Species Differences in Metabolism of Soluble Epoxide Hydrolase Inhibitor,EC1728, Highlight the Importance of Clinically Relevant Screening Mechanisms in Drug Development

There are few novel therapeutic options available for companion animals, and medications rely heavily on repurposed drugs developed for other species. Considering the diversity of species and breeds in companion animal medicine, comprehensive PK exposures in the companion animal patient is often lacking. The purpose of this paper was to assess the pharmacokinetics after oral and intravenous dosing in domesticated animal species (dogs, cats, and horses) of a novel soluble epoxide hydrolase inhibitor, EC1728, being developed for the treatment of pain in animals. Results: Intravenous and oral administration revealed that bioavailability was similar for dogs, and horses (42 and 50% F) but lower in mice and cats (34 and 8%, respectively). Additionally, clearance was similar between cats and mice, but >2× faster in cats vs. dogs and horses. Efficacy with EC1728 has been demonstrated in mice, dogs, and horses, and despite the rapid clearance of EC1728 in cats, analgesic efficacy was demonstrated in an acute pain model after intravenous but not oral dosing. Conclusion: These results demonstrate that exposures across species can vary, and investigation of therapeutic exposures in target species is needed to provide adequate care that addresses efficacy and avoids toxicity.     

Dianthiamides A–E,Proline-Containing Orbitides from Dianthus chinensis

Orbitides are plant-derived small cyclic peptides with a wide range of biological activities. Phytochemical investigation of the whole plants of Dianthus chinensis was performed with the aim to discover new bioactive orbitides. Five undescribed proline-containing orbitides, dianthiamides A–E (1–5), were isolated from a methanolic extract of Dianthus chinensis. Their structures were elucidated by extensive analysis of 1D and 2D NMR and HRESI–TOF–MS as well as ESI–MS/MS fragmentation data. The absolute configuration of the amino acid residues of compounds 1–5 was determined by Marfey’s method. All compounds were tested for their cytotoxic activity, and dianthiamide A (1) exhibited weak activity against A549 cell line with IC₅₀ value of 47.9 μM.     

Synergistic effect of nanoionic destabilization and partial dehydrogenation for enhanced ionic conductivity in MBH4-C60 (M = Li+, Na+) nanocomposites

Journal of Solid State Electrochemistry - In this work, we evaluate the electrochemical properties of MBH4-C60 (M = Li+, Na+) nanocomposites for potential use as a solid-state electrolyte in...     

Prediction of African Swine Fever Virus Inhibitors by Molecular Docking-Driven Machine Learning Models

African swine fever virus (ASFV) causes a highly contagious and severe hemorrhagic viral disease with high mortality in domestic pigs of all ages. Although the virus is harmless to humans, the ongoing ASFV epidemic could have severe economic consequences for global food security. Recent studies have found a few antiviral agents that can inhibit ASFV infections. However, currently, there are no vaccines or antiviral drugs. Hence, there is an urgent need to identify new drugs to treat ASFV. Based on the structural information data on the targets of ASFV, we used molecular docking and machine learning models to identify novel antiviral agents. We confirmed that compounds with high affinity present in the region of interest belonged to subsets in the chemical space using principal component analysis and k-means clustering in molecular docking studies of FDA-approved drugs. These methods predicted pentagastrin as a potential antiviral drug against ASFVs. Finally, it was also observed that the compound had an inhibitory effect on AsfvPolX activity. Results from the present study suggest that molecular docking and machine learning models can play an important role in identifying potential antiviral drugs against ASFVs.     

One-pot Synthesis of a Truncated Cone-shaped Porphyrin Macrocycle and Its Self-assembly into Permanent Porous Material

Here, we report the synthesis of a truncated cone-shaped triangular porphyrinic macrocycle, P₃L₃ , via a single step imine condensation of a cis-diaminophenylporphyrin and a bent dialdehyde-based linker as building units. X-ray diffraction analysis reveals that the truncated cone-shaped P₃L₃ molecules are stacked on top of each other by π⋯π and CH⋯π interactions, to form 1.7 nm wide hollow columns in the solid state. The formation of the triangular macrocycle is corroborated by quantum chemical calculations. The permanent porosity of the P₃L₃ crystals is demonstrated by several gas sorption experiments and powder X-ray diffraction analysis.     

Exploring the Role of Surface States in Emissive Carbon Nanodots: Analysis at Single-Particle Level

Fluorescent carbon nanodots (CDs) have been highlighted as promising semiconducting materials due to their outstanding chemical and optical properties. However, the intrinsic heterogeneity of CDs has impeded a clear understanding of the mechanisms behind their photophysical properties. In this study, as-prepared CDs are fractionated via chromatography to reduce their structural and chemical heterogeneity and analyzed through ensemble and single-particle spectroscopies. Many single particles reveal fluorescence intensity fluctuations between two or more discrete levels with bi-exponential decays. While the intrinsic τ₁ components are uniform among single particles, the τ₂ components from molecule-like emissions spans a wider range of lifetimes, reflecting the inhomogeneity of the surface states. Furthermore, it is concluded that the relative population and chemical states of surface functional groups in CDs have a significant impact on emissive states, brightness, blinking, stability, and lifetime distribution of photoluminescence.     

Silver-doped calcium phosphate nanopowders prepared by electrostatic spraying

Silver-doped calcium phosphate nanopowders were successfully prepared by the cost-effective electrostatic spray-pyrolysis process. The properties of the silver-doped nanopowder annealed at 500°C for 30 min were investigated through X-ray diffraction analysis, field emission scanning electron microscope, and Fourier transform infrared spectroscopy. The silver-doped nanopowders with 70–90 nm particle size showed an antibacterial performance against Escherichia coli.     

A momentum construction for circle-invariant Kähler metrics

Examples of Kähler metrics of constant scalar curvature are relatively scarce. Over the past two decades, several workers in geometry and physics have used symmetry reduction to construct complete Kähler metrics of constant scalar curvature by ODE methods. One fruitful idea--the ``Calabi ansatz'--is to begin with an Hermitian line bundle over a Kähler manifold, and to search for Kähler forms in some disk subbundle, where is the logarithm of the norm function and is a function of one variable.

Our main technical result (Theorem A) is the calculation of the scalar curvature for an arbitrary Kähler metric  arising from the Calabi ansatz. This suggests geometric hypotheses (which we call ``-constancy') to impose upon the base metric  and Hermitian structure  in order that the scalar curvature of  be specified by solving an ODE. We show that -constancy is ``necessary and sufficient for the Calabi ansatz to work' in the following sense. Under the assumption of -constancy, the disk bundle admits a one-parameter family of complete Kähler metrics of constant scalar curvature that restrict to on the zero section (Theorems B and D); an analogous result holds for the punctured disk bundle (Theorem C). A simple criterion determines when such a metric is Einstein. Conversely, in the absence of -constancy the Calabi ansatz yields at most one metric of constant scalar curvature, in either the disk bundle or the punctured disk bundle (Theorem E).

Many of the metrics constructed here seem to be new, including a complete, negative Einstein-Kähler metric on the disk subbundle of a stable vector bundle over a Riemann surface of genus at least two, and a complete, scalar-flat Kähler metric on  .

     

Analysis on motion of Earth’s center of mass observed with CHAMP mission

Geocenter motion (GCM) is one important topic for constructing and maintaining the terrestrial reference frame and its applications. GCM is studied from CHAMP with the multi-step approach in this paper. Geometric orbits of CHAMP in 2001–2006 are precisely determined with the kinematic method only from the satellite-borne GPS zero-difference data. Then a GCM time series is estimated from the precise kinematic orbits based on the theory of satellite dynamics to fit the CHAMP’s real geometric orbits. We compare the series with the geocenter series used in ITRF2005. Then the GCM series are analyzed with Fourier transform and wavelet transformation. The mean motions within 6 years in TX, TY and TZ directions are respectively 0.8 mm, 2.2 mm, and 7.9 mm. The trends of GCM in the three directions are 0.495 mm/a, −0.004 mm/a, and 1.309 mm/a, respectively. The long-term movement (2001–2006) indicates that the crustal figure is changing. The seasonal variations are the main component which may be excitated by the mass redistribution of Earth’s fluid layer, e.g. ocean, atmosphere and continental water. The inter-annual variations are also found in the GCM series measured with CHAMP. Supported by the International S&T Cooperation Program of China (Grant No. 2006DFA21980), the National Hi-tech R&D Program of China (Grant No. 2006AA12z303), the National Natural Science Foundation of China (Grant No. 40774009), and the Natural Science Foundation of Shandong Province, China (Grant No. Y2003E01)