Real Time Analysis of Binding between Rituximab (Anti-CD20 Antibody) and B Lymphoma Cells

CD20, expressed on greater than 90% of B-lymphocytic lymphomas, is an attractive target for antibody therapy. Rituximab is a chimeric murine/human-engineered monoclonal antibody which can selectively deplete CD20-expressing cells in peripheral blood and lymphoid tissues. The immobilization of B-lymphoblast-like Burkitt’s lymphoma Raji cells on the quartz crystal microbalance (QCM) gold electrode surface using arginine–glycine–aspartic acid (RGD) tripeptide was electrochemically confirmed. The real-time processes of attachment of Raji cells on the gold electrode and the subsequent binding of Rituximab to the cells were studied using a QCM biosensor. The interaction between Rituximab and Raji cells led to the increased resonant frequency shifts (Δ<i>f</i>₀) in the studied antibody concentration range from 5 to 250 μg mL^–1 following the Langmuir adsorption model. From these observations, the apparent binding constant between a single-layer of Rituximab and Raji cells was calculated to be 1.6 × 10⁶ M^–1. Control experiments using other therapeutic antibodies (i.e., Trastuzumab and Bevacizumab) and different cells (i.e., T cells and endothelial cells) proved the specific interaction between Rituximab and B cells. The effects of Ca²⁺ and Mn²⁺ ions on the Rituximab–Raji cell interaction were also studied providing the enhanced QCM signals, in particular with Ca²⁺, further indicating that CD20 is a calcium ion channel that can transport these metal ions into the cells and accelerate the cell lysis induced by Rituximab. Thus, the real time capability of QCM and its simplicity of operation are shown to be highly suitable for multipurpose studies on living cells including cell-immobilization, cytotoxicity of drugs, and the cell action mechanisms

Interfacial Bonding of SnSb Alloys with Graphene toward Ultrafast and Cycle-Stable Na-Ion Battery Anodes

Alloy-type materials have aroused wide concern as potential anodes for Na-ion batteries (NIBs) because of their high theoretical capacities and suitable Na-storage potentials. Fabricating composites with carbon matrixes is the most common strategy to solve their key issues of large volume expansion and sluggish reaction kinetics. However, it is still challenging to achieve strong interfacial interaction between alloy-type materials and carbon matrixes, thus largely improving the buffering effect of carbon matrixes on volume change. Herein, we have developed a SnSb-graphene (SnSb-G) hybrid anode with interfacial Sn/Sb–C bonding via a plasma-assisted mechanochemical method. The Sn/Sb–C bonding can enhance the interfacial interaction between SnSb and graphene, which inhibits the detachment of SnSb nanoparticles from graphene upon cycling and promotes the buffering effect of graphene. Meanwhile, the strong interfacial bonding of conductive graphene network to SnSb nanoparticles can greatly facilitate the Na+ storage/transfer along the SnSb/graphene interface, rendering electrode superior performance at high rates. Therefore, as an anode for NIBs, the SnSb-G composite exhibits superb rate capability (301.5 mAh g–1 at 10.0 A g–1) and cyclic stability (85.8%/89.1% capacity retentions at 1.0/2.0 A g–1 after 1000 cycles). Moreover, the assembled full cell delivers a high energy density of 145 Wh kg–1 and superior cycling performance of 333.6 mAh g–1 after 200 cycles, demonstrating its potential for practical application. This work provides new insight to achieve high-performance alloy-type anodes for practical NIBs

Domino Aryne Annulation via a Nucleophilic–Ene Process

1,2-Benzdiyne equivalents possess the unique property that they can react with two aryno­philes through iteratively generated 1,2- and 2,3-aryne intermediates. Upon rational modification on the second leaving group of these aryne precursors, a domino aryne annulation approach was developed through a nucleophilic–ene reaction sequence. Various benzo-fused N-heterocyclic frameworks were achievable under transition metal-free conditions with a broad substrate scope

Domino Aryne Annulation via a Nucleophilic–Ene Process

1,2-Benzdiyne equivalents possess the unique property that they can react with two aryno­philes through iteratively generated 1,2- and 2,3-aryne intermediates. Upon rational modification on the second leaving group of these aryne precursors, a domino aryne annulation approach was developed through a nucleophilic–ene reaction sequence. Various benzo-fused N-heterocyclic frameworks were achievable under transition metal-free conditions with a broad substrate scope

Domino Aryne Annulation via a Nucleophilic–Ene Process

1,2-Benzdiyne equivalents possess the unique property that they can react with two aryno­philes through iteratively generated 1,2- and 2,3-aryne intermediates. Upon rational modification on the second leaving group of these aryne precursors, a domino aryne annulation approach was developed through a nucleophilic–ene reaction sequence. Various benzo-fused N-heterocyclic frameworks were achievable under transition metal-free conditions with a broad substrate scope

Domino Aryne Annulation via a Nucleophilic–Ene Process

1,2-Benzdiyne equivalents possess the unique property that they can react with two aryno­philes through iteratively generated 1,2- and 2,3-aryne intermediates. Upon rational modification on the second leaving group of these aryne precursors, a domino aryne annulation approach was developed through a nucleophilic–ene reaction sequence. Various benzo-fused N-heterocyclic frameworks were achievable under transition metal-free conditions with a broad substrate scope

Polyamidoamine Dendrimer and Oleic Acid-Functionalized Graphene as Biocompatible and Efficient Gene Delivery Vectors

Functionalized graphene has good potential in biomedical applications. To address a better and multiplex design of graphene-based gene vectors, the graphene-oleate-polyamidoamine (PAMAM) dendrimer hybrids were synthesized by the oleic acid adsorption and covalent linkage of PAMAM dendrimers. The micromorphology, electrical charge property, and amount of free amine groups of the graphene-oleate-PAMAM hybrids were characterized, and the peripheral functional groups were identified. The PAMAM dendrimers could be tethered onto graphene surface in high density. The graphene-oleate-PAMAM hybrids exhibit relatively good dispersity and stability in aqueous solutions. To evaluate the potential application of the hybrids in gene delivery vectors, cytotoxicity to HeLa and MG-63 cells and gene (plasmid DNA of enhanced green fluorescent protein) transfection capacity of the hybrids were investigated in detail. The graphene-oleate-PAMAM hybrids show mammalian cell type- and dose-dependent in vitro cytotoxicity. Under the optimal condition, the hybrids possess good biocompatibility and gene transfection capacity. The surface modification of graphene with oleic acid and PAMAM improves the gene transfection efficiency 13 times in contrast to the ultrasonicated graphene. Moreover, the hybrids show better transfection efficiency than the graphene oxide-PAMAM without the oleic acid modification

Discovery of Novel Pyridone-Conjugated Monosulfactams as Potent and Broad-Spectrum Antibiotics for Multidrug-Resistant Gram-Negative Infections

Conjugating a siderophore to an antibiotic is a promising strategy to overcome the permeability-mediated resistance of Gram-negative pathogens. On the basis of the structure of BAL30072, novel pyridone-conjugated monosulfactams incorporating diverse substituents into the methylene linker between the 1,3-dihydroxypyridin-4­(1<i>H</i>)-one and the aminothiazole oxime were designed and synthesized. Structure–activity relationship studies revealed that a variety of substituents were tolerated, with isopropyl (compound <b>12c</b>) and methylthiomethyl (compound <b>16a</b>) showing the best efficacy against multidrug-resistant (MDR) Gram-negative pathogens. In addition, compound <b>12c</b> exhibits a good free fraction rate in an in vitro human plasma protein binding test, along with a low clearance and favorable plasma exposure in vivo. In a murine systemic infection model with MDR Klebsiella pneumoniae, compound <b>12c</b> shows an ED₅₀ of 10.20 mg/kg. Taken together, the results indicate that compound <b>12c</b> is a promising drug candidate for the treatment of serious infections caused by MDR Gram-negative pathogens

Additional file 5: of Large-scale transcriptomic analysis reveals that pridopidine reverses aberrant gene expression and activates neuroprotective pathways in the YAC128 HD mouse

Table S5. Pathway analysis of alternatively spliced genes identified after high dose treatment with pridopidine. (XLSX 31 kb

Additional file 1: of Large-scale transcriptomic analysis reveals that pridopidine reverses aberrant gene expression and activates neuroprotective pathways in the YAC128 HD mouse

Table S1. Adjusted p-val range and fold change range for differential expression and DUEJ genes meeting adj p-val < 0.05 cutoff. (XLSX 11 kb