Objective The aim of the study was to evaluate the antiproliferative potential of simple phenylboronic acid and benzoxaborole derivatives as well as to provide preliminary insight into their mode of action in cancer cells in vitro. Methods The antiproliferative activity was assessed in five diverse cancer cell lines via the SRB method (sulforhodamine B) or MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method after 72 h of treatment. Further studies of the mechanism of action consisted of the influence of the compounds on cell cycle progression and apoptosis induction, which was assessed by flow cytometry, caspase-3 enzymatic activity, fluorescence microscopy and western blot analysis. Results A clear structure-activity relationship was observed for both groups of compounds with several representatives evaluated as highly active antiproliferative agents with low micromolar [Formula: see text] values. 2-Fluoro-6-formylphenylboronic acid (18) and 3-morpholino-5-fluorobenzoxaborole (27) exhibited strong cell cycle arrest induction in G2/M associated with caspase-3 activation in an A2780 ovarian cancer cell line. These events were accompanied by a mitotic catastrophe cell morphology and an increased percentage of aneuploid and tetraploid cells. Further experiments indicated that the compounds were phase cycle-specific agents since cells co-treated with hydroxyurea were less sensitive. The observed cell cycle arrest resulted from significant p21 accumulation and was associated neither with cyclin B1 nor β-tubulin degradation. Conclusion Phenylboronic acid and benzoxaborole derivatives were found to be highly promising antiproliferative and proapoptotic compounds with a cell cycle-specific mode of action. The presented data support their candidacy for further studies as a novel class of potential anticancer agents.

Cellulose hydrogel from aqueous solution of lithium bromide demonstrated excellent tunability of mechanical property and shape. A series of compression tests showed that cellulose hydrogel covered a wide range of mechanical property, where the compressive Young's modulus was controllable from 30 kPa to 1.3 MPa by changing the initial concentration of cellulose solution. Meanwhile, the diameter of the building block of gel, namely nano-fibrous cellulose, was constant at 15-20 nm irrelevant of the initial concentration of cellulose solution. Moreover, thanks to the biocompatibility of cellulose, the cultivation of cartilage tissue was successful in the micro-porous sponge-like cellulose hydrogel prepared by salt-leaching process. These findings show that this environmentally-benign versatile gel offers a new substrate for the biomaterial-based nanomaterial in biomedical applications.

Overexpression of ecto-5'-nucleotidase is found to be linked to cancer progression and other diseases which makes screening of its inhibitors on demand. Unfortunately, there is scarcity of reported ecto-5'-nucleotidase inhibitors because of unavailability of simple, fast and efficient methods to study its inhibition. In this study, we have developed a very fast, reverse polarity capillary electrophoresis based method for screening of ecto-5'-nucleotidase inhibitors. Both EOF and electrophoretic mobility were maintained in same direction by dynamically coating lining of capillary and applying negative voltage, resulting in appearance of both adenosine monophosphate (AMP) and adenosine peaks in less than two minutes. Separations were performed in reverse polarity using -20 kV. Hexadimethrine bromide (HDB) was used as a buffer additive (0.025% in 40 mM borate buffer). An online sample stacking was attained by a special sweeping effect which enabled a long (65 s) injection time without compromise in peak shape. Using this newly developed method, both AMP and adenosine peaks were obtained with a baseline resolution, in less than two minutes. Method was validated by measuring km , and Vmax values of human ecto-5'-nucleotidas and Ki value of standard inhibitor quercitin against this enzyme. Method is simple and fast and can be conveniently optimized for high throughput screening of ecto-5'-nucleotidase inhibitors. This article is protected by copyright. All rights reserved.

Fluorescence signal enhancement induced by the binding of intercalators to DNA has been broadly utilized in various DNA detection methods. In most instances the increase in fluorescence intensity is associated with a concomitant increase of fluorescence lifetime. This increase of the fluorescence lifetime presents an additional opportunity to increase detection sensitivity. In this paper, we present a new approach to significantly enhance the sensitivity in detecting minute DNA concentrations. The approach is based on simultaneous use of time-gated detection and multi-pulse pumping. By using a calibrated burst of short pulses we greatly enhance the contribution of long-lived fluorescence species, thus enabling easy time-gated detection. Using a classic DNA intercalator - Ethidium Bromide (EtBr) - as an example with our novel multi-pulse pumping and time-gated detection technique, we were able to increase detection sensitivity over 70-fold with only 3 pulse excitation. This approach is generic and can be used with any analytical probe (exhibiting about 10 times change in lifetime) that shows an increase in fluorescence signal and fluorescence lifetime upon binding to a target.

The double aminolysis reaction of [Co{N(SiMe3)2}2] by the salt 1-(6-((dicyclohexylphosphaneyl)methyl)pyridin-2-yl)-3-(2,6-diisopropylphenyl)-1H-imidazol-3-ium bromide, which contains one phosphane, one pyridine and one imidazolium groups, of formula [o-Cy2PCH2(C5H3N)(o-C3H3N2DiPP)]Br and abbreviated as (CyPNpyrCim)Br, was previously shown to afford the Co(ii) complex [Co(CyP*NaCNHC)Br] (1) containing a dearomatised picolyl moiety in the tridentate, anionic donor ligand CyP*NaCNHC (Na = anionic amido, P* = vinylic P donor). We now report that formation of 1 is preceded by an intermediate tentatively assignable to the 5-coordinate Co(ii) complex [Co(CyPNpyrCNHC){N(SiMe3)2}Br] (2). The reaction of 1 with LiCH2SiMe3 afforded the dark purple, paramagnetic [Co(CyP*NaCNHC)CH2SiMe3] (3) with a low spin d7 CoII; the electronic configurations of 1 and 3 were corroborated by EPR spectroscopy. Addition of excess (≥4 equiv.) H2SiPh2 to a solution of 1 gave the diamagnetic [Co(CyP(SiHPh2)NCNHC)Br] (4) following Si-H activation and silylation of the ligand backbone at the α-CHP. Reduction of CoII to CoI by silanes is uncommon.

Electronic properties and lattice vibrations are expected to be strongly correlated in metal-halide perovskites, due to the soft fluctuating nature of their crystal lattice. Thus, unveiling electron-phonon coupling dynamics upon ultrafast photoexcitation is necessary for understanding the optoelectronic behavior of the semiconductor. Here, we use impulsive vibrational spectroscopy to reveal vibrational modes of methylammonium lead-bromide perovskite under electronically resonant and non-resonant conditions. We identify two excited state coherent phonons at 89 and 106 cm-1, whose phases reveal a shift of the potential energy minimum upon ultrafast photocarrier generation. This indicates the transition to a new geometry, reached after approximately 90 fs, and fully equilibrated within the phonons lifetime of about 1 ps. Our results unambiguously prove that these modes drive the crystalline distortion occurring upon photo-excitation, demonstrating the presence of polaronic effects.

The distance between nodes of Ranvier, referred to as internode length, positively correlates with axon diameter, and is optimized during development to ensure maximal neuronal conduction velocity. Following myelin loss, internode length is reestablished through remyelination. However, remyelination results in short internode lengths and reduced conduction rates. We analyzed the potential role of neurofilament phosphorylation in regulating internode length during remyelination and myelination. Following ethidium bromide induced demyelination, levels of neurofilament medium (NF-M) and heavy (NF-H) phosphorylation were unaffected. Preventing NF-M lysine-serine-proline (KSP) repeat phosphorylation increased internode length by 30% after remyelination. To further analyze the role of NF-M phosphorylation in regulating internode length, gene replacement was used to produce mice in which all KSP serine residues were replaced with glutamate to mimic constitutive phosphorylation. Mimicking constitutive KSP phosphorylation reduced internode length by 16% during myelination and motor nerve conduction velocity by ~27% without altering sensory nerve structure or function. Our results suggest that NF-M KSP phosphorylation is part of a cooperative mechanism between axons and Schwann cells that together determine internode length, and suggest motor and sensory axons utilize different mechanisms to establish internode length.