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Loss of axonal contact characterizes Schwann cells in benign and malignant peripheral nerve sheath tumors (MPNST) from neurofibromatosis type 1 (NF1) patients. Tumor Schwann cells demonstrate NFl mutations, elevated Ras activity, and aberrant epidermal growth factor receptor (EGFR) expression. Using cDNA microarrays, we found that brain lipid binding protein (BLBP) is elevated in an EGFR-positive subpopulation of Nf1 mutant mouse Schwann cells (Nf1[sup -/-] TXF) that grows away from axons; BLBP expression was not affected by farnesyltransferase inhibitor, an inhibitor of H-Ras. BLBP was also detected in EGFR-positive cell lines derived from Nf1:p53 double mutant mice and human MPNST. BLBP expression was induced in normal Schwann cells following transfection with EGFR but not H-Ras12V. Furthermore, EGFR-mediated BLBP expression was not inhibited by dominant-negative H-Ras, indicating that BLBP expression is downstream of Ras-independent EGFR signaling. BLBP-blocking antibodies enabled process outgrowth from Nf1[sup -/-] TXF cells and restored interaction with axons, without affecting cell proliferation or migration. Following injury, BLBP expression was induced in normal sciatic nerves when nonmyelinating Schwann cells remodeled their processes. These data suggest that BLBP, stimulated by Ras-independent pathways, regulates Schwann cell-axon interactions in normal peripheral nerve and peripheral nerve tumors. [ABSTRACT FROM AUTHOR]

Neutrophils increase production of reactive oxygen species, including superoxide, hydrogen peroxide (H2O2), and hydroxyl radical, to destroy invading microorganisms under pathological conditions. Conversely, oxidative stress conditions, such as the presence of H2O2, induce neutrophil apoptosis, which helps to remove neutrophils after inflammation. However, the detailed molecular mechanisms that are involved in the latter process have not been elucidated. In this study, we investigated the potential role of olfactomedin 4 (Olfm4) in H2O2-induced superoxide production and apoptosis in mouse neutrophils. We have demonstrated that Olfm4 is not required for maximaldosage PMA- and Escherichia coli bacteria-induced superoxide production, but Olfm4 contributes to suboptimal-dosage PMA- and H2O2-induced superoxide production. Using an NADPH oxidase inhibitor and gp91phox-deficient mouse neutrophils, we found that NAPDH oxidase was required for PMA-stimulated superoxide production and that Olfm4 mediated H2O2-induced superoxide production through NADPH oxidase, in mouse neutrophils. We have shown that neutrophils from Olfm4-deficient mice exhibited reduced H2O2-induced apoptosis compared with neutrophils from wild-type mice. We also demonstrated that neutrophils from Olfm4-deficient mice exhibited reduced H2O2-stimulated mitochondrial damage and membrane permeability, and as well as reduced caspase-3 and caspase-9 activity, compared with neutrophils from wild-type mice. Moreover, the cytoplasmic translocation of the proapoptotic mitochondrial proteins Omi/HtrA2 and Smac/DIABLO in response to H2O2 was reduced in neutrophils from Olfm4-deficient mice compared with neutrophils from wild-type mice. Our study demonstrates that Olfm4 contributes to H2O2-induced NADPH oxidase activation and apoptosis in mouse neutrophils. Olfactomedin 4 might prove to be a potential target for future studies on inflammatory neutrophil biology and for inflammatory disease treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] • Five dinitrotoluene isomers are distinguished using terahertz spectroscopy. • DFT calculation method in terahertz region is discussed. • The steric effects lead to vibrational differences in low-frequency vibrations. Identifying dinitrotoluene (DNT) isomers has always been a challenging problem. In this study, five DNT isomers were investigated using terahertz time-domain spectroscopy (THz-TDS), which demonstrated significant spectral differences including variations in absorption positions and intensities. This suggests that THz-TDS is ideal for rapid identification of DNT isomers. We also employed density functional theory to further discuss the origin of these spectral differences. The results indicate that steric effects between substitute groups, rather than inter-molecular hydrogen bonding, lead to differences in low-frequency vibrations. [ABSTRACT FROM AUTHOR]

Serum human chorionic gonadotrophin (HCG) concentration is nearly always used to predict pregnancy but there is little data on the clinical utility of the ratio of HCG21/HCG14 combined with double measurement of serum HCG. A total of 1762 cycles were retrospectively analysed for serum HCG concentration and ratio of HCG21/HCG14 on days 14 and 21 after embryo transfer to determine whether the ratio combined with concentration is the optimal predictor of pregnancy. The medians of HCG concentration on days 14 and 21 combined with the ratio of HCG21/HCG14 were calculated for non-viable, viable and heterotopic pregnancies. HCG concentrations of 290 IU/l on day 14 and 2970 IU/l on day 21 were regarded as the cut-off values to predict viable pregnancy, and values of 630 and 12,000 IU/l, respectively, were regarded as the cut-off values to predict multiple pregnancy. The ratio of HCG21/ HCG14 in the viable pregnancy group was significantly higher than that in the non-viable pregnancy group (15.86 versus 5.27, P < 0.0001). For heterotopic pregnancy, the ratio of HCG21/HCG14 was 11.93. It was concluded that HCG concentration on days 14 and 21 combined with the ratio of HCG21/HCG14 provides a useful predictor of pregnancy outcome. A ratio > 15 may predict viable pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of oral contraceptive pill (OCP) as therapy for endometrial hyperplasia (EH) without atypia in reproductive-aged women compared with oral progestin. Methods: A retrospective cohort study was carried out in our reproductive center. Consecutive patients diagnosed with infertility and non-atypical EH identified through electronic database who met inclusion criteria (n=309). Patients were assigned to two treatment groups: OCP (n=216) and oral progestin (n=93); clinical and reproductive outcomes were recorded. Results: Reversal of EH to normal endometrium, clinical pregnancy, live birth and miscarriage rate. Women in OCP group were younger, had higher prevalence of Polycystic Ovary Syndrome and other uterine pathology and longer duration of infertility than women in progestin group. Reversal of EH was observed in 93.52% women on OCP and in 86.02% women on progestin (p=0.032; adjusted odds ratio [aOR]= 2.35; 95% confidence interval [CI]=1.06-5.21) after the initial course of treatment for 2 to 6 months. Cyclic OCP (n=184) resulted in better response to treatment compared to continuous OCP (n=32) (95.11% vs. 84.38%; p=0.039; aOR =3.60; 95% CI =1.12-11.55). Clinical pregnancy rate in OCP group was marginally higher than progestin group (87/208, 41.83% vs. 27/90, 30.00%; p=0.054). Miscarriage (25.29% vs. 29.63%; p=0.654) and live birth rate (31.25% vs. 21.11%; p=0.074) were comparable between the groups. Conclusion: For the first time we demonstrate that OCP is an effective therapy for nonatypical EH and is associated with higher remission rate compared with oral progestin. Reproductive outcomes are reassuring and comparable between the two groups. [ABSTRACT FROM AUTHOR]

A novel strategy to prepare spherical crystals of 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105) has been developed by introducing polymeric additives into the antisolvent emulsion crystallization. The spherical crystals are induced by modifying the intermolecular hydrogen bonds network of LLM-105. The results show that the concentration of polyvinylpyrrolidone (PVP), which acts as a polymeric additive, is a crucial factor to get quite different morphologies of LLM-105 crystal products. X-like shaped crystals have been produced in the absence of PVP. In contrast, spherical crystals have been obtained in the presence of PVP. Importantly, LLM-105 spherulites with a mean particle size of 78.0 μm can be obtained by adding a proper amount of PVP, which has a narrow size distribution (CV = 31.2). In addition, time-resolved morphological evolution processes of X-like shaped and spherical crystals have been performed. Meanwhile, 1H NMR experiments also have been conducted to understand the intermolecular hydrogen bonds between LLM-105 molecules and the polymer. Inspired by the result of the above experiments, an LLM-105 spherulitic formation mechanism has been proposed. Furthermore, LLM-105 spherulites exhibit more excellent mechanical and safety properties. It is suggested that these spherulites have a great potentiality in the military application. Therefore, this polymer-induced spherical crystallization method is significantly important for the design and fabrication of organic small molecules with spherical shapes. [ABSTRACT FROM AUTHOR]

A novel strategy to fabricate diverse α-Mn2O3 nanostructures from the nitrogen-rich energetic coordination polymer (ECP) [Mn(BTO)(H2O)2]n (BTO = 1H,1′H-[5,5′-bitetrazole]-1,1′-bis(olate)) has been developed by changing the pyrolysis atmosphere. The results show that the energetic constituent and calcination environment are vital factors to get quite different morphologies of pyrolysis products. When the calcination reaction occurs under N2 or O2, rod-shaped mesoporous α-Mn2O3 with a large specific surface of 50.2 m²·g-1 and monodispersed α-Mn2O3 with a size of 10-20 nm can be obtained, respectively, which provides a new platform to prepare specific shapes and sizes of manganese oxides. Inspired by the transformation of 1 under O2 atmosphere, we applied an in situ generated ultrafine α-Mn2O3 catalyst in the decomposition of ammonium perchlorate (AP) using ECP 1 as a precursor. The catalytic process of AP shows a remarkable decreased decomposition temperature (271 °C) and a narrower decomposition interval (from 253 to 275 °C). To our best knowledge, with such a low metal loading (0.65 wt %), the catalytic performance of in situ generated monodispersed ultrafine α-Mn2O3 is by far the best, which suggests that this ultraefficient catalyst has great potential in AP-based propellants. [ABSTRACT FROM AUTHOR]

Two novel metal-organic frameworks, [Ag(ATZ)]n (1) (ATZ = 5-amino-tetrazole) and [Ag2(en)2(AT)]n (2) (en = ethylenediamine, AT = 5,5'-azotetrazolate), were prepared from corresponding Ag(I) salts and have been structurally characterized by elemental analysis, Fourier transform infrared spectroscopy and single crystal and powder X-ray diffraction. The structures of both compounds consist of 2-D three-connected layers that are linked by π-π overlap interactions between the tetrazolate fragments in neighbouring layers to form a 3-D supramolecular structure. The photoluminescence properties of solid samples of 1 and 2 at room temperature and their photocatalytic performance have also been reported and discussed. The results indicate that 1 seems to be a good candidate for a novel inorganic-organic photoactive material with high quantum yield. Moreover, compounds 1 and 2 represent the first examples of coordination polymers with a Ag ion that exhibit high, efficient photocatalytic abilities for dye degradation under UV light and show good stability toward photocatalysis. [ABSTRACT FROM AUTHOR]

Hydroxyurea (HU) is effectively used in the management of β-hemoglobinopathies by augmenting the production of fetal hemoglobin (HbF). However, the molecular mechanisms underlying HU-mediated HbF regulation remain unclear. We previously reported that overexpression of the HU-induced SAR1 gene closely mimics the known effects of HU on K562 and CD34+ cells, including γ-globin induction and cell-cycle regulation. Here, we show that HU stimulated nuclear factor-кB interaction with its cognate-binding site on the SAR1 promoter to regulate transcriptional expression of SAR1 in K562 and CD34+ cells. Silencing SAR1 expression not only significantly lowered both basal and HU-elicited HbF production in K562 and CD34+ cells, but also significantly reduced HU-mediated S-phase cell-cycle arrest and apoptosis in K562 cells. Inhibition of c-Jun N-terminal kinase (JNK)/ Jun phosphorylation and silencing of Giα expression in SAR1-transfected K562 and CD34+ cells reduced both γ-globin expression and HbF level, indicating that activation of Giα/JNK/Jun proteins is required for SAR1-mediated HbF induction. Furthermore, reciprocal coimmunoprecipitation assays revealed an association between forcibly expressed SAR1 and Giα2 or Giα3 proteins in both K562 and nonerythroid cells. These results indicate that HU induces SAR1, which in turn activates γ-globin expression, predominantly through the Giα/JNK/Jun pathway. Our findings identify SAR1 as an alternative therapeutic target for α-globin disorders. [ABSTRACT FROM AUTHOR]

2,4,6,8-Hexanitro-2,4,6,8,10,12-hexaazatetracyclododecane (CL-20) is the most powerful explosive applied, and CL-20-based energetic--energetic co-crystals are promising new alternative explosives with tunable power and safety, resulting in much interest in them. This work discusses the structural, electronic and energetic features of three CL-20 polymorphs, β, γ and ε forms, and three CL-20-based energetic--energetic co-crystals, CL-20/TNT, CL-20/HMX and CL-20/BTF. As a result, we find that, relative to the pure CL-20 polymorphs, the co-crystallization of CL-20 with HMX, TNT and BTF cause little molecular deformation except from some torsion of its nitro groups, and the narrower band gaps. And dominantly, the O⋯O, O⋯H and O⋯N interactions hold all the crystal packing. There is possibly thermodynamic and kinetic dominance in the CL-20/TNT and CL-20/HMX, and CL-20/BTF co-crystallization, respectively, in terms of their formation energy. Further, a rough criterion for predicting energetic co-crystal formation is obtained, as the solubility parameter difference of two coformers of a binary energetic co-crystal is less than 8 MPa0.5. [ABSTRACT FROM AUTHOR]

Chronic granulomatous disease (CGD) patients have recurrent life-threatening bacterial and fungal infections. Olfactomedin 4 (OLFM4) is a neutrophil granule protein that negatively regulates host defense against bacterial infection. The goal of this study was to evaluate the impact of Olfm4 deletion on host defense against Staphylococcus aureus and Aspergillus fumigatus in a murine X-linked gp91phox-deficiency CGD model. We found that intracellular killing and in vivo clearance of S. aureus, as well as resistance to S. aureus sepsis, were significantly increased in gp91phox and Olfm4 double-deficient mice compared with CGD mice. The activities of cathepsin C and its downstream proteases (neutrophil elastase and cathepsin G) and serum levels of IL-1β, IL-6, IL-12p40, CXCL2, G-CSF, and GM-CSF in Olfm4-deficient as well as gp91phox and Olfm4 double-deficient mice were significantly higher than those in WT and CGD mice after challenge with S. aureus. We did not observe enhanced defense against A. fumigatus in Olfm4-deficient mice using a lung infection model. These results show that Olfm4 deletion can successfully enhance immune defense against S. aureus, but not A. fumigatus, in CGD mice. These data suggest that OLFM4 may be an important target in CGD patients for the augmentation of host defense against bacterial infection. [ABSTRACT FROM AUTHOR]

Human serum albumin (HSA) is widely used in clinical and cell culture applications. Conventional production of HSA from human blood is limited by the availability of blood donation and the high risk of viral transmission from donors. Here, we report the production of Oryza sativa recombinant HSA (OsrHSA) from transgenic rice seeds. The level of OsrHSA reached 10.58% of the total soluble protein of the rice grain. Large-scale production of OsrHSA generated protein with a purity >99% and a productivity rate of 2.75 g/kg brown rice. Physical and biochemical characterization of OsrHSA revealed it to be equivalent to plasma-derived HSA (pHSA). The efficiency of OsrHSA in promoting cell growth and treating liver cirrhosis in rats was similar to that of pHSA. Furthermore, OsrHSA displays similar in vitro and in vivo immunogenicity as pHSA. Our results suggest that a rice seed bioreactor produces cost-effective recombinant HSA that is safe and can help to satisfy an increasing worldwide demand for human serum albumin. [ABSTRACT FROM AUTHOR]