Probing the Galactic halo with RR Lyrae stars -- IV. On the Oosterhoff dichotomy of RR Lyrae stars

We use 3653 (2661 RRab, 992 RRc) RR Lyrae stars (RRLs) with 7D (3D position, 3D velocity, and metallicity) information selected from SDSS, LAMOST, and Gaia EDR3, and divide the sample into two Oosterhoff groups (Oo I and Oo II) according to their amplitude-period behaviour in the Bailey Diagram. We present a comparative study of these two groups based on chemistry, kinematics, and dynamics. We find that Oo I RRLs are relatively more metal rich, with predominately radially dominated orbits and large eccentricities, while Oo II RRLs are relatively more metal poor, and have mildly radially dominated orbits. The Oosterhoff dichotomy of the Milky Way's halo is more apparent for the inner-halo region than for the outer-halo region. Additionally, we also search for this phenomenon in the halos of the two largest satellite galaxies, the Large and Small Magellanic clouds (LMC, SMC), and compare over different bins in metallicity. We find that the Oosterhoff dichotomy is not immutable, and varies based on position in the Galaxy and from galaxy-to-galaxy. We conclude that the Oosterhoff dichotomy is the result of a combination of stellar and galactic evolution, and that it is much more complex than the dichotomy originally identified in Galactic globular clusters

One-Step 18

Positron emission tomography (PET) imaging is a useful method to evaluate in situ estrogen receptor (ER) status for the early diagnosis of breast cancer and optimization of the appropriate treatment strategy. The 18F-labeled estradiol derivative has been successfully used to clinically assess the ER level of breast cancer. In order to simplify the radiosynthesis process, one-step 18F-19F isotope exchange reaction was employed for the 18F-fluorination of the tracer of [18F]AmBF3-TEG-ES. The radiotracer was obtained with the radiochemical yield (RCY) of ~61% and the radiochemical purity (RCP) of >98% within 40 min. Cell uptake and blocking assays indicated that the tracer could selectively accumulate in the ER-positive human breast cancer cell lines MCF-7 and T47D. In vivo PET imaging on the MCF-7 tumor-bearing mice showed relatively high tumor uptake (1.4~2.3 %D/g) and tumor/muscle uptake ratio (4~6). These results indicated that the tracer is a promising PET imaging agent for ER-positive breast cancers

Preparation and Biological Evaluation of Two Novel Platinum(II) Complexes Based on the Ligands of Dipicolyamine Bisphosphonate Esters

Two new platinum(II)-based complexes bearing a bone-targeting group were synthesized and characterized. They both have excellent affinity for hydroxyapatite (HA), which is abundant in human bone tissues. Their antitumor activities against five human cancer cell lines (U2OS, A549, HCT116, MDA-MB-231 and HepG2) were evaluated and compared with cisplatin (CDDP). Though the antitumor efficacies of new complexes are lower than that of CDDP, they show higher selectivity against the HepG2 hepatoma cell line than the L02 normal liver cell line. Morphology studies exhibited typical characteristics of cell apoptosis and the cell cycle distribution analysis indicated that the complexes can inhibit cancer cells by inducing cell cycle arrest at the G2/M phase, a similar mechanism of action to CDDP

Rational design of caspase-responsive smart molecular probe for positron emission tomography imaging of drug-induced apoptosis

Purpose: Positron emission tomography (PET) imaging of apoptosis is very important for early evaluation of tumor therapeutic efficacy. A stimuli-responsive probe based on the peptide sequence Asp-Glu-Val-Asp (DEVD), [18F]DEVD-Cys(StBu)-PPG(CBT)-AmBF3 ([18F]1), for PET imaging of tumor apoptosis was designed and prepared. This study aimed to develop a novel smart probe using a convenient radiosynthesis method and to fully examine the sensitivity and specificity of the probe response to the tumor treatment. Methods: The radiolabelling precursor DEVD-Cys(StBu)-PPG(CBT)-AmBF3 (1) was synthesized through multistep reactions. The reduction together with caspase-controlled macrocyclization and self-assembly of 1 was characterized and validated in vitro. After [18F]fluorination in the buffer (pH= 2.5), the radiolabelling yield (RLY), radiochemical purity (RCP) and stability of the probe [18F]1 in PBS and mouse serum were investigated by radio-HPLC. The sensitivity and specificity of [18F]1 for detecting the drug-induced apoptosis was fully evaluated in vitro and in vivo. The effect of cold precursor 1 on the cell uptake and tumor imaging of [18F]1 was also assessed. The level of activated caspase-3 in Hela cells and tumors with or without apoptosis induction was analyzed and compared by western blotting and histological staining. Results: The whole radiosynthesis process of [18F]1 was around 25 min with RLY of 50%, RCP of over 99% and specific activity of 1.45 ± 0.4 Ci/μmol. The probe was very stable in both PBS and mouse serum within 4 h. It can be activated by caspase-3 and then undergo an intermolecular cyclization to form nanosized particles. The retained [18F]1 in DOX-treated HeLa cells was 2.2 folds of that in untreated cells. Within 1 h microPET imaging of the untreated Hela-bearing mice, the injection of [18F]1 resulted in the increase of the uptake ratio of tumor to muscle (T/M) only from 1.74 to 2.18, while in the DOX-treated Hela-bearing mice T/M increased from 1.88 to 10.52 and the co-injection of [18F]1 and 1 even led to the increase of T/M from 3.08 to 14.81. Conclusions: A caspase-responsive smart PET probe [18F]1 was designed and prepared in a kit-like manner. Co-injection of [18F]1 and 1 generated remarkably enhanced tumor uptake and signal-to-noise ratio in the tumor-bearing mice with drug-induced apoptosis, which correlated well with the expression level of activated caspase-3. This early readout of treatment response ensured that the probe [18F]1 could serve as a promising PET imaging probe for timely and noninvasive evaluation of tumor therapy

The Role of the Hydroxyl Group in Propofol–Protein Target Recognition: Insights from ONIOM Studies

Propofol (PFL, 1-hydroxyl-2,6-diisopropylbenzene) is currently used widely as one of the most well-known intravenous anesthetics to relieve surgical suffering, but its mechanism of action is not yet clear. Previous experimental studies have demonstrated that the hydroxyl group of PFL plays a dominant role in the molecular recognition of PFL with receptors that lead to hypnosis. To further explore the mechanism of anesthesia induced by PFL in the present work, the exact binding features and interaction details of PFL with three important proteins, human serum albumin (HSA), the pH-gated ion channel from <i>Gloeobacter violaceus</i> (GLIC), and horse spleen apoferritin (HSAF), were investigated systematically by using a rigorous three-layer ONIOM (M06-2X/6-31+G*:PM6:AMBER) method. Additionally, to further characterize the possible importance of such hydroxyl interactions, a similar set of calculations was carried out on the anesthetically inactive fropofol (FFL, 1-fluoro-2,6-diisopropylbenzene) in which the fluorine was substituted for the hydroxyl. According to the ONIOM calculations, atoms in molecules (AIM) analyses, and electrostatic potential (ESP) analyses, the significance of hydrogen bond, halogen bond, and hydrophobic interactions in promoting proper molecular recognition was revealed. The binding interaction energies of PFL with different proteins were generally larger than FFL and are a significant determinant of their differential anesthetic efficacies. Interestingly, although the hydrogen-bonding effect of the hydroxyl moiety was prominent in propofol, the substitution of the 1-hydroxyl by a fluorine atom did not prevent FFL from binding to the protein via a halogen-bonding interaction. It therefore became clear that multiple specific interactions rather than just hydrogen or halogen bonds must be taken into account to explain the different anesthesia endpoints caused by PFL and FFL. The contributions of key residues in ligand–receptor binding were also quantified, and the calculated results agreed with many available experimental observations. This work will provide complementary insights into the molecular mechanisms of anesthetic action for PFL from a robust theoretical point of view. This will not only assist in interpreting experimental observations but will also help to develop working hypotheses for further experiments and future drug design