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MOTIVATION: To facilitate the process of tailor-making a deep neural network for exploring the dynamics of genomic DNA, we have developed a hands-on package called ezGeno. ezGeno automates the search process of various parameters and network structures and can be applied to any kind of 1D genomic data. Combinations of multiple abovementioned 1D features are also applicable. RESULTS: For the task of predicting TF binding using genomic sequences as the input, ezGeno can consistently return the best performing set of parameters and network structure, as well as highlight the important segments within the original sequences. For the task of predicting tissue-specific enhancer activity using both sequence and DNase feature data as the input, ezGeno also regularly outperforms the hand-designed models. Furthermore, we demonstrate that ezGeno is superior in efficiency and accuracy compared to the one-layer DeepBind model and AutoKeras, an open-source AutoML package. AVAILABILITY AND IMPLEMENTATION: The ezGeno package can be freely accessed at https://github.com/ailabstw/ezGeno. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Genômica , Software , Genoma , Ligação Proteica , Redes Neurais de ComputaçãoRESUMO
3D soft bioscaffolds have great promise in tissue engineering, biohybrid robotics, and organ-on-a-chip engineering applications. Though emerging three-dimensional (3D) printing techniques offer versatility for assembling soft biomaterials, challenges persist in overcoming the deformation or collapse of delicate 3D structures during fabrication, especially for overhanging or thin features. This study introduces a magnet-assisted fabrication strategy that uses a magnetic field to trigger shape morphing and provide remote temporary support, enabling the straightforward creation of soft bioscaffolds with overhangs and thin-walled structures in 3D. We demonstrate the versatility and effectiveness of our strategy through the fabrication of bioscaffolds that replicate the complex 3D topology of branching vascular systems. Furthermore, we engineered hydrogel-based bioscaffolds to support biohybrid soft actuators capable of walking motion triggered by cardiomyocytes. This approach opens new possibilities for shaping hydrogel materials into complex 3D morphologies, which will further empower a broad range of biomedical applications.
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Robótica , Engenharia Tecidual , Engenharia Tecidual/métodos , Materiais Biocompatíveis/química , Hidrogéis/química , Impressão TridimensionalRESUMO
Highly sensitive detection of microRNAs (miRNAs) is of great significance in early diagnosis of cancers. Here, we develop a palindrome-embedded hairpin structure and its target-catalyzed padlock cyclization for rolling circle amplification, named PHP-RCA for simplicity, which can be applied in label-free ultrasensitive detection of miRNA. PHP-RCA is a facile system that consists of only an oligonucleotide probe with a palindrome-embedded hairpin structure (PHP). The two ends of PHP were extended as overhangs and designed with the complementary sequences of the target. Hence, the phosphorylated PHP can be cyclized by T4 DNA ligase in the presence of the target that serves as the ligation template. This ligation has formed a palindrome-embedded dumbbell-shaped probe (PDP) that allows phi29 polymerase to perform a typical target-primed RCA on PDP by taking miRNA as a primer, resulting in the production of a lengthy tandem repeat. Benefits from the palindromic sequences and hairpin-shaped structure in padlock double-stranded structures can be infinitely produced during the RCA reaction and provide numerous binding sites for SYBR Green I, a double-stranded dye, achieving a sharp response signal for label-free target detection. We have demonstrated that the proposed system exhibits a good linear range from 0.1 fM to 5 nM with a low detection limit of 0.1 fM, and the non-target miRNA can be clearly distinguished. The advantages of high efficiency, label-free signaling, and the use of only one oligonucleotide component make the PHP-RCA suitable for ultrasensitive, economic, and convenient detection of target miRNAs. This simple and powerful system is expected to provide a promising platform for tumor diagnosis, prognosis, and therapy.
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Wildlife is increasingly forced to live in close proximity to humans, resulting in human-wildlife conflict and anthropogenic mortality. Carnivores persisting in human-dominated landscapes respond to anthropogenic threats through fine-scaled spatial and temporal behavioral adjustments. Although crucial for conservation, quantitative information on these adjustments is scarce. Taiwan's endangered leopard cat occurs in rural human-dominated landscapes with a high anthropogenic mortality risk. To survive, the nocturnal leopard cat needs suitable habitats for foraging and safe refuge for resting during daytime hours when human activity peaks. In this study, we tracked seven VHF-collared leopard cats. To determine habitat selection patterns, we compared land use at nighttime locations and daytime resting sites with random points and fine-scaled vegetation characteristics at daytime resting sites with random points. Leopard cats selected natural habitats for nighttime hunting and avoided manmade and, to a lesser extent, agricultural habitats or used them according to availability. For daytime resting, leopard cats selected natural habitats and, to a lesser extent semi-natural habitats, such as unused land and abandoned orchards. Resting sites were preferentially situated in natural habitats, with little visibility (<2 m), shrubs, reed and stones, away from areas with high levels of human activity. This suggests leopard cats use a proactive strategy to avoid human encounters, which was supported by the reduced temporal overlap with humans and domestic dogs on agricultural land. Resting sites were placed ca. 1 km apart, 12.9 ± 0.3 m (mean ± SE) from the patch's edges, in patches with a size of 1.21 ± 0.04 ha (mean ± SE). Our results will assist in identifying and preserving suitable resting habitats to support leopard cat conservation.
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Sepsis is a life-threatening systemic organ dysfunction caused by the host's unregulated response to a widespread bacterial infection. Endothelial injury is a major pathophysiologic symptom of sepsis and is considered a critical factor in promoting the progression of disease severity. ELAV like RNA binding protein 1(ELAVL1) is a ubiquitously expressed RNA-binding protein that may play an important role during sepsis. Nonetheless, the molecular mechanisms of ELAVL1 on endothelial cell damage in sepsis have not been well defined. Here, we aimed to confirm the role of ELAVL1 in sepsis-induced endothelial cell damage using lipopolysaccharide (LPS)-induced zebrafish and endothelial cells (ECs) models. We found that zebrafish larvae treated with LPS exhibited systemic endothelial cell damage, mostly manifested as pericardial edema, curved tail, and impaired angiogenesis. LPS treatments also significantly induced the expression levels of inflammatory cytokines (interleukin-6 (IL-6), IL-8, and tumor necrosis factor (TNF)-α) in vivo. In vitro, we observed the increase of ELAVL1 cytoplasmic translocation with LPS treatment. Mechanistically, targeted disruption of the ELAVL1 gene decreased the expression of TNF-α, IL-6, and IL-8 during induction of sepsis and alleviated LPS-induced blood vessel injury in zebrafish. Taken together, our study indicates that ELAVL1 knockdown may alleviate sepsis-induced endothelial cells injury by suppressing cytokine storm. Our research suggests that inhibition of ELAVL1 could reduce the level of inflammatory cytokine production induced by LPS and protect against endothelial cell injury. ELAVL1 might be a potential therapeutic target to block endothelial cells injury associated with sepsis.
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Interleucina-6 , Sepse , Animais , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Células Endoteliais/metabolismo , Peixe-Zebra/metabolismo , Síndrome da Liberação de Citocina/metabolismo , Interleucina-8/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Sepse/tratamento farmacológicoRESUMO
Karst rocky desertification (KRD) has become one of the most serious ecological and environmental problems in karst areas. At present, mapping KRD with a high accuracy and on a large scale is still a difficult problem in the control of KRD. In this study, a random forest (RF) based on maximum information coefficient and correlation coefficient feature selection is proposed to predict KRD. Nine predictors stood out as feature factors to estimate KRD. Rock exposure was the most important predictor, followed by fractional vegetation cover for the prediction of KRD processes. The kappa and classification accuracy indexes were to evaluate the performance of the model. We recorded overall accuracy rate and kappa index values of 94.7% and 0.92 for the testing datasets respectively. The RF model was then used to predict the KRD in 2001, 2011, 2016, and 2020, and it was found that the KRD in the study area has exhibited a positive trend of improvement. Therefore, the use of multisource remote sensing data combined with the RF model can obtain better prediction results of KRD, thereby providing a new idea for large-scale estimation of the KRD in peak-cluster depression.
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Conservação dos Recursos Naturais , Ecossistema , Conservação dos Recursos Naturais/métodos , Depressão , China , Aprendizado de MáquinaRESUMO
Microrobots are recognized as transformative solutions for drug delivery systems (DDSs) because they can navigate through the body to specific locations and enable targeted drug release. However, their realization is substantially limited by insufficient payload capacity, unavoidable drug leakage/deactivation, and strict modification/stability criteria for drugs. Natural puffballs possess fascinating features that are highly desirable for DDSs, including a large fruitbody for storing spores, a flexible protective cap, and environmentally triggered release mechanisms. This report presents a puffball-inspired microrobotic system which incorporates an internal chamber for loading large drug quantities and spatial drug separation, and a near-infrared-responsive top-sealing layer offering strong drug protection and on-demand release. These puffball-inspired microrobots (PIMs) display tunable loading capacities up to high concentrations and enhanced drug protection with minimal drug leakage. Upon near-infrared laser irradiation, on-demand drug delivery with rapid release efficiency is achieved. The PIMs also demonstrate translational motion velocities, switchable motion modes, and precise locomotion under a rotating magnetic field. This work provides strong proof-of-concept for a DDS that combines the superior locomotion capability of microrobots with the unique characteristics of puffballs, thereby illustrating a versatile avenue for development of a new generation of microrobots for targeted drug delivery.
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Sistemas de Liberação de Medicamentos , Fototerapia , Liberação Controlada de Fármacos , Raios Infravermelhos , LocomoçãoRESUMO
OBJECTIVE: To investigate the expression and clinical significance of F0 ATP synthase C subunit (Csub) in patients with ischemic heart disease (IHD). METHODS: The 101 patients with chest pain admitted to the department of emergency of the People's Hospital of Yuhuan from May 2019 to December 2020 were enrolled, including 59 patients with acute myocardial infarction (AMI) and 42 patients with unstable angina pectoris (UAP). At the same time, 50 age-matched healthy subjects in the health examination center were selected as the healthy control (HC). All patients had completed blood sampling before the intervention of drugs or other intervention measures in the emergency room. The content of serum Csub was detected by enzyme linked immunosorbent assay (ELISA), and the relationship between Csub and clinical characteristics was analyzed. At the same time, the contents of hypersensitivity cardiac troponin T (hs-cTnT) and MB isoenzyme of creatine kinase (CK-MB) in blood were detected by electrochemical luminescence. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the value of Csub, hs-cTnT, and CK-MB in the early diagnosis of IHD. RESULTS: The baseline data such as age, gender, and history of the three groups were balanced. There were significant differences in low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), CK-MB, hs-cTnT and B-type natriuretic peptide (BNP), but there were no significant differences in other biochemical indexes. The Csub content in the AMI group and the UAP group were significantly higher than those in the HC group [8.96% (6.37%, 11.53%), 4.27% (3.23%, 6.49%) vs. 1.56% (1.07%, 2.33%), both P < 0.01]. Moreover, the Csub in the AMI group with more severe myocardial ischemia was higher than UAP group [8.96% (6.37%, 11.53%) vs. 4.27% (3.23%, 6.49%), P < 0.01]. A total of 59 patients with AMI were treated with percutaneous coronary intervention (PCI). According to the median of Csub, AMI patients were subdivided into above-median group (29 cases) and below-median group (30 cases). The results showed that there were no significant differences in the number of coronary artery lesion branches, the number of stent implantation and postoperative medication between the two groups. ROC curve analysis showed that the area under the curve (AUC) and 95% confidence interval (95%CI) of Csub, hs-cTnT and CK-MB in the diagnosis of IHD were 0.98 (0.95-1.00), 0.99 (0.99-1.00), 0.94 (0.89-0.99), respectively. The diagnostic efficacy of Csub was slightly lower than that of hs-cTnT but higher than that of CK-MB. When the cut-off value of Csub was 4.74%, the sensitivity and specificity for the diagnosis of IHD were 100% and 87.0%, respectively. CONCLUSIONS: Csub increased significantly in the serum of IHD patients, and further increased with the severity of ischemia. It can be used as a new diagnostic biomarker for the diagnosis and evaluation of the development of myocardial ischemia.
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Isquemia Miocárdica , Intervenção Coronária Percutânea , Trifosfato de Adenosina , Biomarcadores , Humanos , Sensibilidade e Especificidade , Troponina TRESUMO
The main problem we want to solve contains two subjects: The first one is the patient's pressure due to wired physiological signal estimation. With wireless sensor network technique, patients only need to carry a few small nodes, and then the physiological signal can be transmitted in the air. The other subject of the vital problem is that some protocols, like Bluetooth, provide a peer to peer wireless communication technique, but such peer to peer network may need a complex algorithm to find the best data transmission path. In this study, we use the hierarchy routing as network topology that three-layer architecture contains PAN coordinator, router and device. The study focuses on implementation of a prototype electrocardiography (ECG) system which replaces wired connections between sensor points and a central node with wireless links. Successful implementation of the final system would be of benefit to all involved in the use of ECG as access to and movement of the patient would not be impeded by the physical constraints imposed by the cables. Most aspects of the design would also be portable to other sensor applications, making the work relevant to a vast range of systems where movement of sensors is desirable and constrained by hard-wired links.