Danggui Buxue Decoction: Comparative pharmacokinetic research on six bio-active components in different states by ultra-performance liquid chromatography-tandem mass spectrometry after oral administration

Danggui Buxue Decoction is a classic formula containing Astragali Radix and Angelicae Sinensis Radix in a 5:1 ratio and has been extensively used to treat blood deficiency for thousands of years. The aim of the study was to investigate the differences in plasma protein binding, pharmacokinetics, and tissue distribution of Danggui Buxue Decoction in normal and blood-deficient rats by ultra-performance liquid chromatography-tandem mass spectrometry. The effects on peripheral blood routine were verified. The compounds exhibited higher plasma protein binding and absorption in the model group compared to the control group, except formononetin. The six ingredients were distributed widely, and the highest concentrations were detected in the heart and uterus. As has been demonstrated in the previous study of the effect of Danggui Buxue Decoction, its potential is to serve as an effective traditional Chinese medicine formula for treating cardiovascular diseases and impacting estrogenic properties, which reveals the potential target organs of Danggui Buxue Decoction the heart and uterus. Our findings suggested that the absorption and distribution of different components in Danggui Buxue Decoction varies depending on the pathological state, molecular weight, lipid solubility, transporter-mediated efflux, and other factors.     

Synthesis and evaluation of new phosphonated δ-lactam and glutarimide derivatives as angiotensin converting enzyme inhibitors

An efficient synthesis of new γ,δ-insaturated δ-lactam and glutarimide derivatives bearing a phosphonomethyl group from a common allylphosphonate precursor is described. Our approach is based on a two-step procedure involving the preparation of phosphonated-1,5-ketoester and −1,5-diester followed by an amidation–heterocyclization sequence. The first step proceeds via Michael's addition of ethyl acetoacetate and diethyl malonate on an allylphosphonate starting material. The second step consists of a base-promoted intramolecular amidation-cyclization sequence with primary amines, which accounts for the construction of δ-lactams and glutarimide skeletons. We performed the evaluation of angiotensin I-converting enzyme (ACE) inhibition using an in vitro enzyme assay on six new compounds. Five compounds showed potent ACE inhibitory activity, with IC₅₀ values ranging from 0.02 to 0.27 mg/ml. Compared with Captopril, used as a reference drug, two new glutarimide derivatives exhibited higher efficiency ACE inhibition activity.     

Self-assembled luminescent CdSe-ZnS quantum dot bioconjugates prepared using engineered poly-histidine terminated proteins

We report a simple and versatile approach for the conjugation of luminescent CdSe-ZnS core-shell quantum dots (QDs) to proteins through coordination of engineered C-terminal oligohistidine sequences. Several histidine tail containing proteins were self-assembled onto the QD surface using this method. A recombinant antibody specific for the high explosive 2,4,6-trinitrotoluene (TNT) was conjugated to QDs through a carboxy terminal histidine tail and the bioconjugate used to detect TNT by competitive immunoassay. TNT was detected over the range of 10 μg/ml down to 41 ng/ml using the scFv conjugated to QDs. These results open up the possibility to conjugate luminescent QDs to a whole range of proteins to form QD bioconjugates that can be effectively used in bio-oriented applications, such as sensing, imaging, immunoassay and other diagnostics.     

Designer variable repeat length polypeptides as scaffolds for surface immobilization of quantum dots

We demonstrate the use of a series of engineered, variable-length de novo polypeptides to discretely immobilize luminescent semiconductor nanocrystals or quantum dots (QDs) onto functional surfaces. The polypeptides express N-terminal dicysteine and C-terminal hexahistidine residues that flank a variable number (1, 3, 5, 7, 14, 21, 28, or 35) of core beta-strand repeats, with tyrosine, glutamic acid, histidine, and lysine residues located at the turns. Polypeptides have molecular weights ranging from 4 to 83 kDa and retain a rigid structure based on the antiparallel beta-sheet motif. We first use a series of dye-labeled polypeptides to test and characterize their self-assembly onto hydrophilic CdSe-ZnS QDs using fluorescence resonance energy transfer (FRET). Results indicate that peptides maintain their beta-sheet conformation after self-assembly onto the QD surfaces, regardless of their length. We then immobilize biotinylated derivatives of these polypeptides on a NeutrAvidin-functionalized substrate and use them to capture QDs via specific interactions between the peptides' polyhistidine residues and the nanocrystal surface. We found that each of the polypeptides was able to efficiently capture QDs, with a clear correlation between the density of the surface-tethered peptide and the capacity for nanocrystal capture. The versatility of this capture strategy is highlighted by the creation of a variety of one- and two-dimensional polypeptide-QD structures as well as a self-assembled surface-immobilized FRET-based nutrient sensor.     

Demicompactness Results for Strongly Continuous Semigroups,Generators and Resolvents

Let \((U(t))_ {t\ge 0}\) be a strongly continuous semigroup of bounded linear operators on a Banach space X and B be a bounded operator on X. In this paper, we develop some aspects of the theory of semigroup for which U(t)B (respectively, BU(t), BU(t)B) is demicompact for some (respectively, every) \(t>0\). In addition, we study the demicompactness of similar, subspace and product semigroups. We also investigate the demicompactness of the resolvent. We close this paper by giving some conditions guaranteeing the demicompactness of a generator of a strongly continuous semigroup in a Hilbert space.     

Delivering quantum dots into cells: strategies,progress and remaining issues

The use of semiconductor quantum dots (QDs) in biological sensing and labeling continues to grow with each year. Current and projected applications include use as fluorescent labels for cellular labeling, intracellular sensors, deep-tissue and tumor imaging agents, sensitizers for photodynamic therapy, and more recently interest has been sparked in using them as vectors for studying nanoparticle-mediated drug delivery. Many of these applications will ultimately require the QDs to undergo targeted intracellular delivery, not only to specific cells, but also to a variety of subcellular compartments and organelles. It is apparent that this issue will be critical in determining the efficacy of using QDs, and indeed a variety of other nanoparticles, for these types of applications. In this review, we provide an overview of the current methods for delivering QDs into cells. Methods that are covered include facilitated techniques such as those that utilize specific peptide sequences or polymer delivery reagents and active methods such as electroporation and microinjection. We critically examine the benefits and liabilities of each strategy and illustrate them with selected examples from the literature. Several important related issues such as QD size and surface coating, methods for QD biofunctionalization, cellular physiology and toxicity are also discussed. Finally, we conclude by providing a perspective of how this field can be expected to develop in the future.     

Solution-phase single quantum dot fluorescence resonance energy transfer

We present a single particle fluorescence resonance energy transfer (spFRET) study of freely diffusing self-assembled quantum dot (QD) bioconjugate sensors, composed of CdSe-ZnS core-shell QD donors surrounded by dye-labeled protein acceptors. We first show that there is direct correlation between single particle and ensemble FRET measurements in terms of derived FRET efficiencies and donor-acceptor separation distances. We also find that, in addition to increased sensitivity, spFRET provides information about FRET efficiency distributions which can be used to resolve distinct sensor subpopulations. We use this capacity to gain information about the distribution in the valence of self-assembled QD-protein conjugates and show that this distribution follows Poisson statistics. We then apply spFRET to characterize heterogeneity in single sensor interactions with the substrate/target and show that such heterogeneity varies with the target concentration. The binding constant derived from spFRET is consistent with ensemble measurements.     

Effectiveness of dairy treated wastewater and different irrigation systems on the growth,biomass and fruiting of a Tunisian olive orchard (Olea europaea L., cv Chemlali)

Abstract

The effectiveness of dairy treated wastewater (TWW) was evaluated, in comparison with tap water (TW), on a Tunisian olive orchard (Olea europea, cv Chemlali), irrigated manually (MI) and by surface dripping (SDI). To this purpose, tree growth, biomass and fruiting were monthly tested for a one-year period. Similar trunk diameters, nodes/tree, root lengths were obtained, independently of source and system of irrigation. Also, comparable tree length and leaf area, shoots/tree and biomass, were observed between TWW and TW plants. However, such parameters improved under SDI rather than MI. Fruiting occurred only in TWW and TW trees treated by MI. Concerning growth, biomass and fruiting, TWW represented a valid alternative source for the irrigation of olive orchard, especially in Tunisia, already facing the freshwater scarcity. Monitoring of soil, TWW, fruits and oil will be required to validate the use of such effluent for olive orchard irrigation.     

Complex impedance spectroscopy studies of (La0.70−xNdx)Sr0.30Mn0.70Cr0.30O3 (x≤0.30) perovskite compounds

The transport properties of Nd-doped perovskite materials (La_0.7−xNd_x)Sr_0.3Mn_0.7Cr_0.3O₃ (x≤0.30) were investigated using impedance spectroscopy techniques over a wide range of temperatures and frequencies. AC conductance analyses indicate that the conduction mechanism is strongly dependent on temperature and frequency. The DC conductance plots can be described using the small polaron hopping (SPH) model, with an apparent reduction of the polaron activation energy below the Curie temperature T_C. Complex impedance plots exhibit semicircular arcs described by an electrical equivalent circuit. Off-centered semicircular impedance plots show that the Nd-doped compounds obey to a non-Debye relaxation process. The conductivity of grains and grain-boundaries has been estimated. The activation energies calculated from the conductance and from time relaxation analyses are comparable. This indicates that the same type of charge carriers is responsible for both the electrical conduction and relaxation phenomena.