One-pot synthesis of carboxymethyl-dextran coated iron oxide nanoparticles (CION) for preclinical fMRI and MRA applications.

Superparamagnetic iron-oxide nanoparticles are robust contrast agents for magnetic resonance imaging (MRI) used for sensitive structural and functional mapping of the cerebral blood volume (CBV) when administered intravenously. To date, many CBV-MRI studies are conducted with Feraheme, manufactured for the clinical treatment of iron-deficiency. Unfortunately, Feraheme is currently not available outside the United States due to commercial and regulatory constraints, making CBV-MRI methods either inaccessible or very costly to achieve. To address this barrier, we developed a simple, one-pot recipe to synthesize Carboxymethyl-dextran coated Iron Oxide Nanoparticles, namely, "CION", suitable for preclinical CBV-MRI applications. Here we disseminate a step-by-step instruction of our one-pot synthesis protocol, which allows CION to be produced in laboratories with minimal cost. We also characterized different CION-conjugations by manipulating polymer to metal stoichiometric ratio in terms of their size, surface chemistry, and chemical composition, and shifts in MR relaxivity and pharmacokinetics. We performed several proof-of-concept experiments in vivo, demonstrating the utility of CION for functional and structural MRI applications, including hypercapnic CO2 challenge, visual stimulation, targeted optogenetic stimulation, and microangiography. We also present evidence that CION can serve as a cross-modality research platform by showing concurrent in vivo optical and MRI measurement of CBV using fluorescent-labeled CION. The simplicity and cost-effectiveness of our one-pot synthesis method should allow researchers to reproduce CION and tailor the relaxivity and pharmacokinetics according to their imaging needs. It is our hope that this work makes CBV-MRI more openly available and affordable for a variety of research applications.

Comparative RNA-Seq Analysis Uncovers a Complex Regulatory Network for Soybean Cyst Nematode Resistance in Wild Soybean (Glycine soja).

Soybean cyst nematode (SCN) is the most damaging pest of soybean worldwide. The molecular mechanism of SCN resistance remains largely unknown. We conducted a global RNA-seq comparison between a resistant genotype (S54) and a susceptible genotype (S67) of Glycine soja, the wild progenitor of soybean, to understand its regulatory network in SCN defense. The number of differentially expressed genes (DEGs) in S54 (2,290) was much larger than that in S67 (555). A number of defense-related genes/pathways were significantly induced only in S54, while photosynthesis and several metabolic pathways were affected in both genotypes with SCN infection. These defense-associated DEGs were involved in pathogen recognition, calcium/calmodulin-mediated defense signaling, jasmonic acid (JA)/ethylene (ET) and sialic acid (SA)-involved signaling, the MAPK signaling cascade, and WRKY-involved transcriptional regulation. Our results revealed a comprehensive regulatory network involved in SCN resistance and provided insights into the complex molecular mechanisms of SCN resistance in wild soybean.