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This study aimed to investigate whether exosomes secreted by mouse GATA-4-expressing bone marrow mesenchymal stem cells (BMSCs) could induce BMSC differentiation into myocyte precursors, decrease cardiomyocyte apoptosis, and improve cardiac function following myocardial infarction (MI). BMSCs were transduced with a lentivirus carrying a doxycycline (DOX)-inducible GATA-4 or control lentivirus, and secreted exosomes from these BMSCs were collected and co-cultured with BMSCs or cardiomyocytes under hypoxic and serum free conditions. Furthermore, exosomes were injected into mice 48 h after MI. Cardiac function was evaluated by echocardiography at 48, 72, and 96 h after exosome treatment. Quantitative PCR showed that co-culture of BMSCs with GATA-4-BMSC exosomes increased cardiomyocyte-related marker expression. Co-culture of GATA-4-BMSC exosomes with cardiomyocytes in anoxic conditions decreased apoptosis as detected by flow cytometry. Injection of GATA-4-BMSC exosomes in mice 48 h after MI increased cardiac function over the next 96 h; increased cardiac blood vessel density and number of c-kit-positive cells and decreased apoptotic cardiomyocyte cells were also observed. Differential expression of candidate differentiation- and apoptosis-related miRNAs and proteins that may mediate these effects was also identified. Exosomes isolated from GATA-4-expressing BMSCs induce differentiation of BMSCs into cardiomyocyte-like cells, decrease anoxia-induced cardiomyocyte apoptosis, and improve myocardial function after infarction.

Background: The immunosuppressive activity of mesenchymal stem cells (MSCs) has been exploited to induce tolerance after organ transplantation. The indoleamine 2,3-dioxygenase (IDO) may have beneficial effects in the immunoregulatory properties of MSCs. It was recently revealed that exosomes derived from MSCs play important roles in mediating the biological functions of MSCs. This study aimed to explore the roles of exosomes derived from MSCs in the induction of immune tolerance. Methods: Dendritic cells (DCs) and T-cells were cultured with exosomes derived from rat bone marrow MSCs (BMSCs) overexpressing IDO1 or controls. For the in-vivo study, rats received heart transplants and were treated with exosomes from IDO-BMSCs and heart function was evaluated. Flow cytometry was used to detect expression of cell surface markers. Cytokine levels were detected in culture supernatants or serum samples. Protein and microRNA expressions in exosomes were investigated by chips. Results: Exosomes from IDO-BMSCs cultured with DCs and T-cells (1) downregulated CD40, CD86, CD80, MHC-II, CD45RA, CD45RA+CD45RB, OX62, and upregulated CD274 expression, (2) increased the number of regulatory T-cells (Tregs) and decreased the number of CD8+ T-cells, and (3) decreased the levels of pro-inflammatory cytokines, but increased the levels of anti-inflammatory cytokines compared with the other groups. Transplanted rats, which were injected with exosomes from IDO-BMSCs, had reduced allograft-targeting immune responses and improved cardiac allograft function. Exosomes secreted by IDO-BMSCs exhibited significant upregulations of the immunoregulatory protein FHL-1, miR-540-3p, and a downregulation of miR-338-5p. Conclusion: Exosomes derived from IDO-BMSCs can be used to promote immunotolerance and prolong the survival of cardiac allografts.

Expression of indoleamine 2,3-dioxygenase (IDO) in mesenchymal stem cells (MSC) is thought to contribute to MSC-mediated immunosuppression. A lentiviral-based transgenic system was used to generate bone marrow stem cells (BMSC) which stably expressed IDO (IDO-BMSCs). Coculture of IDO-BMSCs with dendritic cells (DC) or T cells was used to evaluate the immunomodulatory effect of IDO-BMSCs. A heterotopic heart transplant model in rats was used to evaluate allograft rejection after IDO-BMSC treatment. Mechanisms of IDO-BMSC-mediated immunosuppression were investigated by evaluating levels of proinflammatory and anti-inflammatory cytokines, and production of Tregs. A significant decrease in DC marker-positive cells and a significant increase in Tregs were observed in IDO-BMSC cocultured. Treatment of transplanted rats with IDO-BMSCs was associated with significantly prolonged graft survival. Compared with the control groups, transplanted animals treated with IDO-BMSCs had a (1) significantly higher ejection fraction and fractional shortening, (2) significantly lower expression of CD86, CD80, and MHCII, and significantly higher expression in CD274, and Tregs, and (3) significantly higher levels of interleukin-10 (IL-10), transforming growth factor beta-1 (TGF-β1), TGF-β2, and TGF-β3, and significantly lower levels of IL-2 and interferon gamma. Our results expand our understanding of the molecular mechanisms underlying suppression of heart allograft rejection via IDO-expressing BMSCs.

Objective：To investigate the clinical value of a minimally-invasive treatment of communicating hydrocephalus using a percutaneous lumboperitoneal （LP） shunt.Method：The clinical and long-term follow-up data of 256 patients suffering from communicating hydrocephalus and undergoing percutaneous LP shunt during 1998 to 2008 were retrospectively analyzed.Results：After the follow-up,which lasted 6 months to 10 years,219 cases of communicating hydrocephalus recovered well （ventricular size returned to normal and symptoms completely disappeared）,25 cases were brought under control （ventricle size reduced by 50% and symptoms partially abated）,and 12 cases showed no obvious changes.Fifteen obese subjects needed modifications of the shunt due to the obstruction of the abdominal end following wrapping,and one subject underwent extubation as the subject was unable to tolerate stimulation of the cauda equina.The effectiveness of shunting was 91.40% and the probability of shunt-tube obstruction,which occurs predominantly in the abdominal end,was only 5.85%,far lower than that of ventriculoperitoneal （VP） shunt.Three subjects had a history of infection following VP shunting.Conclusion：LP shunting is minimally invasive and effective in treating communicating hydrocephalus,with fewer complications.

To improve the quality of high carbon wire rods,combined electromagnetic stirring was introduced in the continuous casting of round billets with a diameter of 250mm at Tianjin Rockcheck Steel Group Co.In this paper,the positioning of final electromagnetic stirring(F-EMS)was determined by nail-shooting method.Furthermore,the effect of mold electromagnetic stirring(M-EMS)on the macrostructure and internal defects in the round billets was investigated to find out the optimal operating parameters for continuous casting of SWRH 82B round billets.The results show the desirable positioning of F-EMS locates 9.7m below the mold level where the molten steel can be effectively driven by electromagnetic force and disperse central composition segregation.The shrinkage cavity is totally eliminated with the rotational M-EMS.The ratio and index of central composition segregation and center porosity can be reduced significantly.Furthermore,the equiaxed crystal ratio is considerably increased to 64%under 480A/3Hz M-EMS and 500A/10Hz F-EMS.Fine microstructure and mechanical property of wire rod are presented after optimization of combined electromagnetic stirring.Accordingly,the probability of occurrence of cup-cone fracture of wire rod is reduced dramatically.

Human monocyte is an important cell type which is involved in various complex human diseases. To better understand the biology of human monocytes and facilitate further studies, we developed the first comprehensive proteome knowledge base specifically for human monocytes by integrating both in vivo and in vitro datasets. The top 2000 expressed genes from in vitro datasets and 779 genes from in vivo experiments were integrated into this study. Altogether, a total of 2237 unique monocyte-expressed genes were cataloged. Biological functions of these monocyte-expressed genes were annotated and classified via Gene Ontology （GO） analysis. Furthermore, by extracting the overlapped genes from in vivo and in vitro datasets, a core gene list including 541 unique genes was generated. Based on the core gene list, further gene-disease associations, pathway and network analyses were performed. Data analyses based on multiple bioinformatics tools produced a large body of biologically meaningful information, and revealed a number of genes such as SAMHDI, G6PD, GPD2 and EN01, which have been reported to be related to immune response, blood biology, bone remodeling, and cancer respectively. As a unique resource, this study can serve as a reference map for future in-depth research on monocytes biology and monocyte-involved human diseases.

Utilizing ANSYS CFX commercial software and volume fraction of fluid （VOF） model, fluctuation behav- ior of steel/slag interface was numerically simulated in continuous casting mold with static magnetic field, and the influence of metal jet characteristics on the behavior of steel/slag interface was investigated. The results indicated that the behavior of steel/slag interface is similar at different process parameters, which is closely related to the characteristic of the flow field. The steel/slag interface has an obvious trough characteristic, which can be divided in- to three zones： frontal valley zone, back valley zone and horizontal zone~ as the magnetic flux density increases, the fluctuation of liquid level increases firstly and then decreases, and a reasonable magnetic flux density can make steel/ slag interface obtain a relatively flat interface, which can prevent slag from being entrapped into liquid steel. For a thin slab continuous casting process, when the casting speed is 4 m/min, a reasonable magnetic flux density is about 0.5 T, and the interfacial fluctuation is weaker. No matter the position of magnetic field is horizontal or vertical, for different operating parameters, there is a corresponding reasonable magnetic field position where the steel/slag inter- face fluctuation can be properly controlled and slag entrapment can be prevented.

The research activities in EPM for several metallic materials are classified in the application of different magnetic field.The following research is exhibited in this article,(1)Effect of magnetic field on solidification process of monotectic alloys;(2)Effect of high magnetic field on fabrication of high-strength and high-conductivity copper alloys;(3)Numerical simulation of magnetic field and fluid flow in continuous casting mold with vertical electromagnetic brake;(4)Research on solidification structure of superalloy with EMS;(5)Effects of static magnetic field on the behavior of meniscus in a mold under argon gas injection.

A two-dimensional axisymmetric finite element model for stress distribution of billet in electromagnetic soft-contact continuous casting mould was established by a two-way coupled method.The contact state between solidified shell and mould was described to simulate the thermal-mechanical behaviors in the soft-contact mould.And the effects of frequencies and currents on stress distribution of billet had been discussed and analyzed.The results show that the equivalent stress of initial solidification shell both at its outer and inner surface decreases but at the bottom the equivalent stress of two sides of shell both increases when the current intensity is 1600 A,and the frequency is 20 kHz,compared with the status of conventional continuous casting.