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More and more studies have revealed that P2 purinergic receptors play a key role in the progression of colorectal cancer (CRC). P2X and P2Y purinergic receptors can be used as promoters and regulators of CRC and play a dual role in the progression of CRC. CRC microenvironment is rich in ATP and its cleavage products (ADP, AMP, Ado), which act as activators of P2X and P2Y purinergic receptors. The activation of P2X and P2Y purinergic receptors regulates the progression of CRC mainly by regulating the function of immune cells and mediating different signal pathways. In this paper, we focus on the specific mechanisms and functional roles of P2X7, P2Y12, and P2Y2 receptors in the growth and progression of CRC. The antagonistic effects of these selective antagonists of P2X purinergic receptors on the growth, invasion, and metastasis of CRC were further discussed. Moreover, different studies have reported that P2X7 receptor can be used as an effective predictor of patients with CRC. All these indicate that P2 purinergic receptors are a key regulator of CRC. Therefore, antagonizing P2 purinergic receptors may be an innovative treatment for CRC.
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Neurological diseases are destructive, mainly characterized by the failure of endogenous repair, the inability to recover tissue damage, resulting in the increasing loss of cognitive and physical function. Although some clinical drugs can alleviate the progression of these diseases, but they lack therapeutic effect in repairing tissue injury and rebuilding neurological function. More and more studies have shown that cell therapy has made good achievements in the application of nerve injury. Olfactory ensheathing cells (OECs) are a special type of glial cells, which have been proved to play an important role as an alternative therapy for neurological diseases, opening up a new way for the treatment of neurological problems. The functional mechanisms of OECs in the treatment of neurological diseases include neuroprotection, immune regulation, axon regeneration, improvement of nerve injury microenvironment and myelin regeneration, which also include secreted bioactive factors. Therefore, it is of great significance to better understand the mechanism of OECs promoting functional improvement, and to recognize the implementation of these treatments and the effective simulation of nerve injury disorders. In this review, we discuss the function of OECs and their application value in the treatment of neurological diseases, and position OECs as a potential candidate strategy for the treatment of nervous system diseases.
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Enfermedades Neurodegenerativas , Traumatismos de los Nervios Periféricos , Humanos , Enfermedades Neurodegenerativas/terapia , Enfermedades Neurodegenerativas/metabolismo , Traumatismos de los Nervios Periféricos/terapia , Traumatismos de los Nervios Periféricos/metabolismo , Axones/metabolismo , Regeneración Nerviosa/fisiología , Bulbo OlfatorioRESUMEN
As a kind of small molecular weight proteins, many peptides have been discovered, including peptides encoded by pri-miRNA (miPEPs). Similar as traditional phytohormone or signaling molecular, these peptides participate in numerous plant growth processes. MicroRNAs (miRNAs) play an important regulatory role in plant stress response. While the roles of miPEPs in response to abiotic stress has not been studied now. In this study, to explore whether miPEPs could contribute to low temperature (4ºC) tolerance of plants, the expression pattern of 23 different vvi-MIRs were analyzed by qRT-PCR in 'Thompson Seedless' (Vitis vinifera) plantlets under cold stress (4ºC) firstly, and vvi-MIR172b and vvi-MIR3635b which showed an elevated expression levels were selected to identify miPEPs. Through transient expression, one small open reading frame (sORF) in each of the two pri-miRNAs could increase the expression of corresponding vvi-MIR, and the amino acid sequences of sORFs were named vvi-miPEP172b and vvi-miPEP3635b, respectively. The synthetic vvi-miPEP172b and vvi-miPEP3635b were applied to the grape plantlets, and the tissue culture plantlets exhibited a higher cold tolerance compared with the control groups. These results revealed the effective roles of miPEPs in plant cold stress resistance for the first time, providing a theoretical basis for the future application of miPEPs to agricultural production.
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MicroARNs , Vitis , Regulación de la Expresión Génica de las Plantas , Vitis/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Frío , Respuesta al Choque por Frío/genética , Plantas/metabolismo , Péptidos/metabolismoRESUMEN
This study examined postural variabilities based on the self-perceived most comfortable postures of 12 participants (six men and six women) when sitting on three commonly used types of chairs (a stool, computer chair, and gaming chair). Participants' global joint angles were recorded and analyzed. Of the chairs studied, the stool was not adjustable, but the computer and gaming chairs were moderately and highly adjustable, respectively. During the test, participants were encouraged to adjust the chairs until they perceived that the most comfortable posture had been reached. The results demonstrated that in a sitting position perceived to be comfortable, the participants' postural variabilities with respect to global joint angle, calculated from five repetitions, were unexpectedly high for all three chair types, at approximately 9.4, 10.2, and 11.1° for head inclination, trunk angle, and knee angle, respectively. The average differences in range for each joint angle among the three chair types were relatively low, with all values within 3°. The result also showed that gender (p < 0.01) and chair type (p < 0.001) significantly affected trunk angle, whereas these variables did not affect head inclination or knee angle (p > 0.05). The preliminary results observed unexpectedly high variabilities in sitting posture when the participants sat at a posture that they perceived to be the most comfortable. The findings also indicated an inherent difference in comfortable sitting posture between genders; women tend to extend their trunk backward more than men. For permanent use with only an initial adjustment and memory-aided seat design, designers should minimize the loads that are borne by body parts over a prolonged period due to an unchanging sitting posture.
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Improving the effective treatment depth of photodynamic therapy (PDT) is an important issue to resolve for its clinical application. In this study, a new biocompatible photosensitizer (PS), namely TQs-PEG4, based on thiadiazolo[3,4-g]quinoxaline (TQ) with ultra-high photoactive property is designed and synthesized. TQs-PEG4 possesses an ultra-high singlet oxygen quantum yield (ΦΔ = 1.04). After encapsulating it with a biodegradable copolymer (DSPE-mPEG2000-cRGD), well distributed organic TQs-PEG4 nanoparticles (NPs) are formed with good water dispersity and excellent active tumor-targeting property. In vitro PDT experiments reveal that TQs-PEG4 NPs present excellent phototoxicities towards different cancer cell lines with an ultra-low dosage (<0.3 µg mL-1). TQs-PEG4 NP mediated PDT significantly inhibited tumor growth even when the tumor was covered with a 6 mm thick piece of pork tissue under 660 nm laser irradiation. Both the histological analysis and biochemical testing demonstrated the good biosafety of TQs-PEG4 NPs towards mice. This study not only develops an ultra-high photoactive organic PS, TQs-PEG4, but also proves the great potential of TQs-PEG4 NPs for application in deep PDT.
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Sistemas de Liberación de Medicamentos , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotosensibilizantes/síntesis química , Quinoxalinas/química , Animales , Neoplasias de la Mama , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Diseño de Fármacos , Femenino , Humanos , Ratones , Ratones Desnudos , Estructura Molecular , Neoplasias Experimentales , Fármacos Fotosensibilizantes/farmacologíaRESUMEN
The rise in the antibiotic resistance rate of Helicobacter pylori has led to an increasing eradication failure of this carcinogenic bacterial pathogen worldwide. This underlines the need for alternative antibacterial strategies against H. pylori infection. Antimicrobial photodynamic therapy (aPDT) is a promising non-pharmacological antibacterial technology. In this study, the selective killing activities of three benzylidene cyclopentanone (BCP) photosensitizers (Y1, P1 and P3) towards H. pylori over normal human gastric epithelial GES-1 cells were evaluated and the ex vivo photodynamic inactivation effect was preliminarily assessed on twelve H. Pylor-infected mice. Results showed that under the irradiation of 24 J/cm2 532 nm laser, Y1, P1 and P3 at 2.5 µM induced a 3-log10 reduction of H. pylori CFU (99.9% killing). Confocal images showed that P3, unlike Y1 and P1, could not be uptaken by GES-1 cells. P3 at 2.5 to 20 µM showed not significant (p > 0.05) phototoxicity to GES-1 cells, nevertheless, Y1 and P1 under the same concentrations exhibited remarkable phototoxicity to GES-1 cells. In the co-culture of H. pylori and GES-1 cells, P3 at 2.5 µM led to a complete eradication of H. pylori under the irradiation of 24 J/cm2 532 nm laser. While for the GES-1 cells, no significant (p > 0.05) phototoxicity was observed under the same aPDT dosage. The ex vivo experiments showed that P3 mediated aPDT resulted in 82.4% to 100% reduction of H. pylori CFU without damaging the gastric mucosa. To sum up, P3 is a promising anti-H. pylori photosensitizer with the ability to selectively photo-inactivate H. pylori while sparing normal gastric tissues.
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Ciclopentanos/química , Helicobacter pylori/efectos de los fármacos , Rayos Láser , Fármacos Fotosensibilizantes/farmacología , Animales , Compuestos de Bencilideno/química , Cationes/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Ciclopentanos/metabolismo , Ciclopentanos/farmacología , Ciclopentanos/uso terapéutico , Modelos Animales de Enfermedad , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Mucosa Gástrica/efectos de la radiación , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/patología , Helicobacter pylori/efectos de la radiación , Helicobacter pylori/ultraestructura , Humanos , Ratones , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/metabolismo , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
PURPOSE: The purpose of the multi-institutional retrospective study was to evaluate whether intraoperative radiotherapy (IORT) has advantages in the treatment of patients with locally advanced pancreatic cancer (LAPC) compared with concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: A total of 103 patients with LAPC whom was treated with IORT (Arm A; n = 50) or CCRT (Arm B; n = 53) from 2015.6 to 2016.7 were retrospectively identified. Data on feasibility, toxicity, and overall survival (OS) were evaluated. RESULTS: Most factors of the two cohorts were similar. The severe adverse events (grade 3 and 4) patients in Arm B were higher than patients in Arm A (34% vs 0%). Disease progression was noted in 38 patients (76%) in Arm A and 37 patients (69.8%) in Arm B. The median survival of patients in Arm A and B were 15.3 months (95% CI, 13.0-17.6 months) and 13.8 months (95% CI, 11.0-16.6 months), respectively. The 1-year survival rate were 66.3% in Arm A (95% CI, 52.3%-80.2%) and 60.9% in Arm B (95% CI, 46.4%-75.4%). There was no significant difference in OS between patients treated with IORT and with CCRT (p = 0.458). CONCLUSION: Our results demonstrated that patients with LAPC treated with IORT showed fewer adverse events, less treatment time, and high feasibility compared to CCRT. Although, IORT has no advantages in survival and tumor control compared with CCRT.
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BACKGROUND: Patients with malignant tumors frequently exhibit hyperactivation of the coagulation system and secondary increased fibrinolytic activity. Fibrinogen and D-dimer are common indicators that are crucial in the coagulation/fibrinolysis system. Both indicators have been verified to have predictive value in the overall survival (OS) of many patients with solid malignancies. AIM: To explore the prognostic significance of fibrinogen combined with D-dimer in pancreatic ductal adenocarcinoma (PDAC) patients undergoing radical R0 resection. METHODS: We retrospectively analyzed the clinical data of 282 patients with PDAC undergoing radical R0 resection in the Cancer Hospital, Chinese Academy of Medical Sciences, between January 2010 and December 2019. The surv_cutpoint function of R language was used to determine the optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration. Enrolled patients were further divided into the any-high group (high preoperative fibrinogen concentration and/or high preoperative D-dimer concentration) and the low-low group (low preoperative fibrinogen and D-dimer concentrations) according to the optimal cutoff values. RESULTS: The optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration were 3.31 g/L and 0.53 mg/L, respectively. Furthermore, multivariate Cox regression analysis showed that the preoperative fibrinogen concentration (HR: 1.603, 95%CI: 1.201-2.140, P = 0.001) and preoperative D-dimer concentration (HR: 1.355, 95%CI: 1.019-1.801, P = 0.036) exhibited obvious correlations with the OS of PDAC patients undergoing radical R0 resection. A prognostic analysis was further performed based on the subgroup results by using fibrinogen combined with D-dimer. The median OS duration of the low-low group (31.17 mo) was significantly longer than that of the any-high group (15.43 mo). Additionally, multivariate Cox regression analysis revealed that the degree of differentiation (P < 0.001), lymph node metastasis (HR: 0.663, 95%CI: 0.497-0.883, P = 0.005), preoperative CA19-9 level (HR: 1.699, 95%CI: 1.258-2.293, P = 0.001), adjuvant therapy (HR: 1.582, 95%CI: 1.202-2.081, P = 0.001) and preoperative combined grouping (HR: 2.397, 95%CI: 1.723-3.335, P < 0.001) were independent predictors of OS in PDAC patients undergoing radical R0 resection. CONCLUSION: Preoperative fibrinogen combined with D-dimer plays a predictive role in OS, and low preoperative fibrinogen and D-dimer concentrations can indicate prolonged OS in PDAC patients undergoing radical R0 resection.
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BACKGROUND: Inflammation plays an important role in tumor progression, and growing evidence has confirmed that the fibrinogen-to-albumin ratio (FAR) is an important prognostic factor for overall survival in malignant tumors. AIM: To investigate the prognostic significance of FAR in patients undergoing radical R0 resection of pancreatic ductal adenocarcinoma (PDAC). METHODS: We retrospectively analyzed the data of 282 patients with PDAC who underwent radical R0 resection at The Cancer Hospital of the Chinese Academy of Medical Sciences from January 2010 to December 2019. The surv_cutpoint function of the R package survminer via RStudio software (version 1.3.1073, http://www.rstudio.org) was used to determine the optimal cut-off values of biological markers, such as preoperative FAR. The Kaplan-Meier method and log-rank tests were used for univariate survival analysis, and a Cox regression model was used for multivariate survival analysis for PDAC patients who underwent radical R0 resection. RESULTS: The optimal cut-off value of FAR was 0.08 by the surv_cutpoint function. Higher preoperative FAR was significantly correlated with clinical symptoms (P = 0.001), tumor location (P < 0.001), surgical approaches (P < 0.001), preoperative plasma fibrinogen concentration (P < 0.001), and preoperative plasma albumin level (P < 0.001). Multivariate analysis showed that degree of tumor differentiation (P < 0.001), number of metastatic lymph nodes [hazard ratio (HR): 0.678, 95% confidence interval (CI): 0.509-0.904, P = 0.008], adjuvant therapy (HR: 1.604, 95%CI: 1.214-2.118, P = 0.001), preoperative cancer antigen 19-9 level (HR: 1.740, 95%CI: 1.288-2.352, P < 0.001), and preoperative FAR (HR: 2.258, 95%CI: 1.720-2.963, P < 0.001) were independent risk factors for poor prognosis in patients with PDAC who underwent radical R0 resection. CONCLUSION: The increase in preoperative FAR was significantly related to poor prognosis in patients undergoing radical R0 resection for PDAC. Preoperative FAR can be used clinically to predict the prognosis of PDAC patients undergoing radical R0 resection.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Albúminas , Carcinoma Ductal Pancreático/cirugía , Fibrinógeno , Humanos , Neoplasias Pancreáticas/cirugía , Pronóstico , Estudios RetrospectivosRESUMEN
Methotrexate (MTX) is a highly renal and liver toxicity drug used in hematological malignancy treatment in children and adults. High-dose methotrexate (HD-MTX) therapy may cause impairment of kidney and decrease the elimination of MTX, at the same time, the serum concentration of MTX increased. Today the treatment for preventing MTX toxicity after renal shutdown is Carboxypeptidase. We report a patient who experienced nephrotoxicity after the HD-MTX infusions during the treatment for non-Hodgkin lymphoma (NHL) and received hemodiafiltration (HDF) with large dose of leucovorin (LV) to treat MTX intoxication. LV is very potent in the prevention of neurotoxicity and administration of LV could protect the normal cells, but the dosage and duration of LV should be according to the MTX concentration. Although a large dose of LV was applied, the patient's condition did not improve. It was found that the HDF with large dose of LV to save the patient and steadily improved the patient's clinical condition.
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Antimetabolitos Antineoplásicos/efectos adversos , Hemodiafiltración , Enfermedades Renales/terapia , Linfoma no Hodgkin/tratamiento farmacológico , Metotrexato/efectos adversos , Antídotos/uso terapéutico , Humanos , Enfermedades Renales/sangre , Enfermedades Renales/inducido químicamente , Enfermedades Renales/diagnóstico , Leucovorina/uso terapéutico , Masculino , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The 8th American Joint Committee on Cancer (AJCC) staging system for pancreatic ductal adenocarcinoma (PDAC) outperforms its previous version in reproducibility but not in survival discrimination. Tumor grade, an indicator of the aggressive biology of PDAC, has been suggested as a reliable prognostic factor. This study aimed to construct a novel staging system with greater prognostication for resectable PDAC by incorporating tumor grade into the 8th AJCC system. METHODS: A total of 9966 patients with resectable PDAC from the Surveillance Epidemiology and End Results (SEER) database were randomly separated into training and interval validation sets. Another 324 patients from our center were included as an external validation set. We proposed a novel staging system by sorting the substages yielded by a combination of T, N, and tumor grade based on their overall survival (OS) and grouping them into several stages. Prognostic homogeneity and discrimination were determined using the likelihood ratio χ 2 and the linear trend χ 2 test, respectively. Prognostic accuracies were evaluated by the area under the receiver operating characteristics curve (AUC). RESULTS: Using the 8th AJCC system, the prognosis of patients within the same stage was quite heterogeneous among different substages. The multivariate Cox model identified the tumor grade (hazard ratio 1.333, 95% confidence interval 1.250-1.423, p < 0.001) was an independent prognostic factor of the OS. In the training set, the AUC, homogeneity, and discriminatory ability were superior for the novel staging system than for the 8th AJCC system (0.642 vs. 0.615, 403.4 vs. 248.6, and 335.1 vs. 218.0, respectively). Similar results were observed in the internal and external validation sets. CONCLUSIONS: The novel staging system incorporating tumor grade into the 8th AJCC system was associated with better prognostic accuracy, homogeneity, and discriminatory ability among resectable PDAC patients. Moreover, the novel staging system also allowed possibly adjuvant chemotherapy decisions.
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A water-soluble photosensitizer, PQs-PEG5, based on a novel pyrazino[2,3-g]quinoxaline (PQ) prototype compound (PQs-5), was designed and synthesized. It has strong linear absorption within 400-600 nm and a desirable two-photon absorption cross section (100-1290 GM) within 740-1000 nm, and it exhibits both a high fluorescence quantum yield (â¼0.55) and singlet oxygen quantum yield (â¼0.47). By carrying out in vitro cell imaging and photodynamic therapy (PDT) experiments on PQs-PEG5 with HeLa and 4T1 cells, it was demonstrated that PQs-PEG5 can present outstanding bioimaging performance and PDT efficacies simultaneously. Under one-photon excitation (1PE) of a 635 nm diode laser (60 mW cm-2, 5 min) or two-photon excitation (2PE) of an 820 nm fs laser (100 mW, 80 MHz, 140 fs, 5 min), PQs-PEG5 (10 µM) could cause HeLa and 4T1 cell death effectively, which indicated its great potential as a novel photosensitizer for both 1PE- and 2PE-PDT applications.
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Antineoplásicos/farmacología , Imagen Óptica , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Quinoxalinas/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Ratones , Estructura Molecular , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/química , Quinoxalinas/síntesis química , Quinoxalinas/química , Solubilidad , Agua/químicaRESUMEN
Effective wound healing has been demonstrated using lactic-co-glycolic acid (PLGA)-coated methylene blue nanoparticles (MPNPs) as a novel susceptible agent for photodynamic antibacterial therapy. Compared with methylene blue (MB) solution, MPNPs have a significantly improved antibacterial effect in vitro and in vivo. The enhanced antibacterial effect is achieved through increased singlet oxygen generation in MPNPs compared to that of MB solution, as a result of the decreased aggregation-induced quenching (ACQ) effect of the MPNPs. The mouse skin infection model experiment proved that MPNP has good antibacterial effects and promotes wound healing.
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In this paper, loofah sponge-based activated carbon (LAC) is prepared via loofah sponge as precursors and KOH as activator. N2 adsorption, X-ray diffraction (XRD) and scanning electron microscope (SEM) were used to characterize the surface morphology and the structure of loofah sponge-based activated carbon. Cyclic voltammetry (CV), galvanostatic charge/discharge cycle and electrochemical impedance spectroscopy (EIS) were utilized to test electrochemical properties of loofah spongebased activated carbon. The results showed that loofah sponge-based activated carbon (LAC-700) prepared at 700 °C has the highest specific surface area (936 m²·g-1). The material delivers specific capacitance of 152.89 F·g-1 at the current density of 0.1 A·g-1, and specific capacitance of 116.69 F·g-1 at the current density of 5 A·g-1 in 30 wt% KOH aqueous electrolyte.
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Two novel thiadiazolo[3,4-g]quinoxaline (TQ) photosensitizers (PSs), TQs-3 and TQs-4, were designed and synthesized. Both of them presented ultra-high singlet oxygen quantum yields under red light irradiation. By carrying out in vitro photodynamic therapy (PDT) experiments using TQs-4 loaded nanoparticles (TQs-4 NPs) to treat three kinds of tumor cell lines: 4T1, HeLa and MCF-7 cells, it was demonstrated that TQs-4 NPs had outstanding PDT efficacies. An ultra-low dose of TQs-4 (0.14 µg mL-1) can realize the death of more than 90% HeLa cells (635 nm, 60 mW cm-2, 10 min), which indicated that TQs-4 show promising potential as a novel PS for PDT applications.
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In this work, sandwich-like Co3O4/graphene nanocomposites were synthesized by a facile hydrothermal process and subsequent thermal treatment. X-ray diffraction and scanning electron microscopy analyses were employed to characterize crystalline structural and morphology. Results demonstrated that approximately 150 nm Co3O4 particles were dispersed among the graphene sheets. The graphene not only enhanced the conductivity of Co3O4/graphene nanocomposites but also improved the structural stability of Co3O4 nanoparticles. As an anode material for lithium-ion batteries (LIBs), the Co3O4/graphene nanocomposites exhibited excellent electrochemical performance, higher rate capability, and longer cycle life than pristine Co3O4. The Co3O4/graphene nanocomposites maintained a specific capacity of 639.8 mAhg-1 at a current density of 0.5C (1C = 890 mAg-1) after 50 cycles with capacity retention rate of 71%. Co3O4/graphene nanocomposites also exhibited excellent rate performance with a discharge capacity of 676.5 mAh g-1 at a current density of 2C. Overall, the sandwich-like Co3O4/graphene nanocomposites are good candidate materials for high-capacity anode for LIBs.
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BACKGROUND: Acute respiratory distress syndrome (ARDS) is a complication caused by pulmonary and/or external factors. In this study, we investigated the protective mechanisms of glabridin in lipopolysaccharide (LPS) induced ARDS in rats. RESULTS: GLA treatment at dose of 30 mg/kg decreased LPS-induced lung W/D ratio and alleviated evident lung histopathological changes. Expressions of TNF-α and IL-18 were suppressed by GLA in plasma. The levels of SPA, MDA and NO in lung were down-regulated significantly in groups administrated with GLA. While the SOD level increased after GLA administration. Additionally, the attenuation of inflammatory responses by GLA was closely associated with p38MAPK/ERK pathway, and the expressions of protein p-p38MAPK and pERK were inhibited by GLA in LPS-induced ARDS rats. MATERIALS AND METHODS: Sixty-four Wistar rats were randomly assigned into control group, Glabridin (GLA) alone group, LPS groups (6 h, 12 h, 24 h), GLA with LPS groups (6 h, 12 h, 24 h). ARDS was induced in rats by intraperitoneal administration of LPS (10 mg/kg). The degree of lung edema was evaluated by calculating the wet/dry weight ratio. The levels of inflammatory mediators, tumor necrosis factor-α (TNF-α) and interleukin-18 (IL-18) were assayed by enzyme-linked immunosorbent assay (ELISA). Surfactant protein A (SPA), malondialdehyde (MDA), nitric oxide (NO) and superoxide dismutase (SOD) were analyzed. Pathological changes of lung tissues were observed by H&E staining. The protein expression of p38MAPK and ERK was detected using immunohistochemical techniques. Lung phosphorylated p38MAPK (p-p38MAPK) and pERK protein expression changes were detected by Western blotting. CONCLUSIONS: Glabridin significantly ameliorated the lung injury induced by LPS in rats via the inhibition of p38MAPK and ERK signaling pathway, antioxidant effect and reducing inflammation.
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Isoflavonas/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Fenoles/farmacología , Síndrome de Dificultad Respiratoria/patología , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/complicaciones , Lesión Pulmonar Aguda/patología , Animales , Western Blotting , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Inmunohistoquímica , Lipopolisacáridos/toxicidad , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar , Síndrome de Dificultad Respiratoria/etiologíaRESUMEN
Fine Yin-Shang bronzes containing lead with puzzlingly highly radiogenic isotopic compositions appeared suddenly in the alluvial plain of the Yellow River around 1400 BC. The Tongkuangyu copper deposit in central China is known to have lead isotopic compositions even more radiogenic and scattered than those of the Yin-Shang bronzes. Most of the Yin-Shang bronzes are tin-copper alloys with high lead contents. The low lead and tin concentrations, together with the less radiogenic lead isotopes of bronzes in an ancient smelting site nearby, however, exclude Tongkuangyu as the sole supplier of the Yin-Shang bronzes. Interestingly, tin ingots/prills and bronzes found in Africa also have highly radiogenic lead isotopes, but it remains mysterious as to how such African bronzes may have been transported to China. Nevertheless, these African bronzes are the only bronzes outside China so far reported that have lead isotopes similar to those of the Yin-Shang bronzes. All these radiogenic lead isotopes plot along ~2.0-2.5 Ga isochron lines, implying that deposits around Archean cratons are the most likely candidates for the sources. African cratons along the Nile and even micro-cratons in the Sahara desert may have similar lead signatures. These places were probably accessible by ancient civilizations, and thus are the most favorable suppliers of the bronzes.