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Background: Toxoplasma gondii infection causes adverse pregnancy outcomes by affecting the expression of immunotolerant molecules in decidual immune cells. Galectin-9 (Gal-9) is widely expressed in decidual macrophages (dMφ) and is crucial for maintaining normal pregnancy by interacting with the immunomodulatory protein T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3). However, the effects of T. gondii infection on Gal-9 expression in dMφ, and the impact of altered Gal-9 expression levels on the maternal–fetal tolerance function of decidual natural killer (dNK) cells, are still unknown. Methods: Pregnancy outcomes of T. gondii-infected C57BL/6 and Lgals9−/− pregnant mice models were recorded. Expression of Gal-9, c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), and Forkhead box protein O1 (FOXO1) was detected by western blotting, flow cytometry or immunofluorescence. The binding of FOXO1 to the promoter of Lgals9 was determined by chromatin immunoprecipitation–polymerase chain reaction (ChIP-PCR). The expression of extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK), cAMP-response element binding protein (CREB), phosphorylated CREB (p-CREB), T-box expressed in T cells (T-bet), interleukin 10 (IL-10), and interferon gamma (IFN-γ) in dNK cells was assayed by western blotting. Results: Toxoplasma gondii infection increased the expression of p-JNK and FOXO1 in dMφ, resulting in a reduction in Gal-9 due to the elevated binding of FOXO1 with Lgals9 promoter. Downregulation of Gal-9 enhanced the phosphorylation of ERK, inhibited the expression of p-CREB and IL-10, and promoted the expression of T-bet and IFN-γ in dNK cells. In the mice model, knockout of Lgals9 aggravated adverse pregnancy outcomes caused by T. gondii infection during pregnancy. Conclusions: Toxoplasma gondii infection suppressed Gal-9 expression in dMφ by activating the JNK/FOXO1 signaling pathway, and reduction of Gal-9 contributed to dysfunction of dNK via Gal-9/Tim-3 interaction. This study provides new insights for the molecular mechanisms of the adverse pregnancy outcomes caused by T. gondii. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) play a crucial role in maintaining maternal-fetal tolerance by expressing some immune-suppressive molecules, such as indoleamine 2,3-dioxygenase (IDO). Toxoplasma gondii (T. gondii) infection can break the immune microenvironment of maternal-fetal interface, resulting in adverse pregnancy outcomes. However, whether T. gondii affects IDO expression in dMDSCs and the molecular mechanism of its effect are still unclear. Here we show, the mRNA level of IDO is increased but the protein level decreased in infected dMDSCs. Mechanistically, the upregulation of transcriptional levels of IDO in dMDSCs is regulated through STAT3/p52-RelB pathway and the decrease of IDO expression is due to its degradation caused by increased SOCS3 after T. gondii infection. In vivo, the adverse pregnancy outcomes of IDO−/− infected mice are more severe than those of wide-type infected mice and obviously improved after exogenous kynurenine treatment. Also, the reduction of IDO in dMDSCs induced by T. gondii infection results in the downregulation of TGF-β and IL-10 expression in dNK cells regulated through Kyn/AhR/SP1 signal pathway, eventually leading to the dysfunction of dNK cells and contributing the occurrence of adverse pregnancy outcomes. This study reveals a novel molecular mechanism in adverse pregnancy outcome induced by T. gondii infection. IDO downregulation in dMDSCs induced by Toxoplasma gondii infection regulates expression of TGF-β and IL-10 through the Kyn/AhR/SP1 signal pathway, eventually contributing to the dysfunction of dNK cells. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) play a key role in maintaining maternal-fetal tolerance for a successful pregnancy, but the role of MDSCs in abnormal pregnancy caused by Toxoplasma gondii infection is unknown. Herein, we revealed a distinct mechanism by which T-cell immunoglobulin domain and mucin domain containing protein-3 (Tim-3), an immune checkpoint receptor that balances maternal-fetal tolerance during pregnancy, contributes to the immunosuppressive function of MDSCs during T. gondii infection. The expression of Tim-3 in decidual MDSCs was significantly downregulated following T. gondii infection. The proportion of monocytic MDSCs population, the inhibitory effect of MDSCs on T-cell proliferation, the levels of STAT3 phosphorylation, and the expression of functional molecules (Arg-1 and IL-10) in MDSCs were all decreased in T. gondii-infected pregnant Tim-3 gene knockout (Tim-3KO) mice compared with infected pregnant WT mice. After treatment with Tim-3-neutralizing Ab in vitro, the expression levels of Arg-1, IL-10, C/EBPβ, and p-STAT3 were decreased, the interaction between Fyn and Tim-3 or between Fyn and STAT3 was weakened, and the binding ability of C/EBPβ to the promoters of ARG1 and IL10 was decreased in human decidual MDSCs with T. gondii infection, while opposite results were observed following treatment with galectin-9 (a ligand for Tim-3). Inhibitors of Fyn and STAT3 also downregulated the expression of Arg-1 and IL-10 in decidual MDSCs and exacerbated adverse pregnancy outcomes caused by T. gondii infection in mice. Therefore, our studies discovered that the decrease of Tim-3 after T. gondii infection could downregulate the functional molecules of Arg-1 and IL-10 expression in decidual MDSCs through the Fyn-STAT3-C/EBPβ signaling pathway and weaken their immunosuppressive function, which eventually contribute to the development of adverse pregnancy outcomes. Author summary: Pregnant women in their first trimester with a primary infection of T. gondii are particularly susceptible resulting in a number of serious adverse pregnancy outcomes. Previous studies have shown that T. gondii infection results in the dysfunction of immune cell function at the maternal-fetal interface, which destroys the function of maternal-fetal immune tolerance for a successful pregnancy. MDSCs have an immunosuppressive capacity and play an important role in the maintenance of normal pregnancy. However, the role of MDSCs in the adverse pregnancy outcomes caused by T. gondii infection remains unknown. Here, we analyzed the effect of an immunosuppressive molecule Tim-3 on the function of decidual MDSCs following T. gondii infection. Our results showed that T. gondii infection downregulated the proportion of monocytic MDSCs population, the inhibitory ability of MDSCs on T cell proliferation, the level of STAT3 phosphorylation, and the expression of functional molecules (Arg-1 and IL-10) in MDSCs from the pregnant Tim-3KO mice compared with the pregnant WT mice. Further study showed that the decrease of Tim-3 expression caused by T. gondii infection could downregulate Arg-1 and IL-10 expression in decidual MDSCs via the Fyn-STAT3-C/EBPβ signaling pathway and weaken their immunosuppressive function. This work suggested that MDSCs dysfunction resulting from the downregulation of Tim-3 after T. gondii infection may be an important mechanism of adverse pregnancy outcomes, which may provide theoretical information for prophylactic and/or therapeutic treatments against the infection-related abnormal pregnancy. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jenvman.2010.03.011 Byline: Xianbing Liu (a), Beibei Liu (b), Tomohiro Shishime (a), Qinqin Yu (b), Jun Bi (b), Tetsuro Fujitsuka (a) Abstract: Environmentalism in China is under transformation from the traditional command and control model to emphasize the advantages of economic tools and encourage the participation of the public. Firms are much more aware of the importance of environmental issues, and some of them have practiced environmental activities beyond compliance. In order to help understand the driving mechanism of proactive corporate environmental behaviors from the firm's perspective, this paper identifies the drivers affecting the proactive environmental management level (EML.sub.p) based on the institutional theory, and gives an empirical study on the firms based in Changshu city of Jiangsu Province, China. The usable data, collected from the 117 valid respondents in a questionnaire survey, indicates that EML.sub.p is still moderately low currently. Less than 10% of the samples are practicing all the six categorized types of voluntary environmental activities. The econometric exercise confirms a significantly positive effect of the externally mimetic pressure on EML.sub.p , which may attribute to a higher sensitivity of Chinese companies to the market factors. However, the roles of the general public and industrial associations are not significant, showing the marginal power of selected normative pressures. Regarding internal factors, firms, which view environmental issues as opportunities and often arrange internal environmental training, are more likely to adopt proactive environmental activities. More concerns from the general public like neighborhood communities and mass media shall be addressed to enhance the normative power to improve EML.sub.p in China from the future perspective. Author Affiliation: (a) Kansai Research Centre, Institute for Global Environmental Strategies (IGES), Hitomirai Building 4F, 1-5-2, Wakinohama Kaigan Dori, Chuo-ku, Hyogo 651-0073, Japan (b) School of Environment, Nanjing University, China Article History: Received 10 March 2009; Revised 1 March 2010; Accepted 23 March 2010

The draft legislation on e-waste prepared by the Chinese national government assigns management responsibility to local governments. It is an urgent task for the municipal government to plan an effective [...]

Finish milling with a ball end mill is a key process in manufacturing high-precision and complex workpieces, such as dies and molds. Because of the complexity of the milling process, it is difficult to evaluate the microcharacteristics of machined surfaces real time, which necessitates the simulation of the process. In this area, the existing related simulation researches mainly focus on scallop height evaluation, but few have presented a whole picture of the microcharacteristics of milled surfaces. This paper develops a comprehensive simulation system based on a Z-map model for predicting surface topographic features and roughness formed in the finish milling process and studies the effect of machining parameters. The adoption of the discretization concept of the tool's cutting motion makes it possible to dynamically track the cutting tool-workpiece interaction with the tool movement and to describe the cutting edges-workpiece discrete cutting interaction more realistically and, therefore, the microcharacteristics of the machined surfaces more accurately. Also, the effects of the cutting tool run-out and wear are incorporated into the developed model through modifying the tool center motion and the cutting-edge shape, respectively. As a fundamental study, the tool-swept envelope has been simulated. The developed simulation system is applied to thoroughly study the surface features formed by the 2.5-axis finish milling process. The application for general three-axis machining is discussed. Additionally, this paper studies the effect of the tool inclination, which is the most common characteristic in 3 + 2- or five-axis milling processes, on the machined surface features. Experiments are carried out to study the milling process and to verify the simulation results. The difference between the simulated and experimental results is discussed, and the reason behind the difference is explored. [DOI: 10.1115/1.2039098]

Serious adverse impacts on the environment and human health from e-waste recycling have occurred in the past and continue to occur in China today, due to a lack of national [...]

An abrasive machining process for ceramics is simulated with a nonlinear thermodynamic constitutive model based on the principle of continuum damage mechanics (CDM). The model consists of a set of parallel Maxwell-type elements arranged in series with a spring. It incorporates stochastic material microstructure through two sets of the newly introduced material parameters, spring-like constants [C.sub.r] and damping-like coefficients [a.sub.r] (r = 1,2, ... ,n). Damage is considered cumulative and related with current stress and damage state in a ceramic workpiece during loading, which constitutes damage evolution. A fourth-order isotropic damage tensor is introduced. This highly nonlinear CDM model is reduced to an incremental formulation and approximated by a 3D nonlinear finite element program based on the Newton-Raphson method. The stress-strain correlation calculated from the current model is presented for alumina, silicon carbide, and silicon nitride. The predicted results of damage versus the depth of cut for the three ceramics subjected to machining with single diamond grit are validated by the experiment. As one example, the development of damage with the movement of the abrasive grit in a silicon nitride workpiece is demonstrated by a contour plot. The final part of this paper presents the calculated distribution of residual stress in a silicon nitride sample and the factors contributing to the distribution are discussed. [DOI: 10.1115/1.1463034]