Passive Prophylactic Administration with a Single Dose of Anti-Fel d 1 Monoclonal Antibodies REGN1908-1909 in Cat Allergen-induced Allergic Rhinitis: A Randomized, Double-Blind, Placebo-controlled Clinical Trial.

Rationale: Sensitization to Fel d 1 (Felis domesticus allergen 1) contributes to persistent allergic rhinitis and asthma. Existing treatment options for cat allergy, including allergen immunotherapy, are only moderately effective, and allergen immunotherapy has limited use because of safety concerns. Objectives: To explore the relationship among the pharmacokinetic, clinical, and immunological effects of anti-Fel d 1 monoclonal antibodies (REGN1908-1909) in patients after treatment. Methods: Patients received REGN1908-1909 (n = 36) or a placebo (n = 37) in a phase 1b study. Fel d 1-induced basophil and IgE-facilitated allergen binding responses were evaluated at baseline and Days 8, 29, and 85. Cytokine and chemokine concentrations in nasal fluids were measured, and REGN1908-1909 inhibition of allergen-IgE binding in patient serum was evaluated. Measurements and Main Results: Peak serum drug concentrations were concordant with maximal observed clinical response. The anti-Fel d 1 IgE/cat dander IgE ratio in pretreatment serum correlated with Total Nasal Symptom Score improvement. The allergen-neutralizing capacity of REGN1908-1909 was observed in serum and nasal fluid and was detected in an inhibition assay. Type 2 cytokines (IL-4, IL-5, and IL-13) and chemokines (CCL17/TARC, CCL5/RANTES [regulated upon activation, normal T-cell expressed and secreted]) in nasal fluid were inhibited in REGN1908-1909-treated patients compared with placebo (P < 0.05 for all); IL-13 and IL-5 concentrations correlated with Total Nasal Symptom Score improvement. Ex vivo assays demonstrated that REGN1908 and REGN1909 combined were more potent than each alone for inhibiting FcεRI- and FcεRII (CD23)-mediated allergic responses and subsequent T-cell activation. Conclusions: A single, passive-dose administration of Fel d 1-neutralizing IgG antibodies improved nasal symptoms in cat-allergic patients and was underscored by suppression of FcεRI-, FcεRII-, and T-helper cell type 2-mediated allergic responses. Clinical trial registered with www.clinicaltrials.gov (NCT02127801).

Low potential detection of indole-3-acetic acid based on the peroxidase-like activity of hemin/reduced graphene oxide nanocomposite.

An amperometric sensor was firstly established for the detection of indole-3-acetic acid (IAA) at low potential based on the hemin/reduced graphene oxide (hemin/rGO) composite. The hemin/rGO nanocomposite was prepared by a simple and facile hydrothermal method without using any reducing agent. It exhibited peroxidase-like activity for the catalytic oxidation of IAA in the presence of oxygen. The consumption of oxygen has a linear relationship with the concentration of IAA in the range from 0.1 to 43µM and from 43 to 183µM. The detection limit was down to 0.074µM. This sensor was unaffected by many interfering substances and stable over time. Such work broadened the application of hemin/rGO and provided a new method for IAA detection.

Hierarchical porous TiO2 fabricated from magnolia grandiflora petals templates for the immobilization and electrical wiring of proteins.

Hierarchical porous titanium dioxide (hp-TiO2) was prepared using natural magnolia grandiflora petals as templates and was further employed for the immobilization of horseradish peroxidase (HRP). Scanning electron microscopy (SEM) and nitrogen adsorption-desorption measurement revealed the wrinkled and porous structure of the obtained hp-TiO2. Fourier transform infrared spectroscopy (FT-IR) indicated the effective immobilization and conformation retention of HRP on hp-TiO2. HRP immobilized on hp-TiO2 exhibited direct, reversible, and surface-controlled redox reaction with the electron transfer rate constant of 5.46 s(-1). Furthermore, the immobilized HRP exhibited a wide linear detection range from 1.0 to 524.0 µM. The detection limit, based on a signal-to-noise ratio of 3, was down to 0.87 µM. The apparent Michaelis-Menten constant (Km(app)) of the immobilized HRP was 0.223 mM. In addition, the sensor possessed appreciable repeatability, reproducibility and remarkable stability for the sensitive determination of H2O2. Thus, this kind of hp-TiO2 can be used as an attractive material for immobilizing proteins and constructing biosensors.

Electrochemical method assisted immobilization and orientation of myoglobin into biomimetic brij 56 film and its direct electrochemistry study.

A simple cyclic voltammetric method was applied to assemble and orient a model protein, namely, myoglobin (Mb), into a biocompatible Brij 56 film. Ultraviolet-visible and circular dichroism spectra indicated that Mb in Brij 56 matrix preserved its secondary structure. Fourier transform infrared spectra confirmed the formation of hydrogen bonds between Mb and Brij 56. These hydrogen bonds acted as the electron tunnel to transfer electrons from Mb's active sites to the underlying glassy carbon electrode. Effective direct electron transfer of Mb was realized with the presence of a couple of quasi-reversible and well-defined redox peaks at -310 mV (vs standard calomel electrode) in the studied potential range. The peaks were attributed to the redox couple of heme Fe(II)/Fe(III) of the well-oriented Mb in Brij 56 matrix. The surface coverage and the electron transfer rate (ks) of Mb immobilized into the Brij 56 film was ∼4.9×10(-11) mol cm(-2) and 72.6±3.0 s(-1), respectively. An excellent electrocatalytic response of the immobilized Mb toward nitrite in the absence of electron transfer mediators was observed. These results emphasized that the biomimetic Brij 56 could be used as an attractive material for immobilizing proteins and constructing biosensors.

Forchlorfenuron detection based on its inhibitory effect towards catalase immobilized on boron nitride substrate.

An enzymatic procedure based on a catalase biosensor for the detection of forchlorfenuron (CPPU) has been reported in this work. Catalase was immobilized on boron nitride (BN) sheets dispersed in chitosan by adsorption. The immobilized catalase exhibited direct electron transfer character and excellent electrocatalytic activity towards H2O2 reduction. After introducing CPPU into the H2O2 containing phosphate buffer solution, the catalase-catalyzed H2O2 reduction current decreased. By measuring the current decrease, CPPU can be determined in the range of 0.5-10.0 µM with the detection limit of 0.07 µM. The non-competitive inhibition behavior of CPPU towards catalase was verified by the Lineweaver-Burk plots. Long stability character has been ascribed to this biosensor. Possible use of this biosensor in flow systems is illustrated. The proposed biosensor has been successfully applied to CPPU determination in fruits samples with satisfactory results.

Preparation, structural diversity and characterization of a family of Cd(II)-organic frameworks.

Two Cd(II)-organic frameworks based on 5-iodoisophthalate (IIP(2-)), {[Cd(IIP)(bte)(H2O)]·H2O}n (1) and [Cd(IIP)(bpp)(H2O)]n (2), were obtained either at an ambient temperature or under solvothermal conditions at 120 °C in the presence of 1,4-bis(1,2,4-triazol-1-yl)ethane (bte) and 1,3-bis(4-pyridyl)propane (bpp) as auxiliary ligands, respectively. 1 is a novel discrete single-walled Cd(II)-organic tube (SWCOT) which further extends into a 3D supramolecular interdigitated microporous columnar architecture supported by C-I···I halogen bonds and hydrogen bonds, while 2 exhibits an interesting two-fold interpenetrated 3D diamond network architecture. When the auxiliary ligands bte or bpp were replaced by a longer spacer ligand with more flexibility, 1,4-bis(triazol-1-ylmethyl)benzene (bbtz), the unique discrete single-walled Cd(II)-organic nanotube (SWCONT), {[Cd(IIP)(bbtz)(H2O)]·H2O}n (3), which further extends into a 3D supramolecular microporous framework supported by face-to-face π···π stacking interactions and hydrogen bonds, was generated at room temperature. Under solvothermal conditions at 120 °C, an interesting two-fold 2D "embracing" (4,4) topological network, [Cd(IIP)(bbtz)(H2O)] (4), which further extends into a two-fold 3D "embracing" supramolecular framework through O-H···O hydrogen bonds, is obtained. 4 loses crystallinity in air, leading to the formation of [Cd(IIP)(bbtz)]·0.5H2O (4A) evidenced by elemental analysis, thermogravimetric analysis (TGA) and powder X-ray diffraction (PXRD). Remarkably, in situ rapid and reversible dehydration-rehydration in static air occurs in 1-3, indicating their potential applications as water absorbent and sensing materials. Dehydrated 1 and 3 show selective gas adsorption of CO2 over N2 and dehydrated 3 can adsorb methanol and ethanol vapors strongly. These compounds exhibit blue fluorescence in the solid state.