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Drug-Target Interaction (DTI) prediction facilitates acceleration of drug discovery and promotes drug repositioning. Most existing deep learning-based DTI prediction methods can better extract discriminative features for drugs and proteins, but they rarely consider multimodal features of drugs. Moreover, learning the interaction representations between drugs and targets needs further exploration. Here, we proposed a simple Mâ¯ulti-modal Gâ¯ating Nâ¯etwork for DTI prediction, MGNDTI, based on multimodal representation learning and the gating mechanism. MGNDTI first learns the sequence representations of drugs and targets using different retentive networks. Next, it extracts molecular graph features of drugs through a graph convolutional network. Subsequently, it devises a multimodal gating network to obtain the joint representations of drugs and targets. Finally, it builds a fully connected network for computing the interaction probability. MGNDTI was benchmarked against seven state-of-the-art DTI prediction models (CPI-GNN, TransformerCPI, MolTrans, BACPI, CPGL, GIFDTI, and FOTF-CPI) using four data sets (i.e., Human, C. elegans, BioSNAP, and BindingDB) under four different experimental settings. Through evaluation with AUROC, AUPRC, accuracy, F1 score, and MCC, MGNDTI significantly outperformed the above seven methods. MGNDTI is a powerful tool for DTI prediction, showcasing its superior robustness and generalization ability on diverse data sets and different experimental settings. It is freely available at https://github.com/plhhnu/MGNDTI.
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INTRODUCTION: Hyperuricemia is a common metabolic disease, which is a risk factor for gouty arthritis and ureteral stones and may also lead to cardiovascular and chronic kidney disease (CDK). Therefore, hyperuricemia should be treated early. Xanthine oxidase inhibitors (XOIs) and uricosuric agents (UAs), which target uric acid, are two types of medications that are used to treat gout and hyperuricemia. XOIs stop the body from producing excessive uric acid, while UAs eliminate it rapidly via the kidneys. Urate transporter 1 (URAT1) belongs to the organic anion transporter family (OAT) and is specifically localized to the apical membrane of the epithelial cells of proximal tubules. Unlike other organic anion transporter family members, URAT1 identifies and transports organic anions that are primarily responsible for urate transport. AREAS COVERED: This article reviews the pharmacokinetics and pharmacodynamics of the existing URAT1 inhibitors to serve as a reference for subsequent drug studies. EXPERT OPINION: The URAT1 inhibitors that are currently used as clinical drugs mainly include dotinurad, benzbromarone, and probenecid. Results indicate that RDEA3170 may be the most promising inhibitor, in addition to SHR4640, URC-102, and MBX-102, which are in the early stages of development.
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Gota , Hiperuricemia , Transportadores de Ânions Orgânicos , Humanos , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Ácido Úrico/metabolismo , Ácido Úrico/uso terapêutico , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Gota/tratamento farmacológico , Transportadores de Ânions Orgânicos/metabolismoRESUMO
Solid polymer electrolytes with large-scale processability and interfacial compatibility are promising candidates for solid-state lithium metal batteries. Among various systems, poly(vinylidene fluoride)-based polymer electrolytes with residual solvent are appealing for room-temperature battery operations. However, their porous structure and limited ionic conductivity hinder practical application. Herein, we propose a phase regulation strategy to disrupt the symmetry of poly(vinylidene fluoride) chains and obtain the dense composite electrolyte through the incorporation of MoSe2 sheets. The electrolyte with high dielectric constant can optimize the solvation structures to achieve high ionic conductivity and low activation energy. The in-situ reactions between MoSe2 and Li metal generate Li2Se fast conductor in solid electrolyte interphase, which improves the Coulombic efficiency and interfacial kinetics. The solid-state Li||Li cells achieve robust cycling at 1 mA cm-2, and the Li||LiNi0.8Co0.1Mn0.1O2 full cells show practical performance at high rate (3C), high loading (2.6 mAh cm-2) and in pouch cell.
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The rapid development of renewable energy systems, electric vehicles, and pulsed equipment requires energy storage media to have a high energy storage density and efficiency in a wide temperature range. The state-of-the-art biaxially oriented polypropylene (BOPP) film is insufficient to meet the growing demand for energy storage devices due to its low energy storage density and working temperature, which make it a research hotspot for developing dielectric energy storage materials. In this manuscript, based on the epoxy materials that have been shown as a potential energy storage medium, we aim to reduce the influence of the benzene ring delocalization structure on the energy storage losses and enhance the efficiency by gradually replacing them with cyclohexane structures to adjust the segment unsaturation of epoxy materials. The results show that by partially reducing the unsaturation of the curing agent, the epoxy material achieves an excellent high-temperature energy storage density of 2.21 J/cm3 at 150 °C and 300 MV/m while maintaining an extremely high energy storage efficiency of 99.2%. Leakage current density and high-voltage dielectric spectroscopy tests confirm that a moderate reduction of the segment unsaturation of epoxy materials can greatly inhibit polarization loss at high temperatures, which may explain their high energy storage efficiency.
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Increasing the cutoff voltage effectively maximizes the available capacity of the state-of-art layered-oxide cathodes (LiTMO2). However, the spontaneous dehydrogenation-oxidation of carbonates in the cathode inner Helmholtz plane (C-IHP) under high voltage/temperature leads to side effects, including weak cathode electrolyte interphase (CEI) and cathode structural collapse. Here, we report a specific adsorption-oxidation (Ad-O) mechanism that dominates the later CEI formation through molecular regulation in C-IHP. The two tailored additives with specific electron-rich groups will enter the C-IHP and mask the active sites of cathodes, thereby reducing the weak CEI generation from conventional carbonates. As-formed hierarchical CEI with inner LiF and outer B-F/-CN rich organic structure will further protect the aggressive cathode from harmful electrolyte corrosion under harsh conditions of high voltages (4.6 V) and elevated temperatures (60 °C). This synergistic strategy guided by the specific Ad-O mechanism enables 3.5 Ah LiNi0.8Co0.1Mn0.1O2/Graphite pouch cells, which remarkably achieve 270 Wh/kg with 450 cycles.
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Realizing durative flattened and dendrite-free zinc (Zn) metal configuration is the key to resolving premature battery failure caused by the internal short circuit, which is highly determined by the crystal growth in the electrocrystallization process. Herein, we report that regulating the molecular structure of the inner Helmholtz plane (HIP) can effectively convert the deposition into activation control by weakening the solvated ion adsorption at the interface. The moderated electrochemical reaction kinetics lower than the adatom self-diffusion rate steers conformal stratiform Zn growth and dominant Zn (0001) texture, achieving crystallographic optimization. Through in situ mediation of electrolyte engineering, orientational plating and stripping behaviors at edge-sites and tailored solvation structure immensely improve the utilization efficiency and total charge passed of Zn metal, even under extreme conditions, including high areal capacity (3â mAh cm-2 ) and wide temperature range (-40-60 °C).
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The dried plant material of medically important plant Actinidia eriantha especially when it remains in the form of powder often look morphologically similar to its related species. The lack of efficient methods to distinguish the authentic material from other similar species leads to chances of adulteration. The molecular authentication of herbal plant materials such as the internal transcribed spacer (ITS) sequences is considered as more reliable method compared to morphological traits. In this study, we aim to evaluate the potential of identification for roots of A. eriantha and its related species by ITS sequences. The lengths of ITS regions ranged from 624 to 636 bp with GC content ranging from 50.96% to 59.55%. A total of 194 variation sites and 46 haplotypes were formed in 185 samples. Among them, the roots of A. eriantha possessed specific sites at 85bp (C), 205bp (T), 493bp (C), 542bp (G), 574bp (C), 582bp (T) and 610bp (G), while A. hemsleyana, A. callosa, A. valvata and A. polygama have their own specific sites. The inter-specific genetic distance among 8 Actinidia species in the range 2.28% to 11.00%. The phylogenetic tree constructed with ITS, ITS1 and ITS2 region showed that the ITS sequences have higher potential for identification in 8 Actinidia species. However, as to A. eriantha, A. hemsleyana and A. valvata, these three barcodes have the same identification ability. The ITS regions indicated that different samples from same species can be grouped together, except for A. arguta and A. melanandrah. In conclusion, the ITS sequences can be used as an efficient DNA barcode for the identification of A. eriantha and its related species.
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Actinidia , Actinidia/genética , Filogenia , Raízes de Plantas/genética , Plantas , PósRESUMO
Designing electrical insulation materials with excellent surface flashover strength in a vacuum environment is crucial for high-power equipment and aerospace devices. In the present paper, the effect of two types of electronegative groups, the halogen-phenyl groups and the aromatic π-conjugated naphthyl groups, is used to greatly improve the vacuum flashover characteristics of polystyrene (PS), a commonly used polymer dielectric material in high-power devices. By polymerization of the monomers containing these electronegative groups, the bulk insulation material as a whole is modified expediently. In comparison to the base polymer PS, the electron affinity of the structures containing strong electronegative groups is studied with first-principles calculations based on the density functional theory. The nanosecond pulsed vacuum flashover testing results show that the vacuum flashover strength is increased by 10% after replacing the PS pendant phenyl groups with fluorophenyl groups and increased by 44% when replaced with the naphthyl groups. Furthermore, the thermally stimulated current and secondary electron emission yield spectroscopies are measured, to study the influence of strong electronegative groups on the trapping characteristics and further the electron-emitting features of the polymer dielectrics, which are closely related to the charged particle multiplication process during the vacuum flashover. The results prove that introducing strong electronegative groups can inhibit the triggering of vacuum flashover, suppress the electron emission, delay the flashover process, and thus greatly increase the vacuum flashover voltage. The study of this paper not only puts forward two groups of easily processable polymers with excellent vacuum flashover strength but also paves ways for the future material design of special insulation polymers.
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Insulation materials with excellent dielectrics-vacuum interface breakdown strength are irreplaceable in equipment such as particle accelerators, fusion ignition, and related aerospace devices. In this article, the segment structure of a typical insulation polymer, polystyrene, has been modified by introducing divinylbenzene to form cross-linking junctures and adjust the cross-linking density. The influence of cross-linking on its electron absorb-emit feature and further on the vacuum pulsed flashover characteristics has been systematically studied. A series of broadband dielectric spectroscopy (BDS) and thermally stimulated current (TSC) experiments indicate that this cross-linking network inhibits the movement of the polar segments, leading to a drastic change in the charge-trapping behavior of dielectric surface layer materials. The trapping charge density is increased, and the trapping energy is transferred to deeper-level regions. These lead to the observed suppression of secondary electron emission (SEE) of highly cross-linked polystyrenes exposed in vacuum. And, quite sensibly, the nanosecond pulsed vacuum flashover tests show that the polystyrenes with higher cross-linking density have enhanced flashover strength. Moreover, to further investigate the relationship between the dielectric SEE behavior and its vacuum flashover process, a 2-D model is established and analyzed on the basis of the particle in the cell with the Monte Carlo collision (PIC-MCC) method.