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The estrogen signalling pathway is highly dynamic and primarily mediated by estrogen receptors (ERs) that transcriptionally regulate the expression of target genes. While transcriptional functions of ERs have been widely studied, their roles in RNA biology have not been extensively explored. Here, we reveal a novel biological role of ER alpha (ERα) in mRNA 3' end processing in breast cancer cells, providing an alternative mechanism in regulating gene expression at the post-transcriptional level. We show that ERα activates poly(A) specific ribonuclease (PARN) deadenylase using in vitro assays, and that this activation is further increased by tumour suppressor p53, a factor involved in mRNA processing. Consistent with this, we confirm ERα-mediated activation of nuclear deadenylation by PARN in samples from MCF7 and T47D breast cancer cells that vary in expression of ERα and p53. We further show that ERα can form complex(es) with PARN and p53. Lastly, we identify and validate expression of common mRNA targets of ERα and PARN known to be involved in cell invasion, metastasis and angiogenesis, supporting the functional overlap of these factors in regulating gene expression in a transactivation-independent manner. Together, these results show a new regulatory mechanism by which ERα regulates mRNA processing and gene expression post-transcriptionally, highlighting its contribution to unique transcriptomic profiles and breast cancer progression.
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Neoplasias de la Mama , Receptor alfa de Estrógeno , Exorribonucleasas , Regulación Neoplásica de la Expresión Génica , ARN Mensajero , Proteína p53 Supresora de Tumor , Humanos , Receptor alfa de Estrógeno/metabolismo , Receptor alfa de Estrógeno/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Exorribonucleasas/metabolismo , Exorribonucleasas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Línea Celular Tumoral , Células MCF-7 , Núcleo Celular/metabolismo , Unión ProteicaRESUMEN
Resistant bacteria have always been of research interest worldwide. In the urban water system, the increased disinfectant usage gives more chances for undesirable disinfection-resistant bacteria. As the strongest oxidative disinfectant in large-scale water treatment, ozone might select ozone-resistant bacteria (ORB), which, however, have rarely been reported and are inexplicit for their resistant mechanisms and physiological characteristics. In this study, six strains of ORB were screened from a water reclamation plant in Beijing. Three of them (O7, CR19, and O4) were more resistant to ozone than all previously reported ORB or even spores. The ozone consumption capacity of extracellular polymeric substances and cell walls was proved to be the main sources of bacterial ozone resistance, rather than intracellular antioxidant enzymes. The transcriptome results elucidated that strong ORB possessed a combined antioxidant mechanism consisting of the enhanced transcription of protein synthesis, protein export, and polysaccharide export genes (LptF, LptB, NodJ, LivK, LviG, MetQ, MetN, and GltU). This study confirmed the existence of ORB in urban water systems and brought doubts to the idea of a traditional control strategy against chlorine-resistant bacteria. A salient "trade-off" effect between the ozone resistance and propagation ability indicated the weakness and potential control approaches of ORB.
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Bacterias , Ozono , Purificación del Agua , Ozono/farmacología , Bacterias/efectos de los fármacos , Desinfectantes/farmacología , DesinfecciónRESUMEN
AIM: This study set out to access the performance of quantitative analysis of contrast-enhanced ultrasound (CEUS) in distinguishing between benign periablational enhancement (BPE) and residual tumor (RT) following radiofrequency ablation (RFA). MATERIALS AND METHODS: 165 tumors from 124 patients with hepatocellular carcinoma between 2021 and 2023 underwent RFA, contrast-enhanced computed tomography (CECT), and CEUS in less than 24 hours. Analysis was done on the quantitative parameters from RT and BPE found by CEUS. RESULTS: Complete ablation was obtained in 89.1% of lesions. When compared to BPE, RT had significantly greater peak intensity (PI), time to peak (TTP), area under the curve (AUC), ratio of PI and base intensity (PI/BI), and enhanced intensity (EI) values (all p<0.05). PI, TTP, AUC, PI/BI, and EI had large areas under the receiver operating (ROC) curves. A binary logistic regression analysis, respectively, demonstrated that PI and PI/BI were independent favorable prognostic variables. CONCLUSIONS: Multiple parameters of quantitative analysis of CEUS can aid in distinguishing immediately between RT and BPE lesions. PI and PI/BI may be a more promising parameter. Immediate CEUS evaluation following RFA may allow immediate retreatment of RT during the same operation time, which reduces patients' hospital stays and financial costs.
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Emerging electrochemical disinfection techniques provide a promising pathway to the biofouling control of reverse osmosis (RO) process. However, the comparative effectiveness and mechanism of it under flow-through conditions with low voltage remains unclear. This study investigated the effect of a flow-through electrode system (FES) with both direct current (DC) and alternating pulse current (AC) on RO biofouling control compared with chlorine disinfection. At the initial stage of biofouling development, the normalized flux of AC-FES (67% on Day 5) was saliently higher than the control group (56% on Day 5). Subsequently, the normalized fluxes of each group tended similarity in their differences until the 20th day. After mild chemical cleaning, the RO membrane in the AC-FES group reached the highest chemical cleaning efficiency of 58%, implying its foulant was more readily removable and the biofouling was more reversible. The biofouling layer in the DC-FES group was also found to be easily cleanable. Morphological analysis suggested that the thickness and compactness of the fouling layers were the major reasons for the fouling behavior difference. The abundance of 4 fouling-related abundant genera (>1%), which were Pseudomonas, Thiobacillus, Sphingopyxis, and Mycobacterium exhibited a salient correlation with the biofouling degree. The operating cost of FES was also lower than that of chlorine disinfection. In summary, AC-FES is a promising alternative to chlorine disinfection in RO biofouling control, as it caused less and easy-cleaning biofouling layer mainly due to two advantages: a) reducing the regrowth potential after disinfection of the bacteria, leading to alleviated initial fouling, (b) reshaping the microbial community to those with weaker biofilm formation capacity.
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Incrustaciones Biológicas , Purificación del Agua , Aguas Residuales , Incrustaciones Biológicas/prevención & control , Cloro , Membranas Artificiales , Ósmosis , Purificación del Agua/métodosRESUMEN
With the widespread use of chlorine disinfection, chlorine-resistant bacteria (CRB) in water treatment systems have gained public attention. Bacterial chlorine resistance has been found positively correlated with extracellular polymeric substance (EPS) secretion. In this study, we selected the most suitable CRB controlling method against eight bacterial strains with different chlorine resistance among chloramine, ozone, and ultraviolet (UV) disinfection, analyzed the resistance mechanisms, clarified the contribution of EPS to disinfection resistance, and explored the role of carbon source metabolism capacity. Among all the disinfectants, UV disinfection showed the highest disinfection capacity by achieving the highest average and median log inactivation rates for the tested strains. For Bacillus cereus CR19, the strain with the highest chlorine resistance, 40 mJ/cm2 UV showed a 1.90 log inactivation, which was much higher than that of 2 mg-Cl2/L chlorine (0.67 log), 2 mg-Cl2/L chloramine (1.68 log), and 2 mg/L ozone (0.19 log). Meanwhile, the UV resistance of the bacteria did not correlate with EPS secretion. These characteristics render UV irradiation the best CRB controlling disinfection method. Chloramine was found to have a generally high inactivation efficiency for bacteria with high chlorine-resistance, but a low inactivation efficiency for low chlorine-resistant ones. Although EPS consumed up to 56.7% of chloramine which an intact bacterial cell consumed, EPS secretion could not explain chloramine resistance. Thus, chloramine is an acceptable CRB control method. Similar to chlorine, ozone generally selected high EPS-secreting bacteria, with EPS consuming up to 100% ozone. Therefore, ozone is not an appropriate method for controlling CRB with high EPS secretion. EPS played an important role in all types of disinfection resistance, and can be considered the main mechanism for bacterial chlorine and ozone disinfection resistance. However, as EPS was not the main resistance mechanism in UV and chloramine disinfection, CRB with high EPS secretion were inactivated more effectively. Furthermore, carbon source metabolism was found related to the multiple resistance of bacteria. Those with low carbon source metabolism capacity tended to have higher multiple resistance, especially to chlorine, ozone, and UV light. Distinctively, among the tested gram-negative bacteria, in contrast to other disinfectants, chloramine resistance was negatively correlated with EPS secretion and positively correlated with carbon source metabolism capacity, suggesting a special disinfection mechanism.
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Desinfectantes , Ozono , Cloro/farmacología , Cloraminas/farmacología , Desinfección , Matriz Extracelular de Sustancias Poliméricas , Halógenos , Bacterias , Desinfectantes/farmacología , Carbono , ClorurosRESUMEN
Learned associations between the rewarding effects of drugs and the context in which they are experienced underlie context-induced relapse. Previous work demonstrates the importance of sparse neuronal populations - called neuronal ensembles - in associative learning and cocaine seeking, but it remains unknown whether the encoding vs. retrieval of cocaine-associated memories involves similar or distinct mechanisms of ensemble activation and reactivation in nucleus accumbens (NAc). We use ArcCreER T2 mice to establish that mostly distinct NAc ensembles are recruited by initial vs. repeated exposures to cocaine, which are then differentially reactivated and exert distinct effects during cocaine-related memory retrieval. Single-nuclei RNA-sequencing of these ensembles demonstrates predominant recruitment of D1 medium spiny neurons and identifies transcriptional properties that are selective to cocaine-recruited NAc neurons and could explain distinct excitability features. These findings fundamentally advance our understanding of how cocaine drives pathological memory formation during repeated exposures.
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Adsorption and coagulation were commonly used to alleviate reverse osmosis (RO) membrane fouling caused by dissolved organic matters (DOM), but the effects of changed composition and structure of DOM in dyeing wastewater after adsorption and coagulation on RO membrane fouling have seldom been studied. This study aimed at resolving the mechanism how the RO membrane fouling during dyeing wastewater treatment was alleviated by using adsorption and coagulation. The dyeing wastewater caused serious RO membrane fouling. Pretreatment with granular activated carbon (GAC), polyferric sulfate (PFS) and polyaluminum chloride (PACl) were conducted. It was shown that GAC could remove most of the DOM (95%) and preferred to adsorb protein, hydrophobic neutrals and fluorescent compounds. Both coagulants of PFS and PACl preferred to remove polysaccharides (the removal rate was 9-19% higher than that of DOM), high-MW compounds and these compounds with high fouling potential. Afterwards, the RO membrane fouling potential of the dyeing wastewater was tested. The GAC and PFS performed well to alleviate fouling. After GAC treatment, the decline rate of RO flux was similar to that of raw wastewater after 6-fold dilution. With pretreatment by PFS or PACl, the fouling potential of dyeing wastewater was much lower than that of raw wastewater after diluted to the same DOM content. Changes in polysaccharides content in the DOM had more effects on RO membrane fouling than that of proteins after these pretreatment. Although the DOM changed significantly after pretreatment, the fouling type was still intermediate blocking.
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Aguas Residuales , Purificación del Agua , Colorantes , Filtración , Membranas Artificiales , ÓsmosisRESUMEN
Fouling of RO membranes has long been a complex but inevitable problem in wastewater reclamation. In this study, a modified intermediate blocking model with two parameters was applied to describe the flux change of RO membranes treating various water samples, including municipal secondary effluent, treated industrial wastewater, surface water, and groundwater. The model was validated by 55 sets of data reported by 13 articles, and the results were promising, with 90% of the determination coefficient (R2) exceeding 0.90. Relatively large flux and high operational pressure were found likely to aggravate membrane fouling. Treated industrial wastewater had the highest fouling potential (fouling constant k: 0.061-2.433) compared to municipal wastewater secondary effluent, surface water, and groundwater, even with similar dissolved organic carbon concentration. With industrial wastewater excluded, water samples exhibited lower fouling potential than organic matter solutions, with the majority (25%â¼75%) of k distributing in 0.03-0.12, much lower compared to the major k range of the latter (0.05-0.28). This suggested a deviation in fouling behaviors between model organic matters and real water samples. Xanthan gum and guar gum were proposed to be model polysaccharides based on their model parameters, which were relatively close to real water samples.
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Purificación del Agua , Materia Orgánica Disuelta , Membranas Artificiales , Ósmosis , Aguas Residuales , AguaRESUMEN
Chlorine disinfection is often used as a pretreatment technology to control biofouling of reverse osmosis (RO) membranes. However, previous studies showed that biofouling of the RO system was aggravated after chlorine disinfection. Chlorine-resistant bacteria (CRB) were presumed to be closely related to the aggravation of fouling caused by chlorine disinfection. In order to analyze the membrane fouling mechanisms of CRB, 5 CRB strains were isolated from the surface of fouled RO membranes for wastewater reclamation, and 3 reference bacterial strains, Sphingopyxis soli BM1-1, Pseudomonas aeruginosa PAO1 and Escherichia coli CGMCC1.3373, were selected for comparative study. The chlorine resistance, membrane fouling potential, secretion and adhesion characteristics of these strains were evaluated. Among these isolated strains, 3 strains showed much higher chlorine resistance than PAO1 under the condition of 0.5, 2, 5 mg/L-Cl2, especially Bacillus CR19 and Bacillus CR2. Furthermore, a significant positive correlation was found between membrane fouling potential and chlorine resistance of all the strains in this study. The membrane fouling potential of the above 8 strains increased monotonically with the increase of chlorine resistance (under the condition of 0.5 mg/L-Cl2). Serious fouling caused by extracellular substances was observed in biofouling layers of the strains with high chlorine resistance, which lead to more severe flux decline. Extracellular polymeric substances (EPS) amount per cell was found to be the main factor related to the chlorine resistance as well as the fouling potential. Computational fluid dynamics (CFD) simulation was used to demonstrate the filtration resistance induced by the secretion of EPS. However, CRB with higher EPS amount may not show higher membrane adhesion potential, and thus may not be the dominant strain on the RO membranes before chlorine disinfection. These CRB with high fouling potential but low membrane adhesion potential, such as Bacillus CR19 and Bacillus CR2, may become the dominant bacteria on the membrane surface after chlorine disinfection and thus aggravate membrane fouling significantly.
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OBJECTIVES: We aimed to construct an induction system for polyploid giant cancer cells (PGCCs), as well as to investigate PGCC features and clinical significance. METHODS: A laryngeal neoplasm-PGCC induction system was constructed using paclitaxel liposomes (PTX). We used western blots to compare expression of epithelial-mesenchymal transition-related proteins, stem cell interrelated proteins, and cyclin-associated proteins. We then measured PGCC count in tissue samples of patients with laryngeal neoplasms and analyzed its relationship with prognosis. Statistical significance was determined using t-tests. RESULTS: PTX successfully induced PGCCs. Western blotting showed that CyclinB1, CDC25C, CDK1, E-cadherin, and EIF-4A expression decreased in PGCCs compared with normal cancer cells, whereas vimentin and CD133 expression increased. Number of PGCCs in laryngeal cancer tissues and overall survival time were inversely correlated (P < .05). CONCLUSIONS: PTX successfully induces PGCC formation in laryngeal carcinoma, which may be the cause of poor prognosis in patients with laryngeal cancer.Level of Evidence: 4.
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The epidemic of COVID-19 has aroused people's particular attention to biosafety. A growing number of disinfection products have been consumed during this period. However, the flaw of disinfection has not received enough attention, especially in water treatment processes. While cutting down the quantity of microorganisms, disinfection processes exert a considerable selection effect on bacteria and thus reshape the microbial community structure to a great extent, causing the problem of disinfection-residual-bacteria (DRB). These systematic and profound changes could lead to the shift in regrowth potential, bio fouling potential, as well as antibiotic resistance level and might cause a series of potential risks. In this review, we collected and summarized the data from the literature in recent 10 years about the microbial community structure shifting of natural water or wastewater in full-scale treatment plants caused by disinfection. Based on these data, typical DRB with the most reporting frequency after disinfection by chlorine-containing disinfectants, ozone disinfection, and ultraviolet disinfection were identified and summarized, which were the bacteria with a relative abundance of over 5% in the residual bacteria community and the bacteria with an increasing rate of relative abundance over 100% after disinfection. Furthermore, the phylogenic relationship and potential risks of these typical DRB were also analyzed. Twelve out of fifteen typical DRB genera contain pathogenic strains, and many were reported of great secretion ability. Pseudomonas and Acinetobacter possess multiple disinfection resistance and could be considered as model bacteria in future studies of disinfection. We also discussed the growth, secretion, and antibiotic resistance characteristics of DRB, as well as possible control strategies. The DRB phenomenon is not limited to water treatment but also exists in the air and solid disinfection processes, which need more attention and more profound research, especially in the period of COVID-19.
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COVID-19 , Microbiota , Bacterias , Desinfección , Humanos , SARS-CoV-2RESUMEN
Membrane fouling is a prominent problem that hinders the stable and efficient operation of the reverse osmosis (RO) system for wastewater reclamation. Previous studies showed that chlorine disinfection, which was commonly used in industrial RO systems as pretreatment, could lead to significant change in microbial community structure and resulted in serious biofouling. In order to prevent biofouling during wastewater reclamation, the effect of ultraviolet (UV) disinfection on RO membrane fouling was investigated and the mechanism was also revealed in this study. With the disinfection pretreatment by UV of 20, 40 and 80 mJ/cm2, the bacteria in the feed water were inactivated significantly with a log reduction of 1.11, 2.55 and 3.61-log, respectively. However, RO membrane fouling aggravated with higher UV dosage. Especially, in the group with the UV dosage of 80 mJ/cm2, the normalized RO membrane flux decreased by 15% compared with the control group after 19-day operation. The morphology of the fouled RO membranes indicated serious biofouling in all groups. The analysis on the microbial amount of the foulants showed that the heterotrophic plate counts (HPC) and ATP content on the fouled RO membranes with and without UV disinfection were at the same level. However, the total organic carbon content of the foulants with the UV dosage of 40 and 80 mJ/cm2 was significantly higher than the control group, with higher content of proteins and polysaccharides as indicated by EEM and FTIR spectrum. Microbial community structure analysis showed that some typical UV-resistant bacteria were selected and remained on the RO membrane after disinfection with high UV dosage, including. These residual bacteria after disinfection with high UV dosage showed higher extracellular polymeric substances (EPS) secretion compared with those without UV disinfection, and thus aggravated RO membrane fouling. Thicker EPS could decrease the transmission of UV rays, and thus bacteria with higher EPS secretion might be selected after UV disinfection.
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Incrustaciones Biológicas , Purificación del Agua , Desinfección , Membranas Artificiales , Ósmosis , Aguas ResidualesRESUMEN
Isoliquiritigenin (2',4',4-trihydroxychalcone, ISL) is one of the most important chalcone compounds which is mainly derived from licorice root and many other plants. It exhibits a remarkable range of potent biological and pharmacological activities such as antioxidative, antitumor, antiaging, anti-inflammatory, anti-diabetic activities, etc. Numerous research teams have demonstrated that ISL posseses the ability to carry out antigrowth and proliferation in various cancer cells in vitro and in vivo. Meanwhile, the underlying mechanisms of ISL that inhibit cancer cell proliferation have not been well explored. However, the poor bioavailability and low water-soluble limit its clinical application. This review aims at providing a comprehensive overview of the pharmacology antitumor activity of ISL and its mechanisms in different malignancy especially in breast cancer cell line and summarize developments of formulation utilized to overcome the barrier between its delivery characteristics and application in clinics over the past 20 years.
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Antineoplásicos/farmacología , Chalconas/farmacología , Animales , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Chalconas/química , Composición de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , HumanosRESUMEN
OBJECTIVE: To evaluate levels of lead (Pb) and cadmium (Cd) in the breast milk in the second postpartum month, to investigate the relationship between Pb/Cd levels in breast milk and some sociodemographic parameters, and to explore whether these levels affect the infants' physical status or the mothers' psychological status (postpartum depression). METHODS: A cross-sectional study was conducted between November 2009 and December 2010. Altogether 170 healthy mothers were enrolled from Nanjing Maternity and Child Health Care Hospital. The inclusion criteria were: voluntary to participate in this study, healthy, with no chronic disease, breastfeeding in the second postpartum month, living in a suburban but not non-industrial area of Nanjing, and not occupationally exposed to toxic metals. All the mothers completed a questionnaire and were evaluated based on the Edinburgh Postpartum Depression Scale (EPDS) to identify the risk of postpartum depression. Pb and Cd levels in breast milk were determined by inductively coupled plasma mass spectroscopy. The infants of these mothers were examined for their z scores of weight for age, length for age, head circumference for age, and body mass index for age. RESULTS: The median breast milk levels of Pb and Cd were 40.6 µg/L and 0.67 µg/L, respectively. In 164 (96.5%) of the 170 samples, Pb levels were higher than the limit reported by the World Health Organization (> 5 µg/L). Breast milk Cd level was > 1 µg/L in 54 (31.8%) mothers. The mothers with a history of anemia had a higher breast milk Pb level than those without a history of anemia (41.1 µg/L vs. 37.9 µg/L, P = 0.050). The median breast milk Cd level in those who were active and passive smokers during pregnancy was significantly higher than that in non-smokers (0.88 µg/L vs. 0.00 µg/L, P = 0.025). The breast milk Cd level in the mothers not taking iron and vitamin supplements for 2 months postpartum was higher than in those taking the supplements (iron supplement: 0.74 µg/L vs. 0.00 µg/L, P = 0.025; vitamin supplement: 0.78 µg/L vs. 0.00 µg/L, P = 0.005). Breast milk Cd level at the second postpartum month was negatively correlated with the z scores of head circumference (r = - 0.248, P = 0.042) and weight for age at birth (r =- 0.241, P = 0.024) in girls. No correlation was found between the breast milk Pb/Cd levels and the EPDS scores. CONCLUSION: Considering the high levels of Pb and Cd in breast milk in this study, breast milk monitoring programs are necessary.
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Cadmio/análisis , Plomo/análisis , Leche Humana/química , Adolescente , Adulto , China , Estudios Transversales , Femenino , Humanos , EmbarazoRESUMEN
Although railway has played a great role in transportation in China, there has been no any study on air pollutants emissions of locomotives until now. Based on the annual statistical data collected by the Chinese Railway Statistic Center, using the emission factor method derived from fuel consumption, the air pollutants emissions of locomotives during 1975-2007 were calculated, and their emission intensities and dynamic characteristics were analyzed. The results show that the emissions of soot, SO2, CO and CnHm from steam and diesel locomotives in china decreased from 3510.6 thousand, 399.7 thousand, 846.0 thousand and 845.3 thousand ton in 1975 to 78.7 thousand, 11.4 thousand, 36.7 thousand and 26.4 thousand ton in 2007, indicating a decrease of 107.0 thousand, 12.1 thousand, 25.3 thousand and 25.6 thousand ton per year, respectively. However, the emissions of NO,showed an increase trend from 34.8 thousand ton in 1975 to 98.3 thousand ton in 2007 with an increase rate of 2.0 thousand ton per year. The emission intensities of soot, SO2, CO and CnHm decreased significantly from 686.2, 78.1, 165.4 and 165.2 g/(hundred converted ton-km) in 1975 to 5.4, 0.8, 2.5 and 1.8 g/(hundred converted ton-km) in 2007, respectively. The emission intensity of NOx fluctuated in the range of 5.0-8.0 g/(hundred converted ton-km). Air pollutants emissions of locomotives accounted for very little of the total emissions in China, and the emission intensities decreased persistently. It shows that railway transportation is a perfect way of saving energy and reducing emission in the sector of transportation.
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Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Vías Férreas , Emisiones de Vehículos/análisis , Monóxido de Carbono/análisis , China , Hidrocarburos/análisis , Óxidos de Nitrógeno/análisis , Dióxido de Azufre/análisisRESUMEN
To investigate the efficacy of dendritic cells and natural killer cells in the inhibition of lung metastasis, we injected dendritic cells and natural killer cells intravascularly into mice bearing B16F10 tumour melanoma cells. This efficiently inhibited tumor growth and prolonged survival. In addition, surviving mice developed a long-lasting memory response against the original tumor when re-challenged with live tumor cells. Intravenous administration of dendritic cells and natural killer cells may be a potential way to treat lung metastasis in patients.
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Células Dendríticas/inmunología , Células Asesinas Naturales/inmunología , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/secundario , Animales , Linfocitos T CD8-positivos/inmunología , Citotoxicidad Inmunológica/inmunología , Vías de Administración de Medicamentos , Femenino , Memoria Inmunológica/inmunología , Inyecciones Intravenosas , Neoplasias Pulmonares/inmunología , Ratones , Ratones Endogámicos C57BLRESUMEN
Professor XU Rui-Zheng's experience in clinical diagnosis and treatment of auricular acupuncture are introduced. He is good at using auricular acupuncture to treat various diseases and symptoms, and he has rich experience in treatment of difficult and complicated cases, reflecting both syndrome differentiation treatment and an organic conception of the human body in treatment, with obviously clinical effect. He sums up clinical experience of many years, attaining the experience of ten wards, i.e. observation, touching, searching, detection, questioning, treatment program, pressing, treatment, regulation, advance.
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Acupuntura Auricular , Medicina Tradicional China , Diagnóstico Diferencial , HumanosRESUMEN
We have previously reported that Kv1.3 channel is expressed in Daudi cells. However, the present study demonstrates that Daudi cell cycle progression is not affected by margatoxin, a Kv1.3 channel blocker, but can be suppressed by tetraethylammonium (TEA) and 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34), a selective blocker of intermediate-conductance Ca(2+)-activated K(+) (IK) channels. Our patch-clamp data indicate that Daudi cells express an IK channel because it has a unit conductance of about 30 pS, is voltage-independent, and can be activated by submicromolar Ca(2+) and blocked by TRAM-34. Fetal bovine serum (FBS) elevated intracellular Ca(2+) concentration ([Ca(2+)](i)) and activated this IK channel. Conversely, Rituximab, a human-mouse chimeric monoclonal antibody of CD20, significantly decreased [Ca(2+)](i) and inhibited the channel. Furthermore, both FBS-induced IK channel expression and cell cycle progression were attenuated by the treatment with LY-294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. These data together suggest that a growth factor(s) in FBS triggers cell cycle progression by elevating both IK channel activity via CD20 and IK channel expression on the cell surface via PI3K. Thus, elevated IK channel activity and expression may account, in part, for Daudi cell malignant growth and proliferation.
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Linfoma de Células B/patología , Canales de Potasio Calcio-Activados/fisiología , Antígenos CD20/metabolismo , Calcio/análisis , Calcio/metabolismo , Ciclo Celular/efectos de los fármacos , Ciclo Celular/fisiología , Línea Celular Tumoral , Cromonas/farmacología , Inhibidores Enzimáticos/farmacología , Citometría de Flujo , Humanos , Proteínas de la Membrana/biosíntesis , Microscopía Confocal , Morfolinas/farmacología , Técnicas de Placa-Clamp , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Bloqueadores de los Canales de Potasio/farmacología , Canales de Potasio Calcio-Activados/efectos de los fármacos , Pirazoles/farmacología , Suero , Tetraetilamonio/farmacología , Regulación hacia Arriba/fisiologíaRESUMEN
OBJECTIVE: To explore the inhibitory effect of KAI1 gene on breast cancer cell growth in vitro. METHODS: Highly metastatic human breast cancer cell line MDA-MB-231 was transfected with pCMV-KAI1 or mock transfected plasmid pCMV with lipofectamine. Western blot was used to determine the expression of target protein of KAI1. The proliferative ability of cells was tested by MTT assay and colony-forming test. The cell cycle pattern was assayed by flow cytometry. The metastatic ability was investigated by cell adhesion and invasion assays. RESULTS: A stable cell clone transfected with KAI1 gene was obtained and over-expression of KAI1 protein was observed. There was a significant decline in cell proliferative ability of pCMV-KAI1 transfected MDA-MB-231 cells in comparison with the mock-transfected ones and non-transfected ones, revealed by MTT assay and colony-forming test (P < 0.05). The ability of adherence and invasion of pCMV-KAI1 transfected cells was significantly reduced in comparison with the other two groups (P < 0.05). Also, flow cytometry analysis revealed that in KAI1 transfected cell group the number of cells in G0/G1 phase increased markedly from 36.78% +/- 0.61% to 64.00% +/- 7.56%, while the number of cells in G2/M phase decreased from 17.88% +/- 0.76% to 7.63% +/- 0.60%, comparing with the non-transfected ones. CONCLUSION: KAI1 gene suppresses the invasive ability of human breast cancer cells in vitro and may inhibit the proliferative ability by changing the cell cycle pattern.