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Messenger RNA (mRNA) is vital for post-transcriptional gene regulation, acting as the direct template for protein synthesis. However, the methods available for predicting mRNA subcellular localization need to be improved and enhanced. Notably, few existing algorithms can annotate mRNA sequences with multiple localizations. In this work, we propose the mRNA-CLA, an innovative multi-label subcellular localization prediction framework for mRNA, leveraging a deep learning approach with a multi-head self-attention mechanism. The framework employs a multi-scale convolutional layer to extract sequence features across different regions and uses a self-attention mechanism explicitly designed for each sequence. Paired with Position Weight Matrices (PWMs) derived from the convolutional neural network layers, our model offers interpretability in the analysis. In particular, we perform a base-level analysis of mRNA sequences from diverse subcellular localizations to determine the nucleotide specificity corresponding to each site. Our evaluations demonstrate that the mRNA-CLA model substantially outperforms existing methods and tools.
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Aprendizaje Profundo , ARN Mensajero , ARN Mensajero/genética , ARN Mensajero/metabolismo , Biología Computacional/métodos , Redes Neurales de la Computación , Humanos , AlgoritmosRESUMEN
The central nervous system sends a neural impulse through an efferent nerve system toward muscles to drive movement. In an electronically artificial neural system, the electronic neural devices and interconnections prevent achieving highly connected and long-distance artificial impulse transmission and exhibit a narrow bandwidth. Here we design and demonstrate light-emitting memristors (LEMs) for the realization of an optoelectronic artificial efferent nerve, in which the LEM combines the functions of a light receiver, a light emitter, and an optoelectronic synapse in a single device. The optical signal from the pre-LEM (presynaptic membrane) acts as the input signal for the post-LEM (postsynaptic membrane), leading to one-to-many transmission, dynamic adjustable transmission, and light-trained synaptic plasticity, thus removing the physical limitation in artificially electronic neural systems. Furthermore, we construct an optoelectronic artificial efferent nerve with LEMs to control manipulators intelligently. These results promote the construction of an artificial optoelectronic nerve for further development of sensorimotor functionalities.
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Plasticidad Neuronal , Sinapsis , Potenciales de Acción , ElectrónicaRESUMEN
The possibility to engineer the van der Waals interactions between graphene layers is crucial for controlling the electronic properties. Using epitaxial graphene with preferential orientations grown on the C-face 6H-SiC as a prototype, we have addressed the annealed structural reconfiguration of graphene layer in view of the evolutions of surface ripples and relative rotation angle (RRA) between lattices. It was found that the heat treatment of graphene layers under vacuum deformed the arcuate ripple surface and subsequently split one ripple into parallel twin pleats, which drastically increased the strains in the films. The originally oriented graphene layers, with small RRA between adjacent layers, were rearranged by the annealing resulting in disordered orientations and larger RRA. After a sufficient annealing, the compressive stress stored in the films was well released to give undistorted graphene lattices. The vacuum annealing is an effective treatment for irreversibly relaxing the graphene structure.
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OBJECTIVE: To investigate the effect of mammalian target of rapamycin(mTOR) inhibitor-rapamycin on cognitive function after chronic cerebral ischemia in mice and its molecular mechanism. METHODS: The chronic cerebral ischemia model was induced by ligation of right common carotid artery (rUCCAO) in 6-week-old ICR mice. The expressions of mTOR, S6K, S6 and corresponding phosphorylated proteins were detected by Western blotting at different time interval (1 h, 3 h, 6 h, 24 h, 3 d, 7 d, 2 w, 4 w, 6 w) after rUCCAO to determine the changes of mTOR signaling pathway. Rapamycin was administrated i.p. at the dose of 3.0 mg/kg 24 h after rUCCAO. Fluoro Jade B staining was used to detect the apoptotic cells. The expressions of Beclin and LC3-â ¡ were detected by Western blotting to determine the status of autophagy. Morris water maze test and Y maze test were performed to evaluate cognitive functions. RESULTS: The mTOR signaling pathway was abnormally activated from 6 h to 6 w after rUCCAO in mouse cortex. The activation of mTOR signaling pathway induced by rUCCAO was reversed by administration of rapamycin, and the apoptotic cell number was significantly decreased (146.1±16.3 vs 84.5±9.6, P<0.05). Meanwhile, the elevation of Beclin and LC3-â ¡ protein induced by rUCCAO was reversed by rapamycin administration. Furthermore, compared with vehicle-treated mice, the latent period[(11.1±2.3) s vs (8.1±1.8) s, P<0.05] and swimming distance[(672.8±128.5) cm vs (558.2±124.9) cm, P<0.05] were significantly decreased and the number of crossing the platform quadrant in Morris water maze increased(2.8±0.9 vs 5.2±0.8, P<0.05) in rapamycin-treated mice. Correct response rate in the Y maze was also increased significantly in rapamycin-treated mice[(38.5±9.2)% vs (64.9±7.9)%, P<0.05]. CONCLUSIONS: Inhibiting mTOR pathway by rapamycin reverses the rUCCAO-induced cognitive impairment partly through the suppression of apoptosis and autophagy.
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Isquemia Encefálica , Cognición , Sirolimus , Serina-Treonina Quinasas TOR , Animales , Isquemia Encefálica/tratamiento farmacológico , Cognición/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Ratones , Ratones Endogámicos ICR , Transducción de Señal/efectos de los fármacos , Sirolimus/farmacología , Sirolimus/uso terapéutico , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
A concise, diversity-oriented approach for the synthesis of naturally occurring 3-amino- and 3-nitro-2,3,6-trideoxypyranose derivatives and analogues thereof from simple sugars has been developed. In addition, we investigated the synthesis of various 3-aminoglycosyl donors and their application in glycosylation reactions. These studies led to the successful synthesis of a tetrasaccharide containing four different 3-aminosugar components using ortho-alkynylbenzoate donors.
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Amino Azúcares/química , Oligosacáridos/síntesis química , Glicosilación , Estructura Molecular , Oligosacáridos/químicaRESUMEN
Accurate prediction of Drug-Target Interactions (DTI) is crucial for drug development. Current state-of-the-art deep learning methods have significantly advanced the field; however, these methods exhibit limitations in predictive performance and the propensity for false negatives. Therefore, we propose EADTN, a simple and efficient ensemble model. We have designed an innovative feature adaptation technique to automatically extract local weights of drugs and targets, and we utilize clustering-enhanced parameter fine-tuning to overcome the issue of false negatives, thereby enhancing its reliability in drug discovery. Based on EADTN, we also propose a Shapley value-based method for identifying key drug substructures, effectively enhancing the model's interpretability. Additionally, we utilized EADTN to reveal potential interactions between NQO1 targets and the drugs SIRT-IN-1 and LY2183240, which were subsequently validated through wet-lab experiments. Experimental evidence demonstrates that EADTN consistently outperforms existing best-performing models across various data sets, promising significant benefits in fields such as drug repositioning.
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Aprendizaje Profundo , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Sirtuina 1/metabolismo , Descubrimiento de Drogas , HumanosRESUMEN
Quantum dot light-emitting diodes (QLEDs), owing to their exceptional performances in device efficiency, color purity/tunability in the visible region and solution-processing ability on various substrates, become a potential candidate for flexible and ultrathin electroluminescent (EL) lighting and display. Moreover, beyond the lighting and display, flexible QLEDs are enabled with endless possibilities in the era of the internet of things and artificial intelligence by acting as input/output ports in wearable integrated systems. Challenges remain in the development of flexible QLEDs with the goals for high performance, excellent flexibility/even stretchability, and emerging applications. In this paper, the recent developments of QLEDs including quantum dot materials, working mechanism, flexible/stretchable strategies and patterning strategies, and highlight its emerging multifunctional integrations and smart applications covering wearable optical medical devices, pressure-sensing EL devices, and neural smart EL devices, are reviewed. The remaining challenges are also summarized and an outlook on the future development of flexible QLEDs made. The review is expected to offer a systematic understanding and valuable inspiration for flexible QLEDs to simultaneously satisfy optoelectronic and flexible properties for emerging applications.
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Interactive display devices integrating multiple functions have become a development trend of display technology. The excellent luminescence properties of perovskite quantum dots (PQDs) make it an ideal luminescent material for the next generation of wide-color gamut displays. Here we design and fabricate dual-function light-sensing/displaying light-emitting devices based on PQDs. The devices can display information as an output port, and simultaneously sense outside light signals as an input port and modulate the display information in a non-contact mode. The dual functions were attributed to the device designs: (1) the hole transport layer in the devices also acts as the light-sensing layer to absorb outside light signals; (2) the introduced hole trapping layer interface can trap holes originating from the light-sensing layer, and thus tune the charge transport properties and the light-emitting intensities. The sensing and display behavior of the device can be further modulated by light signals with different time and space information. This fusion of sensing and display functions has broad prospects in non-contact interactive screens and communication ports.
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Inkjet printing technique is susceptible to form coffer-ring patterns and inhomogeneous films owing to the evaporation and its accompanying hydrodynamics of microscale quantum dot droplet. Pioneer efforts are usually confined to two-dimensional flat substrates and inks with mixed solvents/additives. Herein we demonstrate that physically confined space offers an additional parameter in tailoring such processes of droplets and the following quantum-dot self-assembly deposition, without extra modification of quantum dots or solvent chemistry. Owing to the boundary of physically confined space, two three-phase border lines in both the bottom center (horizontal direction) and the barrier of the bank substrate (vertical direction) arise, inducing dual capillary flows and Marangoni backflows. The evaporation, fluid flow, and film-forming process in physically confined space are studied by introducing well-prepared single-solvent quantum dots inks. The systematical analysis offers valuable instructions including ink preparation, surface modification, and postprocessing evaporation technique for inkjet-printed patterning applications, especially for pixelated display, polychrome patterning, and sensor array.
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The development of artificial skin, such as electronic skin, is critical to emerging artificial intelligence systems. Electronic skins reported to date are mechanically flexible, and can detect various stimuli, but lack the ability to regulate themselves and learn information from the outside world. The integration of bio-inspired multifunction in a single electronic platform is critical to the development of e-skin systems. Here, we demonstrate a self-powered, light-stimulated, smart e-skin based on a photosensitive perovskite material. The electronic skin implements the functions of both tactile sensing and photoelectric neural computing. The strategy for developing such a material system and architecture of the electronic skin meets the requirement of multifunctional smart human-machine interfaces and has promising potential for application in future artificial intelligence systems.
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Inteligencia Artificial , Mecanorreceptores , Compuestos de Calcio , Electrónica , Humanos , Óxidos , Titanio , TactoRESUMEN
Optical security labels play a significant role in protecting both our wealth and health. However, simultaneously meeting the requirements including low-cost fabrication, easy detection, and high-level security is still challenging for security labels. Here, we design an unclonable anti-counterfeiting system with triple-level security by using the inkjet printing technique, which can be authenticated by naked eyes, a portable microscope, and a fluorescence microscope. These labels are achieved by printing microscale quantum dot (QD) ink droplets on premodified substrates with random-distributed glass microspheres. Due to the unique capillary action induced by the glass microspheres, QDs in the ink droplets are deposited around the microspheres, forming microscale multicircular patterns. Multiple pinning of QDs at the three-phase contact lines appears during the evaporation of the droplet, resulting in the formation of a nanoscale labyrinthine pattern around the microspheres. The nanoscale labyrinth pattern and the microscale multicircular microsphere array, together with the printed macroscopic image, constitute a triple-level progressive anti-counterfeiting system. Moreover, the system is compatible with an artificial intelligence-based identification strategy that allows rapid identification and verification of the unclonable security labels.
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Anticounterfeiting techniques based on physical unclonable functions exhibit great potential in security protection of extensive commodities from daily necessities to high-end products. Herein, we propose a facile strategy to fabricate an unclonable super micro fingerprint (SMFP) array by introducing in situ grown perovskite crystals for multilevel anticounterfeiting labels. The unclonable features are formed on the basis of the differential transportation of a microscale perovskite precursor droplet during the inkjet printing process, coupled with random crystallization and Ostwald ripening of perovskite crystals originating from their ion crystal property. Furthermore, the unclonable patterns can be readily tailored by tuning in situ crystallization conditions of the perovskite. Three-dimensional height information on the perovskite patterns are introduced into a security label and further transformed into structural color, significantly enhancing the capacity of anticounterfeiting labels. The SMFPs are characterized with tunable multilevel anticounterfeiting properties, including macroscale patterns, microscale unclonable pattern, fluorescent two-dimensional pattens, and colorful three-dimensional information.