Role of sphingosine-1-phosphate receptors in the tumor microenvironment: prospects for cancer immunotherapy.

OBJECTIVE: Sphingosine-1-phosphate (S1P) is a sphingolipid protein with anti-apoptotic and pro-survival effects on cancer cells via S1P receptors (S1PRs); however, the role of S1PRs in the tumor microenvironment and immune invasion is still unclear. This study investigated the relationship between S1PR expressions and patient survival and clinical manifestations with respect to the tumor microenvironment and immune infiltration. MATERIALS AND METHODS: The expression levels of five S1PRs were obtained from The Cancer Genome Atlas pan-cancer database and the Kaplan-Meier survival analysis was performed. We predicted the relationship between S1PRs expression levels and patient survival using the univariate Cox proportional hazard regression model. Subsequently, we analyzed correlations between S1PRs expression and infiltrating immune cell subtypes using the Kolmogorov-Smirnov test and the infiltration levels of immune and stromal cells in each tumor using the ESTIMATE algorithm and Spearman's test. RESULTS: The five S1PRs exhibited significant heterogeneity in their expression levels. The expression levels correlated with overall patient survival; however, anti-apoptotic or pro-apoptotic features varied depending on the cancer type. The variable effects of S1PRs on tumors may be related to TGF-ß levels. Our results suggest that S1PRs exert distinct influences on the tumor stem cell index and chemotherapeutic drug sensitivity. CONCLUSIONS: This research provides comprehensive information on the importance of S1PRs in the immune microenvironment, stemness score, sensitivity of human cancer drugs, and cancer prognosis. Interestingly, our findings indicate variations in the expression levels and functions of different S1PR family members. This study highlights S1PRs as potential new targets for antitumor (adjuvant) therapy.

Gentiana straminea supplementation improves feed intake, nitrogen and energy utilization, and methane emission of Simmental calves in northwest China.

OBJECTIVE: Native plants can be used as additives to replace antibiotics to improve ruminant feed utilization and animal health. An experiment was conducted to evaluate the effects of Gentiana straminea (GS) on nutrient digestibility, methane emissions, and energy metabolism of Simmental calves. METHODS: Thirty-two (5-week-old) male Simmental clves, with initial body weight (BW) of 155±12 kg were fed the same basal diet of concentrates (26%), alfalfa hay (37%), and oat hay (37%) and were randomly separated into four treatment groups according to the amount of GS that was added to their basal diet. The four different groups received different amounts of GS as a supplement to their basal diet during whole experiment: (0 GS) 0 mg/kg BW, the control; (100 GS) 100 mg/kg BW; (200 GS) 200 mg/kg BW; and (300 GS) 300 mg/kg BW. RESULTS: For calves in the 200 GS and 300 GS treatment groups, there was a significant increase in dry matter (DM) intake (p<0.01), average daily gain (ADG) (p<0.05), organic matter intake (p<0.05), DM digestibility (p<0.05), neutral detergent fibre (NDF) digestibility (p<0.05), and acid detergent fibre (ADF) digestibility (p<0.05). Dietary GS supplementation result in quadratic increases of DM intake (p<0.01), ADG (p<0.05), NDF intake (p<0.05), and ADF intake (p<0.05). Supplementing the basal diet with GS significantly increased nitrogen (N) retention (p<0.001) and the ratio of retention N to N intake (p<0.001). Supplementing the basal diet with GS significantly decreased methane (CH4) emissions (p<0.01), CH4/BW0.75 (p<0.05) and CH4 energy (CH4-E) (p<0.05). Dietary GS supplementation result in quadratic increases of CH4 (p<0.01) and CH4/DM intake (p<0.01). Compared with 0 GS, GS-supplemented diets significantly improved their gross energy intake (p<0.05). The metabolizable energy and digestive energy intake were significantly greater for calves in the 100 GS and 200 GS calves than for 0 GS calves (p<0.05). CONCLUSION: From this study, we conclude that supplementing calf diets with GS could improve utilization of feed, energy, and N, and may reduce CH4 emissions without having any negative effects on animal health.

Origin of short- and medium-range order in supercooled liquid Ge3Sb2Te6 using ab initio molecular dynamics simulations.

Phase-change materials such as Ge-Sb-Te compounds have attracted much attention due to their potential value in electrical data storage. In contrast to the amorphous and crystalline phases, supercooled liquids are far from being deeply understood despite their inevitable role in both amorphization and crystallization processes. To this end, we have studied the dynamics properties and structural characteristics of liquid and supercooled liquid Ge3Sb2Te6 during the fast cooling process. As the temperature decreases, chemical bonds become more homogeneous, but coordination numbers of Ge, Sb and Te atoms change very little. Meanwhile, the structural order of short-range configuration is obviously enhanced. Further studies suggest that Ge-centered, Sb-centered and Te-centered configurations change to the more ordered defective octahedrons mainly by adjusting the bond-angle relationship and bond length, rather than just by changing the coordination environment. It is the more ordered octahedrons that promote the formation of medium-range order. Our findings provide a deep insight into the origin of local structural order in supercooled liquid Ge3Sb2Te6, which is of great importance for the comprehensive understanding of amorphization and crystallization processes.

Optical Properties and Local Structure Evolution during Crystallization of Ga16Sb84 Alloy.

Phase-change memory is one of the most promising candidates for future memory technologies. However, most of the phase-change memories are based on chalcogenides, while other families of materials for this purpose remain insufficiently studied. In this work, we investigate the optical properties and microstructure of Ga16Sb84 by an in-situ ellipsometer and X-ray diffraction. Our experimental results reveal that the Ga16Sb84 films exhibit a relatively high crystallization temperature of ~250 °C, excelling in long data retention. In addition, a large optical contrast exists between the amorphous and crystalline states, which may make it suitable for use in optical discs. Molecular dynamics simulations indicate that a unique local structure order in the amorphous and crystalline phases is responsible for the optical properties observed in the experiment. The similarity found in the short-range orders of the amorphous and crystalline phases is beneficial to better understanding the fast phase transition of phase-change memory.

Hydrogen Peroxide Might Bleach Natural Dentin by Oxidizing Phosphoprotein.

Recent studies suggested that bleaching agents may whiten teeth by oxidizing the fluorescent materials, which are the proteins located in the organic-inorganic interface. Therefore, we postulated that fluorescence of dentin came from dentin phosphoprotein (DPP) and that bleaching agents might bleach dentin by oxidizing DPP. Fifty-six specimens were randomly divided into 4 groups and exposed to distilled water, hydrogen peroxide (HP), ethylenediamine tetraacetic acid disodium salt (EDTA), and acetic acid for 24 h. After measuring the organic and inorganic components, fluorescence, and color characteristics of dentin before and after exposure, we found that when DPP was removed from dentin by EDTA, fluorescent intensity declined proportionally with the reduction in Raman relative intensity, and dentin was whitened considerably, with an Δ E value 6 times higher than that of the distilled water group. On the contrary, due to the incapability of acetic acid to dissolve DPP during decalcification, fluorescent intensity values and tooth color remained nearly unchanged after exposure to acetic acid. Dentin exposed to neutral HP showed no obvious morphologic and organic/inorganic component changes except for the destruction of DPP. Similarly, dramatically decreased fluorescent intensity and lightened color were found in the HP group. Moreover, DPP solution of the HP group exhibited decreased ultraviolet absorbance, especially between 250 and 300 nm, which arose from aromatic amino acids. The results indicated that DPP was responsible for the fluorescent properties of dentin and that HP might bleach dentin by the oxidization of aromatic amino acids in DPP. These findings are of great significance in promoting our further understanding of the mechanism of tooth bleaching and the fluorescent property of normal dentin.

Structural signature and transition dynamics of Sb2Te3 melt upon fast cooling.

Crystalline Sb2Te3 is widely studied due to its important applications in memory materials and topological insulators. The liquid and amorphous structures of this compound as well as the dynamics upon quenching, however, are yet to be fully understood. In this work, we have systematically studied the dynamical properties and local structure of Sb2Te3 at different temperatures using ab initio molecular dynamics simulations. The calculated structure factors agree well with the experimental results. The atomic number density and mean-squared displacement as a function of temperature clearly indicate three states as the temperature decreases, namely, melt, undercooled liquid and glass state, respectively. By analyzing the chemical environments and bond-angle distribution functions, we demonstrate that the most probable short-range motifs in the Sb2Te3 system are defective octahedrons, and they are connected with each other via four-fold rings. This interesting structural feature may be responsible for the high fragility and easy phase transition upon glass forming that is applied in memory devices.

New Insights into Effects of Aromatic Amino Acids on Hydroxyapatite.

Biomimetics inspired by superstructures and extraordinary properties of teeth have resulted in tooth repair and the generation of novel materials. However, little attention has been paid to tooth color, whose origin remains unknown. Based on recent studies, fluorophores-mainly aromatic amino acids (AAAs) in proteins-might be responsible for tooth color. We synthesized carbonated hydroxyapatite (HA; the mineral phase of teeth) in the presence of different amino acids (AAs; the basic units of protein matrix of teeth) as a simplified model of teeth to explore the color source at the AA level. After measuring the fluorescence and color characteristics of HA-AAs before and after bleaching treatment, we found that only HA, synthesized in the presence of AAAs, exhibited remarkable fluorescence and color property. Furthermore, linearly increased fluorescence intensity and deeper color were observed with an increase in AAA content in HA-AAAs. Similarly, significantly decreased absorbance of HA-AAAs between 250 and 300 nm in ultraviolet spectra, declined fluorescence intensity, and decolored performance of HA-AAAs were observed after bleaching treatment. The results showed that AAAs contributed to the fluorescence and color properties of HA and that hydrogen peroxide might whiten HA-AAAs by oxidizing the benzene ring in AAAs. These findings are of great significance in promoting the synthesis of advanced tooth-colored materials and furthering our understanding of the possible mechanisms of hydrogen peroxide. Moreover, our study shed light on the importance of AAAs and might provide new ideas for investigations of biomineralization and biomimetics.

Dynamics and Diffusion Mechanism of Low-Density Liquid Silicon.

A first-order phase transition from a high-density liquid to a low-density liquid has been proposed to explain the various thermodynamic anomies of water. It also has been proposed that such liquid-liquid phase transition would exist in supercooled silicon. Computer simulation studies show that, across the transition, the diffusivity drops roughly 2 orders of magnitude, and the structures exhibit considerable tetrahedral ordering. The resulting phase is a highly viscous, low-density liquid silicon. Investigations on the atomic diffusion of such a novel form of liquid silicon are of high interest. Here we report such diffusion results from molecular dynamics simulations using the classical Stillinger-Weber (SW) potential of silicon. We show that the atomic diffusion of the low-density liquid is highly correlated with local tetrahedral geometries. We also show that atoms diffuse through hopping processes within short ranges, which gradually accumulate to an overall random motion for long ranges as in normal liquids. There is a close relationship between dynamical heterogeneity and hopping process. We point out that the above diffusion mechanism is closely related to the strong directional bonding nature of the distorted tetrahedral network. Our work offers new insights into the complex behavior of the highly viscous low density liquid silicon, suggesting similar diffusion behaviors in other tetrahedral coordinated liquids that exhibit liquid-liquid phase transition such as carbon and germanium.

Spatial pattern and heterogeneity of soil organic carbon and nitrogen in sand dunes related to vegetation change and geomorphic position in Horqin Sandy Land, Northern China.

To assesses the effect of geomorphology, topography, and vegetation changes on spatial pattern of soil organic carbon (C) and total nitrogen (N) in sand dunes, we used the quantitative methods to examine the spatial heterogeneity of vegetation cover, soil organic C, and total N in an 11-year naturally restored mobile dune (RMD11) and a 20-year naturally restored mobile dune (RMD20) that had been fenced to exclude grazing in Horqin Sandy Land, northern China. Our results showed that the vegetation cover, plant density, species number and diversity, soil organic C, and total N increased from RMD11 to RMD20 and increased from the 50 x 50-m plot (crest) to the 100 x 100-m plot (slope) in each dune. Geostatistical analysis showed that the spatial structural variance accounted for the largest proportion of the total sample variance in vegetation cover, soil organic C, and total N in each dune plot. Calculated spatial autocorrelation ranges of vegetation cover, soil organic C, and total N increased from RMD11 to RMD20, indicating that longer time since vegetation restoration results in a more homogeneous distribution of vegetation cover, soil organic C, and total N in sand dunes. In addition, the spatial continuity of vegetation cover, soil organic C, and total N decreased from the 50 x 50-m plot (crest) to the 100 x 100-m plot (slope) in each dune. These results suggest that the spatial distribution of soil organic C and total N in sand dunes is associated closely with geomorphic position related to the dune crest and slope, relative elevation of sampling site, and vegetation cover. Understanding the principles of this relationship between them may guide strategies for the conservation and management of semiarid dune ecosystems.

Development of a bispecific monoclonal antibody to pesticide carbofuran and triazophos using hybrid hybridomas.

A mouse hybrid hybridoma (tetradoma) was derived from fusing hybridomas producing monoclonal antibody to N-methylcarbamate pesticide carbofuran with hybridomas producing monoclonal antibody to organophosphorus pesticide Triazophos. The prepared tetradoma line (12C1 to 2H12) secreted hybrid immunoglobulin exhibiting parental and bispecific binding characteristics. The effect of relevant physicochemical factors on the immunoassay based on the 12C1 to 2H12 bispecific monoclonal antibody had been studied to optimize the ELISA performance. The developed immunoassay showed that the detection limit (I(20)) were 0.36 and 1.89 ng/mL for triazophos and carbofuran, respectively, without obvious cross-reactivity to other related compounds. Water samples spiked with triazophos at 0.5, 1, and 5 ng/mL or carbofuran at 5, 10, and 20 ng/mL were directly analyzed by the developed ELISA format. The mean recovery of triazophos and carbofuran were 108.1% and 107.5%, with variation coefficient of 15.9% and 17.7%, respectively.

Sodium Silicate Reduces Postharvest Decay on Hami Melons: Induced Resistance and Fungistatic Effects.

The effect of sodium silicate (Si) for control of decay was tested in Hami melons (Cucumis melo L. var. inodorus Jacq.). Si significantly inhibited mycelial growth of Alternaria alternata, Fusarium semitectum, and Trichothecium roseum in vitro. Si at 100 mM was more effective than Si at 25 or 50 mM at controlling the diseases caused by the three pathogens, whereas Si at 200 mM was phytotoxic. Si treatments applied at 100 mM pre-inoculation with T. roseum had lower decay incidence and severity than treatments applied post-inoculation. The protection of Si was correlated with the activation of two families of defense-related enzymes, peroxidase and chitinase. Accumulation of both enzymes was induced in fruit treated with Si and challenged by T. roseum 24 h later, and was sustained for at least 9 days in 'New Queen' and 10 days in '8601' at room temperature. It appeared that induced resistance was an important mechanism of disease control in Hami melons treated with Si.

Rapid analysis of momordicoside A in bitter melon by high performance liquid chromatography following solid phase extraction.

A rapid, simple and accurate method for the determination of momordicoside A has been established using solid phase extraction (SPE) followed by high performance liquid chromatography (HPLC). Sample was processed by SPE on a Carb cartridge (3 mL/250 mg), and was then determined by HPLC on a C18 column (4.6 mm i.d. x 250 mm, 5 microns) with V(acetonitrile):V(methanol):V(50 mmol/L potassium dihydrogen phosphate buffer) = 25:20:60 as mobile phase (0.8 mL/min) and UV detection at 208 nm. The calibration curves were linear from 10 mg/L to 1,000 mg/L (r2 = 0.9992). The analytical method was shown to be highly reproducible, giving all of the relative standard deviations and relative mean errors less than 10% for both intra-day and inter-day determinations. The absolute recoveries were greater than 90%.

In vitro pulsatile flow visualization on extracardiac conduits for the right ventricular outflow tract reconstruction: qualitative considerations.

Valved homograft conduits play an important role in the right ventricular outflow tract (RVOT) reconstruction for the surgical treatment of complex congenital heart disease. An excellent immediate rather than long-term outcome could be obtained. The hemodynamics for late failure, however, remained unclear. In vitro pulsatile flow visualization was not conducted before. A simplified right heart duplicator system was set up and driven under physiologic conditions. Polystyrene of 0.18 mm in diameter was applied as the tracing particle. Flow characteristics of models of normal pulmonary circulation as well as pulmonary artery atresia with the RVOT reconstructed utilizing valved and non-valved extracardiac conduits were observed. Flow patterns in the normal pulmonary circulatory model were mainly of axial flow associated with small scope of flow disturbances. A single vortex in the right ventricle was noted in diastole. In the pulmonary artery atresia model, a couple of vortexes were found in the right ventricle, a secondary flow in the main pulmonary artery, and a stronger secondary flow than in the normal pulmonary circulatory model in the two branches in both systole and diastole. A secondary flow was found in the proximal, an axial flow was observed in the distal portion of the extracardiac conduit with normal bioprosthetic valves and a secondary flow was observed in the entire conduit with stenotic bioprosthetic valves. The secondary flow intensity became stronger with the development of the stenosis. Severe insufficiency occurred in the bileaflet ceramic tilting-disc prosthesis during the entire cardiac circle, i.e., the prosthesis was in a maximum open position. Severe reverse flow could be found in the extracardiac conduit in the deceleration phase. Concavity of the crank shaft was found by examination to be filled with tracing particles and the prosthesis became stuck. Model of RVOT reconstruction with non-valved conduit yielded reverse flow inside the extracardiac conduit as well. Secondary flow may occur in normal or diseased extracardiac conduit for RVOT reconstruction. If micro-thrombus of over 0.18 mm in diameter attached in the concave of the crank shaft of a bileaflet tilting-disc prosthesis under a condition of resistance as occurred in the present study, the prosthesis may become stuck. Model of RVOT reconstruction with non-valved extracardiac conduit yielded reverse flow inside the conduit, of which the flow pattern was of greater energy consumption. Thus, a non-valved conduit should be avoided in clinical practice as far as possible.

Detection of rotavirus antigen in tracheal aspirates of infants and children with pneumonia.

Clinical manifestations of respiratory tract infection often precede or coincide with rotavirus gastroenteritis in infants and children. To investigate the possible association between respiratory tract manifestations and rotavirus infection, the authors determined human rotavirus (HRV) antigen and respiratory syncytial virus (RSV) antigen in tracheal aspirates of 58 children with clinically diagnosed pneumonia by enzyme-linked immunosorbent assay (ELISA) and immunofluorescent antibody techniques. HRV antigen was detected in 16 out of the 58 cases (27.6%) and RSV antigen was found positive in 27 cases (46.5%). In four cases both HRV and RSV antigens were detected. The results of our study suggest that rotavirus may occasionally by one of the etiologic agents of acute lower respiratory infections of infants and children and that rotavirus infection may be transmitted via respiratory route. However, further extensive studies are needed for confirmation of the association between rotavirus and respiratory tract infection.