Hypoxia-activated prodrugs of phenolic olaparib analogues for tumour-selective chemosensitisation.

Poly(ADP-ribose)polymerase inhibitors (PARPi) are used for treatment of tumours with a defect in homologous recombination (HR) repair. Combination with radio- or chemotherapy could broaden their applicability but a major hurdle is enhancement of normal tissue toxicity. Development of hypoxia-activated prodrugs (HAPs) of PARPi has potential to restrict PARP inhibition to tumours thereby avoiding off-target toxicity.

Tumor-microenvironment-responsive poly-prodrug encapsulated semiconducting polymer nanosystem for phototherapy-boosted chemotherapy.

Phototherapy-induced hypoxia in the tumor microenvironment (TME) is responsible for diminished therapeutic efficacy. Designing an intelligent nanosystem capable of responding to hypoxia for TME-responsive drug delivery will, to some extent, improve the therapeutic efficacy and reduce side effects. Semiconducting polymers with high photothermal conversion efficiency and photostability have tremendous potential as phototheranostics.

Itaconate is a covalent inhibitor of the isocitrate lyase.

Itaconate is a mammalian antimicrobial metabolite that inhibits the isocitrate lyases (ICLs) of . Herein, we report that ICLs form a covalent adduct with itaconate through their catalytic cysteine residue. These results reveal atomic details of itaconate inhibition and provide insights into the catalytic mechanism of ICLs.

Inexpensive throughfall exclusion experiment for single large trees.

Premise: Drought-induced tree mortality is an emergent threat to forests worldwide, particularly to large trees. Drought-manipulation experiments involving throughfall exclusion (TFE) tend to focus on large plots that can be expensive to establish and maintain and may be unsuitable for large trees or indigenous forests. We set out to establish a relatively inexpensive TFE method in a natural forest with large trees.

Crystal structure and Hirshfeld surface analysis of a new di-thio-glycoluril: 1,4-bis-(4-meth-oxy-phen-yl)-3-methyl-tetra-hydro-imidazo[4,5-]imidazole-2,5(1,3)-di-thione.

In the title di-thio-glycoluril derivative, CHNOS, there is a difference in the torsion angles between the thio-imidazole moiety and the meth-oxy-phenyl groups on either side of the mol-ecule [C-N-C-C = 116.9 (2) and -86.1 (3)°, respectively].

A Domain-Specific Approach for Assessing Physical Activity Efficacy in Adolescents: From Scale Conception to Predictive Validity.

Objective: To develop and test the utility of a domain-specific scale in adolescents for predicting physical activity behaviour.

Design: Two independent studies were conducted. Study 1 examined the psychometric properties of a newly constructed Domain-Specific Physical Activity Efficacy Questionnaire (DSPAEQ) and study 2 tested the utility of the scale for predicting leisure- and school-time physical activity.

Wnt/β-catenin signaling plays an important role in the protective effects of FDP-Sr against oxidative stress induced apoptosis in MC3T3-E1 cell.

Strontium fructose 1,6-diphosphate (FDP-Sr) is a new strontium-containing compound. The primary aim of this study was to clarify whether the structure component of FDP-Sr, FDP could benefit the protective effect of Sr (II) against oxidative stress induced apoptosis, and meanwhile to further explore the important role of Wnt/β-catenin signaling in the anti-apoptosis effect of FDP-Sr in response to oxidative stress induced by H2O2 in an osteoblastic MC3T3-E1 cell line. Results showed that FDP-Sr could improve the osteoblastic differentiation under oxidative stress with induced cell proliferation and improved mineralization.

A pre-clinical pharmacokinetic study in rats of three naturally occurring iridoid glycosides, Picroside-I, II and III, using a validated simultaneous HPLC-MS/MS assay.

A selective and sensitive high-performance liquid chromatography-electro-spray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the simultaneous quantitative determination of Picroside-I, II, and III in rat plasma and tissue homogenate to aid the pre-clinical studies. The chromatographic separation was performed on a Hypersil GOLD AQ C18 column using a gradient elution program with a mobile phase consisting of 2mM ammonium acetate and acetonitrile. The detection was achieved using a triple quadrupole tandem MS in negative ionization multiple reaction monitoring (MRM) mode.

Crystal structure of N'-[(1E)-1-(6-methyl-2,4-dioxo-3,4-di-hydro-2H-pyran-3-yl-idene)eth-yl]benzene-sulfono-hydrazide.

In the title compound, C14H14N2O5S, the mol-ecule exists in the enamine (C=C-NH) tautomeric form. The hydrazone fragment derived from the 3-acetyl-4-hy-droxy-6-methyl-2H-pyran-2-one moiety is approximately planar, with a maximum deviation of 0.1291 (11) Å for the N atom bound to the S atom of the benzensulfono-hydrazide group.

Metabolomic analysis of simvastatin and fenofibrate intervention in high-lipid diet-induced hyperlipidemia rats.

Aim: To investigate the metabolite changes caused by simvastatin or fenofibrate intervention in diet-induced hyperlipidemia rats using a GC-MS-based metabolomic profiling approach.

Methods: SD rats were fed with high-lipid diet for 4 weeks to induce hyperlipidemia, then the rats were fed with normal diet, and orally administered with simvastatin (10 mg·kg(-1)·d(-1)) or fenofibrate (150 mg·kg(-1)·d(-1)) for 2 weeks. Blood samples were collected once a week, and potential biomarkers were examined using commercial assay kits and a metabolomic approach.

Transcriptomics to study the effect of a Mediterranean-inspired diet on inflammation in Crohn's disease patients.

Background: Inflammation is an essential immune response; however, chronic inflammation results in disease including Crohn's disease. Therefore, reducing the inflammation can yield a significant health benefit, and one way to achieve this is through diet. We developed a Mediterranean-inspired anti-inflammatory diet and used this diet in a 6-week intervention in a Crohn's disease population.

Hybrid hollow core fibers with embedded wires as THz waveguides.

We experimentally demonstrate broadband terahertz (THz) pulse propagation through hollow core fibers with two or four embedded Indium wires in a THz time-domain spectroscopy (THz-TDS) setup. The hybrid mode is guided in the air core region with power attenuation coefficients of 0.3 cm(-1) and 0.

Antitumor activity of gold(i), silver(i) and copper(i) complexes containing chiral tertiary phosphines.

The in vitro cytotoxicities of a number of gold(I), silver(I) and copper(I) complexes containing chiral tertiary phosphine ligands have been examined against the mouse tumour cell lines P815 mastocytoma, B16 melanoma [gold(I) and silver(I) compounds] and P388 leukaemia [gold(I) complexes only] with many of the complexes having IC(50) values comparable to that of the reference compounds cis-diamminedichloroplatinum(ll), cisplatin, and bis[1,2-bis(diphenylphosphino) ethane]gold(I) iodide. The chiral tertiary phosphine ligands used in this study include (R)-(2-aminophenyl)methylphenylphosphine; (R,R)-, (S,S)- and (R(*),R(*))-1,2-phenylenebis(methylphenylphosphine); and (R,R)-, (S,S)- and (R(*),R(*))-bis{(2-diphenylphosphinoethyl)phenylphosphino}ethane. The in vitro cytotoxicities of gold(I) and silver(I) complexes containing the optically active forms of the tetra(tertiary phosphine) have also been examined against the human ovarian carcinoma cell lines 41M and CH1, and the cisplatin resistant 41McisR, CH1cisR and SKOV-3 tumour models.