Bonding dissimilar polymer networks in various manufacturing processes

Recently developed devices mimic neuromuscular and neurosensory systems by integrating hydrogels and hydrophobic elastomers. While different methods are developed to bond hydrogels with hydrophobic elastomers, it remains a challenge to coat and print various hydrogels and elastomers of arbitrary shapes, in arbitrary sequences, with strong adhesion. Here we report an approach to meet this challenge. We mix silane coupling agents into the precursors of the networks, and tune the kinetics such that, when the networks form, the coupling agents incorporate into the polymer chains, but do not condensate. After a manufacturing step, the coupling agents condensate, add crosslinks inside the networks, and form bonds between the networks. This approach enables independent bonding and manufacturing. We formulate oxygen-tolerant hydrogel resins for spinning, printing, and coating in the open air. We find that thin elastomer coatings enable hydrogels to sustain high temperatures without boiling

Identification of Ecdysone Hormone Receptor Agonists as a Therapeutic Approach for Treating Filarial Infections

Background A homologue of the ecdysone receptor has previously been identified in human filarial parasites. As the ecdysone receptor is not found in vertebrates, it and the regulatory pathways it controls represent attractive potential chemotherapeutic targets. Methodology/ Principal Findings Administration of 20-hydroxyecdysone to gerbils infected with B. malayi infective larvae disrupted their development to adult stage parasites. A stable mammalian cell line was created incorporating the B. malayi ecdysone receptor ligand-binding domain, its heterodimer partner and a secreted luciferase reporter in HEK293 cells. This was employed to screen a series of ecdysone agonist, identifying seven agonists active at sub-micromolar concentrations. A B. malayi ecdysone receptor ligand-binding domain was developed and used to study the ligand-receptor interactions of these agonists. An excellent correlation between the virtual screening results and the screening assay was observed. Based on both of these approaches, steroidal ecdysone agonists and the diacylhydrazine family of compounds were identified as a fruitful source of potential receptor agonists. In further confirmation of the modeling and screening results, Ponasterone A and Muristerone A, two compounds predicted to be strong ecdysone agonists stimulated expulsion of microfilaria and immature stages from adult parasites. Conclusions The studies validate the potential of the B. malayi ecdysone receptor as a drug target and provide a means to rapidly evaluate compounds for development of a new class of drugs against the human filarial parasites

Ku80 cooperates with CBP to promote COX-2 expression and tumor growth.

Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer

Dynamical alterations of brain function and gut microbiome in weight loss

ObjectiveIntermittent energy restriction (IER) is an effective weight loss strategy. However, little is known about the dynamic effects of IER on the brain-gut-microbiome axis.MethodsIn this study, a total of 25 obese individuals successfully lost weight after a 2-month IER intervention. FMRI was used to determine the activity of brain regions. Metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways in from fecal samples.ResultsOur results showed that IER longitudinally reduced the activity of obese-related brain regions at different timepoints, including the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit. IER longitudinally reduced E. coli abundance across multiple timepoints while elevating the abundance of obesity-related Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis. Correlation analysis revealed longitudinally correlations between gut bacteria abundance alterations and brain activity changes.ConclusionsThere was dynamical alteration of BGM axis (the communication of E. coli with specific brain regions) during the weight loss under the IER

Molecular Evidence for a Functional Ecdysone Signaling System in Brugia malayi

Filarial parasites such as Brugia malayi and Onchocerca volvulus are the causative agents of the tropical diseases lymphatic filariasis and onchocerciasis, which infect 150 million people, mainly in Africa and Southeast Asia. Filarial nematodes have a complex life cycle that involves transmission and development within both mammalian and insect hosts. The successful completion of the life cycle includes four molts, two of which are triggered upon transmission from one host to the other, human and mosquito, respectively. Elucidation of the molecular mechanisms involved in the molting processes in filarial nematodes may yield a new set of targets for drug intervention. In insects and other arthropods molting transitions are regulated by the steroid hormone ecdysone that interacts with a specialized hormone receptor composed of two different proteins belonging to the family of nuclear receptors. We have cloned from B. malayi two members of the nuclear receptor family that show many sequence and biochemical properties consistent with the ecdysone receptor of insects. This finding represents the first report of a functional ecdysone receptor homolog in nematodes. We have also established a transgenic hormone induction assay in B. malayi that can be used to discover ecdysone responsive genes and potentially lead to screening assays for active compounds for pharmaceutical development

A quantitative method to determine the optimal stress field for 2D 8-node quadrilateral hybrid finite element

Abstract A quantitative method is developed to determine the optimal stress field for 2D 8-node quadrilateral hybrid stress element (HQ8). It provides a straightforward way as to that how and why the resulting element can improve its displacement response. A new inner product with material weighting matrix is defined to reveal the relationship in quantity of exact similarity degrees between different stress modes. It is different from the conventional energy product which can only qualitatively determine the orthogonality of stress and strain modes because they are considered as mathematical vectors without physical meaning. The proposed strategy includes two steps. Firstly, the basic stress modes are divided into a set of sub-modes. Secondly, the sub-mode with largest similarity degree with the basic mode is selected as the optimal assumed stress mode for a hybrid element. The optimal stress modes for HQ8 are determined when Poison's ratio is larger than 1/9 which is the case for most materials. Keywords: 8-node quadrilateral hybrid stress element; quantitative method; optimal assumed stress field; material weighting matrix based inner product; largest similarity degre