Employing antagonistic C-X-C motif chemokine receptor 4 antagonistic peptide functionalized NaGdF4 nanodots for magnetic resonance imaging-guided biotherapy of breast cancer.

C-X-C motif chemokine receptor 4 (CXCR4) is a promising therapeutic target of breast cancer because it is overexpressed on cell surface of all molecular subtypes of breast cancer including triplenegative breast cancer (TNBC). Herein, CXCR4 antagonistic peptide-NaGdF4 nanodot conjugates (termed as anti-CXCR4-NaGdF4 NDs) have been constructed for magnetic resonance imaging (MRI)-guided biotherapy of TNBC through conjugation of the C-X-C Motif Chemokine 12 (CXCL12)-derived cyclic peptide with tryptone coated NaGdF4 nanodots (5 ± 0.5 nm in diameter, termed as Try-NaGdF4 NDs). The as-prepared anti-CXCR4-NaGdF4 NDs exhibits high longitudinal relaxivity (r1) value (21.87 mM-1S-1), reasonable biocompatibility and good tumor accumulation ability. The features of anti-CXCR4-NaGdF4 NDs improve the tumor-MRI sensitivity and facilitate tumor biotherapy after injection in mouse-bearing MDA-MB-231 tumor model in vivo. MRI-guided biotherapy using anti-CXCR4-NaGdF4 NDs enables to suppress 46% tumor growth. In addition, about 47% injection dose of anti-CXCR4-NaGdF4 NDs is found in the mouse urine at 24 h post-injection. These findings demonstrate that anti-CXCR4-NaGdF4 NDs enable to be used as renal clearable nanomedicine for biotherapy and MRI of breast cancer.

A Numerical Method for Applying Cohesive Stress on Fracture Process Zone in Concrete Using Nonlinear Spring Element.

Aiming at the numerical simulation of the entire crack propagation process in concrete, a numerical method is proposed, in which cohesive stress on the fracture process zone (FPZ) is simulated and applied by a nonlinear spring element. Using displacement control, the cohesive stress values on the FPZ are obtained from solving a system of nonlinear equations through an iterative process. According to a crack propagation criterion based on initial fracture toughness, the approach adds the spring elements to finite element analysis when simulating mode I crack propagation in standard three-point bending notched concrete beams with different strengths, initial crack ratios (a0/D), and depths (D). The simulated load versus displacement (P-Delta) curves are performed to recalculate the fracture energy and verify the accuracy of cohesion in the proposed method. The simulated load versus crack mouth opening displacement (P-CMOD) curves are consistent with the previous experimental results. Subsequently, the variations of the FPZ length and the crack extension resistance (KR) curves are studied according to the proposed iterative approach. Compared with the existing methods using a noniterative process, the iterative approach generates a larger maximum FPZ length and KR curve where the FPZ length is mainly determined by the fracture energy, tensile strength, and geometry shape of the beam, and the KR curve is primarily determined by the fracture energy and FPZ length. The significant differences in numerical results indicate that the applying cohesion is essential in numerical simulation. It is reasonable to conclude that the proposed nonlinear spring element is more applicable and practical in the numerical simulation of the concrete mode I crack propagation process by improving the accuracy of the cohesion applied on the FPZ.

Two-Dimensional Layered Nanomaterial-Based Electrochemical Biosensors for Detecting Microbial Toxins.

Toxin detection is an important issue in numerous fields, such as agriculture/food safety, environmental monitoring, and homeland security. During the past two decades, nanotechnology has been extensively used to develop various biosensors for achieving fast, sensitive, selective and on-site analysis of toxins. In particular, the two dimensional layered (2D) nanomaterials (such as graphene and transition metal dichalcogenides (TMDs)) and their nanocomposites have been employed as label and/or biosensing transducers to construct electrochemical biosensors for cost-effective detection of toxins with high sensitivity and specificity. This is because the 2D nanomaterials have good electrical conductivity and a large surface area with plenty of active groups for conjugating 2D nanomaterials with the antibodies and/or aptamers of the targeted toxins. Herein, we summarize recent developments in the application of 2D nanomaterial-based electrochemical biosensors for detecting toxins with a particular focus on microbial toxins including bacterial toxins, fungal toxins and algal toxins. The integration of 2D nanomaterials with some existing antibody/aptamer technologies into electrochemical biosensors has led to an unprecedented impact on improving the assaying performance of microbial toxins, and has shown great promise in public health and environmental protection.

Joint Toxicity of Arsenic, Copper and Glyphosate on Behavior, Reproduction and Heat Shock Protein Response in Caenorhabditis elegans.

The soil nematode Caenorhabditis elegans was used in 24-h acute exposures to arsenic (As), copper (Cu) and glyphosate (GPS) and to mixtures of As/Cu and As/GPS to investigate the effects of mixture exposures in the worms. A synergistic type of interaction was observed for acute toxicity with the As/Cu and As/GPS mixtures. Sublethal 24-h exposures of 1/1000, 1/100 and 1/10 of the LC50 concentrations for As, Cu and GPS individually and for As/Cu and As/GPS mixtures were conducted to observe responses in locomotory behavior (head thrashing), reproduction, and heat shock protein expression. Head thrash frequency and reproduction exhibited concentration dependent decreases in both individual and combined exposures to the tested chemical stressors, and showed synergistic interactions even at micromolar concentrations. Furthermore, the HSP70 protein level was significantly increased following exposure to individual and combined chemical stressors in wild-type C. elegans. Our findings establish for the first time the effects of exposure to As/GPS and As/Cu mixtures in C. elegans.