Efficient activation of T cells by human monocyte-derived dendritic cells (HMDCs) pulsed with Coxiella burnetii outer membrane protein Com1 but not by HspB-pulsed HMDCs

<p>Abstract</p> <p>Background</p> <p><it>Coxiella burnetii </it>is an obligate intracellular bacterium and the etiologic agent of Q fever; both coxiella outer membrane protein 1 (Com1) and heat shock protein B (HspB) are its major immunodominant antigens. It is not clear whether Com1 and HspB have the ability to mount immune responses against <it>C. burnetii </it>infection.</p> <p>Results</p> <p>The recombinant proteins Com1 and HspB were applied to pulse human monocyte-derived dendritic cells (HMDCs), and the pulsed HMDCs were used to stimulate isogenic T cells. Com1-pulsed HMDCs expressed substantially higher levels of surface molecules (CD83, CD40, CD80, CD86, CD54, and CD58) and a higher level of interleukin-12 than HspB-pulsed HMDCs. Moreover, Com1-pulsed HMDCs induced high-level proliferation and activation of CD4⁺and CD8⁺cells, which expressed high levels of T-cell activation marker CD69 and inflammatory cytokines IFN-γ and TNF-α. In contrast, HspB-pulsed HMDCs were unable to induce efficient T-cell proliferation and activation.</p> <p>Conclusions</p> <p>Our results demonstrate that Com1-pulsed HMDCs are able to induce efficient T-cell proliferation and drive T cells toward Th1 and Tc1 polarization; however, HspB-pulsed HMDCs are unable to do so. Unlike HspB, Com1 is a protective antigen, which was demonstrated by the adoptive transfer of Com1-pulsed bone marrow dendritic cells into naive BALB/c mice.</p

Electrochemical Reducation of TiO2/Al2O3/C to Ti3AlC2 and Its Derived Two-Dimensional (2D) Carbides

Ti3AlC2 has been directly synthesized from TiO2/Al2O3/C mixture precursors (3TiO2/0.5Al2O3/1.5C and 2TiO2/0.5Al2O3/C) by a molten salt electrolysis process at 900?C and 3.2 V in molten CaCl2. The influence of initial carbon content on the electrosynthesized products has been investigated. The result shows that the main phase of the electrosynthesized products changes from Ti3AlC to Ti2AlC and then to Ti3AlC2 with the increasing carbon content, and the electrosynthesized Ti3AlC2 is carbon deficient. The morphology observation shows that the electrosynthesized Ti3AlC2 particles possess smooth surfaces and dense flake-like microstructure. The reaction mechanism of the electroreduction of TiO2/Al2O3/C mixture precursor has been discussed based on the time- and position-dependent phase constitution analysis. In addition, two-dimensional (2D) Ti3AlC2-derived carbides, i.e., Ti3C2Tx and TiCx have been successfully prepared from the electrosynthesized Ti3AlC2 by a chemical etching process and an electrochemical etching process, respectively. Both derived carbides exhibit the similar layered structure, in which single layer carbides are composed of plentiful nanometer carbides. It is suggested that the molten salt electrolysis process has a great potential to be used for the facile synthesis of Mn+1AXn phases (such as Ti3AlC2) from their oxides precursors, and the synthesized Mn+1AXn phases can be further converted into 2D carbidesauthorsversionPeer reviewe

The progress of research on the application of redox nanomaterials in disease therapy

Redox imbalance can trigger cell dysfunction and damage and plays a vital role in the origin and progression of many diseases. Maintaining the balance between oxidants and antioxidants in vivo is a complicated and arduous task, leading to ongoing research into the construction of redox nanomaterials. Nanodrug platforms with redox characteristics can not only reduce the adverse effects of oxidative stress on tissues by removing excess oxidants from the body but also have multienzyme-like activity, which can play a cytotoxic role in tumor tissues through the catalytic oxidation of their substrates to produce harmful reactive oxygen species such as hydroxyl radicals. In this review, various redox nanomaterials currently used in disease therapy are discussed, emphasizing the treatment methods and their applications in tumors and other human tissues. Finally, the limitations of the current clinical application of redox nanomaterials are considered

Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes

Autism spectrum disorder (ASD) is frequently comorbid with other neurological disorders such as intellectual disability (ID) or global development delay (GDD) and epilepsy. The pathogenesis of ASD is complex. So far, studies have identified more than 1000 ASD risk genes. Most of them were also reported to relate with other neurological diseases, and only several of them have been confirmed as pathogenic genes for autism. Little is known about the roles of these risk genes in neurological diseases with ASD. In the present study, we recruited a cohort of 158 neurological disorder probands with 163 variants of 48 ASD risk genes. Of these, 50 individuals (31.6%) were diagnosed with ASD. In the ASD patient subset, we identified several rarely reported candidate genes including DOLK, USH2A, and HUWE1. In a comparison of patients with neurological disorders with and without ASD, we found that ID/GDD was frequently comorbid with ASD whereas epilepsy was more common in the non-ASD group. Statistical analyses of all possible risk factors implicated that variants in synaptic genes, especially non-voltage-gated ion channel genes and in transcriptional and chromosome genes were related to ASD, but none of the investigated environmental factors was. Our results are useful for the future diagnosis and prognosis of patients with neurological disorders and emphasize the utility of genetic screening

Theory and Practice: Improving Retention Performance through Student Modeling and System Building

The goal of Intelligent Tutoring systems (ITSs) is to engage the students in sustained reasoning activity and to interact with students based on a deep understanding of student behavior. In order to understand student behavior, ITSs rely on student modeling methods to observes student actions in the tutor and creates a quantitative representation of student knowledge, interests, affective states. Good student models are going to effectively help ITSs customize instructions, engage student's interest and then promote learning. Thus, the work of building ITSs and advancing student modeling should be considered as two interconnected components of one system rather than two separate topics. In this work, we utilized the theoretical support of a well-known learning science theory, the spacing effect, to guide the development of an ITS, called Automatic Reassessment and Relearning System (ARRS). ARRS not only validated the effectiveness of spacing effect, but it also served as a testing field which allowed us to find out new approaches to improve student learning by conducting large-scale randomized controlled trials (RCTs). The rich data set we gathered from ARRS has advanced our understanding of robust learning and helped us build student models with advanced data mining methods. At the end, we designed a set of API that supports the development of ARRS in next generation ASSISTments platform and adopted deep learning algorithms to further improve retention performance prediction. We believe our work is a successful example of combining theory and practice to advance science and address real- world problems

Effect of cyanotoxins on the hypothalamic-pituitary-gonadal axis in male adult mouse.

Microcystins LR (MC-LR) are hepatotoxic cyanotoxins that have been shown to induce reproductive toxicity, and Hypothalamic-Pituitary-Gonadal Axis (HPG) is responsible for the control of reproductive functions. However, few studies have been performed to evaluate the effects of MC-LR on HPG axis. This study aimed to investigate the MC-LR-induced toxicity in the reproductive system of mouse and focus on the HPG axis.Adult male C57BL/6 mice were exposed to various concentrations of MC-LR (0, 3.75, 7.50, 15.00 and 30.00 µg/kg body weight per day) for 1 to 14 days, and it was found that exposure to different concentrations of MC-LR significantly disturbed sperm production in the mice testes in a dose- and time-dependent manner. To elucidate the associated possible mechanisms, the serum levels of testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were assessed. Meanwhile, PCR assays were employed to detect alterations in a series of genes involved in HPG axis, such as FSH, LH, gonadotropin-releasing hormone (GnRH) and their complement receptors. Furthermore, the effect of MC-LR on the viability and testosterone production of Leydig cells were tested in vitro.MC-LR significantly impaired the spermatogenesis of mice possibly through the direct or indirect inhibition of GnRH synthesis at the hypothalamic level, which resulted in reduction of serum levels of LH that lead to suppression of testosterone production in the testis of mice.MC-LR may be a GnRH toxin that would disrupt the reproductive system of mice