Cirmtuzumab inhibits Wnt5a-induced Rac1 activation in chronic lymphocytic leukemia treated with ibrutinib.

Signaling via the B cell receptor (BCR) plays an important role in the pathogenesis and progression of chronic lymphocytic leukemia (CLL). This is underscored by the clinical effectiveness of ibrutinib, an inhibitor of Bruton's tyrosine kinase (BTK) that can block BCR-signaling. However, ibrutinib cannot induce complete responses (CR) or durable remissions without continued therapy, suggesting alternative pathways also contribute to CLL growth/survival that are independent of BCR-signaling. ROR1 is a receptor for Wnt5a, which can promote activation of Rac1 to enhance CLL-cell proliferation and survival. In this study, we found that CLL cells of patients treated with ibrutinib had activated Rac1. Moreover, Wnt5a could induce Rac1 activation and enhance proliferation of CLL cells treated with ibrutinib at concentrations that were effective in completely inhibiting BTK and BCR-signaling. Wnt5a-induced Rac1 activation could be blocked by cirmtuzumab (UC-961), an anti-ROR1 mAb. We found that treatment with cirmtuzumab and ibrutinib was significantly more effective than treatment with either agent alone in clearing leukemia cells in vivo. This study indicates that cirmtuzumab may enhance the activity of ibrutinib in the treatment of patients with CLL or other ROR1+ B-cell malignancies

Recent progress of mesoporous silica materials

Since the synthesis of novel mesoporous silica materials in 1992, the materials have become a great demand in many research fields. The authors reviewed the synthesis of mesoporous silica materials and their classification, their formation mechanism, as well as the aspects of controlling porosity and recent progresses of their applications. The mesoporous silica materials may be found great utility in catalysis and nano-technology etc

The economic burden of influenza-associated outpatient visits and hospitalizations in China: a retrospective survey

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Effect of Ti-doping on the framework Structure of Mesoporous silica

The Ti-doped mesoporous silica MCM-41 materials were synthesized under basic condition at room temperature. The characteristics of samples were investigated by using XRD, HREM, IR, and N-2 adsorption techniques. The results show that Ti ions can get into the Si frame work and lead to the vibration of Si-O-Ti bond, with the increase of Ti ion addition, the mesoporous silica framework structure can be disordered and finally deteriorated

Study on the synthesis and mechanism of mesoporous silica with hexastyle structure

The mesoporous silica MCM-41 materials with hexastyle structure were synthesized under strongly acidic condition. The characteristics of samples were investigated by using XRD, N-2 adsorption, HREM, and SEM techniques. The results show that MCM-41 powder with hexastyle structure, which is wormlike in micrometer-scale, consists of thousands of mesoporous channels in nano-scale. The morphogenesis of hexastyle mesoporous silica is due to the accretion of surfactant micella combined with silica oligmers in the low concentration of TEOS

Synthesis of ordered mesoporous aluminosilicate under a low surfactant/silica molar ratio condition

Ordered mesoporous aluminosilicate materials with atomic Si/Al ratios of 16 similar to 64 were synthesized at a very low molar ratio of surfactant/silica (0.12) by using aluminium chloride hexahydrate and TEOS as the sources of aluminium and silicon. The resulting materials were characterized by XRD, TEM, FTIR and nitrogen sorption. As the NaOH/Si molar ratio increases from 0.2 to 0.6, the products obtained change from hexagonal MCM-41 to cubic MCM-48. The quality of the product rapidly deteriorates as the aluminium content of the solid increases beyond a certain limit. XRD shows that the substitution of the silicon by the large aluminium atoms leads to the expansion of the unit cell

QTL Mapping of Combining Ability and Heterosis of Agronomic Traits in Rice Backcross Recombinant Inbred Lines and Hybrid Crosses

BACKGROUND: Combining ability effects are very effective genetic parameters in deciding the next phase of breeding programs. Although some breeding strategies on the basis of evaluating combining ability have been utilized extensively in hybrid breeding, little is known about the genetic basis of combining ability. Combining ability is a complex trait that is controlled by polygenes. With the advent and development of molecular markers, it is feasible to evaluate the genetic bases of combining ability and heterosis of elite rice hybrids through QTL analysis. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we first developed a QTL-mapping method for dissecting combining ability and heterosis of agronomic traits. With three testcross populations and a BCRIL population in rice, biometric and QTL analyses were conducted for ten agronomic traits. The significance of general combining ability and special combining ability for most of the traits indicated the importance of both additive and non-additive effects on expression levels. A large number of additive effect QTLs associated with performance per se of BCRIL and general combining ability, and dominant effect QTLs associated with special combining ability and heterosis were identified for the ten traits. CONCLUSIONS/SIGNIFICANCE: The combining ability of agronomic traits could be analyzed by the QTL mapping method. The characteristics revealed by the QTLs for combining ability of agronomic traits were similar with those by multitudinous QTLs for agronomic traits with performance per se of BCRIL. Several QTLs (1-6 in this study) were identified for each trait for combining ability. It demonstrated that some of the QTLs were pleiotropic or linked tightly with each other. The identification of QTLs responsible for combining ability and heterosis in the present study provides valuable information for dissecting genetic basis of combining ability

Detection of mild to moderate influenza A/H7N9 infection by China's national sentinel surveillance system for influenza-like illness: case series

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Measurement of multispecies concentration and gas temperature in an ammonium-dinitramide-based thruster by tunable diode lasers

In this paper, quantitative experiments were made to measure the concentration of key intermediate products (CO, N2O, and NO) and the gas temperature for combustion flow based on near-infrared and mid-infrared laser absorption spectroscopy. This paper used the developed diagnostic system to study two main ignition modes of a real 1-Newton thruster based on ammonium dinitramide (ADN): steady-state firing and pulse-mode firing over a feed pressure of 5-12 bar. The steady-state firing experiments distinguished the whole process into catalytic decomposition stage and combustion stage, experimentally demonstrating the combustion kinetics mechanism of an ADN monopropellant. Experiments for pulse-mode firing showed the measured multispecies concentration and temperature were consistent with pulse trains, verifying good performance for the thruster pulse-mode firing operation. The performance of the thruster was given based on the optical measurements, and characteristic velocity for the ADN-based thruster standard operation was higher than the corresponding 1-Newton hydrazine thruster. (C) 2018 Optical Society of America</p