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The sensitivity of energetic materials along different crystal directions is not the same and is anisotropic. In order to explore the difference in friction sensitivity of different surfaces, we calculated the structure, excess energy, surface energy, electronic structure, and the nitro group along (1 1 1), (1 1 0), (1 0 1), (0 1 1), (0 0 1), (0 1 0), and (1 0 0) surfaces of EDNA based on density functional theory. The analysis results showed that relative to other surfaces, the (0 0 1) surface has the shortest N-N average bond length, largest N-N average bond population, smallest excess energy and surface energy, widest band gap, and the largest nitro group charge value, which indicates that the (0 0 1) surface has the lowest friction sensitivity compared to other surfaces. Furthermore, the conclusions obtained by analyzing the excess energy are consistent with the results of the N-N bond length and bond population, band gap, and nitro charge. Therefore, we conclude that the friction sensitivity of different surfaces of EDNA can be evaluated using excess energy.
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The risk assessment of heavy metals (HMs) in sewage sludge (SS) is essential before land application. Six HMs in nineteen SS collected in the Yangtze River Delta were analyzed to assess risks to environment, ecosystem, and human health. HMs concentrations were ranked in the order of Zn > Cu > Cr > Ni > Pb > Cd, with Cu, Zn, and Ni in a total of 16% of samples exceeding the legal standard. Zn showed greatest extractability according to EDTA-extractable concentrations. HMs in 16% of SS samples posed heavy contamination to the environment with Zn as the major pollutant. HMs in 26% of samples posed ecological risk to the ecosystem and Cd was the highest risky HM. The probabilistic health risk assessment revealed that HMs posed carcinogenic risks to all populations, but non-carcinogenic risks only to children. This work will provide fundamental information for land application of SS in this area.
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Metales Pesados , Contaminantes del Suelo , Niño , Humanos , Aguas del Alcantarillado , Ecosistema , Monitoreo del Ambiente , Ríos , Cadmio , Contaminantes del Suelo/análisis , Medición de Riesgo , Metales Pesados/análisis , ChinaRESUMEN
The structural, electronic and vibrational properties of solid carbon dioxide phases (I, II, III, and IV) under high pressure are studied using first-principles calculations. The calculated structural parameters are in good agreement with the experimental values. The third-order Birch-Murnaghan equation of state is fitted, and the corresponding parameters are obtained. We obtained the phase boundary points of each phase and plotted the phase diagram of solid carbon dioxide. The influence of pressure on the band structure and density of states is studied. The vibrational properties of the four phases of carbon dioxide were studied in detail, and the infrared and Raman spectra of the four phases were obtained. It can be seen from the calculated spectrum that the number and frequency of vibration peaks are in good agreement with the experimental values. And, we also analyze the influence of pressure on the frequency of vibration mode.
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Certain chemotherapeutics (e.g., oxaliplatin, OXA) can evoke effective antitumor immunity responses by inducing immunogenic cell death (ICD). Unfortunately, tumors always develop multiple immunosuppressive mechanisms, such as the upregulation of immunosuppressive factors, to counteract the effects of immunogenic chemotherapy. Indoleamine 2,3-dioxygenase-1 (IDO1), a tryptophan catabolic enzyme overexpressed in tumor-draining lymph nodes (TDLNs) and tumor tissues, plays a pivotal role in the generation of the immunosuppressive microenvironment. Reversing IDO1-mediated immunosuppression may strengthen the ICD-induced immune response. Herein, we developed a nanoenabled approach for IDO1 pathway interference, which is accomplished by delivering IDO1 siRNA to both TDLNs and tumor tissues with the help of cationic lipid-assisted nanoparticles (CLANs). We demonstrated that the contemporaneous administration of OXA and CLANsiIDO1 could achieve synergetic antitumor effects via promoting dendritic cell maturation, increasing tumor-infiltrating T lymphocytes and decreasing the number of regulatory T cells in a subcutaneous colorectal tumor model. We further proved that this therapeutic strategy is applicable for the treatment of orthotopic pancreatic tumors and offers a strong immunological memory effect, which can provide protection against tumor rechallenge.
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Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Neoplasias/terapia , ARN Interferente Pequeño/administración & dosificación , Tratamiento con ARN de Interferencia/métodos , Animales , Línea Celular Tumoral , Portadores de Fármacos/química , Humanos , Inmunoterapia , Indolamina-Pirrol 2,3,-Dioxigenasa/análisis , Masculino , Ratones Endogámicos BALB C , Nanopartículas/química , Neoplasias/genética , Oxaliplatino/uso terapéutico , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/uso terapéuticoRESUMEN
In this study, we analyzed the global metabolomic changes associated with Toxoplasma gondii infection in mice in the presence or absence of sulfadiazine sodium (SDZ) treatment. BALB/c mice were infected with T. gondii GT1 strain and treated orally with SDZ (250 µg/ml in water) for 12 consecutive days. Mice showed typical manifestations of illness at 20 days postinfection (dpi); by 30 dpi, 20% had survived and developed latent infection. We used ultraperformance liquid chromatography-mass spectrometry to profile the serum metabolomes in control (untreated and uninfected) mice, acutely infected mice, and SDZ-treated and infected mice. Infection induced significant perturbations in the metabolism of α-linolenic acid, purine, pyrimidine, arginine, tryptophan, valine, glycerophospholipids, and fatty acyls. However, treatment with SDZ seemed to alleviate the serum metabolic alterations caused by infection. The restoration of the serum metabolite levels in the treated mice was associated with better clinical outcomes. These data indicate that untargeted metabolomics can reveal biochemical pathways associated with restoration of the metabolic status of T. gondii-infected mice following SDZ treatment and could be used to monitor responses to SDZ treatment. This study provides a new systems approach to elucidate the metabolic and therapeutic effects of SDZ in the context of murine toxoplasmosis.
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Antiprotozoarios/farmacología , Redes y Vías Metabólicas/efectos de los fármacos , Metaboloma/efectos de los fármacos , Sulfadiazina/farmacología , Toxoplasma/efectos de los fármacos , Toxoplasmosis Animal/tratamiento farmacológico , Administración Oral , Animales , Arginina/sangre , Cromatografía Líquida de Alta Presión , Femenino , Glicerofosfolípidos/sangre , Humanos , Metabolómica/métodos , Ratones , Ratones Endogámicos BALB C , Pirimidinas/sangre , Análisis de Supervivencia , Espectrometría de Masas en Tándem , Toxoplasma/crecimiento & desarrollo , Toxoplasmosis Animal/sangre , Toxoplasmosis Animal/mortalidad , Toxoplasmosis Animal/parasitología , Triptófano/sangre , Valina/sangre , Ácido alfa-Linolénico/sangreRESUMEN
BACKGROUND: Accumulating evidence indicates inherited risk in the aetiology of lung cancer, although smoking exposure is the major attributing factor. Family history is a simple substitute for inherited susceptibility. Previous studies have shown some possible yet conflicting links between family history of cancer and EGFR mutation in lung cancer. As EGFR-mutated lung cancer favours female, never-smoker, adenocarcinoma and Asians, it may be argued that there may be some underlying genetic modifiers responsible for the pathogenesis of EGFR mutation. METHODS: We searched four databases for all original articles on family history of malignancy and EGFR mutation status in lung cancer published up to July 2018. We performed a meta-analysis by using a random-effects model and odds ratio estimates. Heterogeneity and sensitivity were also investigated. Then we conducted a second literature research to curate case reports of familial lung cancers who studied both germline cancer predisposing genes and their somatic EGFR mutation status; and explored the possible links between cancer predisposing genes and EGFR mutation. RESULTS: Eleven studies have been included in the meta-analysis. There is a significantly higher likelihood of EGFR mutation in lung cancer patients with family history of cancer than their counterparts without family history, preferentially in Asians (OR = 1.35[1.06-1.71], P = 0.01), those diagnosed with adenocarcinomas ((OR = 1.47[1.14-1.89], P = 0.003) and those with lung cancer-affected relatives (first and second-degree: OR = 1.53[1.18-1.99], P = 0.001; first-degree: OR = 1.76[1.36-2.28, P < 0.0001]). Familial lung cancers more likely have concurrent EGFR mutations along with mutations in their germline cancer predisposition genes including EGFR T790 M, BRCA2 and TP53. Certain mechanisms may contribute to the combination preferences between inherited mutations and somatic ones. CONCLUSIONS: Potential genetic modifiers may contribute to somatic EGFR mutation in lung cancer, although current data is limited. Further studies on this topic are needed, which may help to unveil lung carcinogenesis pathways. However, caution is warranted in data interpretation due to limited cases available for the current study.
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Adenocarcinoma/genética , Mutación de Línea Germinal , Neoplasias Pulmonares/genética , Adenocarcinoma/etnología , Adulto , Anciano , Pueblo Asiatico/genética , Receptores ErbB/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Neoplasias Pulmonares/etnología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Autoinforme , Fumar , Adulto JovenRESUMEN
The aim of this study was to investigate whether phosphorylated Radix Cyathulae officinalis Kuan polysaccharides (pRCPS) used as adjuvant with foot-and-mouth disease vaccine (FMDV) can stimulate specific humoral and cellular immune responses in ICR mice. The results demonstrated that pRCPS significantly up-regulated FMDV-specific IgG, IgG1, IgG2b and IgG2a antibody levels and splenocyte proliferation. pRCPS also promoted the killing activities of cytotoxic T lymphocytes (CTL) and natural killer cells (NK). In addition, pRCPS enhanced the expression levels of IL-2, IL-4, and IFN-γ in CD4⺠T cells and the level of IFN-γ in CD8⺠T cells. Importantly, pRCPS enhanced the expression of MHCII, CD40âº, CD86âº, and CD80⺠in dendritic cells (DCs). This study indicated that phosphorylation modification could increase immune-enhancing activities of RCPS, and pRCPS could promote humoral and cellular immune responses through facilitating DC maturation.
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Células Dendríticas/inmunología , Fiebre Aftosa/inmunología , Inmunidad Celular , Fagocitosis/inmunología , Polisacáridos/uso terapéutico , Adyuvantes Inmunológicos/uso terapéutico , Animales , Diferenciación Celular/inmunología , Citocinas/inmunología , Fiebre Aftosa/prevención & control , Regulación de la Expresión Génica/inmunología , Humanos , Inmunogenicidad Vacunal/inmunología , Interleucina-2/inmunología , Interleucina-4/inmunología , Células Asesinas Naturales/inmunología , Ratones , Fagocitosis/efectos de los fármacos , Fosforilación/inmunología , Raíces de Plantas/química , Raíces de Plantas/inmunología , Polisacáridos/química , Polisacáridos/inmunología , Linfocitos T Citotóxicos/efectos de los fármacos , Linfocitos T Citotóxicos/inmunologíaRESUMEN
BACKGROUND: Altered expression of astrocyte elevated gene-1 (AEG-1) is associated with tumorigenesis and progression. The present study aimed to investigate the clinical and prognostic significance of AEG-1 expression in pancreatic ductal adenocarcinoma (PDAC). METHODS: Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot analyses were employed to assess AEG-1 expression in three pancreatic cancer cell lines and normal pancreatic duct epithelial cells. qRT-PCR and immunohistochemical analyses were performed to detect AEG-1 expression in ten pairs of PDAC and normal pancreas tissues. Immunohistochemistry was then used to examine AEG-1 expression in paraffin-embedded tissues obtained from 105 patients, and its association with clinicopathological parameters including cancer classification was examined. Kaplan-Meier analysis was performed to study the survival rates of patients. RESULTS: Expression of AEG-1 mRNA and protein was markedly higher in pancreatic cancer cell lines than that in the normal pancreatic duct epithelial cells. AEG-1 expression was evidently upregulated in PDAC tissues compared to that of the matched distant normal pancreas tissues. qRT-PCR data revealed that the tumor/non-tumor ratio of AEG-1 expression was >1.5-fold (up to 6.5-fold). Immunohistochemical data showed that AEG-1 protein was detected in 98.09% (103/105) of PDAC tissues; and they were found to be associated with tumor size (P = 0.025), advanced clinical stage (P = 0.004), T classification (P = 0.006), N classification (P = 0.003), and M classification (P = 0.007). Furthermore, Kaplan-Meier analysis showed that patients with high AEG-1-expressed PDAC had shorter overall survival. A multivariate Cox regression analysis revealed that clinical stage, T classification, and AEG-1 expression were the independent prognostic predictors for PDAC. CONCLUSIONS: This study suggests that AEG-1 protein was highly expressed in PDAC and associated with poor prognosis of the patients.
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Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/patología , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Neoplasias Pancreáticas/patología , Anciano , Carcinoma Ductal Pancreático/genética , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Proteínas de la Membrana , Persona de Mediana Edad , Neoplasias Pancreáticas/genética , Proteínas de Unión al ARN , Análisis de SupervivenciaRESUMEN
AIM: Auditory neuropathy (AN) is a hearing disorder characterized by abnormal auditory nerve function with preservation of normal cochlear hair cells. This study was designed to investigate whether treatment with molecular hydrogen (H(2)), which can remedy damage in various organs via reducing oxidative stress, inflammation and apoptosis, is beneficial to ouabain-induced AN in gerbils. METHODS: AN model was made by local application of ouabain (1 mmol/L, 20 mL) to the round window membrane in male Mongolian gerbils. H(2) treatment was given twice by exposing the animals to H(2) (1%, 2%, and 4%) for 60 min at 1 h and 6 h after ouabain application. Before and 7 d after ouabain application, the hearing status of the animals was evaluated using the auditory brainstem response (ABR) approach, the hear cell function was evaluated with distortion product otoacoustic emissions (DPOAE). Seven days after ouabain application, the changes in the cochleae, especially the spiral ganglion neurons (SGNs), were morphologically studied. TUNEL staining and immunofluorescent staining for activated caspase-3 were used to assess the apoptosis of SGNs. RESULTS: Treatment with H(2) (2% and 4%) markedly attenuated the click and tone burst-evoked ABR threshold shift at 4, 8, and 16 kHz in ouabain-exposed animals. Neither local ouabain application, nor H(2) treatment changed the amplitude of DPOAE at 4, 8, and 16 kHz. Morphological study showed that treatment with H(2) (2%) significantly alleviated SGN damage and attenuated the loss of SGN density for each turn of cochlea in ouabain-exposed animals. Furthermore, ouabain caused significantly higher numbers of apoptotic SGNs in the cochlea, which was significantly attenuated by the H(2) treatment. However, ouabain did not change the morphology of cochlear hair cells. CONCLUSION: The results demonstrate that H(2) treatment is beneficial to ouabain-induced AN via reducing apoptosis. Thus, H(2) might be a potential agent for treating hearing impairment in AN patients.
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Pérdida Auditiva Central/inducido químicamente , Pérdida Auditiva Central/terapia , Hidrógeno/uso terapéutico , Ouabaína/efectos adversos , Administración por Inhalación , Animales , Caspasa 3/metabolismo , Cóclea/efectos de los fármacos , Cóclea/patología , Cóclea/fisiopatología , Gases/administración & dosificación , Gases/uso terapéutico , Gerbillinae , Audición/efectos de los fármacos , Pérdida Auditiva Central/patología , Pérdida Auditiva Central/fisiopatología , Hidrógeno/administración & dosificación , MasculinoRESUMEN
Hydrogen peroxide (H2O2) is used as a fuel and propellant in fuel cells and rockets due to its prominent oxidizing and combustion properties. In addition, hydrogen peroxide, as the energetic material with the simplest molecular structure, exhibits general detonation performance under external stimulation. Based on the first-principle method, we calculated the two crystal structure, electronic properties related to sensitivity closely, optical properties of pure hydrogen peroxide, and 48wt.% hydrogen peroxide (H6O4) under pressure. We found that the band gaps of H2O2 and H6O4 become larger under pressure and the former is larger than the latter; neither has the tendency of metallization phase change. The added peak II of TDOS from H6O4 compared with H2O2 come from molecular H2O in crystal structure. The pressure-induced peak (peak 2 and peak II of TDOS from H2O2 and H6O4) splitting is caused by changes (stronger) in the intermolecular hydrogen bond environment in the crystal under pressure. The specific macroscopic optical properties have the characteristics of overall blue-shift under pressure, which is due to the blueshift of the conduction band and the increase of the band gap. We hope to provide some reference and guidance for deeper future research.
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Deformation mechanisms of carbon nanotube (CNT) fibres under tensile loading are studied by means of in situ Raman spectroscopy to detect the CNT deformation and stress distributions in the fibres. The G' band in the Raman spectrum responds distinctly to the tensile stress in Raman shift, width and intensity. The G' band changes with the tensile deformation of the fibre at different stages, namely elastic deformation, strengthening and damage-fracture. It is deduced that the individual CNTs only deform elastically without obvious damage or bond breaking. The yield and fracture of fibres can be due to the slippage among the CNTs.
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The structural, electronic, optical, and vibrational properties of B3N3H6 have been calculated by means of the first-principles density functional theory (DFT) calculations within the generalized gradient approximation (GGA) and the local density approximation (LDA). The calculated structural parameters of B3N3H6 are in good agreement with experimental data. The obtained band structure of B3N3H6 shows that it has an indirect band gap with 5.007 eV, indicating that it presents insulation characteristic. The total and partial density of states (DOS) of B3N3H6 are given, which tell us the states of the orbital occupation. With the band structure and density of states, we have analyzed the optical properties including the complex dielectric function, refractive index, absorption, conductivity, loss function, and reflectivity. By the contrast, it is found that optical anisotropy is observed in the (001) direction and (100) direction. Moreover, the vibrational properties have been obtained and analyzed, showing that B3N3H6 is dynamically stable due to that there is no imaginary frequency. The frequencies associating with the vibrations are given, which show that B3N3H6 has a low mechanical modulus and thermal conductivity.
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In recent years, the important energetic material triaminoguanidinium nitrate (TAGN) has been widely used, and the process of synthesizing TAGN has become more and more perfect. However, there are relatively few theoretical studies on TAGN. This paper uses first-principles calculations to more systematically study the crystal structure, and electronic, vibrational, and thermodynamic properties of TAGN. The calculation results show that the calculated unit cell parameters are relatively consistent with the values obtained through X-ray diffraction experiments. This article describes in detail the state density of the valence electrons of each atom. By analyzing the vibrational properties of TAGN crystal, the vibration mode corresponding to each optical wave is obtained. At the same time, the vibration mode of each peak in the Raman spectrum and the infrared spectrum is described in detail. Then, the calculated value is compared with the experimental value; it can be seen that the error is relatively small. According to the vibration characteristics, a series of thermodynamic functions such as enthalpy (H), Debye temperature (Θ), free energy (F), and entropy (S) are calculated. These thermodynamic functions can provide a certain reference for future research.
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OBJECTIVE: To evaluate the value of chest CT findings and dynamic changes of viral load in patients with novel influenza A (H1N1) infection in clinical diagnosis, differential diagnosis and treatment. METHODS: Fifty-one patients with confirmed novel influenza A (H1N1) according to the diagnostic criteria of the Ministry of Health, received chest X-ray, CT scans (HRCT) and viral load tests in our hospital from May to December of 2009. Based on whether there were signs of pneumonia in CT imaging, the patients were divided into a pneumonia group (n = 31) and a non-pneumonia group (n = 20). The relationship between chest CT changes and viral load was observed and analyzed statistically using SPSS 10.5 software. RESULTS: Patchy consolidations of lungs were the main findings in pneumonia group with influenza A (H1N1) infection, and ground-glass opacities were the main CT findings at acute and convalescent phases. Lobular and segmental shadows of the lungs were diffusely distributed, mostly found in lower lungs, especially the left lung. In some cases, the lung diseases were accompanied with mediastinal lymphadenopathy. Co-existence of pulmonary parenchymal, interstitial and pleural diseases was observed. Peak viral load occurred at the early phase of illness, with the mean initial viral load being 7.7 copies/ml and 4.2 copies/ml in the pneumonia and the non-pneumonia groups respectively. The viral nucleic acid became negative 4 days after antiviral treatment (course of 6 days). Dynamic observation of 3 patients with novel influenza A (H1N1) pneumonia showed that, the viral clearance period preceded the absorption of lung lesions in 2 cases, but viral clearance period of a young patient was significantly prolonged. CONCLUSION: In patients with the novel influenza A (H1N1) infection, the viral load in the pneumonia group was significantly higher than that in the group with normal chest imaging. Dynamic observation on chest imaging and viral load may be beneficial for clinicians to start prompt and effective treatment.
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Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/diagnóstico por imagen , Gripe Humana/virología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Gripe Humana/epidemiología , Masculino , Persona de Mediana Edad , Neumonía Viral/diagnóstico por imagen , Neumonía Viral/epidemiología , Neumonía Viral/virología , Tomografía Computarizada por Rayos X , Carga Viral , Adulto JovenRESUMEN
YWHAZ (also named 14-3-3ζ) is a central hub protein for many signal transduction pathways and plays a significant role in tumor progression. Accumulating evidences have demonstrated that YWHAZ is frequently up-regulated in multiple types of cancers and acts as an oncogene in a wide range of cell activities including cell growth, cell cycle, apoptosis, migration, and invasion. Moreover, YWHAZ was reported to be regulated by microRNAs (miRNAs) or long non-coding RNAs and exerted its malignant functions by targeting downstream molecules like protein kinase, apoptosis proteins, and metastasis-related molecules. Additionally, YWHAZ may be a potential biomarker of diagnosis, prognosis and chemoresistance in several cancers. Targeting YWHAZ by siRNA, shRNA or miRNA was reported to have great help in suppressing malignant properties of cancer cells. In this review, we perform literature and bioinformatics analysis to reveal the oncogenic role and molecular mechanism of YWHAZ in cancer, and discuss the potential clinical applications of YWHAZ concerning diagnosis, prognosis, and therapy in malignant tumors.
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The detailed illustrations of the structures, elastic properties, and Raman and IR vibration modes for [Na(H2O)(N5)]·2H2O (a) and [Mg(H2O)6(N5)2]·4H2O (b) have been presented in this investigation by using the first-principles method based on the density functional theory. Our results indicate that the active centers of both two types of the energetic metal pentazolate hydrates appear on the cyclo-N5. The bonding character of N atoms in the cyclo-N5 is shown to be covalent, and the cyclo-N5 ring can be considered as an anion. Based on the analysis of elastic properties, we conclude that complex a is easier to deform than b, and both complexes are mechanically stable. From the calculated Raman and IR vibration modes, the vibration in the region of 960-1206 cm-1 (for a) and 985-1208 cm-1 (for b) is determined by basically mixing the cyclo-N5 stretching and deformation modes. The vibrational modes of a and b in their highest frequency zones are both related to the stretching of the O-H bonds.
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Nanotechnology has shown great promise in treating diverse diseases. However, developing nanomedicines that can cure autoimmune diseases without causing systemic immunosuppression is still quite challenging. Herein, we propose an all-in-one nanomedicine comprising an autoantigen peptide and CRISPR-Cas9 to restore specific immune tolerance by engineering dendritic cells (DCs) into a tolerogenic phenotype, which can expand autoantigen-specific regulatory T (Treg) cells. In brief, we utilized cationic lipid-assisted poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles to simultaneously encapsulate an autoimmune diabetes-relevant peptide (2.5mi), a CRISPR-Cas9 plasmid (pCas9), and three guide RNAs (gRNAs) targeting costimulatory molecules (CD80, CD86, and CD40). We demonstrated that the all-in-one nanomedicine was able to effectively codeliver these components into DCs, followed by simultaneous disruption of the three costimulatory molecules and presentation of the 2.5mi peptide on the genome-edited DCs. The resulting tolerogenic DCs triggered the generation and expansion of autoantigen-specific Treg cells by presenting the 2.5mi peptide to CD4+ T cells in the absence of costimulatory signals. Using autoimmune type 1 diabetes (T1D) as a typical disease model, we demonstrated that our nanomedicine prevented autoimmunity to islet components and inhibited T1D development. Our all-in-one nanomedicine achieved codelivery of CRISPR-Cas9 and the peptide to DCs and could be easily applied to other autoimmune diseases by substitution of different autoantigen peptides.
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Autoantígenos/inmunología , Sistemas CRISPR-Cas/inmunología , Nanomedicina , Péptidos/inmunología , Animales , Ingeniería Celular , Células Cultivadas , Células Dendríticas , Humanos , Tolerancia Inmunológica , Ratones , Ratones Endogámicos NOD , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
A generalized double-Hertz (D-H) model has been proposed to consider the adhesive contact between an elastic cylinder and an elastic half space under inclined forces. The normal traction is exactly the same as that in the conventional D-H model. The shear traction of finite value is distributed into a slipping zone and a non-slipping zone. In the slipping zone, the shear traction is proportional to the compressive pressure. With the model, adhesive contact behaviour between cylinders has been numerically illustrated. The shear-induced peeling has been demonstrated. The value of the ratio for shear traction to normal traction larger than friction coefficient has been found in part of the non-slipping zone. Those altogether are consistent with experiments.
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Growing tumor cells possess a distinct metabolic phenomenon that allows them to preferentially utilize glucose through aerobic glycolysis, which is referred to as the "Warburg effect." Accumulating evidence suggests that microRNAs (miRNAs) could regulate such metabolic reprogramming. Our microarray analysis and quantitative real-time PCR validation revealed that miR-885-5p was strongly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. To investigate miR-885-5p's biological functions in HCC progression, malignant phenotypes were analyzed in different types of hypoxic model and indicated that overexpression of miR-885-5p significantly inhibited HCC cell proliferation and migration and induced apoptosis in vitro and tumor growth in vivo. Subsequent investigations of whether miR-885-5p regulated the glycometabolic activity of cancer cells demonstrated that forced expression of miR-885-5p in SMMC-7721 cells significantly reduced glucose uptake and lactate production by repressing several key enzymes related to glycolysis. Particularly, miR-885-5p directly targets the 3' UTR of hexokinase 2 (HK2), which is a key enzyme that catalyzes the irreversible first step of glycolysis and associates with poor patient outcomes. The miR-885-5p/HK2 axis strongly links aerobic glycolysis to carcinogenesis and may become a promising therapeutic target and prognostic predictor for HCC patients.
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Interaction between dislocations and grain boundaries (GBs) in the forms of dislocation absorption, emission, and slip transmission at GBs significantly affects size-dependent plasticity in fine-grained polycrystals. Thus, it is vital to consider those GB mechanisms in continuum plasticity theories. In the present paper, a new GB model is proposed by considering slip transmission at GBs within the framework of gradient polycrystal plasticity. The GB model consists of the GB kinematic relations and governing equations for slip transmission, by which the influence of geometric factors including the misorientation between the incoming and outgoing slip systems and GB orientation, GB defects, and stress state at GBs are captured. The model is numerically implemented to study a benchmark problem of a bicrystal thin film under plane constrained shear. It is found that GB parameters, grain size, grain misorientation, and GB orientation significantly affect slip transmission and plastic behaviors in fine-grained polycrystals. Model prediction qualitatively agrees with experimental observations and results of discrete dislocation dynamics simulations.