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The interaction between foot-and-mouth disease virus (FMDV) and the host is extremely important for virus infection, but there are few researches on it, which is not conducive to vaccine development and FMD control. In this study, we designed a porcine genome-scale CRISPR/Cas9 knockout library containing 93,859 single guide RNAs targeting 16,886 protein-coding genes, 25 long ncRNAs, and 463 microRNAs. Using this library, several previously unreported genes required for FMDV infection are highly enriched post-FMDV selection in IBRS-2 cells. Follow-up studies confirmed the dependency of FMDV on these genes, and we identified a functional role for one of the FMDV-related host genes: TOB1 (Transducer of ERBB2.1). TOB1-knockout significantly inhibits FMDV infection by positively regulating the expression of RIG-I and MDA5. We further found that TOB1-knockout led to more accumulation of mRNA transcripts of transcription factor CEBPA, and thus its protein, which further enhanced transcription of RIG-I and MDA5 genes. In addition, TOB1-knockout was shown to inhibit FMDV adsorption and internalization mediated by EGFR/ERBB2 pathway. Finally, the FMDV lethal challenge on TOB1-knockout mice confirmed that the deletion of TOB1 inhibited FMDV infection in vivo. These results identify TOB1 as a key host factor involved in FMDV infection in pigs.
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Vírus da Febre Aftosa , Febre Aftosa , Animais , Camundongos , Receptores ErbB/metabolismo , Febre Aftosa/genética , Vírus da Febre Aftosa/genética , Regulação da Expressão Gênica , RNA Guia de Sistemas CRISPR-Cas , SuínosRESUMO
BACKGROUND: Mammary gland development is a critical process in mammals, crucial for their reproductive success and offspring nourishment. However, the functional roles of key candidate genes associated with teat number, including ABCD4, VRTN, PROX2, and DLST, in this developmental process remain elusive. To address this gap in knowledge, we conducted an in-depth investigation into the dynamic expression patterns, functional implications, and regulatory networks of these candidate genes during mouse mammary gland development. RESULTS: In this study, the spatial and temporal patterns of key genes were characterized in mammary gland development. Using time-series single-cell data, we uncovered differences in the expression of A bcd4, Vrtn, Prox2, and Dlst in cell population of the mammary gland during embryonic and adult stages, while Vrtn was not detected in any cells. We found that only overexpression and knockdown of Abcd4 could inhibit proliferation and promote apoptosis of HC11 mammary epithelial cells, whereas Prox2 and Dlst had no significant effect on these cells. Using RNA-seq and qPCR, further analysis revealed that Abcd4 can induce widespread changes in the expression levels of genes involved in mammary gland development, such as Igfbp3, Ccl5, Tlr2, and Prlr, which were primarily associated with the MAPK, JAK-STAT, and PI3K-AKT pathways by functional enrichment. CONCLUSIONS: These findings revealed ABCD4 as a candidate gene pivotal for regulating mammary gland development and lactation during pregnancy by influencing PRLR expression.
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Transportadores de Cassetes de Ligação de ATP , Glândulas Mamárias Animais , Animais , Feminino , Camundongos , Apoptose/genética , Proliferação de Células , Células Epiteliais/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Glândulas Mamárias Animais/crescimento & desenvolvimento , Glândulas Mamárias Animais/metabolismo , Transdução de Sinais , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismoRESUMO
Speckle patterns generated as coherent optical beams are reflected by scattering elements. Multimode fibers (MMFs) can modify the transverse intensity distribution of speckle patterns with macro perturbations, i.e., pressures, providing a simple and low-cost way to achieve equivalent beam-steering for indoor optical wireless communications (OWCs) with divergent optical beams. However, the received optical power (ROP) variance severely limits the mobility of user terminals. In this paper, the issue is alleviated by using the overfilled launch of MMFs and the diversity gain of multi-receivers. By adjusting the axial spatial coupling distance between the MMF and the single mode fiber (SMF) emitting coherent laser, the number of excited modes of MMF can be significantly increased at 1550â nm with negligible coupling and bending losses. In addition, the signal-to-noise ratio (SNR) enhancement obtained by applying two receivers is theoretically analyzed for the case when either thermal noise or shot noise is dominant. The experimental results demonstrate that the proposed scheme can efficiently compensate for the ROP inhomogeneity, and at the same time it can extend the achievable full steering angle up to 12° at a 1.5-m free-space distance for bit error rate (BER) values of less than 3.8 × 10-3.
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A snap-through bifurcation occurs when a bistable structure loses one of its stable states and moves rapidly to the remaining state. For example, a buckled arch with symmetrically clamped ends can snap between an inverted and a natural state as the ends are released. A standard linear stability analysis suggests that the arch becomes unstable to asymmetric perturbations. Surprisingly, our experiments show that this is not always the case: symmetric transitions are also observed. Using experiments, numerics, and a toy model, we show that the symmetry of the transition depends on the rate at which the ends are released, with sufficiently fast loading leading to symmetric snap-through. Our toy model reveals that this behavior is caused by a region of the system's state space in which any initial asymmetry is amplified. The system may not enter this region when loaded fast (hence remaining symmetric), but will traverse it for some interval of time when loaded slowly, causing a transient amplification of asymmetry. Our toy model suggests that this behavior is not unique to snapping arches, but rather can be observed in dynamical systems where both a saddle-node and a pitchfork bifurcation occur in close proximity.
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Although the rapid expansion of urban rail transit offers convenience to citizens, the issue of subway vibration cannot be overlooked. This study investigates the spatial distribution characteristics of vibration in the Fayuan Temple historic and cultural reserve. It involves using a V001 magnetoelectric acceleration sensor capable of monitoring low amplitudes with a sensitivity of 0.298 V/(m/s2), a measuring range of up to 20 m/s2, and a frequency range span from 0.5 to 100 Hz for in situ testing, analyzing the law of vibration propagation in this area, evaluating the impact on buildings, and determining the vibration reduction scheme. The reserve is divided into three zones based on the vertical vibration level measured during the in situ test as follows: severely excessive, generally excessive, and non-excessive vibration. Furthermore, the research develops a dynamic coupling model of vehicle-track-tunnel-stratum-structure to verify the damping effect of the wire spring floating plate track and periodic pile row. It compares the characteristics of three vibration reduction schemes, namely, internal vibration reduction reconstruction, periodic pile row, and anti-vibration reinforcement or reconstruction of buildings, proposing a comprehensive solution. Considering the construction conditions, difficulty, cost, and other factors, a periodic pile row is recommended as the primary treatment measure. If necessary, anti-vibration reinforcement or reconstruction of buildings can serve as supplemental measures.
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The artificial tactile perception system of this work utilizes a fully connected spiking neural network (SNN) comprising two layers. Its architecture is streamlined and energy-efficient as it directly integrates spiking tactile neurons with piezoresistive sensors and Pt/NbOx/TiN memristors as input neurons. These spiking tactile neurons possess the ability to perceive and integrate pressure stimuli from multiple sensors and encode the information into rate-coded electrical spikes, closely resembling the behavior of a biological tactile neuron. The system's real-time information processing capability is demonstrated through an artificial perceptual learning system that successfully encodes and decodes the Morse code; the artificial perceptual learning system accurately recognizes and displays 26 English letters. Furthermore, the artificial tactile perception system is evaluated for the recognition of the MNIST data set, achieving a classification accuracy of 85.7% with the supervised spiking-rate-dependent plasticity learning rule. The key advantages of this artificial tactile perception system are its simple structure and high efficiency, which contributes to its practicality for various real-world applications.
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Redes Neurais de Computação , Percepção do Tato , Aprendizagem/fisiologia , Neurônios/fisiologia , TatoRESUMO
The as-cast (Fe50Mn30Co10Cr10)97C2Mo1 HEA (high entropy alloy) was prepared and cold-rolled at 70%. Subsequently, annealing heat treatment at different temperatures (900 °C, 950 °C, 1000 °C) was carried out. The microstructure evolution and mechanical properties of the HEA were systematically investigated. The results showed that the HEA annealed at 900 °C and 950 °C exhibited uneven grain size and rich σ precipitation phase at grain boundaries. The grains began to grow and complete recrystallization, and no σ phases were observed in HEA annealed at 1000 °C, which resulted in a higher tensile strength of ~885 MPa and elongation of ~68% compared with other annealed HEAs. The higher volume fraction of annealing twins with 60°<111> orientation was produced in HEA annealed at 1000 °C, which enhanced the tensile strength and plasticity via the Twinning-induced plasticity (TWIP) mechanism.
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Light-assisted Li-O2 batteries exhibit a high round-trip efficiency attributable to the assistance of light-generated electrons and holes in oxygen reduction and evolution reactions. Nonetheless, the excitonic effect arising from Coulomb interaction between electrons and holes impedes carrier separation, thus hindering efficient utilization of photo-energy. Herein, porphyrinic metal-organic frameworks with (Fe2Ni)O(COO)6 clusters are used as photocathodes to accelerate exciton dissociation into charge carriers for light-assisted Li-O2 batteries. The coupling of Ni 3d and Fe 3d orbitals boosts ligand-to-metal cluster charge transfer, and hence drives exciton dissociation and activates O2 for superoxide (â¢O2 -) radicals, rather than singlet oxygen (1O2) under photoexcitation. These enable the light-assisted Li-O2 batteries with a low total overvoltage of 0.28 V and round-trip efficiency of 92% under light irradiation of 100 mW cm-2. This work highlights the excitonic effect in photoelectrochemical processes and provides insights into photocathode design for light-assisted Li-O2 batteries.
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During the cell life cycle, extracellular vesicles (EVs) transport different cargos, including organelles, proteins, RNAs, DNAs, metabolites, etc., that influence cell proliferation and apoptosis in recipient cells. EVs from metastatic cancer cells remodel the extracellular matrix and cells of the tumor microenvironment (TME), promoting tumor invasion and metastatic niche preparation. Although the process is not fully understood, evidence suggests that EVs facilitate genetic material transfer between cells. In the context of NSCLC, EVs can mediate intercellular mitochondrial (Mt) transfer, delivering mitochondria organelle (MtO), mitochondrial DNA (mtDNA), and/or mtRNA/proteinaceous cargo signatures (MtS) through different mechanisms. On the other hand, certain populations of cancer cells can hijack the MtO from TME cells mainly by using tunneling nanotubes (TNTs). This transfer aids in restoring mitochondrial function, benefiting benign cells with impaired metabolism and enabling restoration of their metabolic activity. However, the impact of transferring mitochondria versus transplanting intact mitochondrial organelles in cancer remains uncertain and the subject of debate. Some studies suggest that EV-mediated mitochondria delivery to cancer cells can impact how cancer responds to radiation. It might make the cancer more resistant or more sensitive to radiation. In our review, we aimed to point out the current controversy surrounding experimental data and to highlight new paradigm-shifting modalities in radiation therapy that could potentially overcome cancer resistance mechanisms in NSCLC.
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PURPOSE: To investigate the role of magnetic resonance imaging (MRI) based on radiomics using T2-weighted imaging fat suppression (T2WI-FS) and contrast enhanced T1-weighted imaging (CE-T1WI) sequences in differentiating T1-category nasopharyngeal carcinoma (NPC) from nasopharyngeal lymphoid hyperplasia (NPH). MATERIALS AND METHODS: This study enrolled 614 patients (training dataset: n = 390, internal validation dataset: n = 98, and external validation dataset: n = 126) of T1-category NPC and NPH. Three feature selection methods were used, including analysis of variance, recursive feature elimination, and relief. The logistic regression classifier was performed to construct the radiomics signatures of T2WI-FS, CE-T1WI, and T2WI-FS + CE-T1WI to differentiate T1-category NPC from NPH. The performance of the optimal radiomics signature (T2WI-FS + CE-T1WI) was compared with those of three radiologists in the internal and external validation datasets. RESULTS: Twelve, 15, and 15 radiomics features were selected from T2WI-FS, CE-T1WI, and T2WI-FS + CE-T1WI to develop the three radiomics signatures, respectively. The area under the curve (AUC) values for radiomics signatures of T2WI-FS + CE-T1WI and CE-T1WI were significantly higher than that of T2WI-FS (AUCs = 0.940, 0.935, and 0.905, respectively) for distinguishing T1-category NPC and NPH in the training dataset (Ps all < 0.05). In the internal and external validation datasets, the radiomics signatures based on T2WI-FS + CE-T1WI and CE-T1WI outperformed T2WI-FS with no significant difference (AUCs = 0.938, 0.925, and 0.874 for internal validation dataset and 0.932, 0.918, and 0.882 for external validation dataset; Ps > 0.05). The radiomics signature of T2WI-FS + CE-T1WI significantly performed better than three radiologists in the internal and external validation datasets. CONCLUSION: The MRI-based radiomics signature is meaningful in differentiating T1-category NPC from NPH and potentially helps clinicians select suitable therapy strategies.