Syndecan-1 tagged liposomes as a theranostic nanoparticle for pancreatic adenocarcinoma.

Theranostic nanoparticles are emerging as a novel mechanism for detecting and treating cancer. Due to the difficulties in detection and treatment of pancreatic cancer, these particles could serve within this unique niche. In this study, a Syndecan-1 ligand was utilized to increase tumor specificity of fluorescent dye encapsulated liposomes which were evaluated as a potential theranostic nanoparticle for pancreatic adenocarcinoma. Their diagnostic capabilities and specificity to pancreatic adenocarcinoma were determined in vitro using immunocytochemistry and in vivo using multi-spectral optoacoustic tomography (MSOT). Immunocytochemistry showed that liposomes preferentially bound and released their contents into cells expressing high levels of Insulin-Like Growth Factor 1 Receptor. In an orthotopic pancreatic cancer mouse model, the liposomes preferentially targeted the pancreatic tumor with little off-target binding in the liver and spleen. Peak accumulation of the liposomes in the tumor occurred at 8 h post-injection. MSOT imaging was able to provide high-resolution 3D images of the tumor and liposome location. Ex vivo analysis showed that non-targeted liposomes accumulated in the liver suggesting that specificity of the liposomes for pancreatic adenocarcinoma was due to the presence of the Syndecan-1 ligand. Syndecan-1 tagged liposomes specifically target pancreatic adenocarcinoma both in vitro and in vivo. Once bound, the liposomes released the dye in vitro as indicated by red fluorescence of DNA-bound propidium iodide. The therapeutic drug-delivering capabilities of Syndecan-1 liposomes remain to be tested

Characteristics and physical mechanisms of a rainstorm in Hotan, Xinjiang, China

Owing to global warming, extreme precipitation events in the arid regions of Central Asia have increased, resulting in significant consequences for water resources and ecosystems. Hence, to address the features and corresponding physical mechanisms of these rainstorms, we examined the rainstorm that occurred in Hotan, Xinjiang in June 2021 as a case study. We employed multiple datasets, including meteorological stations, sounding observations, satellite precipitation data, and reanalysis datasets. The results indicate that the Global Precipitation Measurement satellite precipitation product accurately captured the temporal and spatial variations in this rainstorm, as verified against hourly in situ observation data. Some meteorological stations recorded values greater than twice their historical records, such as Luopu, Pishan, Moyu, and Hotan. Moreover, the duration of the precipitation was longer than 2 days. For the physical mechanisms of this rainstorm, the water vapor in this rainstorm is sourced from the 45°–65°N region of the North Atlantic Ocean crosses the Ural Mountains and the West Siberian Plain to southern Xinjiang. The low-pressure levels (e.g., 700 hPa and 850 hPa) have the more water vapor flux and specific humidity than the high-pressure levels. Our findings can aid the understanding of extreme precipitation events in Central Asia and provide a reference for dealing with meteorological disasters, including extreme precipitation, in the context of global climate change

Design, synthesis, and subtype selectivity of 3,6-disubstituted β-carbolines at Bz/GABA(A)ergic receptors. SAR and studies directed toward agents for treatment of alcohol abuse

A series of 3,6-disubstituted β-carbolines was synthesized and evaluated for their in vitro affinities at αxβ3γ2 GABAA/benzodiazepine receptor subtypes by radioligand binding assays in search of α1 subtype selective ligands to treat alcohol abuse. Analogues of β-carboline-3-carboxylate-t-butyl ester (βCCt, 1) were synthesized via a CDI-mediated process and the related 6-substituted β-carboline-3-carboxylates 6 including WYS8 (7) were synthesized via a Sonogashira or Stille coupling processes from 6-iodo βCCt (5). The bivalent ligands of βCCt (32 and 33) were also designed and prepared via a palladium-catalyzed homocoupling process to expand the structure-activity relationships (SAR) to larger ligands. Based on the pharmacophore/receptor model, a preliminary SAR study on 34 analogues illustrated that large substituents at position -6 of the β-carbolines were well tolerated. As expected, these groups are proposed to project into the extracellular domain (LDi region) of GABAA/Bz receptors (see 32 and 33). Moreover, substituents located at position -3 of the β-carboline nucleus exhibited a conserved stereo interaction in lipophilic pocket L1, while N(2) presumably underwent a hydrogen bonding interaction with H1. Three novel β-carboline ligands (βCCt, 3PBC and WYS8), which preferentially bound to α1 BzR subtypes permitted a comparison of the pharmacological efficacies with a range of classical BzR antagonists (flumazenil, ZK93426) from several different structural groups and indicated these β-carbolines were “near GABA neutral antagonists”. Based on the SAR, the most potent (in vitro) α1 selective ligand was the 6-substituted acetylenyl βCCt (WYS8, 7). Earlier both βCCt and 3PBC had been shown to reduce alcohol self-administration in alcohol preferring (P) and high alcohol drinking (HAD) rats but had little or no effect on sucrose self-administration.1–3 These data prompted the synthesis of the β-carbolines presented here

Specific Binding and Mineralization of Calcified Surfaces by Small Peptides

Several small (<25aa) peptides have been designed based on the sequence of the dentin phosphoprotein, one of the major noncollagenous proteins thought to be involved in the mineralization of the dentin extracellular matrix during tooth development. These peptides, consisting of multiple repeats of the tripeptide aspartate-serine-serine (DSS), bind with high affinity to calcium phosphate compounds and, when immobilized, can recruit calcium phosphate to peptide-derivatized polystyrene beads or to demineralized human dentin surfaces. The affinity of binding to hydroxyapatite surfaces increases with the number of (DSS)n repeats, and though similar repeated sequences—(NTT)n, (DTT)n, (ETT)n, (NSS)n, (ESS)n, (DAA)n, (ASS)n, and (NAA)n—also showed HA binding activity, it was generally not at the same level as the natural sequence. Binding of the (DSS)n peptides to sectioned human teeth was shown to be tissue-specific, with high levels of binding to the mantle dentin, lower levels of binding to the circumpulpal dentin, and little or no binding to healthy enamel. Phosphorylation of the serines of these peptides was found to affect the avidity, but not the affinity, of binding. The potential utility of these peptides in the detection of carious lesions, the delivery of therapeutic compounds to mineralized tissues, and the modulation of remineralization is discussed

Reactions of alkanethiol and nitrogen dioxide on oxide-supported gold nanoparticles

Abstract not availabl

Nonlinear approach to flow instability of the orifice-centerline liquid induced by bubble chain rising in shear-thinning fluids

The flow characteristics of orifice-centerline liquid induced by bubble chain rising in carboxymethylcellulose (CMC) aqueous solution have been investigated using nonlinear analysis of the velocity measured by Laser Doppler Anemometry. Both axial and radial velocities are determined under various gas flow rates (Qg), measurement heights (z) and mass concentrations. The results show that for low Qg, z and dilute solution, the characteristic frequency of the power spectrum is consistent with bubbling frequency, with uniform elliptical shape of reconstructed phase space. Largest Lyapunov exponents λ1 in radial direction is approximately 10 times that in the axial direction. Whereas for high Qg, z and concentrated solution, power spectrums are of broad coverage within low frequency range, with the compressed phase portrait and the raised λ1. Especially, the liquid motion has a special feature of binary fraction in the present experiment