No abstract

A subset of cancer stem cells termed 'side population' (SP) cells has been identified in several types of solid tumor and is known to be responsible for the failure of chemotherapy and for cancer relapse. In the present study, the oral squamous cell carcinoma (OSCC) cell line SCC‑55 was used for analysis of the SP cells based on Hoechst 33342 exclusion, via the ATP‑binding cassette (ABC) transporter, with and without verapamil using fluorescence activated cell sorting. The results demonstrated that the presence of SP cells in the SCC‑55 cell line was 2.8%, which was reduced to 0.6% in the presence of verapamil, an inhibitor of the ABC transporter. In addition, following exposure to the chemotherapeutic drug 5‑fluorouracil, a high survival rate was observed in the SP cells due to overexpression of the ABCG2 and B‑cell lymphoma 2 proteins. In addition, overexpression of stem cell surface markers, including CD44 and CD147 was observed in the SP cells. Therefore, these findings suggested that OSCC contains SP cells, which share certain characteristics with stem cells. The coexpression of ABC transporters and stem cell surface markers in SP cells may be associated with resistance to chemotherapeutic agents and also supports a role for these cells in tumor recurrence, metastasis and invasion.

This work could help to better understand the solvent effects on crystal habits and aspect ratio changes at the molecular level, which provide some guidance for solvent selection in industrial crystallization processes. With the catechol crystal habits acquired using both experimental and simulation methods in isopropanol, methyl acetate and ethyl acetate, solvent effects on crystal morphology were explored based on the modified attachment energy model. Firstly, morphologically dominant crystal faces were obtained with the predicted crystal habit in vacuum. Then, modified attachment energies were calculated by the molecular dynamics simulation to modify the crystal shapes in a real solvent environment, and the simulation results were in agreement with the experimental ones. Meanwhile, the surface properties such as roughness and the diffusion coefficient were introduced to analyze the solvent adsorption behaviors and the radial distribution function curves were generated to distinguish diverse types of interactions like hydrogen bonds and van der Waals forces. Results show that the catechol crystal habits were affected by the combination of the attachment energy, surface structures and molecular interaction types. Moreover, the changing aspect ratios of catechol crystals are closely related to the existence of hydrogen bonds which contribute to growth inhibition on specific faces.

No abstract

In industrial crystallization, spherical crystals have gained increasing interest due to their excellent physicochemical properties, such as high bulk density, flowability, stability, etc. However, their formation mechanism is still not well understood and is often oversimplified. In this work, spherical amoxicillin sodium crystals were obtained via a spherulitic growth strategy. It was found that agitation immediately after the addition of crystal seeds was critical for inducing radial noncrystallographic branching and spherulite formation of amoxicillin sodium. Without agitation during the aging period after seed addition, only discrete rodshaped crystals were obtained. The formation mechanism of amoxicillin sodium spherulites was studied using process analytical technology (PAT) tools, including focused beam reflectance measurement (FBRM) and particle video microscope (PVM). The result was indicative of a three-step morphological evolution process: formation of polycrystalline agglomerates, noncrystallographic branching, and spherulite growth. During this process, agitation immediately after seed addition could help to solute diffusion and induce the agglomeration of small crystals that result from secondary nucleation. The polycrystalline agglomerates serve as the cores for further noncrystallographic branching and growth. On this basis, a new spherulitic growth strategy was proposed by the large addition of crystal seeds as the growth substrates of new branching and spherulite growth. High agitation rates during the aging period can increase the mass ratio of spherulites, and high initial supersaturation can promote branching. Compared with the discrete rod-shaped crystals, spherulites self-regulate the final size greatly up to three times and have a higher bulk density as well as much lower hygroscopicity.

No abstract

The solubility of 2,2′-bis­(2-hydroxyethoxy)-1,1′-binaphthalene form B in 12 pure organic solvents (n-propanol, isopropanol, n-butanol, isobutanol, n-pentanol, ethyl formate, methyl acetate, ethyl acetate, n-butyl acetate, isobutyl acetate, methylbenzene, and propanone) was determined from 283.15 to 323.15 K for the first time. The solubility has a positive correlation with temperature. Four thermodynamic models including the modified Apelblat equation, λh equation, van’t Hoff equation, and the NRTL model were used to correlate the solubility data and further evaluated by ARD. Results show that all four models give good correlation. Additionally, the mixing thermodynamic properties of 2,2′-bis­(2-hydroxyethoxy)-1,1′-binaphthalene form B were analyzed based on the NRTL model. Results indicate that the mixing processes of 2,2′-bis­(2-hydroxyethoxy)-1,1′-binaphthalene are spontaneous and entropy-driven. The effects of solvent properties on solubility were discussed from the aspects of polarity, hydrogen bond, cohesive energy density, and steric hindrance. Results show that polarity and steric hindrance of the selected solvents greatly affect the solubility of 2,2’-bis­(2-hydroxyethoxy)-1,1′-binaphthalene form B.

Isostructurality is a potential tool to design crystals with tailored arrangements, especially for multicomponent systems, but research into its formation mechanism is still limited to date. Herein, a family of spironolactone (SPI) isostructural and nonisostructural solvates was investigated to explore the selective formation of isostructural crystals. The SPI framework, dominated by van der Waals forces, is robust and flexible, with different solvent molecules in its channels playing the same structural role. The formation of the SPI isostructural solvate is a delicate energy balance between the energy loss caused by the expansion of the SPI framework and the addition of SPI•••solvent interactions. Besides the size and functional groups of solvent molecules, the directionality of the SPI•••solvent interactions should also be carefully considered in the isostructurality-based crystal design. In addition, weak interactions seem to be regarded as potential design elements for organic host architectures. I sostructurality is defined as different types of molecules occupying the same (or very similar) crystalline arrangements, which is a useful guide for predicting and designing crystals. 1,2 Isostructurality of organic crystals has been proved to be more prevalent than expected, particularly in multicomponent systems, such as a series of related steroids and their solvates. 3−12 The control of isostructurality can overcome dissimilarities in shapes and functional groups of different molecules and systematically fine-tune physicochemical properties following the same blueprint. 7,13−15 Isostructural compounds can be served as heteronuclear seeds to discover desired solids, 4,16−20 and it has also turned out to be feasible for the construction of porous crystal materials. 21−24 Therefore, it is important to investigate deeply the formation mechanism of isostructurality to build molecular crystals with tailored arrangements. However, as the opposite phenomenon of polymorphism, isostructurality has attracted much less attention from scientists, and consequently, research into its formation mechanism and applicability is still limited. Most efforts have been dedicated to the analysis of isostructural packing patterns, the calculation of structural similarities, and the preparation of isostructural cocrystals based on equivalent functional groups. 25,26 In addition, isostructural crystals are designed mainly on forces with a specific strength and direction, like hydrogen bonds and halogen bonds, with little concern for weak hydrogen bonds and van der Waals forces. 10,27,28 Deep comprehension of these weak interactions is essential to expanding new design strategies and applications for multicomponent crystals.