Stereoselective Interactions of Chiral Polyurea Nanocapsules with Albumins.

Exploiting the chirality of nanometric structures to modulate biological systems is an emerging and compelling area of research. In this study, we reveal that chiral polyurea nanocapsules exhibit significant stereoselective interactions with albumins from various sources despite their nearly neutral surface potential. Moreover, these interactions can be modulated by altering the nanocapsule surface composition, offering new opportunities to impact their distribution and, if used as a drug delivery system, the pharmacokinetics of the drug.

Evaluation of nasal delivery systems of olanzapine by desorption electrospray ionization mass spectrometry imaging.

Nose-to-brain delivery presents an attractive administration route for neuroactive drugs that suffer from compromised bioavailability or fail to pass the blood-brain barrier. However, the conventional gauge of effectiveness for intranasal delivery platforms primarily involves detecting the presence of the administered drug within the brain, with little insight into its precise localization within brain structures. This may undermine the therapeutic efficacy of drugs and hinder the design of systems that target specific brain regions.

Adipose tissue composition determines its computed tomography radiodensity.

Objectives: Adipose tissue radiodensity in computed tomography (CT) performed before surgeries can predict surgical difficulty. Despite its clinical importance, little is known about what influences radiodensity. This study combines desorption electrospray ionization mass spectrometry imaging (DESI-MSI) and electrospray ionization (ESI) with machine learning to unveil how chemical composition of adipose tissue determines its radiodensity.

Azapodophyllotoxin Causes Lymphoma and Kidney Cancer Regression by Disrupting Tubulin and Monoglycerols.

A natural compound screen identified several anticancer compounds, among which azapodophyllotoxin (AZP) was found to be the most potent. AZP caused decreased viability of both mouse and human lymphoma and renal cell cancer (RCC) tumor-derived cell lines. Novel AZP derivatives were synthesized and screened identifying compound NSC750212 to inhibit the growth of both lymphoma and RCC both in vitro and in vivo.

SDHB knockout and succinate accumulation are insufficient for tumorigenesis but dual SDHB/NF1 loss yields SDHx-like pheochromocytomas.

Inherited pathogenic succinate dehydrogenase (SDHx) gene mutations cause the hereditary pheochromocytoma and paraganglioma tumor syndrome. Syndromic tumors exhibit elevated succinate, an oncometabolite that is proposed to drive tumorigenesis via DNA and histone hypermethylation, mitochondrial expansion, and pseudohypoxia-related gene expression. To interrogate this prevailing model, we disrupt mouse adrenal medulla SDHB expression, which recapitulates several key molecular features of human SDHx tumors, including succinate accumulation but not 5hmC loss, HIF accumulation, or tumorigenesis.

Desorption electrospray ionization mass spectrometry imaging in discovery and development of novel therapies.

Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) is one of the least specimen destructive ambient ionization mass spectrometry tissue imaging methods. It enables rapid simultaneous mapping, measurement, and identification of hundreds of molecules from an unmodified tissue sample. Over the years, since its first introduction as an imaging technique in 2005, DESI-MSI has been extensively developed as a tool for separating tissue regions of various histopathologic classes for diagnostic applications.

Adipocytes Provide Fatty Acids to Acute Lymphoblastic Leukemia Cells.

Background: There is increasing evidence that adipocytes play an active role in the cancer microenvironment. We have previously reported that adipocytes interact with acute lymphoblastic leukemia (ALL) cells, contributing to chemotherapy resistance and treatment failure. In the present study, we investigated whether part of this resistance is due to adipocyte provision of lipids to ALL cells.

Differential Interactions of Chiral Nanocapsules with DNA.

(1) Background: Chiral nanoparticular systems have recently emerged as a compelling platform for investigating stereospecific behavior at the nanoscopic level. We describe chiroselective supramolecular interactions that occur between DNA oligonucleotides and chiral polyurea nanocapsules. (2) Methods: We employ interfacial polyaddition reactions between toluene 2,4-diisocyanate and lysine enantiomers that occur in volatile oil-in-water nanoemulsions to synthesize hollow, solvent-free capsules with average sizes of approximately 300 nm and neutral surface potential.

Automated Phenotyping Tool for Identifying Developmental Language Disorder Cases in Health Systems Data (APT-DLD): A New Research Algorithm for Deployment in Large-Scale Electronic Health Record Systems.

Purpose Data mining algorithms using electronic health records (EHRs) are useful in large-scale population-wide studies to classify etiology and comorbidities (Casey et al., 2016). Here, we apply this approach to developmental language disorder (DLD), a prevalent communication disorder whose risk factors and epidemiology remain largely undiscovered.

Nanoparticles decorated with granulocyte-colony stimulating factor for targeting myeloid cells.

Dysregulated myeloid cell activity underlies a variety of pathologies, including immunosuppression in malignant cancers. Current treatments to alter myeloid cell behavior also alter other immune cell subpopulations and nonimmune cell types with deleterious side effects. Therefore, improved selectivity of myeloid treatment is an urgent need.

The MYC Oncogene Cooperates with Sterol-Regulated Element-Binding Protein to Regulate Lipogenesis Essential for Neoplastic Growth.

Lipid metabolism is frequently perturbed in cancers, but the underlying mechanism is unclear. We present comprehensive evidence that oncogene MYC, in collaboration with transcription factor sterol-regulated element-binding protein (SREBP1), regulates lipogenesis to promote tumorigenesis. We used human and mouse tumor-derived cell lines, tumor xenografts, and four conditional transgenic mouse models of MYC-induced tumors to show that MYC regulates lipogenesis genes, enzymes, and metabolites.

Combining Desorption Electrospray Ionization Mass Spectrometry Imaging and Machine Learning for Molecular Recognition of Myocardial Infarction.

Lipid profile changes in heart muscle have been previously linked to cardiac ischemia and myocardial infarction, but the spatial distribution of lipids and metabolites in ischemic heart remains to be fully investigated. We performed desorption electrospray ionization mass spectrometry imaging of hearts from in vivo myocardial infarction mouse models. In these mice, myocardial ischemia was induced by blood supply restriction via a permanent ligation of left anterior descending coronary artery.

Distinguishing malignant from benign microscopic skin lesions using desorption electrospray ionization mass spectrometry imaging.

Detection of microscopic skin lesions presents a considerable challenge in diagnosing early-stage malignancies as well as in residual tumor interrogation after surgical intervention. In this study, we established the capability of desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to distinguish between micrometer-sized tumor aggregates of basal cell carcinoma (BCC), a common skin cancer, and normal human skin. We analyzed 86 human specimens collected during Mohs micrographic surgery for BCC to cross-examine spatial distributions of numerous lipids and metabolites in BCC aggregates versus adjacent skin.

Charting the development of cognitive mapping.

Developmental research beginning in the 1970s has suggested that children's ability to form cognitive maps reaches adult levels during early adolescence. However, this research has used a variety of testing procedures, often in real-world environments, which have been difficult to share widely across labs and to use to probe components of mapping, individual differences in success, and possible mechanisms of development and reasons for individual variation. In this study, we charted the development of cognitive mapping using a virtual navigation paradigm, Silcton, that allows for testing samples of substantial size in a uniform way and in which adults show marked individual differences in the formation of accurate route representations and/or in route integration.

Formation of Polymeric Nanocubes by Self-Assembly and Crystallization of Dithiolane-Containing Triblock Copolymers.

Template-free fabrication of non-spherical polymeric nanoparticles is desirable for various applications, but has had limited success owing to thermodynamic favorability of sphere formation. Herein we present a simple way to prepare cubic nanoparticles of block copolymers by self-assembly from aqueous solutions at room temperature. Nanocubes with edges of 40-200 nm are formed spontaneously on different surfaces upon water evaporation from micellar solutions of triblock copolymers containing a central poly(ethylene oxide) block and terminal trimethylene carbonate/dithiolane blocks.

Oncogene KRAS activates fatty acid synthase, resulting in specific ERK and lipid signatures associated with lung adenocarcinoma.

KRAS gene mutation causes lung adenocarcinoma. KRAS activation has been associated with altered glucose and glutamine metabolism. Here, we show that KRAS activates lipogenesis, and this activation results in distinct proteomic and lipid signatures.

Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging.

Background: Surgical resection with microscopically negative margins remains the main curative option for pancreatic cancer; however, in practice intraoperative delineation of resection margins is challenging. Ambient mass spectrometry imaging has emerged as a powerful technique for chemical imaging and real-time diagnosis of tissue samples. We applied an approach combining desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with the least absolute shrinkage and selection operator (Lasso) statistical method to diagnose pancreatic tissue sections and prospectively evaluate surgical resection margins from pancreatic cancer surgery.

The Environmentally Benign form of Pesticide in Hydrodispersive Nanometric form with Improved Efficacy Against Adult Mosquitoes at Low Exposure Concentrations.

Permethrin, a poorly water-soluble synthetic pesticide belonging to the pyrethroid family, was formulated into water-dispersive nanometric form by rapid evaporation of pesticide loaded oil-in-water microemulsion. The mean hydrodynamic diameter of Nanopermethrin was found to be 199.01 ± 1.

Celecoxib Nanoparticles for Therapeutic Angiogenesis.

Controllable induction of blood vessel formation (angiogenesis) presents an important therapeutic goal in ischemic diseases and is also beneficial in various normal physiological processes. In this study, we have shown that nanoparticles of celecoxib, a lipophilic nonsteroidal anti-inflammatory drug, effectively evoke therapeutic angiogenesis in animal models, in both normal and ischemic organs. Celecoxib is widely considered to inhibit angiogenesis, although a recent study suggests that it can instead promote blood vessel growth in cancer cell lines.

Formation of curcumin nanoparticles by flash nanoprecipitation from emulsions.

Nanometric particles of a model hydrophobic substance curcumin were prepared by a novel method, namely, flash nanoprecipitation from a coarse oil-in-water emulsion. The method employs turbulent co-mixing of water with curcumin-loaded emulsion using manually-operated confined impingement jets mixer. A clear and stable dispersion of nanoparticles was formed in this process, and could be converted to dry, easily water-dispersible powder by spray drying.