Multifunctional 4,5-Diphenyl-1H-imidazole-Based Luminogens as Near UV/Deep Blue Emitters/Hosts for Organic Light-Emitting Diodes and Selective Picric Acid Detection

A series of luminophores (construction of diphenylimidazole (m-CF3PTPI) groups functionalized at the N1-positions of imidazole groups) were purposefully designed and synthesized for optoelectronics and for selective detection of nitroaromatic compounds. The luminophores showed deep blue emission in solution, solid, and thin-film matrix with acceptable quantum yield and good thermal stability (5% weight loss at 258–296 °C). From electrochemical analysis as well as theoretical calculations, the energy gaps of HOMO–LUMO are found to be in good agreement and all of them showed good triplet energy. The luminophores can be explored as hosts for phosphorescent organic light-emitting diodes (PhOLEDs). Furthermore, the m-CF3PTPI derivatives were used as emitters for fluorescent OLEDs and hosts (m-CF3PTPI-1 and m-CF3PTPI-2) for triplet dopants in PhOLEDs. Near-UV emissions were observed for all the doped devices that exhibited electroluminescence (EL) peaks at ∼380–395 nm with a Commission International deL’Eclairage (CIEy) coordinate of ∼0.09. Of all the devices, the m-CF3PTPI-5 (3 wt %)-based device demonstrated a maximum external quantum efficiency (EQEmax) of 2.8%, power efficiency (PEmax) of 0.9 lm/W, current efficiency (CEmax) of 1.3 cd/A, and brightness of 953 cd/m2. Moreover, the device was further optimized using a different host approach. SimCP2 displayed the best performance by achieving a high EQEmax of 4.0% that is near the theoretical limit of fluorescent materials

Noninvasive Monitoring of Placenta-Specific Transgene Expression by Bioluminescence Imaging

BACKGROUND: Placental dysfunction underlies numerous complications of pregnancy. A major obstacle to understanding the roles of potential mediators of placental pathology has been the absence of suitable methods for tissue-specific gene manipulation and sensitive assays for studying gene functions in the placentas of intact animals. We describe a sensitive and noninvasive method of repetitively tracking placenta-specific gene expression throughout pregnancy using lentivirus-mediated transduction of optical reporter genes in mouse blastocysts. METHODOLOGY/PRINCIPAL FINDINGS: Zona-free blastocysts were incubated with lentivirus expressing firefly luciferase (Fluc) and Tomato fluorescent fusion protein for trophectoderm-specific infection and transplanted into day 3 pseudopregnant recipients (GD3). Animals were examined for Fluc expression by live bioluminescence imaging (BLI) at different points during pregnancy, and the placentas were examined for tomato expression in different cell types on GD18. In another set of experiments, blastocysts with maximum photon fluxes in the range of 2.0E+4 to 6.0E+4 p/s/cm(2)/sr were transferred. Fluc expression was detectable in all surrogate dams by day 5 of pregnancy by live imaging, and the signal increased dramatically thereafter each day until GD12, reaching a peak at GD16 and maintaining that level through GD18. All of the placentas, but none of the fetuses, analyzed on GD18 by BLI showed different degrees of Fluc expression. However, only placentas of dams transferred with selected blastocysts showed uniform photon distribution with no significant variability of photon intensity among placentas of the same litter. Tomato expression in the placentas was limited to only trophoblast cell lineages. CONCLUSIONS/SIGNIFICANCE: These results, for the first time, demonstrate the feasibility of selecting lentivirally-transduced blastocysts for uniform gene expression in all placentas of the same litter and early detection and quantitative analysis of gene expression throughout pregnancy by live BLI. This method may be useful for a wide range of applications involving trophoblast-specific gene manipulations in utero

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

Enantioselective organocatalysis has become a field of central importance within asymmetric chemical synthesis and appears to be efficient approach toward the construction of complex chiral molecules from simple achiral materials in one-pot transformations under mild conditions with high stereocontrol. This review addresses the most significant synthetic methods reported on chiral-amine-catalyzed tandem Michael conjugate addition of heteroatom-centered nucleophiles to α,β-unsaturated compounds followed by cyclization reactions for the enantioselective construction of functionalized chiral chromenes, thiochromenes and 1,2-dihydroquinolines in optically enriched forms found in a myriad of bioactive natural products and synthetic compounds

Development of A 3D Tissue Slice Culture Model for the Study of Human Endometrial Repair and Regeneration

The human endometrium undergoes sequential phases of shedding of the upper functionalis zone during menstruation, followed by regeneration of the functionalis zone from the remaining basalis zone cells, and secretory differentiation under the influence of the ovarian steroid hormones estradiol (E2) and progesterone (P4). This massive tissue regeneration after menstruation is believed to arise from endometrial stromal and epithelial stem cells residing in the basal layer of the endometrium. Although many endometrial pathologies are thought to be associated with defects in these stem cells, studies on their identification and regulation are limited, primarily due to lack of easily accessible animal models, as these processes are unique to primates. Here we describe a robust new method to study endometrial regeneration and differentiation processes using human endometrial tissue slice cultures incorporating an air-liquid interface into a 3D matrix scaffold of type I collagen gel, allowing sustained tissue viability over three weeks. The 3D collagen gel-embedded endometrial tissue slices in a double-dish culture system responded to ovarian steroid hormones, mimicking the endometrial changes that occur in vivo during the menstrual cycle. These changes included the E2-induced upregulation of Ki-67, estrogen receptor (ER), and progesterone receptor (PR) in all endometrial compartments and were markedly suppressed by both P4 and E2 plus P4 treatments. There were also distinct changes in endometrial morphology after E2 and P4 treatments, including subnuclear vacuolation and luminal secretions in glands as well as decidualization of stromal cells, typical characteristics of a progestational endometrium in vivo. This long-term slice culture method provides a unique in vivo-like microenvironment for the study of human endometrial functions and remodeling during early pregnancy and experiments on stem cell populations involved in endometrial regeneration and remodeling. Furthermore, this model has the potential to enable studies on several endometrial diseases, including endometrial cancers and pregnancy complications associated with defects in endometrial remodeling

Ce(IV) oxidation of alcohols using cetyltrimethylammonium ceric nitrate

1486-1490Cetyltrimethylammonium ceric nitrate (CTACN) has been used to oxidize some primary aliphatic and alicyclic alcohols in acetonitrile medium and the reaction kinetics have been investigated by spectrophotometric method. The decrease in the rate with increased concentration of CTACN has been attributed to the formation of reversed micelles by the oxidant in organic medium. An asymptotic decrease in rate with increase in [CTAB] supports the reversed micellization in the reaction medium. The plots of rate constants with [substrate] reflect the partitioning of the substrate in the reversed micellar system of CTACN. The kinetic isotope effect (kH/kD) of 1.97 has been attributed to the dehydrogenation mechanism for the oxidation of alcohols

Solution behaviour of cetyltrimethylammonium ceric nitrate

2229-2232Conductance, viscosity, surface tension and density of the aqueous solution of cetyltrilmethylammonium ceric nitrate have been measured at different temperatures. Surface excess concentration, apparent molar volume and degree of association have been calculated. An increased ionic association with increasing temperature has been observed. This is attributed to a temperature induced micellization phenomenon. The resultant thermodynamic parameters derived from specific conductance also support the micellization process, wherein the dissociation of large ceric counter ion assists the aggregation.</span

Clinical studies with Cannabis in India – A need for guidelines for the investigators and ethics committees

Cannabis is one of the world's oldest cultivated plants and the most commonly used recreational drug worldwide. The plant relevant for medicinal use is Cannabis sativa that has two pharmacologically active ingredients – delta-9-tetrahydrocannabinol that is psychoactive and cannabidiol that does not have psychotropic activity. The policy tapestry of Cannabis has undergone a significant change in the past few decades worldwide. Different countries have diverse policies, ranging from classifying use of Cannabis as illicit, to legalization of its use, both for medicinal and recreational purposes. Cannabis products are approved for use, for instance, in multiple sclerosis and Dravet syndrome (US Food Drug and Administration). Against this backdrop, we find that the knowledge foundations for use of Cannabis in clinical trials in India are still evolving. Conducting ethical research within a clinical trials framework is essential to understand dosing, formulation, shelf life, drug–drug interaction, tolerability, and safety before establishing its utility for various indications. In the absence of guidelines or a regulatory framework for conduct of these studies, the various Institutional Ethics Committees (IECs), which are responsible for reviewing projects related to Cannabis, face unique challenges with respect to the basic requirements. The principal investigators (PIs) are equally strained to find local guidance, recommendations, and literature in support of their application to the respective IEC, thus leading to an impasse and delay in initiating the proposed clinical studies with Cannabis. The present article addresses considerations, questions, and issues that affect the conduct of these clinical studies and recommends mandatory documents and some suggested guidelines for use by both PIs and IECs to take studies with Cannabis forward until such time that an interdisciplinary regulatory framework is firmed up by regulatory authority

Variable Cre Recombination Efficiency in Placentas of Cyp19-Cre ROSA^mT/mG Transgenic Mice

The aromatase-Cre recombinase (Cyp19-Cre) transgenic mouse model has been extensively used for placenta-specific gene inactivation. In a pilot study, we observed unexpected phenotypes using this mouse strain, which prompted an extensive characterization of Cyp19-Cre placental phenotypes using ROSAmT/mG transgenic reporter mice. The two strains were mated to generate bi-transgenic Cyp19-Cre;ROSAmT/mG mice following a standard transgenic breeding scheme, and placental and fetal tissues were analyzed on embryonic day 17.5. Both maternal and paternal Cre inheritance were analyzed by mating the respective Cyp19-Cre and ROSAmT/mG males and females. The genotype results showed the expected percentage of Cyp19-Cre;ROSAmT/mG fetuses (73%) and Cre mRNA was expressed in all of the Cyp19-Cre placentas. However, surprisingly, only about 50% of the Cyp19-Cre;ROSAmT/mG placentas showed Cre-mediated recombinase activity as demonstrated by placental enhanced green fluorescent protein (EGFP) expression. Further genetic excision analysis of the placentas revealed consistent results showing the absence of excision of the tdTomato in all of the Cyp19-Cre;ROSAmT/mG placentas lacking EGFP expression. Moreover, among the EGFP-expressing placentas, there was wide variability in recombination efficiency, even in placentas from the same litter, leading to a mosaic pattern of EGFP expression in different zones and cell types of the placentas. In addition, we observed a significantly higher percentage of Cre recombination activity in placentas with maternal Cre inheritance. Our results show frequent mosaicism, inconsistent recombination activity, and parent-of-origin effects in placentas from Cyp19-Cre;ROSAmT/mG mice, suggesting that tail-biopsy genotype results may not necessarily indicate the excision of floxed genes in Cyp19-Cre positive placentas. Thus, placenta-specific mutagenesis studies using the Cyp19-Cre model require extensive characterization and careful interpretation of the placental phenotypes for each floxed allele

VEGF Maintains Maternal Vascular Space Homeostasis in the Mouse Placenta through Modulation of Trophoblast Giant Cell Functions

Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that acts primarily on endothelial cells, but numerous studies suggest that VEGF also acts on non-endothelial cells, including trophoblast cells. Inhibition of VEGF signaling by excess production of the endogenous soluble VEGF receptor sFlt1 in trophoblast cells has been implicated in several pregnancy complications. Our previous studies and other reports have shown that VEGF directly regulates placental vascular development and functions and that excess VEGF production adversely affects placental vascular development. Trophoblast giant cells (TGCs) line the maternal side of the placental vasculature in mice and function like endothelial cells. In this study, we specifically examined the effect of excess VEGF signaling on TGC development associated with defective placental vascular development using two mouse models an endometrial VEGF overexpression model and a placenta-specific sFlt1 knockdown model. Placentas of endometrial VEGF-overexpressing dams at embryonic days (E) 11.5 and 14.5 showed dramatic enlargement of the venous maternal spaces in junctional zones. The size and number of the parietal TGCs that line these venous spaces in the placenta were also significantly increased. Although junctional zone venous blood spaces from control and VEGF-overexpressing dams were not markedly different in size at E17.5, the number and size of P-TGCs were both significantly increased in the placentas from VEGF-overexpressing dams. In sFlt1 knockdown placentas, however, there was a significant increase in the size of the sinusoidal TGC-lined, alkaline phosphatase-positive maternal blood spaces in the labyrinth. These results suggest that VEGF signaling plays an important role in maintaining the homeostasis of the maternal vascular space in the mouse placenta through modulation of TGC development and differentiation, similar to the effect of VEGF on endothelial cells in other vascular beds