SummaryAplastic anaemia (AA) is thought to be an autoimmune-mediated disease with active destruction of haematopoietic cells through a T helper type 1 (Th1) cell response. Interleukin (IL)-17 is a potent proinflammatory cytokine produced by activated memory T cells. Recent studies indicate that IL-17 might be an essential effector cytokine in the T-cell mediated autoimmune process. It can drive the production of tumour necrosis factor-a (TNF-a), IL-1 b, IL-6 and IL-8 by a variety of cells. The present study investigated the genetic and protein expression of IL-17 in patients with AA. The effect of IL-17 on IL-6 and IL-8 production by macrophages was also studied. AA patients showed an elevated expression of IL17A mRNA in bone marrow mononuclear cells and peripheral blood mononuclear cells. Higher IL-17 in bone marrow and peripheral blood plasma was also observed in AA patients compared with normal controls. IL-17 induced the production of IL-6 and IL-8 by macrophages both from patients with AA and normal controls. IL-17 stimulation also resulted in the production of TNF-a. These results suggested that elevated expression of IL-17 and IL-17-induced IL-6, IL-8 and TNF-a may be involved in the mechanisms of AA.

T helper 17 (Th17) cells and regulatory T (Treg) cells, along with Th1 and Th2 cells, may contribute to the development of immune thrombocytopenia (ITP). The imbalance of Th17/Treg toward Th17 cells has been shown to play a pivotal role in the peripheral immune response. Notch signaling has been implicated in peripheral T-cell activation and effector cell differentiation. However, the role of Th17/Treg in the pathogenesis of ITP and the effect of Notch signaling on Th17/Treg imbalances remain largely elusive in ITP. In vitro, we treated peripheral blood mononuclear cells (PBMCs) from ITP and healthy controls with g-secretase inhibitor (DAPT). Th17 cells and Treg cells were measured by flow cytometry and IL-17, IL-21, and IL-10 secretion by enzyme immunoassay technique. The mRNA expression of Ntoch1, Hes1, Hey1, RORgt, and Foxp3 was investigated by RT-PCR. Cell proliferation and apoptosis were determined by the Cell Counting Kit-8 and apoptosis detection kit. We demonstrated that DAPT was effective in inhibiting mRNA expression of Notch signaling molecules. In untreated cultured PBMCs from ITP patients, we observed elevated Th17 cell and IL-21 levels and RORgt mRNA expression, decreased Treg cells and Foxp3 mRNA expression, and an increased ratio of Th17/Treg and RORgt/Foxp3. After inactivating Notch signal by DAPT, Th17 cells and Th17/Treg ratio were dose dependently decreased and accompanied by the reduction of IL-17 in culture supernatants and RORgt mRNA expression in ITP patients. However, no significant difference was found for Treg cells and Foxp3 mRNA expression, RORgt/Foxp3 ratio, and IL-21 and IL-10 levels after DAPT treatment in ITP patients. We also present evidence that the effect of DAPT inhibition on the Th17 cell response was associated with downregulation of RORgt and IL-17 transcription using human in vitro polarization. In conclusion, our findings highlight the importance of Notch signaling in Th17/Treg imbalances in ITP. Inactivation of Notch signaling might be a potential immunoregulatory strategy in ITP patients.

MXenes are normally used for energy storage applications. However, large nanosheets and restacking are detrimental to the ion diffusion and thus limit its rate capability. Here, a strategy to prepare flexible and porous MXene−M supercapacitor electrodes can simultaneously enlarge the interlayer spacing between layers and create holes in the layers. As a result, Ti 3 C 2 T x −Mn presents an excellent lifespan, with still 248 F g −1 after 100 000 cycles at a current density of 100 A g −1 . Moreover, Ti 3 C 2 T x −Mn-based symmetric all-solid-state supercapacitor exhibits outstanding volumetric energy up to 52.4 mWh cm −3 and retains 38.4 mWh cm −3 at an ultrahigh volumetric power density of 55.3 W cm −3 . We believe this work provides an idea for the later regulation of MXene layer spacing and the design of porous structures, and can be widely used in the next-generation high-energy density and power density practical applications.

Acute myeloid leukemia (AML) is a hematological tumor in which progress T helper (Th) subsets including Th22, Th17, and Th1 cells play a pivotal role. However, the role of T helper (Th) subsets in the immune pathogenesis of AML remains unclear. Here, we investigated frequencies of Th22, Th17, pure Th17, and Th1 cells in the peripheral blood (PB) of AML patients. We demonstrated that Th22, Th17, and pure Th17 in newly-diagnosed (ND) and non-complete remission (Non-CR) AML patients and plasma IL-22 in ND AML patients were significantly increased. Retinoid-related orphan receptor C (RORC) expression was significantly elevated in CR and Non-CR AML patients. However, Th1 in ND AML patients and IL-17 in ND, Non-CR or CR AML patients was significantly decreased compared with controls. Moreover, Th22 and IL-22 showed positive correlation with pure Th17, but Th22 showed negative correlation with Th1 in ND AML patients. RORC showed positive correlation with Th22 and approximately positive correlation with pure Th17 in Non-CR patients. PB blast cell showed positive correlation with Th22 and negative correlation with Th1 in ND AML patients. Our results indicate that Th22 and pure Th17 cells conjointly contribute to the pathogenesis of AML and might be promising novel clinical index for AML.

It is a big challenge to homogenize heterogeneous catalysts with molecular catalytic performance. With this target in mind, herein, we describe a facile strategy for direct incorporation of single catalytic sites in 3D open porous aromatic frameworks (PAFs). The synthesis of the PAF (denoted as PAF‐76) as well as its derivatives (PAF‐76‐M, M=Fe, Mn, Zn) was achieved by the use of tetrakis(4‐bromophenyl)methane as tetrahedral nodes and tetrakis(4‐bromophenyl)porphyrin as planar nodes. The connection of monomers into an extended network of PAF‐76 was monitored by 13C NMR and FTIR spectroscopies. The prepared PAF‐76s showed 3D porous structures with surface areas of 450–700 m2 g−1, pore volumes of 0.3–0.4 cm3 g−1, and pore sizes around 1.2 nm. The direct incorporation of metalloporphyrin components into the PAF‐76‐M frameworks has allowed the uniform distribution of metal ionic sites throughout the PAF‐76‐M particles. The combined merits of isolated metal sites and suitable pore size make PAF‐76 a good candidate for heterogeneous catalysis. The catalytic performances of the porphyrin/metalloporphyrin‐based active sites in the PAF‐76s were evaluated by aerobic oxidation reactions of styrene, which are usually carried out with homogeneous systems. Metal‐functionalized PAF‐76s (PAF‐76‐M) exhibit enhanced turnover frequencies for styrene conversion (16.9–50.9 mol mol(M)−1 h−1) compared with molecular catalysts (0–35.0 mol mol(M)−1 h−1), and improved selectivity toward phenylacetaldehyde (85.7–99 %) in contrast to their corresponding monomers (0–75.5 %). The robustness of PAF‐76 in terms of high thermal stability, good recyclability, and excellent solvent resistance showed that these PAF‐76 materials hold great promise for developing heterogeneous catalysts.

Chronic autoimmune thrombocytopenic purpura (AITP) is characterized by platelet-specific autoantibody production that is influenced by enhanced antiplatelet T-helper cell reactivity. Costimulatory signals are absolutely required for T-cell activation and play key roles in the decision between tolerance and immunity. In this study we cultured T cells isolated from patients with chronic AITP to investigate the effects of the B7-blocking agent cytologic T-lymphocyte-associated antigen 4-immunoglobulin (CTLA4-Ig), and cyclosporin A (CsA), alone or in combination, on induction of platelet-specific Tcell anergy. The data showed that in most cases CTLA4-Ig and/or CsA could induce tolerance toward platelet antigens based on anergy. It could be overcome by stimulation with unrelated antigens, demonstrating its platelet specificity. The anergy is associated with lack of interleukin 2 (IL-2) and withheld by exogenous IL-2, emphasizing the pivotal role of IL-2 suppression in the induction of plateletspecific anergy. We also prospectively evaluated the efficacy of CsA therapy in patients with refractory AITP and observed that the response to CsA treatment in vivo was associated with the IntroductionChronic autoimmune thrombocytopenic purpura (AITP) is an autoimmune disorder characterized by antiplatelet autoantibody-mediated platelet destruction. Autoantibody production in AITP is associated with both T-cell activation and T-B cognate interaction. [1][2][3][4] Patients with AITP have enhanced T-cell reactivity against platelets that is measurable at both the bulk polyclonal T-cell level 5,6 and at the clonal level. 7,8 Optimal T-cell activation requires 2 signals. The first signal is based on T-cell receptor (TCR) recognition of peptide/major histocompatibility complex (MHC) complexes. The second signal is provided by interaction of CD28, CD2, and leukocyte factor antigen-1 (LFA-1) on T cells with their costimulatory ligands B7 (CD80 and CD86), LFA-3, and intercellular adhesion molecule-1 (ICAM-1), respectively, on antigenpresenting cells (APCs). Because the CD28 costimulatory pathway does not depend on intracellular calcium, the B7-CD28/CTLA-4 (cytologic T-lymphocyte-associated antigen 4) interaction is considered to provide the main signal that confers cyclosporin A (CsA)-resistant interleukin 2 (IL-2) production, whereas costimulation through other accessory molecules such as CD2 is calcium dependent and thus could be blocked by CsA. [9][10][11] B7 costimulation is involved not only in the induction stage of autoimmune response but also in the effector activation of autoreactive T cells for propagating autoimmune disease. 12-16 Semple et al 6 has observed an enhanced expression of CD80 on platelets from patients with AITP, implicating a role of B7/CD28 costimulation in the pathogenesis of AITP. 6 T-cell response(s) could be inhibited by administration of the cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin (CTLA4-Ig), a fusion protein comprising the extracellular domain of CTLA-4 and the Fc portion of human IgG...

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Highly stable and proton-conductive NH2-MIL-53 metal–organic framework nanomaterials have been successfully synthesized in an ionothermal system.