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In the Netherlands, women aged 50-75 years are invited to receive breast cancer screening every two years. The PRISMA (Personalised RISk-based MAmmascreening) study was designed to investigate the added value of risk-based mammography screening. 43,000 screened women completed a web-based questionnaire comprising established risk factors and PROMs for breast cancer. There is no universally accepted data model for the collection of breast cancer risk factors. Objective: To reduce ambiguity of data schemas in the domain and increase secondary use of client-reported outcomes through FAIRification, i.e. ensuring data are Findable, Accessible, Interoperable, and Reusable. To create a FAIR semantic data model out of the PRISMA questionnaire. Solution: Step 1. 43,000 screened women completed a web-based questionnaire comprising established risk factors and PROMs for breast cancer. Step 2. After several inventory meetings with different stakeholders, a consensus was reached on which data elements were important criteria to discover, share and reuse the PRISMA data. The resulting 67data elements were grouped into 15main classes Linked Data representations for each CDE were constructed, by mapping to existing ontological terms Step 3. The data elements identified in the PRISMA study can be instantiated according to the core elements (role, entity, process, measurement, attribute) in SIO and connected using the established property. Added Value: FAIR data model, a potential template for breast cancer research groups to other PROMs and Real-World Experience questionnaires. Next steps: create use cases that the PRISMA semantic data schema can support consider the interoperability with other standard, like the electronic health record (EHR)

A magnetic mesoporous expanded perlite-based (EPd-APTES@Fe3O4) composite was designed and synthesized as a novel adsorbent for enrichment of rare earth ions in aqueous solution. Effect of various factors including the pH of solution, contact time and adsorbent dosage on the adsorption behaviors of yttrium(III) by the EPd-APTES@Fe3O4 nano-material composites from aqueous solution was investigated. The maximum adsorption capacity of the as-prepared materials for yttrium(III) ions was 383.2 mg/g. Among the various isotherm models, the Freundlich isotherm model could well described for the adsorption of the rare earth ions at pH 5.5 and 298.15 K. The kinetic analysis indicated that the adsorption process followed the pseudo-second order kinetics model, and the rate-determining step might be chemical adsorption. Thermodynamic parameters declared that the adsorption process was endothermic. In addition, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and the quantum chemical calculation indicated that the yttrium(III) ions were captured on the EPd-APTES@Fe3O4 surface mainly by coordination with functional group of -NH2. More importantly, the adsorption-desorption studies indicated that the EPd-APTES@Fe3O4 nano-material composites had a high stability and good recyclability.

Huge π-conjugated system of carbon nanotubes (CNTs) endows the two-dimensional carbon-based nanomaterials with special affinity towards aromatic organic compounds such as asphaltenes. Based on the ...

Additional file 1 : Table S1. Results of soil chemical properties in different small watershed of Cinnamonmum migao. Table S2. Results of soil chemical properties in different Different fruit stages of C. migao. Table S3. Significance of environment factors influencing C. migao fruit of different minor watershed. Table S4. Elution procedure. Table S5. Chemical component content of C. migao fruit from different fruit stages. Table S6. Chemical component content of C. migao fruit from different minor watershed. Table S7. Climatic characteristics of the nine collections sites. Table S8. Significance of climate factors and soil factor relative. Figure S1. The OTU and Shannon index dilution curves of rhizosphere soil fungal community in C.migao; Dilution curve is to randomly select a certain number of sequences from the samples, count the alpha diversity index of the corresponding samples of these sequences, draw the curve with the amount of data extracted as the abscissa and the value of alpha diversity index as the ordinate, and judge whether the data amount of this sequencing is sufficient according to whether the curve is smooth or not. Figure S2. Heatmap of fungal in Rhizosphere Soil of C.migao; (A), (B) Phylum; (C), (D) Class; (E), (F) Order; (G), (H)Family; (I), (J)Species(exclude “unclassifired” taxa). Figure S3. Network analysis (two-factor). The red line represents a positive correlation and the green line represents a negative correlation; (A), different small watersheds (B), different fruit periods. Figure S4. Kruskal-wallis rank sum test. (a), (different small watersheds); (b), (different fruit periods); *representative the p

As a novel heat shock protein 90 inhibitor, AT-533 exhibits various biological activities in vitro, including anti-viral, anti-tumor and anti-inflammatory activities. Moreover, AT-533 gel, a gel dosage form of AT-533, has been suggested to have anti-keratitis and herpes simplex virus type-1 infection-induced effects on the skin lesions of animals. However, the safety evaluation of AT-533 and AT-533 gel has, to the best of our knowledge, not been examined in in vivo toxicological tests. Therefore, these toxicological tests were carried out in the present study. A 30-day subacute toxicity test for AT-533 was conducted at doses of 1, 2 and 4 mg/kg in Sprague-Dawley rats, while that for AT-533 gel was conducted using a single dose of 5 g/kg. The toxicological tests showed that a high-dose of AT-533 caused lethality and side effects in Sprague-Dawley rats. However, no mortality, loss of appetite and body weight, adverse reactions, or toxicologically relevant alterations in hematology, biochemistry and macroscopic findings (except for skin) occurred in rats exposed to low-dose AT-533 and single-dose AT-533 gel (5 g/kg) during a 30-day subacute dermic toxicity study. The aforementioned results suggested that AT-533 gel is non-toxic for Sprague-Dawley rats, as shown by a dermic subacute toxicity test and that except for slight skin irritation, AT-533 gel had almost no side effects when administered percutaneously for 30 days.

Systemic lupus erythematosus (SLE) is an autoimmune disease involving the inflammatory damages of multiple organs. Lupus nephritis (LN) as the manifestation in the kidney occurs in more than 50% of SLE patients and is a major cause of morbidity and mortality. Current treatments consist of immunosuppressants that always lead to compromised immune responses with increased risks of infections as the major side effect. To minimize this side effect, it is crucial to develop new treatments that are more natural and specific. Vitamin A, particularly in the form of its functional metabolite, retinoic acid, has shown some beneficial effects against LN in both lupus-prone mouse models and clinical cases. However, a more systemic evaluation of vitamin A treatment in lupus had not been investigated. In our study, we found paradoxical effects of all-trans-retinoic acid (tRA) on lupus-like disease in MRL/lpr lupus-prone mice. Starting at 6 weeks old when the inflammatory environment had been established in MRL/lpr mice, tRA administration reduced immune cell numbers in the secondary lymphoid organs and improved glomerulonephritis. However, circulating autoantibodies and inflammation in renal tubulointerstitium and other organs were increased. The detrimental effects of tRA were not present in MRL control mice, which didn't have an established inflammatory environment at 6 weeks old as shown in MRL/lpr mice, suggesting that the pro-inflammatory effects of tRA are dependent on the pre-existing inflammatory environment. Therefore, to successfully apply vitamin A-based treatment, it is important to avoid the detrimental effects of tRA on lupus by identifying and then specifically eliminating the critical pro-inflammatory immune cell types in lupus. As treatments usually start after the onset of apparent symptoms in patients at the effector stage of autoimmune responses, targeting the inflammatory contributors at this stage appears to be more practical and critical. Among different types of leukocytes, we chose to focus on dendritic cells (DCs), because they are highly diverse and critical in the immune responses as a bridge between the innate and adaptive immune systems. Plasmacytoid DCs (pDCs) as a candidate target have been demonstrated to be crucial for the initiation of lupus development by producing IFNα. However, we demonstrated that although pDCs produced a large amount of IFNα during disease initiation, those from late-stage lupus mice were found to be defective in producing IFNα, suggesting that pDC-targeted treatments should be performed at the initiation stage. This will depend on the progress in early diagnosis in the future. Besides pDCs, we identified a CD11c+ cell population absent at the early-stage but gradually accumulating at the late-stage in the kidneys of lupus mice. These cells have a phenotype of mature monocyte-derived DCs, with particularly high CX3CR1 expression on the surface. Consistent with their pathogenic cytokine profile, in vivo administration of anti-CX3CR1-saporin conjugates to dysfunction these cells in MRL/lpr mice significantly reduced proteinuria scores. Ex vivo activation of renal-infiltrating CD4+ T cells showed increased survival rate, proliferation and IFN-γ production of activated CD4+ T cells when they were cultured with these renal-infiltrating CD11c+ cells. These results suggest that the renal-infiltrating CD11c+ cells are pathogenic and promote inflammation in the kidney at the later effector stage of lupus by interacting with renal-infiltrating CD4+ T cells. In conclusion, although vitamin A showed anti-inflammatory effects on reducing glomerulonephritis, its use in lupus treatment should be guarded due to the other potential pro-inflammatory effects induced by the pre-existing inflammatory environment. IFNα-producing pDCs and CX3CR1highCD11c+ monocyte-derived DCs could be specific therapeutic targets to reduce the established inflammation at the early stage and late stage of LN, respectively. Therefore, it is worthwhile to further investigate the comprehensive effects of combination therapy on lupus, with vitamin A administration and pDCs-specific depletion at the early stage, and CX3CR1highCD11c+ monocyte-derived DCs-specific depletion at the late stage. Ph. D.

Background Systemic lupus erythematosus, characterized by persistent inflammation, is a complex autoimmune disorder with no known cure. Immunosuppressants used in treatment put patients at a higher risk of infections. New knowledge of disease modulators, such as symbiotic bacteria, can enable fine-tuning of parts of the immune system, rather than suppressing it altogether. Results Dysbiosis of gut microbiota promotes autoimmune disorders that damage extraintestinal organs. Here we report a role of gut microbiota in the pathogenesis of renal dysfunction in lupus. Using a classical model of lupus nephritis, MRL/lpr, we found a marked depletion of Lactobacillales in the gut microbiota. Increasing Lactobacillales in the gut improved renal function of these mice and prolonged their survival. We used a mixture of 5 Lactobacillus strains (Lactobacillus oris, Lactobacillus rhamnosus, Lactobacillus reuteri, Lactobacillus johnsonii, and Lactobacillus gasseri), but L. reuteri and an uncultured Lactobacillus sp. accounted for most of the observed effects. Further studies revealed that MRL/lpr mice possessed a “leaky” gut, which was reversed by increased Lactobacillus colonization. Lactobacillus treatment contributed to an anti-inflammatory environment by decreasing IL-6 and increasing IL-10 production in the gut. In the circulation, Lactobacillus treatment increased IL-10 and decreased IgG2a that is considered to be a major immune deposit in the kidney of MRL/lpr mice. Inside the kidney, Lactobacillus treatment also skewed the Treg-Th17 balance towards a Treg phenotype. These beneficial effects were present in female and castrated male mice, but not in intact males, suggesting that the gut microbiota controls lupus nephritis in a sex hormone-dependent manner. Conclusions This work demonstrates essential mechanisms on how changes of the gut microbiota regulate lupus-associated immune responses in mice. Future studies are warranted to determine if these results can be replicated in human subjects. Electronic supplementary material The online version of this article (doi:10.1186/s40168-017-0300-8) contains supplementary material, which is available to authorized users.

To date, there are 18 histone deacetylase (HDAC) enzymes, divided into four classes, which alter protein function by removing acetyl groups from lysine residues. Prior studies report that non-selective HDAC inhibitors decrease disease in lupus mouse models. Concern for adverse side effects of non-selective HDAC inhibition supports investigation of selective-HDAC inhibition. We hypothesized that a selective HDAC-6 inhibitor (HDAC6i) will alleviate disease in a mouse model of lupus by increasing acetylation of alphatubulin. Intraperitoneal injections of the selective HDAC6i ACY-1083 (0.3 mg/kg, 1 mg/kg, or 3 mg/kg), vehicle control, or dexamethasone were administered to 21-week-old, female NZB/W mice, 5 days a week, for 13 weeks. Disease progression was evaluated by proteinuria, serum levels of anti-dsDNA antibody, cytokines and immunoglobulins, and post mortem evaluation of nephritis and T cell populations in the spleen. HDAC6i treatment decreased proteinuria, glomerular histopathology, IgG, and C3 scores when compared to vehicle-treated mice. Within glomeruli of HDAC6i-treated mice, there was increased acetylation of alpha-tubulin and decreased NF-κB. Additionally, HDAC6i decreased serum IL-12/IL-23 and Th17 cells in the spleen. Taken together, these results suggest HDAC6 inhibition may decrease lupus nephritis in NZB/W mice via mechanisms involving acetylation of alphatubulin and decreased NF-κB in glomeruli as well as inhibition of Th17 cells.

To solve the problems in current sizing equation, a new sizing equation that has optimal selection of specific loading which result in minimum stator diameter was proposed. The new sizing equation features as: using stator diameter as variable, using thermal loading as the proportional coefficient, providing a way to get the optimal selection of specific loading and containing more information relating the detailed implementation of the machine compared with the current one. The proposed sizing equation was used to redesign the Prius motor, getting a more compact design result without any losses in performance.

A new design procedure and corresponding design criteria of IPM machine is presented in the paper. The procedure interconnects the vehicle performance with the design parameters of an IPM machine. The presented design procedure has a three-layer structure, with different layer deals with different requirements. Design constrains and rules in the second layer are summarized as design criteria, which guarantee the machine is well designed and safety operated.