Mechanogeneration of Acid from Oxime Sulfonates

The generation of acid under mechanical force is potentially useful for initiating proton-catalyzed changes in polymeric materials. Here we demonstrate that oxime sulfonatesknown photoacid generatorsare also acid generators when activated mechanically. NMR analysis of products suggests that the ultrasound-induced mechanochemical scission of the oxime sulfonate mechanophore also generates a ketone functional moiety, in addition to acid. Both acid and ketone moieties are useful for developing stress-responsive polymeric materials for autonomous self-healing applications

B.gb

The complete mitochondrial genome of Allium fistulosum L.</p

Development and Evaluation of a Parallel Reaction Monitoring Strategy for Large-Scale Targeted Metabolomics Quantification

Recent advances in mass spectrometers which have yielded higher resolution and faster scanning speeds have expanded their application in metabolomics of diverse diseases. Using a quadrupole-Orbitrap LC–MS system, we developed an efficient large-scale quantitative method targeting 237 metabolites involved in various metabolic pathways using scheduled, parallel reaction monitoring (PRM). We assessed the dynamic range, linearity, reproducibility, and system suitability of the PRM assay by measuring concentration curves, biological samples, and clinical serum samples. The quantification performances of PRM and MS1-based assays in Q-Exactive were compared, and the MRM assay in QTRAP 6500 was also compared. The PRM assay monitoring 237 polar metabolites showed greater reproducibility and quantitative accuracy than MS1-based quantification and also showed greater flexibility in postacquisition assay refinement than the MRM assay in QTRAP 6500. We present a workflow for convenient PRM data processing using Skyline software which is free of charge. In this study we have established a reliable PRM methodology on a quadrupole-Orbitrap platform for evaluation of large-scale targeted metabolomics, which provides a new choice for basic and clinical metabolomics study

Programmable Payload Release from Transient Polymer Microcapsules Triggered by a Specific Ion Coactivation Effect

Stimuli-responsive materials activated by a pair of molecular or ionic species are of interest in the design of chemical logic gates and signal amplification schemes. There are relatively few materials whose coactivated response has been well-characterized. Here, we demonstrate a specific ion coactivation (SICA) effect at the interfaces of transient polymer solids and liquid solutions. We found that depolymerization of the transient polymer, cyclic poly­(phthalaldehyde) (cPPA), exhibited a SICA effect when the cPPA core–shell microcapsules were suspended in ion-containing acidic methanol solutions. Significant acceleration in cPPA depolymerization rate is triggered by the combination of acid and ion coactivators. Intriguingly, the SICA effect is related to the Hofmeister behavior. The SICA effect is primarily determined by anions, and cations exhibit a secondary effect that modulates the coactivation strength. Based on these observations, we developed cPPA programmable microcapsules whose payload release rates depend on the composition and concentration of the salt/acidic-methanol solutions

Glucuronidation of β-lap in HT29 cell S9 fractions.

<p>HT29 cells S9 were incubated with β-lap according to the details in methods. (A) A typical Michaelis-Menten kinetics of β-lap glucuronidation in HT29 cells S9 fractions; (B) UGT1A siRNA treated HT29 cells S9 fractions significantly decreases β-lap glucuronidation; (C) Inhibitory potency of propofol on β-lap glucuronidation in HT29 cell S9 fractions. Results are presented as mean ± 3 SEM of three independent experiments (***P<0.001, UGT1A siRNA treatment vs. negative control cells).</p

Impact of Intermolecular Distance on Singlet Fission in a Series of TIPS Pentacene Compounds

Singlet fission has attracted considerable interest for its potential application in organic photovoltaics. However, the underlying microscopic mechanism is not well understood and the molecular parameters that govern SF efficiency remain unclear. We herein study the primary exciton photogeneration and evolution in the thin film of a series of pentacene derivatives (TIPS-Pn and ADPD-Pn) using femtosecond transient absorption spectroscopy. With a favorable “long-edge on” packing motif, the singlet-excited slip-stacked TIPS-Pn and ADPD-Pn molecules undergo ultrafast fission to produce triplet excitonic states with time constants of ∼0.3 ps. More importantly, the ADPD-Pn compound features a considerably higher triplet yield than TIPS-Pn (162 ± 10% vs 114 ± 15%). The enhanced electronic coupling as a result of closer interchromophore distance (3.33 Å for ADPD-Pn vs 3.40 Å for TIPS-Pn) is suggested to account for the much higher triplet yield for ADPD-Pn relative to that for TIPS-Pn, proving SF can be readily modulated by adjusting the intermolecular distance

UDP-Glucuronosyltransferase 1A Determinates Intracellular Accumulation and Anti-Cancer Effect of β-Lapachone in Human Colon Cancer Cells

<div><p>β-lapachone (β-lap), an NAD(P)H:quinone oxidoreductase 1 (NQO1) targeting antitumor drug candidate in phase II clinical trials, is metabolically eliminated via NQO1 mediated quinone reduction and subsequent UDP-glucuronosyltransferases (UGTs) catalyzed glucuronidation. This study intends to explore the inner link between the cellular glucuronidation and pharmacokinetics of β-lap and its apoptotic effect in human colon cancer cells. HT29 cells S9 fractions exhibited high glucuronidation activity towards β-lap, which can be inhibited by UGT1A9 competitive inhibitor propofol. UGT1A siRNA treated HT29 cells S9 fractions displayed an apparent low glucuronidation activity. Intracellular accumulation of β-lap in HCT116 cells was much higher than that in HT29 cells, correlated with the absence of UGT1A in HCT116 cells. The cytotoxic and apoptotic effect of β-lap in HT29 cells were much lower than that in HCT116 cells; moreover, β-lap triggered activation of SIRT1-FOXO1 apoptotic pathway was observed in HCT116 cells but not in HT29 cells. Pretreatment of HT29 cells with UGT1A siRNA or propofol significantly decreased β-lap’s cytotoxic and apoptotic effects, due to the repression of glucuronidation and the resultant intracellular accumulation. In conclusion, UGT1A is an important determinant, via switching NQO1-triggered redox cycle to metabolic elimination, in the intracellular accumulation of β-lap and thereafter its cytotoxicity in human colon cancer cells. Together with our previous works, we propose that UGTs determined cellular pharmacokinetics is an important determinant in the apoptotic effects of NQO1 targeting substrates serving as chemotherapeutic drugs.</p></div

UGT1A Diminishes β-lap -induced ROS Formation.

<p>Cells were pretreated with UGT1A siRNA or scrambled siRNA (negative control) for 24 h, or pretreated with propofol (100 μM)/ NAC (5 μM)/ catalase (4000 U) for 1 h. Then, cells were exposed to β-lap (5 μM) for 2 h and ROS assay or GSSG/GSH ratio assay was performed. (A) ROS formation and GSSG/GSH ratio in HCT116 cells pretreated with propofol/NAC/catalase; (B) ROS formation and GSSG/GSH ratio in HT29 cells pretreated with propofol/NAC/catalase; (C) ROS formation and GSSG/GSH ratio in HT29 cells pretreated with siRNA/NAC/catalase. Results are presented as mean ± 3 SEM of at least three independent experiments (*P<0.05, **P<0.01, ***P<0.001, β-lap treatment vs. control cells; #P<0.05, ##P<0.01, NAC pretreatment vs. corresponding β-lap only; $P<0.05,$$P<0.01,$ $$P<0.001, catalase pretreatment vs. corresponding β-lap only).</p

UGT1A compromises β-lap induced cytotoxicity.

<p>Cells were pretreated with propofol (100 μM) for 1 h or UGT1A siRNA for 24 h. Then, Cells were exposed to gradient concentrations of β-lap (0, 1.25, 2.5, 5, 10, 20 μM) for 24 h and MTT assay was performed. (A) β-lap induced cytotoxicity in HCT116 cells with propofol/NAC/catalase pretreatment; (B) β-lap induced cytotoxicity in HT29 cells with propofol/NAC/catalase pretreatment; (C) β-lap induced cytotoxicity in HT29 cells with siRNA/NAC/catalase pretreatment. Results are presented as mean ± 6 SEM of at least three independent experiments (*P<0.05, **P<0.01, ***P<0.001, propofol/siRNA pretreatment vs. β-lap only; #P<0.05, ##P<0.01, ###P<0.001, NAC and propofol/siRNA pretreatment vs. propofol/siRNA only; $$P<0.01, $$ $P<0.001, catalase and propofol/siRNA pretreatment vs. propofol/siRNA only).</p