The mechanisms underlying immunomodulatory ability of mesenchymal stromal cells (MSCs) remain unknown. Recently, studies suggested that the immunomodulatory activity of MSCs is largely mediated by paracrine factors. Among which, exosome is considered to play a major role in the communication between MSCs and target tissue. The aim of our study is to investigate the effect of MSCs-derived exosome on peripheral blood mononuclear cells (PBMCs), especially T cells. We find that the MSCs-derived exosome extracted from healthy donors' bone marrow suppressed the secretion of pro-inflammatory factor TNF-α and IL-1β, but increased the concentration of anti-inflammatory factor TGF-β during in vitro culture. In addition, exosome may induce conversion of T helper type 1 (Th1) into T helper type 2 (Th2) cells and reduced potential of T cells to differentiate into interleukin 17-producing effector T cells (Th17). Moreover, the level of regulatory T cells (Treg) and cytotoxic T lymphocyte-associated protein 4 were also increased. These results suggested that MSC-derived exosome possesses the immunomodulatory properties. However, it showed no effects on the proliferation of PBMCs or CD3+ T cells, but increases the apoptosis of them. In addition, indoleamine 2, 3-dioxygenase (IDO) was previously shown to mediate the immunoregulation of MSCs, which was increased in PBMCs co-cultured with MSCs. In our study, IDO showed no significant changes in PBMCs exposed to MSCs-derived exosome. We conclude that exosome and MSCs might differ in their immune-modulating activities and mechanisms.

The measurement of polymer growth is an essential element in characterization of assembly. We have developed a precise method of measuring the growth of sickle hemoglobin polymers by observing the time required for polymers to traverse a photolytically produced channel between a region in which polymers are created and a detection region. The presence of the polymer is functionally detected by observing its ability to create new polymers through the well-established process of heterogeneous nucleation. Using this method, we have determined the rate constants for monomer addition to and release from polymer ends, as well as their temperature dependences. At 25°C we find k(+) = 84 ± 2 mM⁻¹ s⁻¹ and k(-) = 790 ± 80 molecules/s from each end. These numbers are in accord with differential interference contrast measurements, and their ratio gives a solubility measured on individual fibers. The single-fiber solubility agrees with that measured in sedimentation experiments. The concentration dependence of the monomer addition rate is consistent with monomer addition, but not oligomer addition, to growing polymers. The concentration dependence suggests the presence of an activation enthalpy barrier, and the rate of monomer addition is not diffusion-limited. Analysis of the temperature dependence of the monomer addition rate reveals an apparent activation energy of 9.1 ± 0.6 kcal/mol.

The development of antiferroelectric (AFE) materials with high recoverable energy-storage density (W rec ) and energy-storage efficiency (η) is of great importance for meeting the requirements of miniaturization and integration for advanced pulse power capacitors. However, the drawbacks of traditional AFE materials, namely, high critical field (E cr ) and low W rec , make them unsuitable to be utilized in practical applications. To increase W rec and η, here we report an effective approach using the transient liquid-phase sintering and the softening of antiferroelectric order to decrease the porosity, enhance the dielectric breakdown strength (DBS), and increase the maximum electric-field-induced polarization (P max ) of the AFE ceramics. On the basis of this concept, a novel solid solution of (1 − x)PbHfO 3 −xPb(Mg 1/2 W 1/2 )O 3 [(1 − x)PHf−xPMW] was designed and prepared in the form of ceramics by the solid-state reaction method. Their crystal structures, phase transitions, dielectric properties, and energy-storage properties were investigated systemically. X-ray diffraction analysis indicates the formation of solid solution with a partial order on the B site at room temperature in a broad composition range. Dielectric measurements reveal that the AFE to ferroelectric (FE) phase-transition temperature shifts toward room temperature with the increasing Pb(Mg 1/2 W 1/2 )O 3 (PMW) content. The optimal energy-storage performance is found for the 0.90PHf−0.10PMW ceramic with the highest W rec of 3.7 J/cm 3 (at a relatively low electric field of 155 kV/cm) and a favorable η of 72.5% among all of the studied compositions, which is much superior to that of the so far reported perovskite ceramics under the similar electric fields. This is the first reported PHf-based solid solution with ultrahigh energy-storage density. The enhanced energy-storage performance can be attributed to the improved DBS and enhanced P max (45 μC/cm 2 ) due to the incorporation of PMW that leads to dense microstructure and softens the antiferroelectricity. The results show that the (1 − x)PHf−xPMW ceramics form a new family of promising AFE candidates with significantly enhanced DBS, W rec , and η. This work also demonstrates the design methodology for developing not only the PbHfO 3 -based but also other new AFE−AFE solid solution material for high-energy-storage applications.

Purpose The purpose of this paper is to investigate how audit fees change in responding to the financial crisis of 2008. It also examines auditors’ perceived risk and how they priced the risk in the financial crisis. Design/methodology/approach Using a sample of 20,930 firm-year observations, this paper examines the change of audit fees before, during and after the financial crisis, as well as the relationship between audit fees and restatements. Furthermore, this study investigates whether this relationship between audit fees and restatements strengthened during the financial crisis. Findings The paper finds that audit fees increase as a result of the macro-systemic risks from the crisis. It also finds that there is a significantly positive relationship between audit fees and restatements, which is a proxy of risk factors related to poor financial reporting quality and poor audit quality. However, the results show that there is no significant change of the fees–restatements relationship in the financial crisis period. Research limitations/implications The main limitation of this study is that no definite answer can be provided for the question that whether auditors believe that poor audit quality and audit failures are leading up to the financial crisis. The test rejects the alternative hypothesis. However, it does not necessarily prove the null hypothesis is true. Originality/value This paper contributes to the current literature by analyzing not only the impact of the financial crisis on audit fees, but also how the accounting profession views its own role in the financial crisis.

The standard treatment for aplastic anemia (AA) in young patients is a matched sibling hematopoietic stem cell transplant. Transfusion of a chronic AA patient with allogeneic bone marrow–derived mesenchymal stromal cells (BMMSCs) is currently being developed as a cell-based therapy, and the safety and efficacy of such transfusions are being continuously improved. Nevertheless, the mechanisms by which BMMSCs exert their therapeutic effects remain to be elucidated. In this study, mesenchymal stromal cells (MSCs) obtained from bone marrow donors were concentrated and intravenously injected into 15 chronic AA patients who had been refractory to prior immunosuppressive therapy. We showed that BMMSCs modulate the levels of Th1, Th2, Th17 and Treg cells, as well as their related cytokines in chronic AA patients. Furthermore, the percentages of Th1 and Th17 cells among the H-MSCs decreased significantly, while the percentage Treg cells increased. The Notch/RBP-J/FOXP3/RORγt pathway was involved in modulating the Treg/Th17 balance after MSCs were transfused in vitro. Additionally, the role played by transfused MSCs in regulating the Treg/Th17 balance via the Notch/RBP-J/FOXP3/RORγt pathway was further confirmed in an AA mouse model. In summary, in humans with chronic AA, BMMSCs regulate the Treg/Th17 balance by affecting the Notch/RBP-J/FOXP3/RORγt pathway.