Myelodysplastic syndromes (MDS) are age-dependent stem cell malignancies that share biological features of activated adaptive immune response and ineffective hematopoiesis. Here we report that myeloid-derived suppressor cells (MDSC), which are classically linked to immunosuppression, inflammation, and cancer, were markedly expanded in the bone marrow of MDS patients and played a pathogenetic role in the development of ineffective hematopoiesis. These clonally distinct MDSC overproduce hematopoietic suppressive cytokines and function as potent apoptotic effectors targeting autologous hematopoietic progenitors. Using multiple transfected cell models, we found that MDSC expansion is driven by the interaction of the proinflammatory molecule S100A9 with CD33. These 2 proteins formed a functional ligand/receptor pair that recruited components to CD33's immunoreceptor tyrosine-based inhibition motif (ITIM), inducing secretion of the suppressive cytokines IL-10 and TGF-β by immature myeloid cells. S100A9 transgenic mice displayed bone marrow accumulation of MDSC accompanied by development of progressive multilineage cytopenias and cytological dysplasia. Importantly, early forced maturation of MDSC by either all-trans-retinoic acid treatment or active immunoreceptor tyrosine-based activation motif-bearing (ITAM-bearing) adapter protein (DAP12) interruption of CD33 signaling rescued the hematologic phenotype. These findings indicate that primary bone marrow expansion of MDSC driven by the S100A9/CD33 pathway perturbs hematopoiesis and contributes to the development of MDS.

As a large number of strain sensors are put into practical use, their stability should be considered, especially in harsh environments containing water or microorganisms, which could affect strain sensing. Herein, a novel strategy to overcome liquid interference is proposed. The strain sensor is constructed with a sandwich architecture through layer‐by‐layer (LBL) spray‐coating of a 3‐(aminopropyl)triethoxysilane (APTES) bonding layer and multi‐walled carbon nanotubes/graphene (MWCNT/G) conductive layers on an elastomeric polydimethysiloxane (PDMS) substrate, and is further decorated with silver (Ag) nanoparticles and the (heptadecafluoro‐1,1,2,2‐tetradecyl) trimethoxysilane (FAS, F in short) to obtain a F/Ag/MWCNG/G‐PDMS (FAMG) strain sensor. The superhydrophobicity and underwater oleophobicity of the outer cover layer causes this FAMG strain sensor surface to exhibit stable strain sensing resistant to liquid interference upon stretching in the Cassie−Baxter wetting state, and resistance to bacterial adhesion (Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli)). The sensor attains ultrasensitivity (with a maximum gauge factor of 1989 in the condition of liquid interference), broad strain range (0.1–170%), fast response time (150 ms), and stable response after 1000 stretching–releasing cycles. The ultrasensitivity is provided by propagation of cracks in MWCNT/G conductive layers and terminal fracture of the intermediate separating layers (APTES/MWCNT/G). The microbridge effect of MWCNTs and slippage of APTES/MWCNT/G provide a large strain range. The FAMG strain sensor is successfully used to monitor a series of human activities and an electronic bird under artificial rain and bacterial droplets, indicating the potential use of this sensor in complex environments.

Hepatitis-associated aplastic anemia (HAAA) is a variant of severe aplastic anemia (SAA) in which bone marrow failure follows an acute attack of hepatitis. Its pathogenesis is poorly understood. We investigated the prevalence of HAAA among cases of newly diagnosed SAA presenting to our hospital between January 1998 and February 2013, and analyzed the clinical and immune characteristics of HAAA and non-hepatitis-associated SAA (non-HASAA) patients. The prevalence of HAAA among cases of SAA was 3.8% (36/949), and the majority of patients (33/36) were seronegative for a known hepatitis virus. Compared with non-HASAA patients, HAAA patients had a larger proportion of CD8+ T cells, a lower ratio of CD4+/CD8+ T cells, and a smaller proportion of CD4+CD25+ regulatory T cells. There was no significant difference in peripheral blood count, bone marrow cellularity, or the number of blood transfusions received between HAAA and non-HASAA patients. HAAA patients had a higher early infection rate and more infection-related mortality in the first 2 years after diagnosis than non-HASAA patients, and their 2-year survival rate was lower. The results demonstrate that HAAA patients have a more severe T cell imbalance and a poorer prognosis than non-HASAA patients.

The aim of the present study was to investigate the number and function of CD8+HLA-DR+ cells, which are considered to be activated cytotoxic T lymphocytes (CTLs), in peripheral blood to further examine the pathogenesis of severe aplastic anemia (SAA). Thirty-eight patients with SAA were included in the present study. Patients were screened for paroxysmal nocturnal hemoglobinuria by flow cytometry using anti-CD55 and anti-CD59 antibodies. The number of CD8+HLA-DR+ T cells was measured by three-color flow cytometry using anti-CD8-peridinin chlorophyll, anti-CD3-fluorescein isothiocyanate (FITC) and anti-HLA-DR-FITC antibodies. The expression of perforin, granzyme B, tumor necrosis factor-β (TNF-β) and FasL in CD8+HLA-DR+ T cells was detected by flow cytometry with the appropriate monoclonal antibodies. Total RNA was prepared from purified CD8+HLA-DR+ cells of healthy controls and SAA patients, and then polymerase chain reaction (PCR) was performed. Apoptosis of CD8+HLA-DR+ cells was detected by flow cytometry following staining with Annexin V. The proportion of CD8+HLA-DR+ T cells was analyzed by flow cytometry in peripheral blood and was identified to be significantly higher in untreated SAA than in remission patients and in the controls. The expression of perforin, granzyme B, TNF-β and FasL in CD8+HLA-DR+ T cells was analyzed by flow cytometry and PCR, which revealed increased expression in the untreated SAA group compared with that in the control group. Furthermore, the apoptosis of CD3- bone marrow cells from normal individuals was enhanced following co-culture with CD8+HLA-DR+ T cells from untreated SAA patients. In conclusion, the present study demonstrated that CD8+HLA-DR+ T cells may contribute to bone marrow failure in SAA.

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