart clothing wearable biosensing devices.
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Fibroínas , Grafite , Dispositivos Eletrônicos Vestíveis , Fibroínas/química , Grafite/química , Celulose/química , Resistência à Tração , Seda/químicaRESUMO
Reactive oxygen species (ROS) damage to the intestinal barrier is a side effect of prolonged hyperoxia therapy in neonates, which impairs growth and development of the intestine and promotes intestinal diseases. However, the research on clinical prevention and treatment is lacking. Therefore, we investigated the molecular mechanisms of the neonate intestinal response against hyperoxia-derived ROS to find targets for intestinal barrier damage prevention. Human intestinal epithelial cells were incubated under hyperoxia (85% oxygen) to build an in vitro model. ROS and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway were inhibited to detect the MAPK/ERK pathway, nuclear factor erythroid factor 2-related factor 2 (Nrf2), hypoxia-inducible factor-1α (Hif-1α), and interleukin-17D (IL-17D) expression. Nrf2 was inhibited to detect Hif-1α and IL-17D expression. Hif-1α was inhibited to detect Nrf2, IL-17D, and tight junction proteins expression and apoptosis. Cells were treated with human recombinant IL-17D to detect TNF-α, IL-1ß, IL-10, and tight junction proteins expression. ROS, Nrf2, Hif-1α, and IL-17D were upregulated and the MAPK/ERK pathway was activated under hyperoxia. But ROS inhibition downregulated the MAPK/ERK pathway, Nrf2, Hif-1α, and IL-17D. MAPK/ERK pathway inhibition downregulated Nrf2, Hif-1α, and IL-17D. Nrf2 inhibition downregulated Hif-1α and IL-17D. Hif-1α inhibition downregulated Nrf2, IL-17D, tight junction proteins, and exacerbated apoptosis. The recombinant IL-17D downregulated TNF-α, IL-1ß, but upregulated IL-10 and tight junction proteins. We concluded that Hyperoxia-generated ROS activated the MAPK/ERK pathway to regulate Nrf2, Hif-1α, and IL-17D expression. Nrf2 and Hif-1α were interdependent and promoted IL-17D. Importantly, Hif-1α and IL-17D expression protected the intestinal epithelial barrier.
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Hiperóxia , Interleucina-27 , Humanos , Recém-Nascido , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Interleucina-10/metabolismo , Interleucina-27/metabolismo , Intestinos , Sistema de Sinalização das MAP Quinases , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Junções Íntimas/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Exercise, as the cornerstone of pulmonary rehabilitation, is recommended to chronic obstructive pulmonary disease (COPD) patients. The underlying molecular basis and metabolic process were not fully elucidated. METHODS: Sprague-Dawley rats were classified into five groups: non-COPD/rest ( n â=â8), non-COPD/exercise ( n â=â7), COPD/rest ( n â=â7), COPD/medium exercise ( n â=â10), and COPD/intensive exercise ( n â=â10). COPD animals were exposed to cigarette smoke and lipopolysaccharide instillation for 90 days, while the non-COPD control animals were exposed to room air. Non-COPD/exercise and COPD/medium exercise animals were trained on a treadmill at a decline of 5° and a speed of 15 m/min while animals in the COPD/intensive exercise group were trained at a decline of 5° and a speed of 18 m/min. After eight weeks of exercise/rest, we used ultrasonography, immunohistochemistry, transmission electron microscopy, oxidative capacity of mitochondria, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI), and transcriptomics analyses to assess rectal femoris (RF). RESULTS: At the end of 90 days, COPD rats' weight gain was smaller than control by 59.48â±â15.33âg ( P â=â0.0005). The oxidative muscle fibers proportion was lower ( P â<â0.0001). At the end of additional eight weeks of exercise/rest, compared to COPD/rest, COPD/medium exercise group showed advantages in weight gain, femoral artery peak flow velocity (Δ58.22 mm/s, 95% CI: 13.85-102.60 mm/s, P â=â0.0104), RF diameters (Δ0.16âmm, 95% CI: 0.04-0.28âmm, P â=â0.0093), myofibrils diameter (Δ0.06 µm, 95% CI: 0.02-0.10âµm, P â=â0.006), oxidative muscle fiber percentage (Δ4.84%, 95% CI: 0.15-9.53%, P â=â0.0434), mitochondria oxidative phosphorylate capacity ( P â<â0.0001). Biomolecules spatial distribution in situ and bioinformatic analyses of transcriptomics suggested COPD-related alteration in metabolites and gene expression, which can be impacted by exercise. CONCLUSION: COPD rat model had multi-level structure and function impairment, which can be mitigated by exercise.
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Doença Pulmonar Obstrutiva Crônica , Ratos , Animais , Ratos Sprague-Dawley , Doença Pulmonar Obstrutiva Crônica/metabolismo , Pulmão/metabolismo , Mitocôndrias Musculares/metabolismo , MetabolomaRESUMO
Phase 3 clinical trials and real-world effectiveness studies showed that China's two main inactivated COVID-19 vaccines are very effective against serious illness. In November 2021, an outbreak occurred in the Inner Mongolia Autonomous Region that provided an opportunity to assess the vaccine effectiveness (VE) of these inactivated vaccines against COVID-19 caused by the delta variant. We evaluated VE with a retrospective cohort study of close contacts of infected individuals, using a generalized linear model with binomial distribution and log-link function to estimate risk ratios (RR) and VE. A total of 8842 close contacts were studied. Compared with no vaccination and adjusted for age, presence of comorbidity, and time since last vaccination, full vaccination reduced symptomatic infection by 62%, pneumonia by 64% and severe COVID-19 by 90%; reductions associated with homologous booster doses were 83% for symptomatic infection, 92% for pneumonia and 100% for severe COVID-19. There was no significant decline in two-dose VE for any outcome for up to 325 days following the last dose. There were no differences by vaccine brand. Inactivated vaccines were effective against delta-variant illness, and were highly effective against pneumonia and severe COVID-19; VE was increased by booster doses.
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IL-17D is a new member of the IL-17 family. Currently, it is believed that IL-17D can directly act on immune cells or may indirectly modulate immune responses by regulating cytokine expression. Herein, we hypothesized that IL-17D regulates the expression of chemokines in intestinal epithelial cells, in turn modulating the immune response within intestinal mucosa under hyperoxia. To explore this notion, newborn rats were divided into a hyperoxia group (85 % O2) and control group (21 % O2). Small intestinal tissues were obtained from neonatal rats at 3, 7, 10, and 14 days. Similarly, intestinal epithelial cells were treated by hyperoxia (85 % O2) as the hyperoxia group or were incubated under normal oxygen (21 % O2) as the control group. Finally, intestinal epithelial cells subjected to hyperoxia were treated with recombinant IL-17D and IL-17D antibodies for 24, 48, and 72 h. Immunohistochemistry, western blot, and reverse transcription-quantitative polymerase chain reaction were used to detect the expression levels of chemokines and chemokine receptors in intestinal tissues of newborn rats and intestinal epithelial cells. We found that hyperoxia affected chemokine expression both in vivo and in vitro. Under hyperoxia, IL-17D promoted the expression of CCL2, CCL25, CCL28, and CCR9 in intestinal epithelial cells while downregulating CCR2, CCR5, CCL5, and CCL20. Our findings provide a basis for further study on the effects of hyperoxia-induced intestinal inflammation and intestinal injury.
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Gastroenterite , Hiperóxia , Interleucina-27 , Mucosa Intestinal , Oxigênio , Animais , Ratos , Quimiocinas/imunologia , Células Epiteliais/imunologia , Gastroenterite/etiologia , Gastroenterite/imunologia , Hiperóxia/complicações , Hiperóxia/imunologia , Fatores Imunológicos , Interleucina-27/imunologia , Mucosa Intestinal/imunologia , Intestinos/imunologia , Oxigênio/toxicidade , Receptores de Quimiocinas/imunologiaRESUMO
The good interaction between the ceramic powder and the binder system is vital for ceramic injection molding and prevents the phase separation during processing. Due to the non-polar structure of polyolefins such as high-density polyethylene (HDPE) and the polar surface of ceramics such as zirconia, there is not appropriate adhesion between them. In this study, the effect of adding high-density polyethylene grafted with acrylic acid (AAHDPE), with high polarity and strong adhesion to the powder, on the rheological, thermal and chemical properties of polymer composites highly filled with zirconia and feedstocks was evaluated. To gain a deeper understanding of the effect of each component, formulations containing different amounts of HDPE and or AAHDPE, zirconia and paraffin wax (PW) were prepared. Attenuated total reflection spectroscopy (ATR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and rotational and capillary rheology were used for the characterization of the different formulations. The ATR analysis revealed the formation of hydrogen bonds between the hydroxyl groups on the zirconia surface and AAHDPE. The improved powder-binder adhesion in the formulations with more AAHDPE resulted in a better powder dispersion and homogeneous mixtures, as observed by SEM. DSC results revealed that the addition of AAHDPE, PW and zirconia effect the melting and crystallization temperature and crystallinity of the binder, the polymer-filled system and feedstocks. The better powder--binder adhesion and powder dispersion effectively decreased the viscosity of the highly filled polymer composites and feedstocks with AAHDPE; this showed the potential of grafted polymers as binders for ceramic injection molding.
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PURPOSE: Ewing sarcoma and osteosarcoma are primary bone sarcomas occurring most commonly in adolescents. Metastatic and relapsed disease are associated with dismal prognosis. Although effective for some soft tissue sarcomas, current immunotherapeutic approaches for the treatment of bone sarcomas have been largely ineffective, necessitating a deeper understanding of bone sarcoma immunobiology. EXPERIMENTAL DESIGN: Multiplex immunofluorescence analysis of immune infiltration in relapsed versus primary disease was conducted. To better understand immune states and drivers of immune infiltration, especially during disease progression, we performed single-cell RNA sequencing (scRNAseq) of immune populations from paired blood and bone sarcoma tumor samples. RESULTS: Our multiplex immunofluorescence analysis revealed increased immune infiltration in relapsed versus primary disease in both Ewing sarcoma and osteosarcoma. scRNAseq analyses revealed terminally exhausted CD8+ T cells expressing co-inhibitory receptors in osteosarcoma and an effector T-cell subpopulation in Ewing sarcoma. In addition, distinct subsets of CD14+CD16+ macrophages were present in Ewing sarcoma and osteosarcoma. To determine pathways driving tumor immune infiltration, we conducted intercellular communication analyses and uncovered shared mechanisms of immune infiltration driven by CD14+CD16+ macrophages and unique pathways of immune infiltration driven by CXCL10 and CXCL12 in osteosarcoma. CONCLUSIONS: Our study provides preclinical rationale for future investigation of specific immunotherapeutic targets upon relapse and provides an invaluable resource of immunologic data from bone sarcomas.