Lead-free piezoelectric ceramics derived from the solid solution of (1−x)(Na0.5Bi0.5)TiO3–xBiAlO3 (NBT-BA) (x=0–0.10) have been synthesized by solid state reactions. A pure perovskite phase was formed for x≤0.08. The temperature dependence of dielectric constant indicates an increased broadness of the dielectric peak as the amount of BA increases. The large dielectric loss of NBT ceramics at low frequency and high temperature has been significantly reduced by the substitution of BA. The high coercive field is decreased and ferroelectric hysteresis loops were displayed at room temperature. The NBT-BA ceramics exhibit improved ferroelectric and piezoelectric properties compared to pure NBT ceramics, with Pr=52 μC/cm2, Ec=44 kV/cm, d33=130 pC/N, and kp=0.23 for 0.92NBT–0.08BA.

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A new lead-free perovskite solid solution of ͑1−x͒BaTiO 3 -xBiAlO 3 ͑x = 0.02, 0.05, 0.10, and 0.15͒ that exhibits ferroelectric properties and relaxor behavior has been synthesized by solid state reactions. X-ray diffraction patterns show a transformation from the tetragonal symmetry into a rhombohedral symmetry as a result of the substitutions of Bi 3+ on the A site and Al 3+ on the B site in the crystal lattice of BaTiO 3 . The temperature and frequency dependences of the dielectric constant indicate a crossover from a normal ferroelectric to relaxor behavior. The degree of deviation from the Curie-Weiss law is found to increase with the increasing amount of BiAlO 3 . The high-temperature slope of the dielectric peak for x = 0.05, 0.1 and, 0.15 can be well described by a Lorenz-type relation. Typical relaxor behavior is observed for x = 0.15 with the temperature of the dielectric peak T m = 360 K at 1 kHz, while ferroelectric hysteresis loop is displayed at room temperature. This suggests that the long-range polar order from the end member BaTiO 3 persists and coexists with polar nanoregions induced by the chemical disorder following the coupled substitutions in the solid solution.

Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by progressive inflammation and tissue damage in salivary glands and lacrimal glands. Our previous studies showed that myeloid-derived suppressor cells (MDSCs) exhibited impaired immunosuppressive function during disease progression in patients with SS and mice with experimental Sjögren’s syndrome (ESS), but it remains unclear whether restoring the function of MDSCs can effectively ameliorate the development of ESS. In this study, we found that murine olfactory ecto-mesenchymal stem cell-derived exosomes (OE-MSC-Exos) significantly enhanced the suppressive function of MDSCs by upregulating arginase expression and increasing ROS and NO levels. Moreover, treatment with OE-MSC-Exos via intravenous injection markedly attenuated disease progression and restored MDSC function in ESS mice. Mechanistically, OE-MSC-Exo-secreted IL-6 activated the Jak2/Stat3 pathway in MDSCs. In addition, the abundant S100A4 in OE-MSC-Exos acted as a key factor in mediating the endogenous production of IL-6 by MDSCs via TLR4 signaling, indicating an autocrine pathway of MDSC functional modulation by IL-6. Taken together, our results demonstrated that OE-MSC-Exos possess therapeutic potential to attenuate ESS progression by enhancing the immunosuppressive function of MDSCs, possibly constituting a new strategy for the treatment of Sjögren’s syndrome and other autoimmune diseases.

Although the expansion of myeloid-derived suppressor cells (MDSCs) has been reported in autoimmune disorders, it is largely unclear how MDSCs contribute to the development of primary Sjögren syndrome (pSS). In this study, we found significantly increased MDSCs with gradually diminished suppressive capacity during disease development in mice with experimental Sjögren syndrome (ESS). The ligand for glucocorticoid-induced TNFR family-related protein (GITRL) was increased along ESS progression, whereas the increased GITRL was found to attenuate the immunosuppressive function of MDSCs. Moreover, blocking GITR signal in MDSCs significantly restored their immunosuppressive function and alleviated ESS progression in mice. In pSS patients, expanded MDSCs were found to express low levels of arginase. Significantly increased serum GITRL levels were closely correlated with patients with higher Sjögren syndrome disease activity index. Furthermore, treatment with recombinant GITRL markedly reduced the immunosuppressive function of human MDSCs. Together, our studies have demonstrated a critical role of GITRL in modulating the suppressive function of MDSCs, which may facilitate the validation of GITRL as a therapeutic target for the treatment of pSS.

Olfactory ecto-mesenchymal stem cells (OE-MSCs) are a novel population of resident stem cells in the olfactory lamina propria with strong immunosuppressive function. Exosomes released by MSCs are considered to carry various mRNAs, microRNAs and proteins from cells and function as an extension of MSCs. However, it remains unclear whether exosomes derived from OE-MSCs (OE-MSCs-Exos) possess any immunoregulatory functions. In this study, we found that OE-MSCs-Exos possessed strong suppressive function in CD4+T cell proliferation, accompanied by reduced IL-17, IFN-γ and enhanced TGF-β, IL-10 secreted by T cells. In experimental colitis mice, treatment of OE-MSCs-Exos markedly alleviated the severity of disease, and Th1/Th17 subpopulations were remarkably reduced whereas Treg cells were increased after OE-MSCs-Exos treatment. Mechanistically, OE-MSCs-Exos were demonstrated to inhibit the differentiation of Th1 and Th17 cells, but promote the induction of Treg cells in vitro. Taken together, our findings identified a novel function of OE-MSCs-Exos in regulating T-cell responses, indicating that OE-MSCs-Exos may represent a new cell-free therapy for the treatment of IBD and other inflammatory diseases.

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Lung cancer is a global health problem. The search for new therapeutic approaches for the treatment of lung cancer is important. Here, we reported that the AKT inhibitor perifosine and the MEK\ERK inhibitor MEK-162 synergistically induced lung cancer cell (A549 and H460 lines) growth inhibition and apoptosis. The combined efficiency was significantly higher than either agent alone. For the molecular study, perifosine and MEK-162 worked together to concurrently block AKT, mammalian target of rapamycin (mTOR) complex 1 (mTORC1), and MEK-ERK signalings in lung cancer cells, while either agent alone only affected one or two signalings with lower efficiency. In vivo, MEK-162 and perifosine co-administration dramatically inhibited A549 lung cancer xenograft growth, without inducing apparent toxicities. The synergistic activity in vivo was again superior than either agent alone. Thus, perifosine and MEK-162 combination is biologically plausible by acting through effects on different proliferation and survival-related signaling pathways. Our in vitro and in vivo results support the feasibility of investigating the synergism regimen in clinical tests.