Edited by Peter CresswellThe antibody Fc region regulates antibody cytotoxic activities and serum half-life. In a therapeutic context, however, the cytotoxic effector function of an antibody is often not desirable and can create safety liabilities by activating native host immune defenses against cells expressing the receptor antigens. Several amino acid changes in the Fc region have been reported to silence or reduce the effector function of antibodies. These earlier studies focused primarily on the interaction of human antibodies with human Fc-␥ receptors, and it remains largely unknown how such changes to Fc might translate to the context of a murine antibody. We demonstrate that the commonly used N297G (NG) and D265A, N297G (DANG) variants that are efficacious in attenuating effector function in primates retain potent complement activation capacity in mice, leading to safety liabilities in murine studies. In contrast, we found an L234A, L235A, P329G (LALA-PG) variant that eliminates complement binding and fixation as well as Fc-␥-dependent, antibody-dependent, cell-mediated cytotoxity in both murine IgG2a and human IgG1. These LALA-PG substitutions allow a more accurate translation of results generated with an "effectorless" antibody between mice and primates. Further, we show that both human and murine antibodies containing the LALA-PG variant have typical pharmacokinetics in rodents and retain thermostability, enabling efficient knobs-into-holes bispecific antibody production and a robust path to generating highly effector-attenuated bispecific antibodies for preclinical studies.

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Single-crystal beta-MnO(2) nanotubes with diameters in the range 200-500 nm and lengths up to several micrometers were successfully prepared by a simple hydrothermal method through oxidizing MnSO(4) with NaClO(3) in the presence of poly(vinyl pyrrolidone) (PVP). It was found that the formation process of beta-MnO(2) nanotubes included two primary evolution stages over time: (1) the MnOOH nanoparticles initially formed in the hydrothermal system and anisotropic growth to nanorods and nanorod aggregates, and (2) the MnOOH nanorods transformed into beta-MnO(2) tubular structure and grown into beta-MnO(2) nanotubes due to continuous growth through a dissolution-recrystallization process eventually. Based on a series of experimental analysis, the formation mechanism of these nanostructures was discussed briefly. The present study has enlarged the family of nanotubes available and offers a possible new, general route to one-dimensional single-crystalline nanotubes of other materials.

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A simple and efficient approach of preparing copper oxide/reduced graphene oxide (CuO/rGO) nanocomposite has been demonstrated. CuO/rGO nanocomposites were successfully synthesized through a one-step redox reaction between graphene oxide (GO) sheets and cuprous ions in CuCl without extra reducing agent. Notably, the reduction of GO and the deposition of CuO on the rGO sheets occurred simultaneously during the reaction process, resulting in a uniform and tight distribution of CuO nanoparticles on the reduced GO sheets. Furthermore, the as-prepared CuO/rGO composite (CuCl = 0.02 g) had a large BET surface area (235 m 2 g 21 ) and a porous structure with macropores and mesopores. The as-prepared nanocomposite was exploited in the catalytic oxidation of catechol in aqueous media. The results indicated that the as-prepared copper oxide/rGO nanocomposite exhibited a higher electrocatalytic activity towards catechol oxidation than original CuO nanoparticles or reduced graphene oxide samples. This strategy opens a new facile and simple chemical route to synthesize copper oxide/rGO nanocomposites with excellent properties.

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BACKGROUND: Host biomarkers predict disease severity in adults with community-acquired pneumonia (CAP). We evaluated the association of the white blood cell (WBC) count, absolute neutrophil count (ANC), C-reactive protein (CRP), and procalcitonin with the development of severe outcomes in children with CAP. METHODS:We performed a prospective cohort study of children 3 months to 18 years of age with CAP in the emergency department. The primary outcome was disease severity: mild (discharged from the hospital), mild-moderate (hospitalized but not moderate-severe or severe), moderate-severe (eg, hospitalized with receipt of intravenous fluids, supplemental oxygen, complicated pneumonia), and severe (eg, intensive care, vasoactive infusions, chest drainage, severe sepsis). Outcomes were examined within the cohort with suspected CAP and in a subset with radiographic CAP.RESULTS: Of 477 children, there were no statistical differences in the median WBC count, ANC, CRP, or procalcitonin across severity categories. No biomarker had adequate discriminatory ability between severe and nonsevere disease (area under the curve [AUC]: 0.53-0.6 for suspected CAP and 0.59-0.64 for radiographic CAP). In analyses adjusted for age, antibiotic use, fever duration, and viral pathogen detection, CRP was associated with moderate-severe disease (odds ratio 1.12; 95% confidence interval, 1.0-1.25). CRP and procalcitonin revealed good discrimination of children with empyema requiring chest drainage (AUC: 0.83) and sepsis with vasoactive infusions (CRP AUC: 0.74; procalcitonin AUC: 0.78), although prevalence of these outcomes was low.CONCLUSIONS: WBC count, ANC, CRP, and procalcitonin are generally not useful to discriminate nonsevere from severe disease in children with CAP, although CRP and procalcitonin may have some utility in predicting the most severe outcomes. WHAT'S KNOWN ON THIS SUBJECT: Prognostic tools are limited for children with community-acquired pneumonia (CAP). Host biomarkers, including C-reactive protein (CRP) and procalcitonin, have been shown to be associated with severe clinical outcomes in adults with CAP. Data in children are limited.WHAT THIS STUDY ADDS: White blood cell count, CRP, and procalcitonin are generally not useful to discriminate overall disease severity in children with CAP. CRP and procalcitonin may have utility in predicting the most severe outcomes, but research is necessary to validate these findings.

Metastatic breast cancer is incurable. The goal of this study was to develop a positron emission tomography (PET)/near-infrared fluorescent (NIRF) probe for imaging of CD105 expression in breast cancer experimental lung metastasis. TRC105, a chimeric anti-CD105 antibody, was dual-labeled with a NIRF dye (IRDye 800CW) and 89Zr to yield 89Zr-Df-TRC105-800CW. Luciferase-transfected 4T1 murine breast cancer cells were injected intravenously into female mice to establish the tumor model. Bioluminescence imaging (BLI) was carried out to non-invasively monitor the lung tumor burden. PET imaging revealed that 4T1 lung tumor uptake of 89Zr-Df-TRC105-800CW was 8.7±1.4, 10.9±0.5, and 9.7±1.1 %ID/g at 4, 24, and 48 h post-injection (n = 4), with excellent tumor contrast. Biodistribution studies, blocking, control studies with 89Zr-Df-cetuximab-800CW, ex vivo BLI/PET/NIRF imaging, and histology all confirmed CD105 specificity of the tracer. Broad clinical potential of TRC105-based agents was shown in many tumor types, which also enabled early detection of small metastasis and intraoperative guidance for tumor removal.