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Valbenazine (VBZ) is a selective synaptic vesicle monoamine transporter 2 (VMAT2) inhibitor that counteracts the increased activity of the dopamine system by inhibiting VMAT2 activity, reducing the uptake and storage of monoamines from the cytoplasm into presynaptic vesicles, and decreasing the concentration of monoamines released into the synapse. VBZ is the first drug approved by the US FDA for using in adult patients with tardive dyskinesia. Compound P109 is a structural modification product of VBZ, which is substituted by cyclopropane methyl at position 9. It has similar pharmacological activity and pharmacological mechanism as VBZ. In order to study its metabolites in the human liver microsome incubation system, a Waters Eclipse Plus C18 column (150 mm×2.1 mm×3.5 μm) was used for separation, and 0.1% formic acid water (A)-0.1% formic acid acetonitrile (B) as the mobile phase for gradient elution. The high performance liquid chromatography coupled with four stage electrostatic field Orbitrap mass spectrometry (UHPLC-Q ExactiveTM-Orbitrap MS) was used to analyze samples in positive ion mode. Nine compounds (including P109 and its 8 metabolites) were screened, and retention time, accurate mass measurement results and fragmentation patterns were all characterized. By using the Xcaliber4.2 workstation, the accurate molecular mass was used to infer the possible element composition, and then combined with the mass spectrometry fragment information for data processing. The molecular formula prediction module was used to predict the molecular formula of the parent ion and the fragment ion, and to identify the structure of in vitro metabolites of P109. The results showed that P109 undergoes three main metabolic pathways via human liver microsomes: 1) Oxidation reaction occurs to produce compounds 2, 4 and 9; 2) Hydrolysis reaction occurs to produce metabolites 1, 3, 7 and 8; 3) Decyclopropanemethyl reaction occurs to produce metabolite 5. The reaction phenotypes of seven cytochrome P450 isoenzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4) were studied using specific chemical inhibitor inhibition method. The content of P109 metabolites was determined by HPLC-MS/MS, and the data was analyzed by Excel software. The results showed that oxidative metabolites and dehydrogenation metabolite were mainly metabolized by CYP3A4, and the secondary metabolic subtype was CYP2C8. The decyclopropane-methyl metabolites were mainly metabolized by CYP2C8, and the secondary metabolites were CYP3A4 and CYP2D6. Hydrolysis of metabolites involved multiple subtypes of enzymes. This study can help to clarify the metabolic pathways of drugs in vivo, which is of great significance to the research of pharmacokinetics, pharmacodynamics, and drug safety evaluation. At the same time, it provides theoretical support for extrapolating the results of in vitro experiments to in vivo experiments.

Objective: This study aimed to investigate the best storage conditions for anthocyanin indicator films. Methods: The double-layer indicator films containing anthocyanins were investigated. The mechanical properties (tensile strength and elongation at break), thickness, color and antioxidant properties (DPPH free radical scavenging ability, total phenol content and ABTS free radical scavenging ability) of double-layer indicator films containing anthocyanins were determined at different storage time (0, 7, 14, 21, 28 and 35 d) and temperature (25, 4 and -18 ℃). Results: The results showed that the thickness of the indicator films was generally maintained at about 0.15 mm, and the color change of the film stored at -18 ℃ was the smallest. The antioxidant activities of the films stored at 25 ℃ were higher than those stored at 4 and -18 ℃, especially the DPPH free radical scavenging ability was the highest. Conclusion: The optimal storage temperature of the film is 25 ℃, and the optimal storage time is 28 d.

Aqueous zinc ion batteries (ZIBs) are considered as promising energy storage devices in the post-lithium-ion era, due to their high energy density, low cost, high safety, and environmental benignity, however their commercialization is hindered by the sluggish diffusion kinetics of cathode materials due to the large hydrate Zn2+ radius. In this work, we propose a unique structure inheritance strategy for preparing Bi2S3 micro-straws in which a metal–organic framework (MOF) denoted as Bi-PYDC (PYDC2− = 3,5-pyridinedicarboxylate) with a string of [Bi2O2]2+ chains is judiciously selected as the structure-directing template to induce the formation of micro-straws based on a topochemical reaction. The distinctive hollow structure significantly enhances the ionic storage kinetics. Impressively, the obtained battery exhibits an ultra-long cycle life of more than 10 000 cycles at a current density of 1 A g−1 while maintaining a capacity of more than 153.4 mA h g−1. In addition, the Zn2+ insertion/extraction mechanism of Bi2S3 micro-straws is also investigated by multiple analytical methods, revealing the involvement of Zn2+ rather than H+ in the electrochemical storage process. This work may lead a new direction for constructing high performance cathodes of Zn-ion batteries through a MOF-based structure-directing template. [ABSTRACT FROM AUTHOR]

3D Bi2S3 materials were prepared by the trisodium citrate (Na3Cit)-assisted solvothermal method and applied to aqueous zinc ion batteries (AZIBs) to explore the effect of the electrode material morphology on the electrochemical performance. As the concentration of Na3Cit increases, the 3D assembly morphology evolves from coral-like to sphere-like to snowflake-like structures. The electrochemical test results show that the electrode materials of various morphologies possess excellent cycle life, but the specific capacity varies greatly depending on the morphology. Impressively, the Bi2S3-1.2 electrode has the best electrochemical performance, with a capacity of 203.5 mA h g−1 after 4000 charge/discharge cycles at 0.5 A g−1. Furthermore, the Bi2S3-1.2 electrode delivers an ultralong lifetime of over 10 000 cycles with a capacity of 150.2 mA h g−1 at 1 A g−1. This work demonstrates a feasible route to prepare ultra-long cycle life AZIBs. [ABSTRACT FROM AUTHOR]

Recently, the skyrocketing interest in smart wearable devices has led to innovations in energy-harvesting materials. Flexible thermoelectric (TE) materials have thus developed rapidly, but in this process TE performances have been over pursued, leaving the research of more practical TE self-supporting films at a less advanced level. In this work, Ag2Se/nylon self-supporting composite films with both excellent flexibility and leading TE performances (874.3 and 1825.1 μW m−1 K−2 with 80 and 90 wt% Ag2Se contents) were prepared by sequential chemical silver plating, selenization reaction and vacuum hot-pressing processes using nylon mesh as the flexible backbone, and the excellent photothermal (PT) effect of Ag2Se was introduced into the TE field for the first time to build a homogeneous synchronous photo-thermoelectric generator (PTEG). The PTEG can produce a high output voltage and power of 8.8 mV and 8.36 μW with low power NIR light irradiation of 100 mW cm−2 without a cooling source, and considerable output characteristics under visible light irradiation of different intensities can also be acquired. The superior output power can be attributed to the outstanding TE and PT characteristics of the sample, as well as the thickness optimization due to the self-supporting film. This work provides a new idea for preparing high performance flexible TE self-supporting films and developing PTEGs with high output characteristics, and the PTEGs are expected to be applied to self-powered systems for wearable devices. [ABSTRACT FROM AUTHOR]