Investigating pharmacokinetic profiles of Centella asiatica using machine learning and PBPK modelling.

Physiologically based pharmacokinetic (PBPK) modeling serves as a valuable tool for determining the distribution and disposition of substances in the body of an organism. It involves a mathematical representation of the interrelationships among crucial physiological, biochemical, and physicochemical parameters. A lack of the values of pharmacokinetic parameters can be challenging in constructing a PBPK model. Herein, we propose an artificial intelligence framework to evaluate a key pharmacokinetic parameter, the intestinal effective permeability (Peff). The publicly available Peff dataset was utilized to develop regression machine learning models. The XGBoost model demonstrates the best test accuracy of R-squared (R2, coefficient of determination) of 0.68. The model is then applied to compute the Peff of asiaticoside and madecassoside, the parent compounds found in Centella asiatica. Subsequently, PBPK modeling was conducted to evaluate the biodistribution of the herbal substances following oral administration in a rat model. The simulation results were evaluated and validated, which agreed with the existing in vivo studies in rats. This in silico pipeline presents a potential approach for investigating the pharmacokinetic parameters and profiles of drugs or herbal substances, which can be used independently or integrated into other modeling systems.

Crystallographic and Spectroscopic Investigations on Oxidative Coordination in the Heteroleptic Mononuclear Complex of Cerium and Benzoxazine Dimer.

Among lanthanide-based compounds, cerium compounds exhibit a significant role in a variety of research fields due to their distinct tetravalency, high economic feasibility, and high stability of Ce(IV) complexes. Herein, a systematic investigation of crystallographic information, chemical properties, and mechanistic formation of the novel Ce(IV) complex synthesized from cerium(III) nitrate hexahydrate and 2,2'-(methylazanediyl)bis(methylene)bis(4-methylphenol) (MMD) ligand has been explored. According to the analysis of the crystallographic information, the obtained complex crystal consists of the Ce(IV) center coordinated with two nitrate ligands and two bidentate coordinated (N-protonated and O,O-deprotonated) MMD ligands. The fingerprint plots and the Hirshfeld surface analyses suggest that the C-H⋯O and C-H⋯π interactions significantly contribute to the crystal packing. The C-H⋯O and C-H⋯π contacts link the molecules into infinite molecular chains propagating along the [100] and [010] directions. Synchrotron powder X-ray diffraction (XRD) and X-ray absorption spectroscopy (XAS) techniques have been employed to gain an understanding of the oxidative complexation of Ce(IV)-MMD complex in detail. This finding would provide the possibility to systematically control the synthetic parameters and wisely design the precursor components in order to achieve the desired properties of novel materials for specific applications.

Crystal structure and Hirshfeld surface analysis of the product of the ring-opening reaction of a di-hydro-benzoxazine: 6,6'-[(cyclo-hexyl-aza-nedi-yl)bis-(methyl-ene)]bis-(2,4-di-methyl-phenol).

In the title unsymmetrical tertiary amine, C24H33NO2, which arose from the ring-opening reaction of a di-hydro-benzoxazine, two 2,4-di-methyl-phenol moieties are linked by a 6,6'-(cyclo-hexyl-aza-nedi-yl)-bis-(methyl-ene) bridge: the dihedral angle between the dimethyl-phenol rings is 72.45 (7)°. The cyclo-hexyl ring adopts a chair conformation with the exocyclic C-N bond in an equatorial orientation. One of the phenol OH groups forms an intra-molecular O-H⋯N hydrogen bond, generating an S(6) ring, and a short intra-molecular C-H⋯O contact is also present. In the crystal, O-H⋯O hydrogen bonds link the mol-ecules into C(10) chains propagating along the [100] direction. The Hirshfeld surface analysis of the title compound confirms the presence of these intra- and inter-molecular inter-actions. The corresponding fingerprint plots indicate that the most significant contacts in the crystal packing are H⋯H (76.4%), H⋯C/C⋯H (16.3%), and H⋯O/O⋯H (7.2%).

A gold coated polystyrene ring microarray formed by two-step patterning: construction of an advanced microelectrode for voltammetric sensing.

A two-step patterning process was developed based on nanosphere lithography and plasma etching to fabricate an array of electrodes with two different gold ring structures: the arrays of Au micro-ring electrode (Au-MRE) and Au covered with polystyrene micro-ring electrode (Au-PS-MRE). The Au-MRE structure was fabricated by etching a monolayer of polystyrene (PS) spheres on indium tin oxide (ITO) surface to generate PS rings on ITO glass. PS rings served as a mask in secondary etching for blocking an interaction of oxygen plasma and ITO surface to create a ring-patterned ITO surface. Then, the PS residue was removed and gold was deposited. The site-selective electrodeposition of gold was carried out and an array of a gold ring structure was formed on the ITO glass. The Au-PS-MRE structure was fabricated by keeping the PS residue from second etching before deposition of gold. The Au-PS-MRE microelectrode was studied by using hexacyanoferrate as an electrochemical probe where it displayed steady state current in cyclic voltammetry. The respective calibration plots were acquired at a working potential of 0.31 V and 0.12 V (vs. Ag/AgCl) for oxidation and reduction reaction, respectively. The sensitivity is as high as 163.4-220.7 µA·mM-1·mm-2 which is larger by a factor of 95-132 compared to a conventional gold film macroelectrode. The detection limit (at a signal-to-noise ratio of 3) is 2.2 µM. This approach thus yields relatively effective and low-cost fabrication without resorting to high resolution instruments. Conceivably, the technique may be used to produce microelectrode arrays on a large scale. Graphical abstract Schematic presentation of a novel fabrication process of micro-ring electrode arrays. Two-step patterning based on nanosphere lithography leads to electrodes with great electrochemical performance. Direct deposition metal in the presence of polystyrene (PS) mask induces the formation of a new structure with arrays of gold covered with PS microring on the indium tin oxide (ITO) coated glass. The microelectrode-like behavior has been achieved using this fabrication process.

Mechanical strain can switch the sign of quantum capacitance from positive to negative.

Quantum capacitance is a fundamental quantity that can directly reveal many-body interactions among electrons and is expected to play a critical role in nanoelectronics. One of the many tantalizing recent physical revelations about quantum capacitance is that it can possess a negative value, hence allowing for the possibility of enhancing the overall capacitance in some particular material systems beyond the scaling predicted by classical electrostatics. Using detailed quantum mechanical simulations, we found an intriguing result that mechanical strains can tune both signs and values of quantum capacitance. We used a small coaxially gated carbon nanotube as a paradigmatical capacitor system and showed that, for the range of mechanical strain considered, quantum capacitance can be adjusted from very large positive to very large negative values (in the order of plus/minus hundreds of attofarads), compared to the corresponding classical geometric value (0.31035 aF). This finding opens novel avenues in designing quantum capacitance for applications in nanosensors, energy storage, and nanoelectronics.

Anomalous piezoelectricity in two-dimensional graphene nitride nanosheets.

Piezoelectricity is a unique property of materials that permits the conversion of mechanical stimuli into electrical and vice versa. On the basis of crystal symmetry considerations, pristine carbon nitride (C3N4) in its various forms is non-piezoelectric. Here we find clear evidence via piezoresponse force microscopy and quantum mechanical calculations that both atomically thin and layered graphitic carbon nitride, or graphene nitride, nanosheets exhibit anomalous piezoelectricity. Insights from ab inito calculations indicate that the emergence of piezoelectricity in this material is due to the fact that a stable phase of graphene nitride nanosheet is riddled with regularly spaced triangular holes. These non-centrosymmetric pores, and the universal presence of flexoelectricity in all dielectrics, lead to the manifestation of the apparent and experimentally verified piezoelectric response. Quantitatively, an e11 piezoelectric coefficient of 0.758 C m(-2) is predicted for C3N4 superlattice, significantly larger than that of the commonly compared α-quartz.

Boron nitride-graphene nanocapacitor and the origins of anomalous size-dependent increase of capacitance.

Conventional wisdom suggests that decreasing dimensions of dielectric materials (e.g., thickness of a film) should yield increasing capacitance. However, the quantum capacitance and the so-called "dead-layer" effect often conspire to decrease the capacitance of extremely small nanostructures, which is in sharp contrast to what is expected from classical electrostatics. Very recently, first-principles studies have predicted that a nanocapacitor made of graphene and hexagonal boron nitride (h-BN) films can achieve superior capacitor properties. In this work, we fabricate the thinnest possible nanocapacitor system, essentially consisting of only monolayer materials: h-BN with graphene electrodes. We experimentally demonstrate an increase of the h-BN films' permittivity in different stack structures combined with graphene. We find a significant increase in capacitance below a thickness of ∼5 nm, more than 100% of what is predicted by classical electrostatics. Detailed quantum mechanical calculations suggest that this anomalous increase in capacitance is due to the negative quantum capacitance that this particular materials system exhibits.