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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.

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]

The mechanical properties of thermally conductive composites are the key to realize their applications. Strength of materials is of significance, furthermore the toughness of materials also should attract more concern. Actually, few researchers have reported the simultaneous improvement of strength and toughness of anisotropic thermally and electrically conductive composites. Therefore, this study aims to obviously improve the in-plane thermal and electrical conductivities of nylon composites, which display superior tensile strength and toughness, compared to other thermally conductive composites. The nylon composite papers, prepared through a facile method involving vacuum-assisted filtration and compression molding processes, present a laminate structure and compact graphene nanoplatelet (GNP) stacks inside composites. On account of the special structure, the nylon composite papers show a super-high in-plane thermal conductivity of 16.0 W m−1 K−1 and electrical conductivity of 18.0 S cm−1 at a filler loading of 14.6 wt%. Surprisingly, the composite papers still exhibit a high strength of 48.3 MPa, which is comparable to that of a pure nylon film. In addition, the elongation at break of the composite paper with 14.6 wt% GNPs is as high as 34.2%, ultimately endowing the composite papers with a good toughness of 13.15 MJ m−3. The nylon composite papers successfully achieve the integration of excellent thermal and electrical conductivities, and superior strength and toughness, showing huge application values in the field of intelligent electronic device. [ABSTRACT FROM AUTHOR]

In this paper, a turn-on fluorescent probe (DBE) was designed and synthesized for probing bisulfite (HSO3−) by coupling dehydroabietic acid-based benzimidazole derivatives with ethyl cyanoacetate moiety. The structure of the compound was characterized using its UV-Vis, 1H-NMR, 13C-NMR and HRMS spectra. The probe showed significant selectivity and sensitivity towards HSO3− compared to other analytes in DMF/PBS buffer (3/7, v/v, 10 mM, pH = 7.4), and exhibited a detection limit at the nanomolar level (3.2 nM), fast response time (140 s) and good pH stability (6–10) in living systems. Furthermore, this probe was successfully utilized for the fluorescence imaging of HSO3− in living zebrafish and MCF-7 cells with remarkable lysosome-targeting properties. [ABSTRACT FROM AUTHOR]

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 Zn 2+ radius. In this work, we propose a unique structure inheritance strategy for preparing Bi 2 S 3 micro-straws in which a metal-organic framework (MOF) denoted as Bi-PYDC (PYDC 2- = 3,5-pyridinedicarboxylate) with a string of [Bi 2 O 2 ] 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 Zn 2+ insertion/extraction mechanism of Bi 2 S 3 micro-straws is also investigated by multiple analytical methods, revealing the involvement of Zn 2+ 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.

The needle-thread integrative embedding needle consists of needle handle, needle core, thread, locker and needle guard. The thread is fixed in the core by the locker. With the needle inserted into acupoint, the locker is separated from the thread, while the thread is embedded directly into acupoint, to achieve one acupoint with one needle. This type of thread embedding needle is operated simply and safely without cross infection occurrence, easy to carry.

3D Bi 2 S 3 materials were prepared by the trisodium citrate (Na 3 Cit)-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 Na 3 Cit 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 Bi 2 S 3 -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 Bi 2 S 3 -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.

Sugars are essential regulatory molecules involved in plant growth and development and defense response. Although the relationship between sugars and disease resistance has been widely discussed, the underlying molecular mechanisms remain unexplored. Ring rot caused by Botryosphaeria dothidea (B. dothidea), which severely affects fruit quality and yield, is a destructive disease of apples (Malus domestica Borkh.). The present study found that the degree of disease resistance in apple fruit was closely related to glucose content. Therefore, the gene encoding a hexokinase, MdHXK1, was isolated from the apple cultivar 'Gala', and characterized during the defense response. Overexpression of MdHXK1 enhanced disease resistance in apple calli, leaves and fruits by increasing the expression levels of genes related to salicylate (SA) synthesis (PHYTOALEXIN DEFICIENT 4, PAD4; PHENYLALANINE AMMONIA-LYASE, PAL; and ENHANCED DISEASE SUSCEPTIBILITY 1, EDS1) and signaling (PR1; PR5; and NONEXPRESSER OF PR GENES 1, NPR1) as well as increasing the superoxide (O 2- ) production rate and the hydrogen peroxide (H 2 O 2 ) content. Overall, the study provides new insights into the MdHXK1-mediated molecular mechanisms by which glucose signaling regulates apple ring rot resistance., (© 2021 Scandinavian Plant Physiology Society.)