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[This corrects the article DOI: 10.3389/fimmu.2024.1353695.].
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Objectives: This study aimed to analyze active compounds and signaling pathways of CH applying network pharmacology methods, and to additionally verify the molecular mechanism of CH in treating AP. Materials and methods: Network pharmacology and molecular docking were firstly used to identify the active components of CH and its potential targets in the treatment of AP. The pancreaticobiliary duct was retrogradely injected with sodium taurocholate (3.5%) to create an acute pancreatitis (AP) model in rats. Histological examination, enzyme-linked immunosorbent assay, Western blot and TUNEL staining were used to determine the pathway and mechanism of action of CH in AP. Results: Network pharmacological analysis identified 168 active compounds and 276 target proteins. In addition, there were 2060 targets associated with AP, and CH had 177 targets in common with AP. These shared targets, including STAT3, IL6, MYC, CDKN1A, AKT1, MAPK1, MAPK3, MAPK14, HSP90AA1, HIF1A, ESR1, TP53, FOS, and RELA, were recognized as core targets. Furthermore, we filtered out 5252 entries from the Gene Ontology(GO) and 186 signaling pathways from the Kyoto Encyclopedia of Genes and Genomes(KEGG). Enrichment and network analyses of protein-protein interactions predicted that CH significantly affected the PI3K/AKT signaling pathway, which played a critical role in programmed cell death. The core components and key targets showed strong binding activity based on molecular docking results. Subsequently, experimental validation demonstrated that CH inhibited the phosphorylation of PI3K and AKT in pancreatic tissues, promoted the apoptosis of pancreatic acinar cells, and further alleviated inflammation and histopathological damage to the pancreas in AP rats. Conclusion: Apoptosis of pancreatic acinar cells can be enhanced and the inflammatory response can be reduced through the modulation of the PI3K/AKT signaling pathway, resulting in the amelioration of pancreatic disease.
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Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Farmacología en Red , Pancreatitis , Transducción de Señal , Animales , Pancreatitis/tratamiento farmacológico , Pancreatitis/metabolismo , Pancreatitis/patología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/química , Ratas , Transducción de Señal/efectos de los fármacos , Masculino , Modelos Animales de Enfermedad , Apoptosis/efectos de los fármacos , Ratas Sprague-Dawley , Mapas de Interacción de ProteínasRESUMEN
China has the world's largest carbon market in terms of greenhouse gas emissions, but its system needs to be improved and enhanced. In comparison, the European carbon market stands as the most mature and well-developed carbon market globally. Carbon trading prices, serving as a barometer for the carbon market, are significantly influenced by investor behavior. Therefore, it is necessary to analyze the characteristics of carbon trading prices in both China and Europe, considering the impact of investor trading intervals and psychological expected returns. This study utilizes the Zipf method to characterize the dynamic behavior of carbon trading prices between China and Europe, conducting a comparative analysis. The results show distinctive asymmetry in the behavior of carbon trading prices in both markets. In the Chinese market, when τ < 277, the absolute deviation da(τ, ε) value gradually changes but consistently indicates a bullish trend. However, when τ ≥ 277, the da(τ, ε) value surges rapidly, reflecting a pronounced bullish sentiment among investors toward carbon trading prices in China. In the European market, within the sample period, regardless of variations in τ and ε, the da(τ, ε) value shows a linear upward trend, indicating a significant overall bullishness in prices. This suggests a higher probability of long-term bullishness in carbon trading prices. Investors' investment time scale (τ) and expected returns (ε) both influence the behavior of carbon trading prices in both China and Europe. Generally, a longer τ implies a higher probability of bullishness. As for ε, higher values lead to more extreme judgments on price movements, resulting in greater distortion in carbon trading prices. Short-term investors (τ<1 month) anticipate extreme fluctuations, exhibiting random behavior when ε < 0.15 and converging rapidly to extreme values of 1 or 0 when ε ≥ 0.15. Long-term investors (τ>quarter) are less biased, expressing a bullish outlook on both Chinese and European carbon prices. With increasing ε, the probability of bullishness either increases or decreases rapidly until reaching the saturation point. Once saturated, there is no further distortion in carbon price behavior. Furthermore, the Chinese carbon market displays a positive trend in carbon trading prices and a higher probability of long-term bullishness. For the European market, lower expected returns contribute to considerable carbon trading price fluctuations, exacerbating risk and uncertainty. The results of this study contribute to understanding the diverse trading behaviors in Chinese and European carbon markets and provide guidance for avoiding extreme volatility in carbon trading prices.
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Carbono , Gases de Efecto Invernadero , China , Inversiones en Salud , Europa (Continente)RESUMEN
Objective: To investigate the variation of ferroptosis-related markers in HaCaT cell photoaging models induced by ultraviolet-B (UVB). Methods: UVB-treated HaCaT cells served as the model (UVB group) for cellular photoaging, whereas untreated HaCaT cells served as the control group. HaCaT cells were exposed to UVB and the ferroptosis inhibitor Ferrostatin-1 (Fer-1) as part of the UVB+Fer-1 group, and co-cultured with the ferroptosis inducer Erastin as part of the UVB+Erastin group. Reactive oxygen species (ROS) detection kit and senescence-related ß galactosidase (SA-ß-gal) staining were used to evaluate the senescence of HaCaT cells. Lipid reactive oxygen species were detected by C11 BODIPY581/591 probe and mitochondrial morphology was observed by transmission electron microscopy. The mRNA expressions of glutathione peroxidase 4 (GPX4) and ferroptosis-suppressor-protein 1 (FSP1) were detected by real-time reverse transcription-PCR (RT-RCP), and the level of GPX4 protein was measured by immunofluorescence assay. Results: The UVB group had considerably greater levels of ROS, SA-ß-gal, and lipid reactive oxygen species than the control group. The UVB group's mitochondrial volume was reduced, the membrane density increased, and the mitochondrial crest decreased or even disappeared. GPX4 and FSP1 expression levels were similarly found to be lower in the UVB group. Furthermore, the positive rate of SA-ß-gal and lipid reactive oxygen species in the UVB+Fer-1 group was much lower than in the UVB group, but it was reverse in the UVB+Erastin group. This study showed that induced ferroptosis can aggravate aging, and vice versa. Conclusion: According to the findings, ferroptosis may be linked to UVB-induced skin photoaging, which could be attenuated by inhibition of ferroptosis.
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Background: Hepatocellular carcinoma is a rapidly advancing malignancy with a poor prognosis. Therefore, further research is needed on its potential pathogenesis and therapeutic targets. Methods: In this study, the relevant datasets were downloaded from the TCGA database and the key modules were identified using WGCNA in the necroptosis-related gene set, while single-cell datasets were scored using the necroptosis gene set. Differential genes in the high- and low-expression groups were determined using the WGCNA module genes as intersection sets to identify key genes involved in necroptosis in liver cancer. Then, prognostic models were constructed using LASSO COX regression followed by multi-faceted validation. Finally, model genes were found to be correlated with key proteins of the necroptosis pathway and used to identify the most relevant genes, followed by their experimental validation. Subsequently, on the basis of the analysis results, the most relevant SFPQ was selected for cell-level verification. Results: We constructed a prognosis model that included five necroptosis-related genes (EHD1, RAC1, SFPQ, DAB2 and PABPC4) to predict the prognosis and survival of HCC patients. The results showed that the prognosis was more unfavorable in the high-risk group compared to the low-risk group, which was corroborated using ROC curves and risk factor plots. In addition, we further checked the differential genes using GO and KEGG analyses and found that they were predominantly enriched in the neuroactive ligand-receptor interaction pathway. The results of the GSVA analysis demonstrated that the high-risk group was mainly enriched in DNA replication, regulation of the mitotic cycle, and regulation of various cancer pathways, while the low-risk group was predominantly enriched in the metabolism of drugs and xenobiotics using cytochrome P450. SFPQ was found to be the main gene that affects the prognosis and SFPQ expression was positively correlated with the expression of RIPK1, RIPK3 and MLKL. Furthermore, the suppression of SFPQ could inhibit hyper-malignant phenotype HCC cells, while the WB results showed that inhibition of SFPQ expression also resulted in lower expression of necroptosis proteins, compared to the sh-NC group. Conclusions: Our prognostic model could accurately predict the prognosis of patients with HCC to further identify novel molecular candidates and interventions that can be used as alternative methods of treatment for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Pronóstico , Bases de Datos Factuales , Necroptosis , Proteínas de Transporte VesicularRESUMEN
Liver metastasis of colorectal cancer (CRC) is the critical cause of CRC-related death due to its unique immunosuppressive microenvironment. In this study we generated a gemcitabine-loaded synthetic high-density lipoprotein (G-sHDL) to reverse immunosuppression in livers with CRC metastases. After intravenous injection, sHDL targeted hepatic monocyte-derived alternatively activated macrophages (Mono-M2) in the livers of mice bearing both subcutaneous tumors and liver metastases. The G-sHDL preferentially eradicated Mono-M2 in the livers with CRC metastases, which consequently prevented Mono-M2-mediated killing of tumor antigen-specific CD8+ T cells in the livers and thus improved the densities of tumor antigen-specific CD8+ T cells in the blood, tumor-draining lymph nodes and subcutaneous tumors of the treated mice. While reversing the immunosuppressive microenvironment, G-sHDL also induced immunogenic cell death of cancer cells, promoted maturation of dendritic cells, and increased tumor infiltration and activity of CD8+ T cells. Collectively, G-sHDL inhibited the growth of both subcutaneous tumors and liver metastases, and prolonged the survival of animals, which could be further improved when used in conjunction with anti-PD-L1 antibody. This platform can be a generalizable platform to modulate immune microenvironment of diseased livers.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Ratones , Animales , Gemcitabina , Linfocitos T CD8-positivos/metabolismo , Lipoproteínas HDL , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Macrófagos/metabolismo , Antígenos de Neoplasias , Microambiente Tumoral , Línea Celular TumoralRESUMEN
BACKGROUND: The inflammatory response induced by intestinal ischaemiaâreperfusion injury (I/R) is closely associated with infectious complications and mortality in critically ill patients, and the timely and effective clearance of apoptotic cells is an important part of reducing the inflammatory response. Studies have shown that the efferocytosis by phagocytes plays an important role. Recently, studies using small intestine organoid models showed that macrophage efferocytosis could promote the repair capacity of the intestinal epithelium. However, no studies have reported efferocytosis in the repair of I/R in animal models. RESULTS: We used an in vivo efferocytosis assay and discovered that macrophage efferocytosis played an indispensable role in repairing and maintaining intestinal barrier function after I/R. In addition, the specific molecular mechanism that induced macrophage efferocytosis was Cth-ERK1/2 dependent. We found that Cth drove macrophage efferocytosis in vivo and in vitro. Overexpression/silencing Cth promoted/inhibited the ERK1/2 pathway, respectively, which in turn affected efferocytosis and mediated intestinal barrier recovery. In addition, we found that the levels of Cth and macrophage efferocytosis were positively correlated with the recovery of intestinal function in clinical patients. CONCLUSION: Cth can activate the ERK1/2 signalling pathway, induce macrophage efferocytosis, and thus promote intestinal barrier repair. Video Abstract.
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Cistationina gamma-Liasa , Intestinos , Sistema de Señalización de MAP Quinasas , Macrófagos , Animales , Cistationina gamma-Liasa/metabolismo , Macrófagos/metabolismo , Fagocitosis , Transducción de Señal , Humanos , Ratones , Intestinos/lesiones , Intestinos/fisiologíaRESUMEN
In June 2020, an observation experiment of O3 and its precursors was carried out in Linyi City, Shandong Province. Based on the observation data and MCM photochemical model simulation, the formation mechanism and control mechanism of an ozone pollution case in mid-June were analyzed. The study found that, despite the high precipitation during the observation period, ozone concentrations rapidly accumulated and exceeded the limits once the weather cleared, with the 1-h average and 8-h φ (O3) exceeding the national ambient air quality standards on 10 days (32% in frequency)and 14 days (45%), respectively. The diurnal variation in O3 concentration was unimodal and accompanied by the afternoon peak at 16:00. MCM simulation results showed that the daily net reaction rate of O3 was 20×10-9 h-1, and HO2·+NO and RO2·(except CH3O2·)+NO contributed 49.0%-51.1% and 37.3%-40.2% of O3 generation, respectively. The contribution of the·OH+NO2 reaction to the total consumption of O3 was 35.1%-57.4%. The results of VOCs reactivity, relative incremental reactivity (RIR), and the EKMA curve method showed that the generation of O3 was more sensitive to alkenes (mainly trans-2-pentene and trans-2-butene)and aromatics (mainly m/p-xylene and toluene)but was negatively sensitive to NOx. In other words, the reduction in VOCs concentration would lead to the decrease in O3 concentration, whereas the reduction in NOx concentration would lead to the increase in O3 concentration. PMF source analysis results showed that volatile sources used by solvents and vehicle exhaust emissions contributed significantly to the above key precursor VOC species. Considering the titration effect of NO from vehicle exhaust emissions on ozone, controlling the use of volatile sources of solvents can realize the control of O3 pollution accurately and efficiently.
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Contaminantes Atmosféricos , Ozono , Compuestos Orgánicos Volátiles , Contaminantes Atmosféricos/análisis , China , Monitoreo del Ambiente , Análisis Factorial , Ozono/análisis , Compuestos Orgánicos Volátiles/análisisRESUMEN
Garlic leaf blight caused by Stemphylium eturmiunum was first reported in Jiangsu Province in China. The dicarboximide fungicide (DCF) procymidone is reported to possess broad-spectrum action in inhibiting filamentous fungi and is widely used to control leaf disease of various plants. Of 41 Stemphylium eturmiunum isolates collected in this study from commercial garlic farms in Pizhou and Dafeng counties of Jiangsu Province, eight isolates were resistant to procymidone. The following three phenotypes were categorized according to in vitro responses to DCFs: sensitive, low resistance to iprodione and procymidone, and high resistance to all iprodione and procymidone. The fitness of all resistant isolates was decreased in accordance with data on mycelial growth, conidiation, and virulence. After treatment with 10 µg/ml of procymidone for 4 h, mycelial intracellular glycerol concentrations of resistant isolates were significantly lower than those of sensitive isolates. Positive cross-resistance was observed between dicarboximides and phenylpyrroles, but there was no cross-resistance between dicarboximides and fluazinam or difenoconazole in the two resistant phenotypes. Nucleotide sequence alignment of two-component histidine kinase genes from sensitive and resistant isolates indicated that amino acid mutations were located at the histidine kinase, adenylyl cyclase, methyl-accepting chemotaxis protein and at the phosphatase domain of the N-terminal region and the response regulator domain of the C-terminal region. To our knowledge, this is the first report of DCF resistance in Stemphylium eturmiunum, and these findings will help establish a rational strategy to manage DCF-resistant populations of Stemphylium eturmiunum in the field.
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Ascomicetos , Ajo , Ascomicetos/genética , Compuestos Bicíclicos con Puentes , Farmacorresistencia Fúngica/genéticaRESUMEN
There is an urgent need for developing nonprecious metal catalysts to replace Pt-based electrocatalysts for oxygen reduction reaction (ORR) in fuel cells. Atomically dispersed M-Nx/C catalysts have shown promising ORR activity; however, enhancing their performance through modulating their active site structure is still a challenge. In this study, a simple approach was proposed for preparing atomically dispersed iron catalysts embedded in nitrogen- and fluorine-doped porous carbon materials with five-coordinated Fe-N5 sites. The C@PVI-(DFTPP)Fe-800 catalyst, obtained through pyrolysis of a bio-inspired iron porphyrin precursor coordinated with an axial imidazole from the surface of polyvinylimidazole-grafted carbon black at 800 °C under an Ar atmosphere, exhibited a high electrocatalytic activity with a half-wave potential of 0.88 V versus the reversible hydrogen electrode for ORR through a four-electron reduction pathway in alkaline media. In addition, an anion-exchange membrane electrode assembly (MEA) with C@PVI-(DFTPP)Fe-800 as the cathode electrocatalyst generated a maximum power density of 0.104 W cm-2 and a current density of 0.317 mA cm-2. X-ray absorption spectroscopy demonstrated that a single-atom catalyst (Fe-Nx/C) with an Fe-N5 active site can selectively be obtained; furthermore, the catalyst ORR activity can be tuned using fluorine atom doping through appropriate pre-assembling of the molecular catalyst on a carbon support followed by pyrolysis. This provides an effective strategy to prepare structure-performance-correlated electrocatalysts at the molecular level with a large number of M-Nx active sites for ORR. This method can also be utilized for designing other catalysts.
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Breast cancer is the most vicious killer for women, and tumor metastasis is one of the leading causes of breast cancer therapy failure. In this study, a new pH-sensitive polymer (polyethylene glycol-block-poly[(1,4-butanediol)-diacrylate-ß-N,N-diisopropylethylenediamine], BDP) was synthesized. Based on BDP, docetaxel/silibinin co-delivery micelles (DSMs) was constructed. DSM had a well-defined spherical shape under the transmission electron microscope with average hydrodynamic diameter of 85.3±0.4 nm, and were stable in the bloodstream but could dissociate to release the chemotherapeutic agents in the low pH environment of the endo/lysosomes in the tumor cells. Compared with free drugs, DSM displayed greatly enhanced cellular uptake, higher cytotoxicity and a stronger anti-metastasis effect against mouse breast cancer cell line 4T1. In 4T1 tumor-bearing mice treated with DSM (twice a week for 3 weeks), the inhibition rate on tumor growth and metastasis reached 71.9% and 80.1%, respectively. These results reveal that DSM might be a promising drug delivery system for metastatic breast cancer therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Silimarina/farmacología , Taxoides/farmacología , Resinas Acrílicas/química , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/química , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Docetaxel , Relación Dosis-Respuesta a Droga , Sistemas de Liberación de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Concentración de Iones de Hidrógeno , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Micelas , Polietilenglicoles/química , Silibina , Silimarina/administración & dosificación , Silimarina/química , Relación Estructura-Actividad , Taxoides/administración & dosificación , Taxoides/química , Células Tumorales CultivadasRESUMEN
In developing tissues, cell polarization and proliferation are regulated by morphogens and signaling pathways. Cells throughout the Drosophila wing primordium typically show subcellular localization of the unconventional myosin Dachs on the distal side of cells (nearest the center of the disc). Dachs localization depends on the spatial distribution of bonds between the protocadherins Fat (Ft) and Dachsous (Ds), which form heterodimers between adjacent cells; and the Golgi kinase Four-jointed (Fj), which affects the binding affinities of Ft and Ds. The Fj concentration forms a linear gradient while the Ds concentration is roughly uniform throughout most of the wing pouch with a steep transition region that propagates from the center to the edge of the pouch during the third larval instar. Although the Fj gradient is an important cue for polarization, it is unclear how the polarization is affected by cell division and the expanding Ds transition region, both of which can alter the distribution of Ft-Ds heterodimers around the cell periphery. We have developed a computational model to address these questions. In our model, the binding affinity of Ft and Ds depends on phosphorylation by Fj. We assume that the asymmetry of the Ft-Ds bond distribution around the cell periphery defines the polarization, with greater asymmetry promoting cell proliferation. Our model predicts that this asymmetry is greatest in the radially-expanding transition region that leaves polarized cells in its wake. These cells naturally retain their bond distribution asymmetry after division by rapidly replenishing Ft-Ds bonds at new cell-cell interfaces. Thus we predict that the distal localization of Dachs in cells throughout the pouch requires the movement of the Ds transition region and the simple presence, rather than any specific spatial pattern, of Fj.
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Moléculas de Adhesión Celular/metabolismo , Polaridad Celular/fisiología , Proteínas de Drosophila/metabolismo , Drosophila/fisiología , Modelos Biológicos , Alas de Animales/fisiología , Animales , Cadherinas/metabolismo , Simulación por Computador , Drosophila/citología , Regulación del Desarrollo de la Expresión Génica/fisiología , Glicoproteínas de Membrana/metabolismo , Miosinas/metabolismo , Organogénesis/fisiología , Alas de Animales/citologíaRESUMEN
Despite the fact that five kinds of uranium nitrides, i.e., uranium mononitrides (UN, R3Ì m and Fm3Ì m), a uranium dinitride (UN2, Fm3Ì m), and uranium sesquinitrides (α-U2N3, Ia3Ì ; ß-U2N3,P3Ì m1), have been confirmed, until now the phase relations are not well understood because of the puzzling nonstoichiometric issue. This work reinvestigated the crystallographic structures of these phases using cluster formula theory. The principal clusters (cuboctahedron with six squares and eight triangles) in these phases were determined. N atoms can occupy either six octahedral sites (square face centers) or eight tetrahedral sites (formed by a center atom and a triangle) in the principal cluster of 13 U atoms, resulting in these diversified phases and the nonstoichiometric issue. Also, phase transformations at certain temperatures and pressures (from CaF2-type UN2 to Mn2O3-type U2N3, from Mn2O3-type U2N3 to NaCl-type UN, and from NaCl-type UN to HgIn-type UN) were deduced by tracking the bond and angle changes of a simplified cluster [U-U6N6]. This investigation provides an in-depth understanding of the phase relations in a U-N system.
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OBJECTIVE: To study the expression of RUNX3 in colorectal adenocarcinoma tissues and its correlation with microvessel density (MVD), and investigate the clinical pathological prognostic significance of RUNX3 and MVD in patients with colorectal cancer. METHODS: The expression value of RUNX3 and MVD in 70 specimens' colorectal adenocarcinoma tissues were detected by immunohistochemistry staining technique. The correlation between their expression and the clinicopathologic features was also investigated. RESULTS: The expression value of RUNX3 and the positive rates of RUNX3 in colorectal adenocarcinoma tissues were 3.25 ± 1.14 and 25.71% (18/70). The expression value of MVD in colorectal adenocarcinoma tissues was 13.14 ± 3.23. Expression of RUNX3 and MVD value were correlated with CEA, serosal invasion, liver metastasis, lymph node metastasis, and TNM stage (P < 0.01). The expression value of RUNX3 had negative correlations with that of MVD. CONCLUSIONS: The high expression of RUNX3 could inhibit tumor microvascular generation in order to have negative control response on invasion and distant metastasis.
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We describe an experimental instrument used for measuring nondestructively the residual stress using short wavelength X-ray, tungsten kα1. By introducing a photon energy screening technology, the monochromatic X-ray diffraction of tungsten kα1 was realized using a CdTe detector. A high precision Huber goniometer is utilized in order to reduce the error in residual stress measurement. This paper summarizes the main performance of this instrument, measurement depth, stress error, as opposed to the neutron diffraction measurements of residual stress. Here, we demonstrate an application on the determination of residual stress in an aluminum alloy welded by the friction stir welding.
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AIM: To improve the therapeutic efficacy of cancer treatments, combinational therapies based on nanosized drug delivery system (NDDS) has been developed recently. In this study we designed a new NDDS loaded with an anti-metastatic drug silibinin and a photothermal agent indocyanine green (ICG), and investigated its effects on the growth and metastasis of breast cancer cells in vitro. METHODS: Silibinin and ICG were self-assembled into PCL lipid nanoparticles (SIPNs). Their physical characteristics including the particle size, zeta potential, morphology and in vitro drug release were examined. 4T1 mammalian breast cancer cells were used to evaluate their cellular internalization, cytotoxicity, and their influences on wound healing, in vitro cell migration and invasion. RESULTS: SIPNs showed a well-defined spherical shape with averaged size of 126.3±0.4 nm and zeta potential of -10.3±0.2 mV. NIR laser irradiation substantially increased the in vitro release of silibinin from the SIPNs (58.3% at the first 8 h, and 97.8% for the total release). Furthermore, NIR laser irradiation markedly increased the uptake of SIPNs into 4T1 cells. Under the NIR laser irradiation, both SIPNs and IPNs (PCL lipid nanoparticles loaded with ICG alone) caused dose-dependent ablation of 4T1 cells. The wound healing, migration and invasion experiments showed that SIPNs exposed to NIR laser irradiation exhibited dramatic in vitro anti-metastasis effects. CONCLUSION: SIPNs show temperature-sensitive drug release following NIR laser irradiation, which can inhibit the growth and metastasis of breast cancer cells in vitro.
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Neoplasias de la Mama/patología , Verde de Indocianina/administración & dosificación , Verde de Indocianina/farmacología , Nanopartículas/administración & dosificación , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/patología , Silimarina/administración & dosificación , Silimarina/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Femenino , Humanos , Verde de Indocianina/farmacocinética , Verde de Indocianina/uso terapéutico , Nanopartículas/química , Nanopartículas/efectos de la radiación , Tamaño de la Partícula , Silibina , Silimarina/farmacocinética , Silimarina/uso terapéutico , Cicatrización de Heridas/efectos de los fármacosRESUMEN
OBJECTIVE: To study the expression of caveolin-1 in colorectal adenocarcinoma tissues and its correlation with microlymphatic vessel density (LMVD), and to investigate the clinical pathological prognostic significance of caveolin-1 and LMVD in patients with colorectal cancer. METHODS: The expression of caveolin-1 and LMVD in 45 specimens of normal colorectal tissues, and 90 specimens of colorectal adenocarcinoma tissues were detected by immunohistochemistry technique. The correlation between their expression and the clinicopathologic features was analyzed. Multivariable Cox regression was used to analyze the association between the laboratory indices and overall survival time. RESULTS: The positive rates of caveolin-1 in colorectal adenocarcinoma tissues were significantly higher than those in normal colorectal tissues (P < 0.01). LMVD in colorectal adenocarcinoma tissues were significantly higher than those in normal colorectal tissues (P < 0.01). Mean LMVD in group with caveolin-1 positive was significantly higher than in that with caveolin-1 negative. The median survival time was 26.7 months. Cox regression analysis showed that the caveolin-1 expression, invation depth, lymph node metastasis, TNM stage, liver metastasis and LMVD were independent risk factors of overall survival time of patients with colorectal carcinoma. CONCLUSIONS: Caveolin-1 may contribute to the lymphangiogenesis in the tumor. During the occurrence and development of colorectal adenocarcinoma, there is a close relationship between the expression of caveolin-1 and lymphatic microvessel of tumor. Caveolin-1 expression and microlymphatic vessel density are significant prognostic value of colorectal carcinoma.
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The Sludge granulation in an anaerobic reactor consists of two steps: nucleation and maturation of nuclei. Nucleation as the starting point is of particular importance. In this paper, the nucleation of flocculent sludge as seed under weak, strong and violent hydrodynamic shear conditions is studied with an original quantitative method, and then the satisfactory linear correlations between the average sludge diameters and the operation time during the nucleation are demonstrated. Nucleation under strong shear conditions with a shear rate of about 8.28 s(-1), corresponding to superficial liquid and gas velocities of 2.66 and 0.24 m h(-1), develops fastest compared to weak shear conditions with a shear rate of about 0.04 s(-1) and violent shear conditions with a shear rate of about 12.42 s(-1) with the average augmentation rate of average sludge diameter of 0.57, 0.40 and 0.41 microm day(-1) respectively. One of the major mechanisms of the shear force on nucleation is that a high shear force accelerates the extracellular protein secretion of sludge. Although high extracellular protein content benefits nucleation, it is also shown that the extracellular proteins over-produced above around 80.5mg gVSS(-1) leads nuclei to weaken and inhibit nucleation. So the violent shear force would result in disruption and wash-out of nuclei. However, the high extracellular polymers could intensify the shear force by raising the viscosity in the reactor, thus, in practice, it is important to monitor the shear conditions and extracellular protein content of sludge simultaneously in high rate reactors for stable operation.