Orientational Order in Dense Colloidal Liquids and Glasses.

We construct structural order parameters based on local angular and radial distribution functions in dense colloidal suspensions. All the order parameters show significant correlations to local dynamics in the supercooled and glass regime. In particular, the correlations between the orientational order and dynamical heterogeneity are consistently higher than those between the conventional two-body structural entropy and local dynamics. The structure-dynamics correlations can be explained by a excitation model with the energy barrier depending on local structural order. Our results suggest that in dense disordered packings, local orientational order is higher than translational order, and plays a more important role in determining the dynamics in glassy systems.

Application of Nano-Delivery Systems in Lymph Nodes for Tumor Immunotherapy.

Immunotherapy has become a promising research "hotspot" in cancer treatment. "Soldier" immune cells are not uniform throughout the body; they accumulate mostly in the immune organs such as the spleen and lymph nodes (LNs), etc. The unique structure of LNs provides the microenvironment suitable for the survival, activation, and proliferation of multiple types of immune cells. LNs play an important role in both the initiation of adaptive immunity and the generation of durable anti-tumor responses. Antigens taken up by antigen-presenting cells in peripheral tissues need to migrate with lymphatic fluid to LNs to activate the lymphocytes therein. Meanwhile, the accumulation and retaining of many immune functional compounds in LNs enhance their efficacy significantly. Therefore, LNs have become a key target for tumor immunotherapy. Unfortunately, the nonspecific distribution of the immune drugs in vivo greatly limits the activation and proliferation of immune cells, which leads to unsatisfactory anti-tumor effects. The efficient nano-delivery system to LNs is an effective strategy to maximize the efficacy of immune drugs. Nano-delivery systems have shown beneficial in improving biodistribution and enhancing accumulation in lymphoid tissues, exhibiting powerful and promising prospects for achieving effective delivery to LNs. Herein, the physiological structure and the delivery barriers of LNs were summarized and the factors affecting LNs accumulation were discussed thoroughly. Moreover, developments in nano-delivery systems were reviewed and the transformation prospects of LNs targeting nanocarriers were summarized and discussed.

Activation of brain lactate receptor GPR81 aggravates exercise-induced central fatigue.

Exercise-induced fatigue is a complex physiological phenomenon and is greatly influenced by central mechanisms in brain. As one of the most abundant circulating carbon metabolites, l-lactate in brain has been considered to be an important supplementary fuel during exercise; however, whether it plays a signaling role in fatigue remains largely obscure. In this study, our results initially revealed that brain l-lactate levels were increased after an exhaustive swimming session in several brain regions including motor cortex, hippocampus, and cerebellum. Then, we examined the specific role of brain lactate receptor, also known as hydroxycarboxylic acid receptor 1 (GPR81), in exercise-induced fatigue. We found that intracerebroventricular injection of either d-lactate (an enantiomer that could mediate activation of GPR81 as l-lactate) or a potent GPR81 agonist 3-chloro-5-hydroxybenzoic acid (CHBA), significantly decreased the swimming time to fatigue. After being subjected to the same weight-loaded swimming for 30 min, no obvious changes of blood lactate levels, gastrocnemius pAMPK/AMPK ratio, and glycogen contents were observed between intracerebroventricular CHBA-injected mice and vehicle-treated ones, which suggested a comparable degree of peripheral fatigue. Meanwhile, there were higher extracellular γ-aminobutyric acid (GABA) levels and lower extracellular glutamate levels and glutamate/GABA ratio in motor cortex of the intracerebroventricular CHBA-injected mice than that of vehicle-treated ones, indicating a greater extent of central fatigue in CHBA-injected mice than that in vehicle animals. Collectively, our results suggested that an increased level of brain l-lactate acts as a signaling molecule via activating GPR81, which in turn exacerbates central fatigue during exercise.

Oxidoreduction potential controlling for increasing the fermentability of enzymatically hydrolyzed steam-exploded corn stover for butanol production.

BACKGROUND: Lignocellulosic biomass is recognized as an effective potential substrate for biobutanol production. Though many pretreatment and detoxification methods have been set up, the fermentability of detoxicated lignocellulosic substrate is still far lower than that of starchy feedstocks. On the other hand, the number of recent efforts on rational metabolic engineering approaches to increase butanol production in Clostridium strains is also quite limited, demonstrating the physiological complexity of solventogenic clostridia. In fact, the strain performance is greatly impacted by process control. developing efficient process control strategies could be a feasible solution to this problem. RESULTS: In this study, oxidoreduction potential (ORP) controlling was applied to increase the fermentability of enzymatically hydrolyzed steam-exploded corn stover (SECS) for butanol production. When ORP of detoxicated SECS was controlled at - 350 mV, the period of fermentation was shortened by 6 h with an increase of 27.5% in the total solvent (to 18.1 g/L) and 34.2% in butanol (to 10.2 g/L) respectively. Silico modeling revealed that the fluxes of NADPH, NADH and ATP strongly differed between the different scenarios. Quantitative analysis showed that intracellular concentrations of ATP, NADPH/NADP+, and NADH/NAD+ were increased by 25.1%, 81.8%, and 62.5%. ORP controlling also resulted in a 2.1-fold increase in butyraldehyde dehydrogenase, a 1.2-fold increase in butanol dehydrogenase and 29% increase in the cell integrity. CONCLUSION: ORP control strategy effectively changed the intracellular metabolic spectrum and significantly improved Clostridium cell growth and butanol production. The working mechanism can be summarized into three aspects: First, Glycolysis and TCA circulation pathways were strengthened through key nodes such as pyruvate carboxylase [EC: 6.4.1.1], which provided sufficient NADH and NADPH for the cell. Second, sufficient ATP was provided to avoid "acid crash". Third, the key enzymes activities regulating butanol biosynthesis and cell membrane integrity were improved.

TMT-based proteomics analysis of the cerebral cortex of TauT knockout rats.

BACKGROUND: Taurine serves a variety of nutritional and physiological roles, and it is mostly transported in cells via taurine transporter (TauT). The effect of taurine transporter in cerebral cortex is still unknown. We employed TMT label-based proteomics to find differences in proteins in the cerebral cortex of TauT knockout rats in this investigation. The goal of this research was to see how TauT deletion affected protein alterations in brain tissue and to see if there was a new research area for TauT. METHODS: The cerebral cortex of TauT knockout rats and wild-type control rats were analyzed using TMT-based proteomics, and differentially expressed proteins were analyzed by bioinformatics analysis means such as GO and KEGG, the association between the proteins was found by PPI, and biologically significant and interesting proteins were selected for verification by WB and immunohistochemistry. RESULTS: There were total of 8275 proteins found, but only 35 differentially expressed proteins were identified (27 up-regulated and 8 down-regulated), and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the biological pathways and functional classification of the proteins. The results show that these differentially expressed proteins are mainly enriched in lysine degradation, cell cycle, chronic myeloid leukemia, and longevity regulating pathways-multiple species, renal cell carcinoma, pathways in cancer, etc. To verify the proteomic data, we analyzed the expression of Annexin6 and Pik3r2 by western blotting and immunofluorescence. The results are consistent with proteomics, which proves the reliability of our proteomics data. CONCLUSION: Through TMT-based proteomics, we have a comprehensive understanding of the effect of TauT knockout on the changes of other proteins in the cerebral cortex, providing new evidence for further understanding the function of TauT.

Inhibition of HIF-1α-AQP4 axis ameliorates brain edema and neurological functional deficits in a rat controlled cortical injury (CCI) model.

Traumatic brain injury (TBI) is an important cause of death in young adults and children. Till now, the treatment of TBI in the short- and long-term complications is still a challenge. Our previous evidence implied aquaporin 4 (AQP4) and hypoxia inducible factor-1α (HIF-1α) might be potential targets for TBI. In this study, we explored the roles of AQP4 and HIF-1α on brain edema formation, neuronal damage and neurological functional deficits after TBI using the controlled cortical injury (CCI) model. The adult male Sprague Dawley rats were randomly divided into sham and TBI group, the latter group was further divided into neutralized-AQP4 antibody group, 2-methoxyestradiol (2-ME2) group, and their corresponding control, IgG and isotonic saline groups, respectively. Brain edema was examined by water content. Hippocampal neuronal injury was assessed by neuron loss and neuronal skeleton related protein expressions. Spatial learning and memory deficits were evaluated by Morris water maze test and memory-related proteins were detected by western blot. Our data showed that increased AQP4 protein level was closely correlated with severity of brain edema after TBI. Compared with that in the control group, both blockage of AQP4 with neutralized-AQP4 antibody and inhibition of HIF-1α with 2-ME2 for one-time treatment within 30-60 min post TBI significantly ameliorated brain edema on the 1st day post-TBI, and markedly alleviated hippocampal neuron loss and spatial learning and memory deficits on the 21st day post-TBI. In summary, our preliminary study revealed the short-term and long-term benefits of targeting HIF-1α-AQP4 axis after TBI, which may provide new clues for the selection of potential therapeutic targets for TBI in clinical practice.

Rapid determination of capsaicin concentration in soybean oil by terahertz spectroscopy.

Capsaicin is the key composition of pepper and can be used as a marker of gutter oil for detection. The feasibility of rapid detection of capsaicin concentration in soybean oil was studied by terahertz spectroscopy. Genetic algorithm (GA) and principal component analysis (PCA) as the pretreatment method were used to obtain the best spectral features. Least square-support vector machine (LS-SVM), back propagation neural network (BPNN), and partial least squares (PLS) were combined with the pretreatment method to obtain the best determination model. The BPNN was combined with GA to obtain the best quantitative prediction results with the correlation coefficient of prediction (RP ), prediction root mean square error (RMSEP), the ratio of prediction to deviation (RPD), and range error ratio (RER) were 0.9309, 0.4030 µg/kg, 17.0421, and 2.4813, respectively. Furthermore, the detection limit of capsaicin could achieve 1.25 µg/kg in soybean oil and the accuracy of discrimination was up to 100% in the prediction set using the LS-SVM combined with GA pre-treatment. The results suggested that terahertz spectroscopy together with chemometric methods would be a promising technique for rapid determination of capsaicin concentration in soybean oil. Meanwhile, it is necessary to perform further experiments with real gutter oil samples before applying the method in practice. PRACTICAL APPLICATION: The combination of terahertz spectroscopy technology and chemometrics is a promising method for the rapid determination of capsaicin concentration in soybean oil with high efficiency.

Monitoring the growth of Fusarium graminearum in wheat kernels using multispectral imaging with chemometric methods.

Wheat is an important agricultural economic crop providing energy and nutrition for human beings. However, wheat kernels are easily contaminated with Fusarium graminearum that is harmful to human health. In this study, a rapid and nondestructive detection method has been developed to identify the degree of contamination and determine the count of Fusarium graminearum in wheat kernels using multispectral imaging technology. Based on genetic algorithm (GA) and principal component analysis (PCA) data preprocessing methods combined with partial least squares (PLS), support vector machine (SVM) and back propagation neural network (BPNN) chemometric methods, identification and quantitative determination models were established. The best result was obtained by GA-BPNN with an accuracy of up to 100% in the identification of the degree of contamination in wheat kernels at different contamination periods. Comparison of the results from different methods revealed that the best prediction of the count of Fusarium graminearum was obtained by GA-SVM with the correlation coefficient (R) in the calibration set and prediction set being 0.9663 and 0.9292, while the root mean square error (RMSE) in the calibration set and prediction set was 0.5992 and 0.6725 CFU g-1, respectively. It can be concluded that the combination of multispectral imaging and chemometric methods was potentially useful for rapid and nondestructive detection of cereal fungi in practice.

Novel HIF-1-target gene isthmin1 contributes to hypoxia-induced hyperpermeability of pulmonary microvascular endothelial cells monolayers.

Hypoxia-induced pulmonary microvascular endothelial cell (PMVEC) monolayers hyperpermeability is vital for vascular leakage, which participates in vascular diseases, such as acute lung injury (ALI) and high-altitude pulmonary edema (HAPE). We previously observed that PMVEC permeability was markedly elevated in hypoxia when cocultured with primary type II alveolar epithelial cells (AECII) in which isthmin1 (ISM1) was highly upregulated. However, whether the upregulation of ISM1 plays a role in hypoxia-induced PMVEC hyperpermeability is unclear. In this study, we assessed the role of AECII-derived ISM1 in hypoxia-induced PMVEC hyperpermeability with an AECII/PMVEC coculture system and uncovered the underlying mechanism whereby hypoxia stimulates ISM1 gene expression. We found that ISM1 gene expression was upregulated in cultured AECII cells exposed to hypoxia (3% O2) and that AECII-derived ISM1 participated in hypoxia-induced hyperpermeability of PMVEC monolayers, as small interference RNA (siRNA)-mediated knockdown of ISM1 in AECII markedly attenuated the increase in PMVEC permeability in coculture system under hypoxia. In addition, we confirmed that ISM1 was regulated by hypoxia-inducible factor-1α (HIF1α) according to the evidence that silencing of HIF1α inhibited the hypoxia-mediated upregulation of ISM1. Mechanismly, overexpression of HIF1α transcriptionally activated ISM1 gene expression by directly binding to the conserved regulatory elements upstream of the ism1 locus. We identified a novel HIF-1-target gene ISM1, which involves in hyperpermeability of pulmonary microvascular endothelial cell monolayers under hypoxia. Our in vitro cell experiments implied that the upregulated ISM1 derived from alveolar epithelium might be a vital modulator in hypoxia-induced endothelial hyperpermeability and thereby implicates with hypoxic pulmonary-related diseases.

Cortical gyrification and its relationships with molecular measures and cognition in children with the FMR1 premutation.

Neurobiological basis for cognitive development and psychiatric conditions remains unexplored in children with the FMR1 premutation (PM). Knock-in mouse models of PM revealed defects in embryonic cortical development that may affect cortical folding. Cortical-folding complexity quantified using local gyrification index (LGI) was examined in 61 children (age 8-12 years, 19/14 male/female PM carriers, 15/13 male/female controls). Whole-brain vertex-wise analysis of LGI was performed for group comparisons and correlations with IQ. Individuals with aberrant gyrification in 68 cortical areas were identified using Z-scores of LGI (hyper: Z ≥ 2.58, hypo: Z ≤ - 2.58). Significant group-by-sex-by-age interaction in LGI was detected in right inferior temporal and fusiform cortices, which correlated negatively with CGG repeat length in the PM carriers. Sixteen PM boys (hyper/hypo: 7/9) and 10 PM girls (hyper/hypo: 2/5, 3 both) displayed aberrant LGI in 1-17 regions/person while 2 control boys (hyper/hypo: 0/2) and 2 control girls (hyper/hypo: 1/1) met the same criteria in only 1 region/person. LGI in the precuneus and cingulate cortices correlated positively with IQ scores in PM and control boys while negatively in PM girls and no significant correlation in control girls. These findings reveal aberrant gyrification, which may underlie cognitive performance in children with the PM.

Piezoelectric Energy Harvesting from Suspension Structures with Piezoelectric Layers.

In this paper, we propose a generator for piezoelectric energy harvesting from suspension structures. This device consists of a leaf spring and eight pairs of piezoelectric layers attached to inner and outer surfaces. We present a special type of leaf spring, which can magnify the force from the workload to allow the piezoelectric layers to achieve larger deformation. The generator is to solve the problem of vibration energy reutilization in a low-frequency vibration system. To verify the efficiency of the proposed configuration, a series of experiments are operated. The results indicate that the resonance frequency (25.2 Hz) obtained from the sweep experiment is close to the simulation result (26.1 Hz). Impedance-matching experiments show that the sum of the output power attains 1.7 mW, and the maximum single layer reaches 0.6 mW with an impedance matching of 610 KΩ, and the instantaneous peak-peak power density is 3.82 mW/cm3. The capacitor-charging performance of the generator is also excellent under the series condition. For a 4.7 µF capacitor, the voltage is charged to 25 V in 30 s and limited at 32 V in 80 s. These results demonstrate the exploitable potential of piezoelectric energy harvesting from suspension structures.

Microstructure and Isothermal Oxidation of Ir-Rh Spark Plug Electrodes.

High-temperature oxidation tests were performed on pure iridium, rhodium, and the iridium alloys, IrRh10, IrRh25, and IrRh40, at 1100 °C in a stable air environment for 60 h. The results of the oxidation were analyzed by X-ray photoelectron spectroscopy (XPS). Microstructural changes of the Ir-Rh alloys were characterized by scanning electron microscopy (SEM). XPS analysis results show that the main oxide of the Ir-Rh alloy in a 1100 °C environment was Rh2O3, and SEM analysis shows that the surfaces of the Ir-Rh alloys after oxidation formed both linear and ellipse-shaped corrosion pits, and had the same direction with the wire-drawing process. The oxidation behavior of Ir-Rh alloys, including the mass change, the reason for the mass loss, and the role of Rh in improving oxidation resistance performance, are discussed.

Optimization of selenoprotein P and other plasma selenium biomarkers for the assessment of the selenium nutritional requirement: a placebo-controlled, double-blind study of selenomethionine supplementation in selenium-deficient Chinese subjects.

BACKGROUND: The intake of selenium needed for optimal health has not been established. Selenoproteins perform the functions of selenium, and the selenium intake needed for their full expression is not known. OBJECTIVE: This study sought to determine the intake of selenium required to optimize plasma selenoprotein P (SEPP1) and to compare SEPP1 with other plasma selenium biomarkers. DESIGN: A 40-wk placebo-controlled, double-blind study of selenium repletion was carried out in 98 healthy Chinese subjects who had a daily dietary selenium intake of 14 micro g. Fourteen subjects each were assigned randomly to daily dose groups of 0, 21, 35, 55, 79, 102, and 125 micro g Se as l-selenomethionine. Plasma glutathione peroxidase (GPX) activity, SEPP1, and selenium were measured. A biomarker was considered to be optimized when its value was not different from the mean value of the subjects receiving larger supplements. RESULTS: The SEPP1 concentration was optimized at 40 wk by the 35- micro g supplement, which indicated that 49 micro g/d could optimize it. GPX activity was optimized by 21 micro g (total ingestion: 35 micro g/d). The selenium concentration showed no tendency to become optimized. CONCLUSIONS: The present results indicate that SEPP1 concentration is the best plasma biomarker studied for assessing optimal expression of all selenoproteins, because its optimization required a larger intake of selenium than did GPX activity. On the basis of the selenium intake needed for SEPP1 optimization with adjustments for body weight and individual variation, ap 75 micro g Se/d as selenomethionine is postulated to allow full expression of selenoproteins in US residents. This trial was registered at clinicaltrials.gov as NCT00428649.

[Effect of zinc on thymulin level in mice].

OBJECTIVE: In order to investigate the roles of the different levels of zinc nutrition status on the thymulin of the mice. METHODS: The experiment included two periods: zinc depleted period and repletion period. In the depleted period, mice were divided into 3 dose groups: zinc deficient group (ZD, 5.2 mg/kg), zinc pair-fed group (PZ) and normal zinc group(NZ,25.6 mg/kg). In the repletion period, mice were divided into 3 dose groups: ZD group, DZ-NZ group and PZ-NZ group. RESULTS: The results showed that a signification decrease of thymulin level was observed as a result of zinc deficiency and was increased rapidly follow zinc supplement, while the plasma zinc was kept the same level. CONCLUSION: The thymulin is a sensitive biomarker for assess the zinc status.

Effectiveness of selenium supplements in a low-selenium area of China.

BACKGROUND: Selenium is an essential micronutrient with a recommended dietary allowance for adults of 55 mug/d. It functions as an essential constituent of selenoproteins. Although there is no evidence of selenium deficiency in the United States, people in many other areas of the world are selenium deficient, with the consequence that they are unable to express their selenoproteins fully. OBJECTIVE: We carried out a supplementation trial in a selenium-deficient population in China to assess the requirement for selenium as selenite and as selenomethionine. DESIGN: One hundred twenty subjects with an average selenium intake of 10 mug/d were randomly assigned and administered tablets containing no selenium or amounts as high as 66 mug Se/d for 20 wk. Plasma was sampled before supplementation and at 4-wk intervals during supplementation and was assayed for the 2 plasma selenoproteins, glutathione peroxidase and selenoprotein P. RESULTS: Full expression of glutathione peroxidase was achieved with 37 mug Se/d as selenomethionine and with 66 mug/d as selenite. Full expression of selenoprotein P was not achieved at the highest doses of either form. CONCLUSIONS: Full expression of selenoprotein P requires a greater selenium intake than does full expression of plasma glutathione peroxidase. This suggests that selenoprotein P is a better indicator of selenium nutritional status than is glutathione peroxidase and that the recommended dietary allowance of selenium, which was set with the use of glutathione peroxidase as the index of selenium status, should be revised. Selenium as selenomethionine had nearly twice the bioavailability of selenium as selenite.

[Effect of zinc on immune function in mice spleen lymphocytes].

OBJECTIVE: In order to study the effects of different levels of zinc nutrition status on the immune function of mice spleen lymphocytes. METHODS: The experiment included two periods: zinc depleted period and repletion period. In the depleted period, mice were divided into 3 dose groups: zinc deficient group (ZD, 5.2mg/kg), zinc pair-fed group (PZ) and normal zinc group (NZ, 25.6 mg/kg). In the repletion period, mice were divided into 3 dose groups: ZD group, DZ-NZ group and PZ-NZ group. It was measured some biomarkers of immunity to assess the zinc nutritional status, including lymphocytes amount, lymphocytes proliferation index and IL-2 activity. RESULTS: The lymphocytes counts of ZD group spleen showed significant decline at seventy days fed zinc deficiency diets. The counts of ZD-NZ group were increased after 22 days of taking normal zinc diet. Zinc deficiency could suppressed the proliferation of the spleen lymphocytes. The spleen lymphocytes proliferation of the ZD-NZ group showed a moderate but non-significant increase compared with the ZD group. Zinc deficiency could decrease IL-2 production. The production of IL-2 of ZD group was lower than those of ZP (P < 0.05), IL-2 production increased following zinc supplement. CONCLUSION: It is found that zinc status can affect the immune function. Production of IL-2 in spleen lymphocyte is affected evidently by zinc.

[Coxsackievirus B3 infection and Keshan disease].

To study the relationship between the infection of enteroviruses and the etiology of keshan disease, we examined the 30 blood samples from the latent-chronic KD patients from Mianning, Xider, Derchang county of Sichuan Province with LDE-PCR (long distance enterovirus-specific RT PCR), two sensitive and specific ELISAs (one for CVB1-6 IgM and the other for CVB1-6 IgG), and three-primer RT PCR specific for CVB3. Results show that: 1) The infection rate of enteroviruses in the samples from the latent-chronic KD patients is higher than from the control group (80% VS 0%, P < 0.01); 2) The CVB1-6 antibody positive rate in latent-chronic KD is higher than that of the control group (IgM, 33% VS 0%, P < 0.01; IgG, 23% VS 0%, P < 0.01); 3) 16.6% (4/24) of enteroviruses positive samples or 40% (4/10) of CVB1-6 IgM antibody positive samples can be identified as CVB3. So, the infection of enter viruses maybe involves in the cause and development of latent-chronic keshan disease, and at least we conclude that the mutation of CVB3 is not the only cause of KD.

[Capillary zone electrophoresis for determination of thymulin in human plasma].

AIM: To establish a capillary zone electrophoresis (CZE) method for determination of thymulin in human blood plasma. Thymulin is a nonapeptide produced by the thymic epithelium. METHODS: The uncoated capillary used was 75 microns ID x 57 cm (50 cm effective length). The experimental conditions were as follows: the running buffer was phosphate-borate buffer containing 50 mmol.L-1 Na2B4O7-10 mmol.L-1 Na2HPO4 (pH 9.10); running voltage was 12 kV; operated temperature was 25 degrees C; running time was 13 minutes, detective wavelength was 200 nm. RESULTS: The linear range of the thymulin standard curve was 1-10 micrograms.mL-1, gamma = 0.9990, the average recovery was 70.97% with RSD of 3.32%, the RSD of reproducibility was 3.05%. CONCLUSION: The method of CZE for determination of thymulin in human plasma is simple and reliable.