_In vivo_ photoacoustic molecular imaging with simultaneous multiple selective targeting using antibody-conjugated gold nanorods

The use of gold nanorods for photoacoustic molecular imaging in vivo with simultaneous multiple selective targeting is reported. The extravasation of multiple molecular probes is demonstrated, and used to probe molecular information of cancer cells. This technique allows molecular profiles representing tumor characteristics to be obtained and a heterogeneous population of cancer cells in a lesion to be determined. The results also show that the image contrast can be enhanced by using a mixture of different molecular probes. In this study, HER2, EGFR, and CXCR4 were chosen as the primary target molecules for examining two types of cancer cells, OECM1 and Cal27. OECM1 cells overexpressed HER2 but exhibited a low expression of EGFR, while Cal27 cells showed the opposite expression profile. Single and double targeting resulted in signal enhancements of up to 3 dB and up to 5 dB, respectively, and hence has potential in improving cancer diagnoses

Multi-task unscented Kalman inversion (MUKI): a derivative-free joint inversion framework and its application to joint inversion of geophysical data

In the geophysical joint inversion, the gradient and Bayesian Markov Chain Monte Carlo (MCMC) sampling-based methods are widely used owing to their fast convergences or global optimality. However, these methods either require the computation of gradients and easily fall into local optimal solutions, or cost much time to carry out the millions of forward calculations in a huge sampling space. Different from these two methods, taking advantage of the recently developed unscented Kalman method in computational mathematics, we extend an iterative gradient-free Bayesian joint inversion framework, i.e., Multi-task unscented Kalman inversion (MUKI). In this new framework, information from various observations is incorporated, the model is iteratively updated in a derivative-free way, and a Gaussian approximation to the posterior distribution of the model parameters is obtained. We apply the MUKI to the joint inversion of receiver functions and surface wave dispersion, which is well-established and widely used to construct the crustal and upper mantle structure of the earth. Based on synthesized and real data, the tests demonstrate that MUKI can recover the model more efficiently than the gradient-based method and the Markov Chain Monte Carlo method, and it would be a promising approach to resolve the geophysical joint inversion problems.Comment: 13 pages, 4 figure

Systematic Analysis of Sequences and Expression Patterns of Drought-Responsive Members of the HD-Zip Gene Family in Maize

Background: Members of the homeodomain-leucine zipper (HD-Zip) gene family encode transcription factors that are unique to plants and have diverse functions in plant growth and development such as various stress responses, organ formation and vascular development. Although systematic characterization of this family has been carried out in Arabidopsis and rice, little is known about HD-Zip genes in maize (Zea mays L.). Methods and Findings: In this study, we described the identification and structural characterization of HD-Zip genes in the maize genome. A complete set of 55 HD-Zip genes (Zmhdz1-55) were identified in the maize genome using Blast search tools and categorized into four classes (HD-Zip I-IV) based on phylogeny. Chromosomal location of these genes revealed that they are distributed unevenly across all 10 chromosomes. Segmental duplication contributed largely to the expansion of the maize HD-ZIP gene family, while tandem duplication was only responsible for the amplification of the HD-Zip II genes. Furthermore, most of the maize HD-Zip I genes were found to contain an overabundance of stress-related ciselements in their promoter sequences. The expression levels of the 17 HD-Zip I genes under drought stress were also investigated by quantitative real-time PCR (qRT-PCR). All of the 17 maize HD-ZIP I genes were found to be regulated by drought stress, and the duplicated genes within a sister pair exhibited the similar expression patterns, suggesting their conserved functions during the process of evolution

Liquid–Liquid Phase Separation Prediction of Proteins in Salt Solution by Deep Neural Network

Liquid–liquid phase separation (LLPS) underlies the formation of membrane-free organelles in eukaryotic cells and plays an important role in the development of some diseases. The phase boundary of metastable liquid–liquid phase separation as well as the cloud point temperature of some globular proteins characterize the phase behavior of proteins and have been widely studied theoretically and experimentally. In the present study, we used a regression and classification neural network to deal with the phase behavior of lysozyme and bovine serum albumin (BSA). We predicted the cloud point temperature and solubility of a lysozyme solution containing sodium chloride by regression and the reentrant phase behavior of BSA in YCl3 solution containing a surfactant dodecyl dimethyl amine oxide (DDAO) by classification. Specifically, our network model is capable of predicting (a) the solubility of lysozyme in the range: pH 4.0–5.4, temperature 0–25 °C, and NaCl concentration 2–7% (w/v); (b) the cloud point temperature of lysozyme in the range: pH 4.0–4.8, NaCl concentration 2–7%, and lysozyme concentration 0–400 mg/mL; and (c) the phase behavior of BSA in the range: DDAO 1–60 mM, BSA 30–100 mg/mL, and YCl3 1–20 mM. We experimentally tested the model at some prediction points with a high accuracy, which means that deep neural networks can be applicable in qualitative and quantitive analysis of liquid–liquid phase separation

The Association between 5-Hydroxytryptamine Receptor 1B rs13212041 Polymorphism and Trait Anxiety in Chinese Han College Subjects

Trait anxiety is a vulnerable personality factor for anxiety and depression. High levels of trait anxiety confer an elevated risk for the development of anxiety and other psychiatric disorders. There is evidence that 5-hydroxytryptamine receptor 1B (5-HT1B) gene polymorphisms play an important role in emotional disorders. Genotyping for four single-nucleotide polymorphisms (SNP) (rs11568817, rs130058, rs6297, and rs13212041) was conducted for 388 high trait anxious (HTA) individuals and 463 low traitanxious (LTA) individuals in Chinese Han college subjects. The results showed that the frequencies of the C-allele and TC + CC genotype of rs13212041 in the LTA individuals were higher than that in the HTA individuals (p = 0.025 and p = 0.014, respectively). Both the C-allele and TC + CC genotype were associated with trait anxiety decreasing (OR = 0.771 and OR = 0.71, respectively). Furthermore, different gene model analysis also showed that the C allele was a protective factor for trait anxiety in Chinese Han college subjects. These findings suggest that 5-HT1B rs13212014 may play a role in trait anxiety among China Han college subjects. The rs13212014 polymorphism may be involved in decreasing the risk of trait anxiety. These results also provide a novel insight into the molecular mechanism underlying trait anxiety

ITRAQ-Based Proteomics Analysis of Triptolide On Human A549 Lung Adenocarcinoma Cells

Background/Aims: Triptolide (TP) is a diterpenoid triepoxide extracted from the traditional Chinese medical herb Tripterygium wilfordii that exerts prominent broad-spectrum anticancer activity to repress proliferation and induce cancer cell apoptosis through various molecular pathways. We previously observed that TP inhibits the progression of A549 cells and pancreatic cancer cells (PNCA-1) in vitro. However, the complex molecular mechanism underlying the anticancer activity of TP is not well understood. Methods: To explore the molecular mechanisms by which TP induces lung cancer cell apoptosis, we investigated changes in the protein profile of A549 cells treated with TP using a proteomics approach (iTRAQ [isobaric tags for relative and absolute quantitation] combined with NanoLC-MS/MS [nano liquid chromatography-mass spectrometry]). Changes in the profiles of the expressed proteins were analyzed using the bioinformatics tools OmicsBean and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and were verified using western blotting. Apoptosis and cell cycle effects were analyzed using flow cytometry. Results: TP induced apoptosis in A549 cells and blocked A549 cells at the G2/M phase. Using iTRAQ technology, we observed 312 differentially expressed proteins associated in networks and implicated in different KEGG pathways. Gene Ontology (GO) analysis showed the overviews of dysregulated proteins in the biological process (BP), cell component (CC), and molecular function (MF) categories. Moreover, some candidate proteins involved in PARP1/AIF and nuclear Akt signaling pathways or metastasis processes were validated by western blotting. Conclusion: TP exerted anti-tumor activity on non-small cell lung cancer (NSCLC) A549 lung adenocarcinoma cells by dysregulating tumor-related protein expression. Herein, we provide a preliminary study of TP-related cytotoxicity on A549 cells using proteomics tools. These findings may improve the current understanding of the anti-tumor effects of TP on lung cancer cells and may reveal candidate proteins as potential targets for the treatment of lung cancer