Synthesis and properties of sulfhydryl-reactive near-infrared cyanine fluorochromes for fluorescence imaging

Near-infrared fluorochromes (NIRF) are useful compounds for diverse biotechnology applications and for in vivo biomedical imaging. Such NIRF must have high quantum yield, be biocompatible, and be conjugatable to a wide variety of proteins, peptides, and other affinity ligands. Here, we describe the synthesis of four new nonsymmetrical sulfhydryl-reactive cyanine NIRF with excellent optical and chemical properties. Each fluorochrome was designed to contain an iodoacetamido group that reacts specifically with sulfhydryl-containing molecules. The synthesized fluorochromes were used to label model peptides and sulfhydryl-containing biomolecules.     

Fate and Phytotoxicity of CeO2 Nanoparticles on Lettuce Cultured in the Potting Soil Environment

Cerium oxide nanoparticles (CeO₂ NPs) have been shown to have significant interactions in plants. Previous study reported the specific-species phytotoxicity of CeO₂ NPs by lettuce (Lactuca sativa), but their physiological impacts and vivo biotransformation are not yet well understood, especially in relative realistic environment. Butterhead lettuce were germinated and grown in potting soil for 30 days cultivation with treatments of 0, 50, 100, 1000 mg CeO₂ NPs per kg soil. Results showed that lettuce in 100 mg·kg^-1 treated groups grew significantly faster than others, but significantly increased nitrate content. The lower concentrations treatment had no impact on plant growth, compared with the control. However, the higher concentration treatment significantly deterred plant growth and biomass production. The stress response of lettuce plants, such as Superoxide dismutase (SOD), Peroxidase (POD), Malondialdehyde(MDA) activity was disrupted by 1000 mg·kg^-1 CeO₂ NPs treatment. In addition, the presence of Ce (III) in the roots of butterhead lettuce explained the reason of CeO₂ NPs phytotoxicity. These findings demonstrate CeO₂ NPs modification of nutritional quality, antioxidant defense system, the possible transfer into the food chain and biotransformation in vivo.     

Cytokine and Antibody Based Diagnostic Algorithms for Sputum Culture-Positive Pulmonary Tuberculosis

Background

Tuberculosis (TB) is one of the most serious infectious diseases globally and has high mortality rates. A variety of diagnostic tests are available, yet none are wholly reliable. Serum cytokines, although significantly and frequently induced by different diseases and thus good biomarkers for disease diagnosis and prognosis, are not sufficiently disease-specific. TB-specific antibody detection, on the other hand, has been reported to be highly specific but not sufficiently sensitive. In this study, our aim was to improve the sensitivity and specificity of TB diagnosis by combining detection of TB-related cytokines and TB-specific antibodies in peripheral blood samples.

Methods

TB-related serum cytokines were screened using a human cytokine array. TB-related cytokines and TB-specific antibodies were detected in parallel with microarray technology. The diagnostic performance of the new protocol for active TB was systematically compared with other traditional methods.

Results

Here, we show that cytokines I-309, IL-8 and MIG are capable of distinguishing patients with active TB from healthy controls, patients with latent TB infection, and those with a range of other pulmonary diseases, and that these cytokines, and their presence alongside antibodies for TB-specific antigens Ag14-16kDa, Ag32kDa, Ag38kDa and Ag85B, are specific markers for active TB. The diagnostic protocol for active TB developed here, which combines the detection of three TB-related cytokines and TB-specific antibodies, is highly sensitive (91.03%), specific (90.77%) and accurate (90.87%).

Conclusions

Our results show that combining detection of TB-related cytokines and TB-specific antibodies significantly enhances diagnostic accuracy for active TB, providing greater accuracy than conventional diagnostic methods such as interferon gamma release assays (IGRAs), TB antibody Colloidal Gold Assays and microbiological culture, and suggest that this diagnostic protocol has potential for clinical application.     

Impact of Childhood Abuse on the Risk of Non-Suicidal Self-Injury in Mainland Chinese Adolescents

Background

Childhood abuse has been associated with significant increases in non-suicidal self-injury (NSSI) behaviors in adolescents; however, only general definitions of this risk indicator have been examined. This study identified relationships between specific forms of childhood abuse and NSSI in mainland Chinese adolescents.

Method

A total of 14,221 cases were retained from an epidemiological study involving adolescents from junior and senior middle schools. Information relating to the perpetrator, perceived harm, timing of exposure to different types of childhood abuse, and NSSI were obtained. Logistic regression was used to analyze relationships between each form of childhood abuse and NSSI.

Results

Approximately 51.0% of the students reported at least one abusive childhood experience. Nearly one in four students (24.9%) reported that they had engaged in NSSI in the past 12 months. Each type of childhood abuse, occurring at any time within the first 16 years of life, especially in situations of continuous exposure, was significantly associated with NSSI. A significant graded relationship was found between number of abusive childhood experiences and NSSI. Students maltreated by parents or others were at high risk of engaging in NSSI, the risk was greater in students maltreated by both; students who had been exposed to childhood abuse with no perceived harm still demonstrated an elevated risk for NSSI. The pattern of associations did not vary by gender.

Conclusions

These findings suggest that experiencing any of various forms of childhood abuse should be considered a risk factor for NSSI during adolescence. Further research should focus upon psychosocial, neural, and genetic factors that might moderate or mediate the onset of NSSI in adolescents who have experienced childhood abuse.     

Molecular dynamics study of the proposed proton transport pathways in [FeFe]-hydrogenase

Possible proton transport pathways in Clostridium pasteurianum (CpI) [FeFe]-hydrogenase were investigated with molecular dynamics simulations. This study was undertaken to evaluate the functional pathway and provide insight into the hydrogen bonding features defining an active proton transport pathway. Three pathways were evaluated, two of which consist of water wires and one of predominantly amino acid residues. Our simulations suggest that protons are not transported through water wires. Instead, the five-residue motif (Glu282, Ser319, Glu279, H₂O, Cys299) was found to be the likely pathway, consistent with previously made experimental observations. The pathway was found to have a persistent hydrogen bonded core (residues Cys299 to Ser319), with less persistent hydrogen bonds at the ends of the pathway for both H₂ release and H₂ uptake. Single site mutations of the four residues have been shown experimentally to deactivate the enzyme. The theoretical evaluation of these mutations demonstrates redistribution of the hydrogen bonds in the pathway, resulting in enzyme deactivation. Finally, coupling between the protein dynamics near the proton transport pathway and the redox partner binding regions was also found as a function of H₂ uptake and H₂ release states, which may be indicative of a correlation between proton and electron movement within the enzyme.     

Continuum simulations of acetylcholine diffusion with reaction-determined boundaries in neuromuscular junction models

The reaction-diffusion system of the neuromuscular junction has been modeled in 3D using the finite element package FEtk. The numerical solution of the dynamics of acetylcholine with the detailed reaction processes of acetylcholinesterases and nicotinic acetylcholine receptors has been discussed with the reaction-determined boundary conditions. The simulation results describe the detailed acetylcholine hydrolysis process, and reveal the time-dependent interconversion of the closed and open states of the acetylcholine receptors as well as the percentages of unliganded/monoliganded/diliganded states during the neuro-transmission. The finite element method has demonstrated its flexibility and robustness in modeling large biological systems.     

Epigallocatechin-3-Gallate Ameliorated Iron Accumulation and Apoptosis and Promoted Neuronal Regeneration and Memory/Cognitive Functions in the Hippocampus Induced by Exposure to a Chronic High-Altitude Hypoxia Environment

We aimed to explore the protective effects and potential treatment mechanism of Epigallocatechin-3-gallate (EGCG) in an animal model of chronic exposure in a natural high-altitude hypoxia (HAH) environment. Behavioral alterations were assessed with the Morris water maze test. Iron accumulation in the hippocampus was detected by using DAB enhanced Perls’ staining, MRI, qPCR and colorimetry, respectively. Oxidative stress (malondialdehyde, MDA), apoptosis (Caspase-3), and neural regeneration (brain-derived neurotrophic factor, BDNF) were detected by using ELISA and western blotting. Neural ultrastructural changes were evaluated by transmission electron microscopy (TEM). The results showed that learning and memory performance of rats decreased when exposure to HAH environment. It was followed by iron accumulation, dysfunctional iron metabolism, reduced BDNF and the upregulation of MDA and Caspase-3. TEM confirmed the ultrastructural changes in neurons and mitochondria. EGCG reduced HAH-induced cognitive impairment, iron deposition, oxidative stress, and apoptosis and promoted neuronal regeneration against chronic HAH-mediated neural injury.

     

花生对非繁殖期雌性黑线仓鼠细胞免疫和血液指标的影响

食物的数量和质量是影响动物免疫功能的重要因素。野生动物在选择食物时是否会优先选择有利于其健康的食物？为解决该问题,我们以黑线仓鼠(Cricetulus barabensis)为研究对象,通过饲喂其喜食食物花生(Arachis hypogaea),然后检测反映健康状况的细胞免疫能力和血液指标。将30只非繁殖期成年雌性黑线仓鼠随机分为正常饲料组(normal fodder group,NF,n=10)、花生加饲料组(normal fodder plus peanuts group,NP,n=10)和花生组(Peanut,n=10),饲喂39 d后检测各项指标。结果发现Peanut组的体重增加,NP和Peanut组的摄食量降低。NP组注射植物血球凝集素(Phytohaemagglutinin,PHA)后12 h的PHA反应显著高于NF组。3组间白细胞数和淋巴细胞数在统计学上没有显著差异,但NP和Peanut组白细胞数比NF组分别高22.9%和25.0%,淋巴细胞数分别高15.0%和22.5%。NP和Peanut组红细胞数和红细胞压积显著高于NF组,而Peanut组血小板数显著高于NF和NP组。这些结果表明饲喂花生能增强黑线仓鼠的细胞免疫能力、输氧能力和凝血功能,这可能是其喜食花生的生理原因。