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1.
Comput Biol Med ; 169: 107844, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38103482

RESUMO

Based on deep learning, pancreatic cancer pathology image segmentation technology effectively assists pathologists in achieving improved treatment outcomes. However, compared to traditional image segmentation tasks, the large size of tissues in pathology images requires a larger receptive field. While methods based on dilated convolutions or attention mechanisms can enhance the receptive field, they cannot capture long-range feature dependencies. Directly applying self-attention mechanisms to capture long-range dependencies results in intolerable computational complexity. To address these challenges, we introduce a channel and spatial self-attention (CS) Module designed for efficiently capturing both channel and spatial long-range feature dependencies in pancreatic cancer pathological images. Specifically, the channel and spatial self-attention module consists of an adaptive channel self-attention module and a window-shift spatial self-attention module. The adaptive channel self-attention module adaptively pools features to a fixed size to capture long-range feature dependencies. While the window-shift spatial self-attention module captures spatial long-range dependencies in a window-based manner. Additionally, we propose a re-weighted cross-entropy loss to mitigate the impact of long-tail distribution on performance. Our proposed method surpasses state-of-the-art on both our Pancreatic Cancer Pathology Image (PCPI) dataset and the GlaS challenge dataset. The mDice and mIoU have achieved 73.93% and 59.42% in our PCPI dataset.


Assuntos
Neoplasias Pancreáticas , Humanos , Entropia , Processamento de Imagem Assistida por Computador
2.
Analyst ; 149(1): 196-204, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38013467

RESUMO

Oxidative stress, a condition involving an imbalance between reactive oxygen species (ROS) and antioxidants, is closely linked to epilepsy, contributing to abnormal neuronal excitability. This study introduces a novel fluorescent probe, the MDP probe, designed for the efficient detection of malondialdehyde (MDA), a critical biomarker associated with oxidative stress. The MDP probe offers several key advantages, including high sensitivity with a low detection limit of 0.08 µM for MDA, excellent selectivity for MDA even in the presence of interfering substances, and biocompatibility, making it suitable for cell-based experiments. The probe allows for real-time monitoring of MDA levels, enabling dynamic studies of oxidative stress. In vivo experiments in mice demonstrate its potential for monitoring MDA levels, particularly in epilepsy models, which could have implications for disease research and diagnosis. Overall, the MDP probe represents a promising tool for studying oxidative stress, offering sensitivity and specificity in cellular and in vivo settings. Its development opens new avenues for exploring the role of oxidative stress in various biological processes and diseases, contributing to advancements in healthcare and biomedical research.


Assuntos
Corantes Fluorescentes , Estresse Oxidativo , Camundongos , Animais , Malondialdeído , Corantes Fluorescentes/toxicidade , Fluorescência , Espécies Reativas de Oxigênio
3.
Hum Brain Mapp ; 44(17): 6245-6257, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37837649

RESUMO

Rumination is closely linked to the onset and maintenance of major depressive disorder (MDD). Prior neuroimaging studies have identified the association between self-reported rumination trait and the functional coupling among a network of brain regions using resting-state functional magnetic resonance imaging (MRI). However, little is known about the underlying neural circuitry mechanism during active rumination in MDD. Degree centrality (DC) is a simple metric to denote network integration, which is critical for higher-order psychological processes such as rumination. During an MRI scan, individuals with MDD (N = 45) and healthy controls (HC, N = 46) completed a rumination state task. We examined the interaction effect between the group (MDD vs. HC) and condition (rumination vs. distraction) on vertex-wise DC. We further characterized the identified brain region's functional involvement with Neurosynth and BrainMap. Network-wise seed-based functional connectivity (FC) analysis was also conducted for the identified region of interest. Finally, exploratory correlation analysis was conducted between the identified region of interest's network FCs and self-reported in-scanner affect levels. We found that a left superior frontal gyrus (SFG) region, generally overlapped with the frontal eye field, showed a significant interaction effect. Further analysis revealed its involvement with executive functions. FCs between this region, the frontoparietal, and the dorsal attention network (DAN) also showed significant interaction effects. Furthermore, its FC to DAN during distraction showed a marginally significant negative association with in-scanner affect level at the baseline. Our results implicated an essential role of the left SFG in the rumination's underlying neural circuitry mechanism in MDD and provided novel evidence for the conceptualization of rumination in terms of impaired executive control.


Assuntos
Transtorno Depressivo Maior , Humanos , Encéfalo/diagnóstico por imagem , Córtex Pré-Frontal , Função Executiva , Lobo Frontal , Imageamento por Ressonância Magnética , Mapeamento Encefálico
4.
Sci Total Environ ; 897: 165374, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37422230

RESUMO

Fungi represent the dominant eukaryotic group of organisms in anoxic marine sedimentary ecosystems, ranging from a few centimeters to ~ 2.5 km below seafloor. However, little is known about how fungi can colonize anaerobic subseafloor environments for tens of millions of years and whether they play a role in elemental biogeochemical cycles. Based on metabolite detection, isotope tracer and gene analysis, we examined the anaerobic nitrogen conversion pathways of 19 fungal species (40 strains) isolated from1.3 to 2.5 km coal-bearing sediments below seafloor. Our results show for the first time that almost all fungi possess anaerobic denitrification, dissimilatory nitrate reduction to ammonium (DNRA), and nitrification pathways, but not anaerobic ammonium oxidation (anammox). Moreover, the distribution of fungi with different nitrogen-conversion abilities in subseafloor sediments was mainly determined by in situ temperature, CaCO3, and inorganic carbon contents. These findings suggest that fungi have multiple nitrogen transformation processes to cope with their requirements for a variety of nitrogen sources in nutrient deficient anaerobic subseafloor sedimentary environments.


Assuntos
Compostos de Amônio , Ecossistema , Nitrogênio/análise , Nitratos/análise , Compostos de Amônio/metabolismo , Fungos/metabolismo , Oxirredução , Desnitrificação
5.
Front Microbiol ; 14: 1216714, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37455735

RESUMO

Introduction: Aspergillussydowii is an important filamentous fungus that inhabits diverse environments. However, investigations on the biology and genetics of A. sydowii in subseafloor sediments remain limited. Methods: Here, we performed de novo sequencing and assembly of the A. sydowii 29R-4-F02 genome, an isolate obtained from approximately 2.4 km deep, 20-million-year-old coal-bearing sediments beneath the seafloor by employing the Nanopore sequencing platform. Results and Discussion: The generated genome was 37.19 Mb with GC content of 50.05%. The final assembly consisted of 11 contigs with N50 of 4.6 Mb, encoding 12,488 putative genes. Notably, the subseafloor strain 29R-4-F02 showed a higher number of carbohydrate-active enzymes (CAZymes) and distinct genes related to vesicular fusion and autophagy compared to the terrestrial strain CBS593.65. Furthermore, 257 positively selected genes, including those involved in DNA repair and CAZymes were identified in subseafloor strain 29R-4-F02. These findings suggest that A. sydowii possesses a unique genetic repertoire enabling its survival in the extreme subseafloor environments over tens of millions of years.

6.
Neural Regen Res ; 18(7): 1563-1569, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36571363

RESUMO

The neuronal differentiation of mesenchymal stem cells offers a new strategy for the treatment of neurological disorders. Thus, there is a need to identify a noninvasive and sensitive in vivo imaging approach for real-time monitoring of transplanted stem cells. Our previous study confirmed that magnetic resonance imaging, with a focus on the ferritin heavy chain 1 reporter gene, could track the proliferation and differentiation of bone marrow mesenchymal stem cells that had been transduced with lentivirus carrying the ferritin heavy chain 1 reporter gene. However, we could not determine whether or when bone marrow mesenchymal stem cells had undergone neuronal differentiation based on changes in the magnetic resonance imaging signal. To solve this problem, we identified a neuron-specific enolase that can be differentially expressed before and after neuronal differentiation in stem cells. In this study, we successfully constructed a lentivirus carrying the neuron-specific enolase promoter and expressing the ferritin heavy chain 1 reporter gene; we used this lentivirus to transduce bone marrow mesenchymal stem cells. Cellular and animal studies showed that the neuron-specific enolase promoter effectively drove the expression of ferritin heavy chain 1 after neuronal differentiation of bone marrow mesenchymal stem cells; this led to intracellular accumulation of iron and corresponding changes in the magnetic resonance imaging signal. In summary, we established an innovative magnetic resonance imaging approach focused on the induction of reporter gene expression by a neuron-specific promoter. This imaging method can be used to noninvasively and sensitively detect neuronal differentiation in stem cells, which may be useful in stem cell-based therapies.

7.
Front Pharmacol ; 13: 1014160, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36278232

RESUMO

5-fluorouracil (5-FU) is one of the most widely used chemotherapy drugs for malignant tumors. However, intestinal mucositis caused by 5-FU is a severe dose-limiting toxic effect and even leads to treatment interruption. Isoliquiritigenin (ISL) is one of the main active compounds of licorice, which is a traditional Chinese herbal medicine commonly used in inflammation and gastrointestinal diseases. It is speculated that ISL have protective effects on intestinal mucositis. However, no such studies have been reported. Therefore, to investigate the impact of ISL on 5-Fu-induced intestinal mucositis, a strategy based on network prediction and pharmacological experimental validation was proposed in this study. Firstly, the targets and mechanism of ISL in alleviating 5-Fu-induced gastrointestinal toxicity were predicted by network analysis. And the results were further confirmed by molecular docking. Then, a mouse model of intestinal mucositis was established by intraperitoneal injection of 5-FU (384 µmol/kg) to verify the prediction of network analysis. The network analysis results suggested that PTGS2 (Prostaglandin G/H synthase 2) and NOS2 (Nitric oxide synthase, inducible) might be the critical targets of ISL for reducing the intestinal toxicity of 5-FU. In addition, KEGG and GO enrichment analysis revealed that the HIF-1, TNF, MAPK, IL-17, PI3K-Akt, Ras, NF-kappa B signaling pathway, and biological processes of the inflammatory response, apoptosis regulation, NO production and NF-kappa B transcription factor activity might be involved in the mechanism of ISL against intestinal mucositis. Subsequent animal experiments showed that ISL could reduce the weight loss, leukopenia and mucosal damage caused by 5-FU. Compared with the intestinal mucositis model, the protein expressions of PTGS2, NOS2, TNFα (Tumor necrosis factor-alpha) and NF-κB p65 (nuclear factor kappa-B P65) were decreased after ISL treatment. In conclusion, this study is the fist time to find that ISL can attenuate 5-FU-induced intestinal mucositis in mice. Its anti-mucositis effect may be through regulating TNF/NF-κB pathway and inhibiting inflammatory mediators PTGS2 and NOS2. It will provide a potential candidate for the prevention and treatment of chemotherapy-induced intestinal mucositis.

8.
Cell Biol Int ; 46(9): 1367-1377, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35842774

RESUMO

High intake of phytoestrogen has been reported to be associated with the prevention of colorectal cancer (CRC). Calycosin belongs to the phytoestrogen that has been shown to suppress CRC cells in our previous study. However, its anticancer activity and molecular mechanisms have not been elucidated. In this study, we analyzed the effect of calycosin on the viability and apoptosis of human CRC HCT116 and SW480 cells via MTT assay, flow cytometry assay, and caspase-3/7 activity assay. The protein expressions of estrogen receptor ß (ERß), PTEN, and PI3K/Akt signal pathways were determined by Western blot analysis. And then, the alterations of biological behavior in CRC cells transfected with ERß siRNA were analyzed. Mouse xenograft models were further performed to detect the antitumor effect in vivo. The results show that calycosin reduces CRC cell viability, induces cell apoptosis, and suppresses xenograft tumor growth. The protein expressions of ERß and PTEN are significantly upregulated following calycosin treatment, whereas p-AKT/AKT ratio and Bcl-2 level are downregulated. Suppressing ERß with siRNA partially attenuates the reduction in viability and apoptosis induced by calycosin. Our results indicate that calycosin shows inhibitory effects on CRC cells, which might be obtained by targeting ERß, upregulating PTEN, and inhibiting the PI3K/Akt signal pathway.


Assuntos
Neoplasias Colorretais , Receptor beta de Estrogênio , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/metabolismo , Receptor beta de Estrogênio/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Isoflavonas , Camundongos , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fitoestrógenos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/farmacologia , Transdução de Sinais
9.
Child Dev ; 93(6): 1793-1803, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35726966

RESUMO

Visual working memory (WM) plays a pivotal role in integrating fragments into meaningful units, but no study has addressed how visual WM integration takes place in children. The current study examined whether WM integration emerges once preschoolers master Gestalt cue and can retain two representations in WM (automatic integration hypothesis), or still needs time to mature (maturation-of-integration hypothesis). Four experiments (N = 168, 81 females, 4- to 6-year-olds, Chinese, in Hangzhou, China, from 2016.10 to 2021.11) were conducted. Although 4-year-olds can retain two objects in WM and benefit from Gestalt cues in simultaneous display (Cohen's ds >1.00), they failed when memory arrays were presented sequentially. Meanwhile, 5- and 6-year-olds consistently demonstrated WM integration ability (all Cohen's ds >0.69), supporting the maturation-of-integration hypothesis.


Assuntos
Sinais (Psicologia) , Memória de Curto Prazo , Criança , Feminino , Humanos , Pré-Escolar , Povo Asiático , China
10.
Polymers (Basel) ; 14(11)2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35683935

RESUMO

Liquid metal (LM)-polymer composites that combine the thermal and electrical conductivity of LMs with the shape-morphing capability of polymers are attracting a great deal of attention in the fields of reconfigurable electronics and soft robotics. However, investigation of the synergetic effect between the shape-changing properties of LMs and polymer matrices is lacking. Herein, a self-healable and recyclable dual-shape memory composite, comprising an LM (gallium) and a Diels-Alder (DA) crosslinked crystalline polyurethane (PU) elastomer, is reported. The composite exhibits a bilayer structure and achieves excellent shape programming abilities, due to the phase transitions of the LM and the crystalline PU elastomers. To demonstrate these shape-morphing abilities, a heat-triggered soft gripper, which can grasp and release objects according to the environmental temperature, is designed and built. Similarly, combining the electrical conductivity and the dual-shape memory effect of the composite, a light-controlled reconfigurable switch for a circuit is produced. In addition, due to the reversible nature of DA bonds, the composite is self-healable and recyclable. Both the LM and PU elastomer are recyclable, demonstrating the extremely high recycling efficiency (up to 96.7%) of the LM, as well as similar mechanical properties between the reprocessed elastomers and the pristine ones.

11.
Psychoradiology ; 2(1): 32-42, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38665141

RESUMO

Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder (MDD), reproducible findings are lacking, probably reflecting mostly small sample sizes and heterogeneity in analytic approaches. To address these issues, the Depression Imaging REsearch ConsorTium (DIRECT) was launched. The REST-meta-MDD project, pooling 2428 functional brain images processed with a standardized pipeline across all participating sites, has been the first effort from DIRECT. In this review, we present an overview of the motivations, rationale, and principal findings of the studies so far from the REST-meta-MDD project. Findings from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network, in whole-brain topological properties, in dynamic features, and in functional lateralization. These well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven research. Following these fruitful explorations, DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations. A state-of-the-art, surface-based preprocessing pipeline has also been introduced to improve sensitivity. Functional images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diagnosis boundaries. In addition, large-scale longitudinal studies targeting brain network alterations following antidepressant treatment, aggregation of diffusion tensor images, and the development of functional magnetic resonance imaging-guided neuromodulation approaches are underway. Through these endeavours, we hope to accelerate the translation of functional neuroimaging findings to clinical use, such as evaluating longitudinal effects of antidepressant medications and developing individualized neuromodulation targets, while building an open repository for the scientific community.

12.
Stem Cell Res Ther ; 12(1): 284, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980305

RESUMO

BACKGROUND: Existing evidence has shown that mesenchymal stem cells (MSCs) can undergo malignant transformation, which is a serious limitation of MSC-based therapies. Therefore, it is necessary to monitor malignant transformation of MSCs via a noninvasive imaging method. Although reporter gene-based magnetic resonance imaging (MRI) has been successfully applied to longitudinally monitor MSCs, this technique cannot distinguish the cells before and after malignant transformation. Herein, we investigated the feasibility of using a tumor-specific promoter to drive reporter gene expression for MRI detection of the malignant transformation of MSCs. METHODS: The reporter gene ferritin heavy chain (FTH1) was modified by adding a promoter from the tumor-specific gene progression elevated gene-3 (PEG3) and transduced into MSCs to obtain MSCs-PEG3-FTH1. Cells were induced to undergo malignant transformation via indirect coculture with C6 glioma cells, and these transformed cells were named MTMSCs-PEG3-FTH1. Western blot analysis of FTH1 expression, Prussian blue staining and transmission electron microscopy (TEM) to detect intracellular iron, and MRI to detect signal changes were performed before and after malignant transformation. Then, the cells before and after malignant transformation were inoculated subcutaneously into nude mice, and MRI was performed to observe the signal changes in the xenografts. RESULTS: After induction of malignant transformation, MTMSCs demonstrated tumor-like features in morphology, proliferation, migration, and invasion. FTH1 expression was significantly increased in MTMSCs-PEG3-FTH1 compared with MSCs-PEG3-FTH1. Prussian blue staining and TEM showed a large amount of iron particles in MTMSCs-PEG3-FTH1 but a minimal amount in MSCs-PEG3-FTH1. MRI demonstrated that the T2 value was significantly decreased in MTMSCs-PEG3-FTH1 compared with MSCs-PEG3-FTH1. In vivo, mass formation was observed in the MTMSCs-PEG3-FTH1 group but not the MSCs-PEG3-FTH1 group. T2-weighted MRI showed a significant signal decrease, which was correlated with iron accumulation in the tissue mass. CONCLUSIONS: We developed a novel MRI model based on FTH1 reporter gene expression driven by the tumor-specific PEG3 promoter. This approach could be applied to sensitively detect the occurrence of MSC malignant transformation.


Assuntos
Glioma , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Carcinógenos , Ferritinas/genética , Expressão Gênica , Genes Reporter , Imageamento por Ressonância Magnética , Camundongos , Camundongos Nus
13.
J Biol Chem ; 296: 100484, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33647316

RESUMO

Mutations in the human gene encoding the neuron-specific Eag1 voltage-gated K+ channel are associated with neurodevelopmental diseases, indicating an important role of Eag1 during brain development. A disease-causing Eag1 mutation is linked to decreased protein stability that involves enhanced protein degradation by the E3 ubiquitin ligase cullin 7 (CUL7). The general mechanisms governing protein homeostasis of plasma membrane- and endoplasmic reticulum (ER)-localized Eag1 K+ channels, however, remain unclear. By using yeast two-hybrid screening, we identified another E3 ubiquitin ligase, makorin ring finger protein 1 (MKRN1), as a novel binding partner primarily interacting with the carboxyl-terminal region of Eag1. MKRN1 mainly interacts with ER-localized immature core-glycosylated, as well as nascent nonglycosylated, Eag1 proteins. MKRN1 promotes polyubiquitination and ER-associated proteasomal degradation of immature Eag1 proteins. Although both CUL7 and MKRN1 contribute to ER quality control of immature core-glycosylated Eag1 proteins, MKRN1, but not CUL7, associates with and promotes degradation of nascent, nonglycosylated Eag1 proteins at the ER. In direct contrast to the role of CUL7 in regulating both ER and peripheral quality controls of Eag1, MKRN1 is exclusively responsible for the early stage of Eag1 maturation at the ER. We further demonstrated that both CUL7 and MKRN1 contribute to protein quality control of additional disease-causing Eag1 mutants associated with defective protein homeostasis. Our data suggest that the presence of this dual ubiquitination system differentially maintains Eag1 protein homeostasis and may ensure efficient removal of disease-associated misfolded Eag1 mutant channels.


Assuntos
Canais de Potássio Éter-A-Go-Go/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Ribonucleoproteínas/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Animais , Células Cultivadas , Retículo Endoplasmático/metabolismo , Proteólise , Proteostase , Ratos , Ratos Sprague-Dawley , Técnicas do Sistema de Duplo-Híbrido
14.
ACS Appl Bio Mater ; 4(9): 6865-6873, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-35006986

RESUMO

Recording ion fluctuations surrounding biological cells with a nanoelectronic device offers seamless integration of nanotechnology into living organisms and is essential for understanding cellular activities. The concentration of potassium ion in the extracellular fluid (CK+ex) is a critical determinant of cell membrane potential and must be maintained within an appropriate range. Alteration in CK+ex can affect neuronal excitability, induce heart arrhythmias, and even trigger seizure-like reactions in the brain. Therefore, monitoring local fluctuations in real time provides an early diagnosis of the occurrence of the K+-induced pathophysiological responses. Here, we modified the surface of a silicon nanowire field-effect transistor (SiNW-FET) with K+-specific DNA-aptamers (AptK+) to monitor the real-time variations of CK+ex in primary cultured rat embryonic cortical neurons or human embryonic stem cell-derived cardiomyocytes. The binding affinity of AptK+ to K+, determined by measuring the dissociation constant of the AptK+-K+ complex (Kd = 10.1 ± 0.9 mM), is at least 38-fold higher than other ions (e.g., Na+, Ca2+, and Mg2+). By placing cultured cortical neurons over an AptK+/SiNW-FET device, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) stimulation raised the CK+ex dose-dependently to 16 mM when AMPA concentration was >10 µM; this elevation could be significantly suppressed by an AMPA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione. Likewise, the stimulation of isoproterenol to cardiomyocytes raised the CK+ex to 6-8 mM, with a concomitant increase in the beating rate. This study utilizing a robust nanobiosensor to detect real-time ion fluctuations surrounding excitable cells underlies the importance of ion homeostasis and offers the feasibility of developing an implant device for real-time monitoring.


Assuntos
Nanofios , Animais , Íons , Nanofios/química , Potássio/metabolismo , Ratos , Silício/química , Transistores Eletrônicos , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/farmacologia
15.
Front Neurorobot ; 14: 63, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33132890

RESUMO

Existing mobile robots cannot complete some functions. To solve these problems, which include autonomous learning in path planning, the slow convergence of path planning, and planned paths that are not smooth, it is possible to utilize neural networks to enable to the robot to perceive the environment and perform feature extraction, which enables them to have a fitness of environment to state action function. By mapping the current state of these actions through Hierarchical Reinforcement Learning (HRL), the needs of mobile robots are met. It is possible to construct a path planning model for mobile robots based on neural networks and HRL. In this article, the proposed algorithm is compared with different algorithms in path planning. It underwent a performance evaluation to obtain an optimal learning algorithm system. The optimal algorithm system was tested in different environments and scenarios to obtain optimal learning conditions, thereby verifying the effectiveness of the proposed algorithm. Deep Deterministic Policy Gradient (DDPG), a path planning algorithm for mobile robots based on neural networks and hierarchical reinforcement learning, performed better in all aspects than other algorithms. Specifically, when compared with Double Deep Q-Learning (DDQN), DDPG has a shorter path planning time and a reduced number of path steps. When introducing an influence value, this algorithm shortens the convergence time by 91% compared with the Q-learning algorithm and improves the smoothness of the planned path by 79%. The algorithm has a good generalization effect in different scenarios. These results have significance for research on guiding, the precise positioning, and path planning of mobile robots.

16.
Bioorg Med Chem ; 28(5): 115325, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31982241

RESUMO

G-Quadruplex DNAs, formed by G-rich DNA sequences in human genes, are promising targets for design of cancer drugs. In this study, two naphthalimide substituted styryl dyes with different sizes of aromatic groups were synthesized. The spectral analysis showed that the dye X-2 with a large aromatic group formed aggregates in buffer solution displaying very weak fluorescence intensity, and disaggregated in the presence of G-Quadruplex DNAs with large intensity enhancements (up to ~1800 fold). Moreover, X-2 displayed good selectivity to G-Quadruplex DNAs. In contrast, dye X-3 with the smaller aromatic group had much lower fluorescence enhancements and poor selectivity to G-Quadruplex DNAs, suggesting that the suitably sized aromatic ring was essential for the interaction with G-Quadruplex. Further binding studies suggested that X-2 mainly bound on G-quartet surface through end-stacking mode. Cytotoxicity assay showed that both of the two dyes showed good anti-proliferative activities against the cancer cell lines and less cytotoxicity in non-malignant cell lines, which were better than a standard drug 5-fluorouracil. In addition, living cell imaging was also studied and demonstrated the potential applications of the new dye X-2 in bioassays and cell imaging.


Assuntos
Antineoplásicos/farmacologia , DNA/química , Corantes Fluorescentes/farmacologia , Naftalimidas/farmacologia , Estirenos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Sítios de Ligação/efeitos dos fármacos , Bovinos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Quadruplex G/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Naftalimidas/síntese química , Naftalimidas/química , Relação Estrutura-Atividade , Estirenos/síntese química , Estirenos/química
17.
Polymers (Basel) ; 11(12)2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31817825

RESUMO

High breakdown strength and low dielectric loss are necessary for the outdoor insulator using silicone rubber (SR) composites. In this work, polydopamine coated mica (mica-PDA) was synthesized via bioinspired dopamine self-polymerization, and mica-PDA-filled SR composite (SR/mica-PDA-VTMS) was prepared using vinyl tri-methoxysilane (VTMS) as a silane coupling agent which serves as the molecular bridges between the organic rubber and the inorganic filler. The SR/mica-PDA-VTMS composite demonstrated dense and uniform morphology where the filler was well dispersed. Due to the strong interfacial interactions between filler and rubber, the SR/mica-PDA-VTMS composite exhibits much lower dielectric loss compared to the other mica-filled SR composites, which was comparable to the prepared alumina-tri-hydrate-filled SR composites. Moreover, the breakdown strength of ~31.7 kV/mm and tensile strength of 5.4 MPa were achieved for the SR/mica-PDA-VTMS composite, much higher than those of the other as-prepared SR composites.

18.
PLoS One ; 14(9): e0223101, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31557248

RESUMO

Research has found that preschoolers' imitation demonstrates in-group bias and is guided by behavior efficacy. However, little is known about whether children's sensitivity to behavior efficacy affects their in-group imitation. This study aimed to investigate preschoolers' imitation tendency when group preference and behavior efficacy are in conflict. Participants were 4-year-old (N = 72) and 6-year-old (N = 72) preschoolers in China. They observed two demonstrators (one in-group and one out-group) pressing two different buttons, respectively, to turn on a music box, and were then asked to try it themselves. In the experimental condition, the out-group demonstrator always succeeded, whereas the in-group demonstrator failed half the time. The results showed that more 6-year-old children imitated the less-effective behaviors of the in-group demonstrator, whereas 4-year-old children showed no such inclination. Two control conditions confirmed that children chose to imitate in-group rather than out-group members (Control 1: both in-group and out-group demonstrators succeeded all four times), and could imitate according to efficacy (Control 2: two in-group demonstrators succeeded two and four times, respectively). These results indicated that 6-year-olds faithfully followed the in-group modeled behavior, regardless of behavior efficacy. Results are discussed through the social function of in-group imitative learning.


Assuntos
Comportamento Infantil/psicologia , Comportamento Imitativo , Aprendizagem , Comportamento Social , Criança , Pré-Escolar , China , Feminino , Humanos , Masculino
19.
Sensors (Basel) ; 19(16)2019 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-31405244

RESUMO

The intelligent inspection of power lines and other difficult-to-access structures and facilities has been greatly enhanced by the use of Unmanned Aerial Vehicles (UAVs), which allow inspection in a safe, efficient, and high-quality fashion. This paper analyzes the characteristics of a scene containing power equipment and the operation mode of UAVs. A low-cost virtual scene is created, and a training sample for the power-line components is generated quickly. Taking a vibration-damper as the main object, an assembled detector based on geometrical constraint (ADGC) is proposed and is used to analyze the virtual dataset. The geometric positional relationship is used as the constraint, and the Faster R-CNN, Deformable Part Model (DPM), and Haar cascade classifiers are combined, which allows the features of different classifiers, such as contour, shape, and texture to be fully used. By combining the characteristics of virtual data and real data using UAV images, the power components are detected by the ADGC. The result produced by the detector with relatively good performance can help expand the training set and achieve a better detection model. Moreover, this method can be smoothly transferred to other power-line facilities and other power-line scenarios.

20.
Int J Mol Sci ; 19(12)2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30487393

RESUMO

Mutations in the skeletal muscle-specific CLC-1 chloride channel are associated with the human hereditary disease myotonia congenita. The molecular pathophysiology underlying some of the disease-causing mutations can be ascribed to defective human CLC-1 protein biosynthesis. CLC-1 protein folding is assisted by several molecular chaperones and co-chaperones, including FK506-binding protein 8 (FKBP8). FKBP8 is generally considered an endoplasmic reticulum- and mitochondrion-resident membrane protein, but is not thought to contribute to protein quality control at the cell surface. Herein, we aim to test the hypothesis that FKBP8 may regulate CLC-1 protein at the plasma membrane. Surface biotinylation and subcellular fractionation analyses reveal that a portion of FKBP8 is present at the plasma membrane, and that co-expression with CLC-1 enhances surface localization of FKBP8. Immunoblotting analyses of plasma membrane proteins purified from skeletal muscle further confirm surface localization of FKBP8. Importantly, FKBP8 promotes CLC-1 protein stability at the plasma membrane. Together, our data underscore the importance of FKBP8 in the peripheral quality control of CLC-1 channel.


Assuntos
Membrana Celular/metabolismo , Canais de Cloreto/metabolismo , Proteínas de Ligação a Tacrolimo/metabolismo , Complexo de Golgi/metabolismo , Células HEK293 , Humanos , Proteínas de Membrana/metabolismo , Músculo Esquelético/metabolismo , Estabilidade Proteica
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