Assumption-free morphological quantification of single anisotropic nanoparticles and aggregates

Characterizing the morphometric parameters of noble metal nanoparticles for sensing and catalysis is a persistent challenge due to their small size and complex shape. Herein, we present an approach to determine the volume, surface area, and curvature of non-symmetric anisotropic nanoparticles using electron tomography and design- based stereology without the use of segmentation tools or modeling of the particles. Finally, we apply these tools to aggregates to estimate their fractal dimension

A novel sample holder for 4D live cell imaging to study cellular dynamics in complex 3D tissue cultures

Three dimensional (3D) co-cultures to mimic cellular dynamics have brought significant impacts in tissue engineering approaches for biomedical research. Herein, we present a novel sample holder combined with time-lapse fluorescence imaging technique, referred as 4D live cell imaging, allowing direct visualization of various cells up to 24 hours. We further extended our approach to monitor kinetics and dynamics of particle uptake by cells and translocation across tissue membranes

Biodistribution of single and aggregated gold nanoparticles exposed to the human lung epithelial tissue barrier at the air-liquid interface

The lung represents the primary entry route for airborne particles into the human body. Most studies addressed possible adverse effects using single (nano)particles, but aerosolic nanoparticles (NPs) tend to aggregate and form structures of several hundreds nm in diameter, changing the physico-chemical properties and interaction with cells. Our aim was to investigate how aggregation might affect the biodistribution; cellular uptake and translocation over time of aerosolized NPs at the air-blood barrier interface using a multicellular lung system

Carbon nanodots: Opportunities and limitations to study their biodistribution at the human lung epithelial tissue barrier

Inhalation of combustion-derived ultrafine particles (≤0.1 μm) has been found to be associated with pulmonary and cardiovascular diseases. However, correlation of the physicochemical properties of carbon-based particles such as surface charge and agglomeration state with adverse health effects has not yet been established, mainly due to limitations related to the detection of carbon particles in biological environments. The authors have therefore applied model particles as mimics of simplified particles derived from incomplete combustion, namely, carbon nanodots (CNDs) with different surface modifications and fluorescent properties. Their possible adverse cellular effects and their biodistribution pattern were assessed in a three- dimensional (3D) lung epithelial tissue model. Three different CNDs, namely, nitrogen, sulfur codoped CNDs (N,S-CNDs) and nitrogen doped CNDs (N-CNDs-1 and N- CNDs-2), were prepared by microwave-assisted hydrothermal carbonization using different precursors or different microwave systems. These CNDs were found to possess different chemical and photophysical properties. The surfaces of nanodots N- CNDs-1 and N-CNDs-2 were positively charged or neutral, respectively, arguably due to the presence of amine and amide groups, while the surfaces of N,S-CNDs were negatively charged, as they bear carboxylic groups in addition to amine and amide groups. Photophysical measurements showed that these three types of CNDs displayed strong photon absorption in the UV range. Both N-CNDs-1 and N,S-CNDs showed weak fluorescence emission, whereas N-CNDs-2 showed intense emission. A 3D human lung model composed of alveolar epithelial cells (A549 cell line) and two primary immune cells, i.e., macrophages and dendritic cells, was exposed to CNDs via a pseudo-air-liquid interface at a concentration of 100 μg/ml. Exposure to these particles for 24 h induced no harmful effect on the cells as assessed by cytotoxicity, cell layer integrity, cell morphology, oxidative stress, and proinflammatory cytokines release. The distribution of the CNDs in the lung model was estimated by measuring the fluorescence intensity in three different fractions, e.g., apical, intracellular, and basal, after 1, 4, and 24 h of incubation, whereby reliable results were only obtained for N-CNDs-2. It was shown that N-CNDs-2 translocate rapidly, i.e., >40% in the basal fraction within 1 h and almost 100% after 4 h, while ca. 80% of the N-CNDs-1 and N,S-CNDs were still located on the apical surface of the lung cells after 1 h. This could be attributed to the agglomeration behavior of N-CNDs-1 or N,S-CNDs. The surface properties of the N-CNDs bearing amino and amide groups likely induce greater uptake as N-CNDs could be detected intracellularly. This was less evident for N,S- CNDs, which bear carboxylic acid groups on their surface. In conclusion, CNDs have been designed as model systems for carbon-based particles; however, their small size and agglomeration behavior made their quantification by fluorescence measurement challenging. Nevertheless, it was demonstrated that the surface properties and agglomeration affected the biodistribution of the particles at the lung epithelial barrier in vitro

Development of an Industrial Process Based on the Groebke– Blackburn–Bienaymé Multicomponent Reaction: Efficient Preparation of 3-Aminoimidazo[1,2-a]pyrazines

Abstract 3-aminoimidazo[1,2,a]pyrazine is an important scaffold found in many drugs. This scaffold is rapidly accessible via a Groebke–Blackburn-Bienaymé cyclisation starting from an aminopyrazine, an aldehyde and an isocyanide. A scale-up process of this multicomponent reaction has been successfully achieved in high yield and excellent purity. The scope and limitations of this process leading to various 3 aminoimidazo[1,2,a]pyrazines are disclosed

A Chiral Phosphoramidite Reagent for the Synthesis of Inositol Phosphates

There is a paucity of chiral phosphoramidite reagents or chiral catalysis methods for the synthesis of biologically relevant inositol phosphates. A new <i>C</i>₂-symmetrical chiral phosphoramidite has been developed and successfully applied to the synthesis of a set of chiral inositol bisphosphates. The reagent allowed bis-phosphorylation and chiral resolution, resulting in a concise synthetic route, thus expanding the toolbox available for the preparation of biologically relevant inositol phosphates in high optical purity

A Chiral Phosphoramidite Reagent for the Synthesis of Inositol Phosphates

There is a paucity of chiral phosphoramidite reagents or chiral catalysis methods for the synthesis of biologically relevant inositol phosphates. A new <i>C</i>₂-symmetrical chiral phosphoramidite has been developed and successfully applied to the synthesis of a set of chiral inositol bisphosphates. The reagent allowed bis-phosphorylation and chiral resolution, resulting in a concise synthetic route, thus expanding the toolbox available for the preparation of biologically relevant inositol phosphates in high optical purity

Morbidity and mortality weekly report, Vol. 4, no. 25, July 1, 1955

Provisional information on selected notifiable diseases in the United States and on deaths in selected cities for week ended June 25, 1955 -- Number of deaths in 108 selected citiesEpidemiological reports: Rabies in animals -- Psittacosis -- Encephalitis -- Diarrhea of the newborn -- Shigellosis -- Gastro-enteritisTable 1. Cases of specified notifiable diseases: continental United States -- Table 2. Cases of specified notifiable diseases: United States, each division and state, Alaska, Hawaii, and Puerto Rico for weeks ended June 26, 1954 and June 25, 1955 -- Table 3. Deaths in selected cities by geographic division -- Table 4. Deaths in selected cities for week ended June 25, 1955

Small-Molecule Allosteric Triggers of Clostridium difficile Toxin B Auto-proteolysis as a Therapeutic Strategy

ISSN:2451-945