Low-barrier hydrogen bond between phosphate and the amide group in phosphopeptide

As the conversion between the monoionic (1) and diionic (2) form of the phosphate occurs, the phosphorylated peptides or proteins can not only cause the formation of a hydrogen bond between the phosphate group and the amide group but also change the strength of the hydrogen bond to form low-barrier hydrogen bonds (LBHBs). This reversible protonation of the phosphate group, which changes both the electrostatic properties of the phosphate group and the strength of the hydrogen bond, provides a possible mechanism in regulating protein function.     

N,N,N',N'-Tetrakis(2-quinolylmethyl)-2-hydroxy-1,3-propanediamine (Htqhpn) as a supporting ligand for a low-valent (mu-O)2 tetranuclear manganese core

A new heptadentate N6-O1 ligand, N,N,N',N'-tetrakis(2-quinolylmethyl)-2-hydroxy-1,3-propanediamine (Htqhpn), was synthesized and used to generate compounds with linearly ordered MnIIMnIIIMnIIIMnII tetranuclear cores. This is the lowest valent tetranuclear manganese complex that exhibits a (mu2-O)2Mn2 core in the molecule. The electron paramagnetic resonance and magnetic measurements of these tetranuclear complexes suggest moderately strong antiferromagnetic coupling for the central MnIII2 core, with weak coupling between the MnII and MnIII centers.     

Cationic polymerization of vinyl ethers with alkyl or ionic side groups in ionic liquids

Controlled cationic polymerization of isobutyl vinyl ether was demonstrated to proceed in an ionic liquid (IL), 1‐butyl‐3‐octylimidazolium bis(trifluoromethanesulfonyl)imide, using a 1‐(isobutoxy)ethyl acetate/TiCl₄ initiating system, ethyl acetate as an added base, and 2,6‐di‐tert‐butylpyridine as a proton trap reagent. Judicious choices of metal halide catalysts, counteranions of ILs, and additives were essential for controlling the polymerization. The polymerization proceeded much faster in the IL than in CH₂Cl₂, indicating an increased population of ionic active species in the IL due to the high polarity. Polymers with a relatively narrow molecular weight distribution were obtained in the IL with a bis(trifluoromethanesulfonyl)imide ( ) anion even in the absence of an added base, which suggested possible interactions of the counteranion of the IL with the growing carbocations. Moreover, the direct cationic polymerization of a vinyl ether with pendant imidazolium salts, 1‐(2‐vinyloxyethyl)‐3‐methylimidazolium bis(trifluoromethanesulfonyl)imide, proceeded in a homogeneous state in 1‐methyl‐3‐octylimidazolium bis(trifluoromethanesulfonyl)imide. The solubilities of the obtained polymers were readily tuned by counteranion exchange. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1774–1784     

Global detection and semi‐quantification of Fritillaria alkaloids in Fritillariae Ussuriensis Bulbus by a non‐targeted multiple reaction monitoring approach

Methods based on triple quadrupole tandem mass spectrometry have been widely used and reported as highly selective and sensitive methods for quantifying substances of herbal medicines. However, most of them were limited to targeted components, due to the difficulties to optimize the multiple reaction monitoring transitions without authentic standards. This study proposed a novel strategy for non‐targeted optimization of multiple reaction monitoring method based on the diagnostic ion guided family classifications, tandem mass spectrometry database establishment, and transitions and collision energy screening. Applying this strategy, 59 Fritillaria alkaloids in Fritillariae Ussuriensis Bulbus have been classified, and 51 of these Fritillaria alkaloids were successfully detected by the optimal multiple reaction monitoring method. For semi‐quantification, the easy‐to‐obtain Fritillaria alkaloids of each type, such as verticinone for cevanine type and peimisine for jervine type, were used as the reference standards to calibrate the other Fritillaria alkaloids in the same type. The method was demonstrated a good linearity (R² > 0.998) with satisfactory accuracy and precision, and the lower limits of quantification of verticinone and peimisine were estimated to be 0.076 and 0.216 pg, respectively. In addition, the results suggested that the proposed strategy might obtained high quality metabolomics data in discrimination of Fritillaria unibracteata and Fritillaria ussuriensis.     

Single-molecule detection with a two-photon fluorescence microscope with fast-scanning capabilities and polarization sensitivity

We describe a laser-scanning two-photon fluorescence microscope that is capable of observing single molecules with excellent temporal resolution and three-dimensional spatial resolution. To demonstrate the capabilities of the instrument we present single-molecule fluorescence data obtained in several different scanning modes. In addition, a polarization-sensitive detection scheme can provide detailed three-dimensional information about the orientations of molecules in any of these scanning modes.     

Box-counting dimension without boxes: computing D0 from average expansion rates

We propose an efficient iterative scheme for calculating the box-counting (capacity) dimension of a chaotic attractor in terms of its average expansion rates. Similar to the Kaplan-Yorke conjecture for the information dimension, this scheme provides a connection between a geometric property of a strange set and its underlying dynamical properties. Our conjecture is demonstrated analytically with an exactly solvable two-dimensional hyperbolic map, and numerically with a more complicated higher-dimensional nonhyperbolic map.     

Betulinic Acid Restricts Human Bladder Cancer Cell Proliferation In Vitro by Inducing Caspase-Dependent Cell Death and Cell Cycle Arrest,and Decreasing Metastatic Potential

Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid and generally found in the bark of birch trees (Betula sp.). Although several studies have been reported that BA has diverse biological activities, including anti-tumor effects, the underlying anti-cancer mechanism in bladder cancer cells is still lacking. Therefore, this study aims to investigate the anti-proliferative effect of BA in human bladder cancer cell lines T-24, UMUC-3, and 5637, and identify the underlying mechanism. Our results showed that BA induced cell death in bladder cancer cells and that are accompanied by apoptosis, necrosis, and cell cycle arrest. Furthermore, BA decreased the expression of cell cycle regulators, such as cyclin B1, cyclin A, cyclin-dependent kinase (Cdk) 2, cell division cycle (Cdc) 2, and Cdc25c. In addition, BA-induced apoptosis was associated with mitochondrial dysfunction that is caused by loss of mitochondrial membrane potential, which led to the activation of mitochondrial-mediated intrinsic pathway. BA up-regulated the expression of Bcl-2-accociated X protein (Bax) and cleaved poly-ADP ribose polymerase (PARP), and subsequently activated caspase-3, -8, and -9. However, pre-treatment of pan-caspase inhibitor markedly suppressed BA-induced apoptosis. Meanwhile, BA did not affect the levels of intracellular reactive oxygen species (ROS), indicating BA-mediated apoptosis was ROS-independent. Furthermore, we found that BA suppressed the wound healing and invasion ability, and decreased the expression of Snail and Slug in T24 and 5637 cells, and matrix metalloproteinase (MMP)-9 in UMUC-3 cells. Taken together, this is the first study showing that BA suppresses the proliferation of human bladder cancer cells, which is due to induction of apoptosis, necrosis, and cell cycle arrest, and decrease of migration and invasion. Furthermore, BA-induced apoptosis is regulated by caspase-dependent and ROS-independent pathways, and these results provide the underlying anti-proliferative molecular mechanism of BA in human bladder cancer cells.     

Phloridzin Acts as an Inhibitor of Protein-Tyrosine Phosphatase MEG2 Relevant to Insulin Resistance

Inhibition of the megakaryocyte protein tyrosine phosphatase 2 (PTP-MEG2, also named PTPN9) activity has been shown to be a potential therapeutic strategy for the treatment of type 2 diabetes. Previously, we reported that PTP-MEG2 knockdown enhances adenosine monophosphate activated protein kinase (AMPK) phosphorylation, suggesting that PTP-MEG2 may be a potential antidiabetic target. In this study, we found that phloridzin, isolated from Ulmus davidiana var. japonica, inhibits the catalytic activity of PTP-MEG2 (half-inhibitory concentration, IC₅₀ = 32 ± 1.06 μM) in vitro, indicating that it could be a potential antidiabetic drug candidate. Importantly, phloridzin stimulated glucose uptake by differentiated 3T3-L1 adipocytes and C2C12 muscle cells compared to that by the control cells. Moreover, phloridzin led to the enhanced phosphorylation of AMPK and Akt relevant to increased insulin sensitivity. Importantly, phloridzin attenuated palmitate-induced insulin resistance in C2C12 muscle cells. We also found that phloridzin did not accelerate adipocyte differentiation, suggesting that phloridzin improves insulin sensitivity without significant lipid accumulation. Taken together, our results demonstrate that phloridzin, an inhibitor of PTP-MEG2, stimulates glucose uptake through the activation of both AMPK and Akt signaling pathways. These results strongly suggest that phloridzin could be used as a potential therapeutic candidate for the treatment of type 2 diabetes.     

β-Boswellic Acid Inhibits RANKL-Induced Osteoclast Differentiation and Function by Attenuating NF-κB and Btk-PLCγ2 Signaling Pathways

Osteoporosis is a systemic metabolic bone disorder that is caused by an imbalance in the functions of osteoclasts and osteoblasts and is characterized by excessive bone resorption by osteoclasts. Targeting osteoclast differentiation and bone resorption is considered a good fundamental solution for overcoming bone diseases. β-boswellic acid (βBA) is a natural compound found in Boswellia serrata, which is an active ingredient with anti-inflammatory, anti-rheumatic, and anti-cancer effects. Here, we explored the anti-resorptive effect of βBA on osteoclastogenesis. βBA significantly inhibited the formation of tartrate-resistant acid phosphatase-positive osteoclasts induced by receptor activator of nuclear factor-B ligand (RANKL) and suppressed bone resorption without any cytotoxicity. Interestingly, βBA significantly inhibited the phosphorylation of IκB, Btk, and PLCγ2 and the degradation of IκB. Additionally, βBA strongly inhibited the mRNA and protein expression of c-Fos and NFATc1 induced by RANKL and subsequently attenuated the expression of osteoclast marker genes, such as OC-STAMP, DC-STAMP, β3-integrin, MMP9, ATP6v0d2, and CtsK. These results suggest that βBA is a potential therapeutic candidate for the treatment of excessive osteoclast-induced bone diseases such as osteoporosis.