As an important task in bioinformatics, protein secondary structure prediction (PSSP) is not only beneficial to protein function research and tertiary structure prediction, but also to promote the ...design and development of new drugs. However, current PSSP methods cannot sufficiently extract effective features. In this study, we propose a novel deep learning model WGACSTCN, which combines Wasserstein generative adversarial network with gradient penalty (WGAN-GP), convolutional block attention module (CBAM) and temporal convolutional network (TCN) for 3-state and 8-state PSSP. In the proposed model, the mutual game of generator and discriminator in WGAN-GP module can effectively extract protein features, and our CBAM-TCN local extraction module can capture key deep local interactions in protein sequences segmented by sliding window technique, and the CBAM-TCN long-range extraction module can further capture the key deep long-range interactions in sequences. We evaluate the performance of the proposed model on seven benchmark datasets. Experimental results show that our model exhibits better prediction performance compared to the four state-of-the-art models. The proposed model has strong feature extraction ability, which can extract important information more comprehensively.
Analyzing the carbon-emission-reduction mechanism from the perspective of air pollution control auditing is of great practical significance for China to implement the dual-carbon strategy. Based on ...the panel data of 30 Chinese provinces from 2004 to 2018, we examine whether and how the auditing of air pollution control has an impact on carbon emission reduction by using multiple regression method and the mediating analysis. Our analyses show that air pollution control auditing can significantly restrain carbon emissions but has no impact on carbon emission intensity. Further research suggests that (1) the bottom-up audit represented by local audit institutions is more effective than the top-down audit represented by the National Audit Office; (2) air pollution control auditing follows a simple and direct method to curb carbon emissions by output reduction, regulation, and shutdown, rather than promoting technological progress and green transformation of enterprises in a high-quality development mode. Those findings provide an improvement direction for air pollution control auditing to contribute to carbon emission reduction and supply relevant policy references for implementing the dual carbon strategy.
Autologous fat grafting has been widely applied in cosmetic breast augmentation in recent years. However, nontuberculous mycobacteria infection, as one of the multiple complications described in the ...literature, has been less well discussed.
The aims of the study were to report 5 cases of nontuberculous mycobacteria infection after autologous fat injection for the cosmetic breast augmentation and to explore its causes.
In this noncomparative, retrospective, and interventional case series, we identified 5 patients with nontuberculous mycobacteria infection. All patients had a history of previous autologous fat injection into the breast for cosmetic purpose, performed in different plastic facilities.
Five patients developed nontuberculous mycobacteria infection after autologous fat injection for cosmetic breast augmentation and came to our group for treatment. Grafted fat removal through multiple debridement and long-term intravenous and oral antibiotic therapy were required in our cases.
The number of nontuberculous mycobacteria infection after autologous fat injection into the breast is increasing. Surgeons should be aware of the complication, which rarely manifests during the procedure itself. Strict aseptic principles should be obeyed throughout the surgery.
With the widespread development of chest computed tomography (CT), the detection rate of pulmonary nodules has increased; therefore, the classification of benign vs. malignant nodules has become a ...common problem in the clinic. MicroRNA, a potential tool, is expected to become a good choice for diagnosing and studying the occurrence and development of diseases through the vector of bronchoalveolar lavage fluid extracellular vesicles (BALF-EVs). In this study, radial endobronchial ultrasound (R-EBUS) was used to locate pulmonary nodules in patients. BALF was obtained, EVs were isolated, and small RNA sequencing was performed to screen differentially expressed miRNAs between benign and malignant pulmonary nodules. The binding targets and underlying mechanisms of the differentially expressed miRNAs were verified by in vitro and in vivo experiments. R-EBUS localization and sampling was used to obtain BALF, and EVs were successfully isolated and characterized. Differentially expressed miRNAs in BALF-EVs of patients with benign vs. malignant pulmonary nodules were screened by high-throughput small RNA sequencing. A new miRNA, miR-1246b, was identified. We found that FGF14 was the binding target of miR-1246b by luciferase assay. Subsequent mechanistic studies showed that miR-1246b inhibited the expression of FGF14 in lung cancer cells, further leading to ERK phosphorylation and epithelial-to-mesenchymal transition (EMT), which ultimately contributed to lung cancer cell proliferation, migration and invasion. In summary, our study demonstrates that the detection of miRNAs in BALF-EVs, a means of liquid biopsy, could assist in distinguishing malignant nodules from benign nodules. miR-1246b, which was extracted from BALF-EVs, targets FGF14 to promote lung cancer cell proliferation, migration and invasion.
TrkB as a potential synaptic and behavioral tag Lu, Yuan; Ji, Yuanyuan; Ganesan, Sundar ...
The Journal of neuroscience,
2011-Aug-17, 2011-08-17, 20110817, Letnik:
31, Številka:
33
Journal Article
Recenzirano
Odprti dostop
Late-phase long-term potentiation (L-LTP), a cellular model for long-term memory (LTM), requires de novo protein synthesis. An attractive hypothesis for synapse specificity of long-term memory is ..."synaptic tagging": synaptic activity generates a tag, which "captures" the PRPs (plasticity-related proteins) derived outside of synapses. Here we provide evidence that TrkB, the receptor of BDNF (brain-derived neurotrophic factor), may serve as a "synaptic tag." TrkB is transiently activated by weak theta-burst stimulation (TBS) that induces only early-phase LTP (E-LTP). This TrkB activation is independent of protein synthesis, and confined to stimulated synapses. Induction of L-LTP by strong stimulation in one synaptic pathway converts weak TBS-induced E-LTP to L-LTP in a second, independent pathway. Transient inhibition of TrkB around the time of weak TBS to the second pathway diminished L-LTP in that pathway without affecting the first one. Behaviorally, weak training, which induces short-term memory (STM) but not LTM, can be consolidated into LTM by exposing animals to novel but not familiar environment 1 h before training. Inhibition of TrkB during STM training blocked such consolidation. These results suggest TrkB as a potential tag for synapse-specific expression of L-LTP and LTM.
Asthma is a chronic inflammatory disease, characterized by airway inflammation, hyperresponsiveness, and bronchial smooth muscle contraction. Qingfei Xiaoyan Wan (QFXYW), a traditional Chinese ...formula, has been shown to exert anti-asthma effects and immune response in multiple diseases.
In this study, we evaluated the therapeutic mechanism of QFXYW in the suppression of allergic asthma by integrating of transcriptomics and system pharmacology.
BALB/c mice were sensitized with ovalbumin (OVA) to establish the allergic asthma model, and its success was confirmed with behavioral observations. Lung histopathological analysis, inflammatory pathology scores, transcription factors were used to evaluate the effects of QFXYW on allergic asthma. The therapeutic mechanism of QFXYW in treating allergic asthma through integrated transcriptomics and system pharmacology was then determined: hub genes were screened out by topological analysis and functional enrichment analysis were performed to identify key signaling pathway. Subsequently, quantitative RP-PCR and protein array were performed to detect the mRNA of hub genes and to predict the key pathway in OVA-induced allergic asthma, respectively.
Our results demonstrated that QFXYW could significantly attenuate inflammatory cell infiltration, mucus secretion, and epithelial damage. The transcriptomics analysis found the six hub genes with the highest values- CXCL10, CXCL2, CXCL1, IL-6, CCL-5, and CCL-4 were screened out. Functional enrichment analysis showed that the differentially expressed genes (DEGs) were mainly enriched in the inflammatory response and cytokine signaling pathway. Moreover, the quantitative RT-PCR verification experiment found the CXCL2 and CXCL1 were significantly suppressed after treatment with QFXYW. The results of protein array showed that QFXYW inhibited the multi-cytokines of OVA-induced allergic asthma via cytokine signaling pathway.
QFXYW may have mediated OVA-induced allergic asthma mainly through the hub genes CXCL2, CXCL1, and the cytokine signaling pathway. This finding will offer a novel strategy to explore effective and safe mechanism of Traditional Chinese Medicine (TCM) formula to treat allergic asthma.
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•Traditional Chinese formula Qingfei Xiaoyan Wan (QFXYW) shows anti-asthma effects.•QFXYW inhibits the multi-cytokines of asthma via the cytokine signaling pathway.•Hub genes CXCL2, CXCL1 are significantly suppressed by QFXYW.•It presents the possibility for development of new safe drugs for allergic asthma.
Cell-free protein synthesis has been developed as a critical platform in synthetic biology. Unlike the cell-based synthesis system, cell-free system activates transcriptional and translational ...mechanisms in vitro, and can control protein synthesis by artificially adding components or chemicals. However, the control method puts forward higher requirements in terms of accurate and non-toxic control, which cannot be achieved by chemical substances. For cell-free system, physical signal is a kind of ideal spatiotemporal control approach to replace chemical substances, realizing high accuracy with little side effect. Here we review the methods of using physical signals to control gene expression in cell-free systems, including studies based on light, temperature, electric field, and magnetic force. The transfer of these switches into cell-free system further expands the flexibility and controllability of the system, thus further expanding the application capability of cell-free systems. Finally, existing problems such as signal source and signal transmission are discussed, and future applications in pharmaceutical production, delivery and industrial production are further looked into.
Reinforced cellular responses to endoplasmic reticulum (ER) stress are caused by a variety of pathological conditions including cancers. Human rhomboid family-1 protein (RHBDF1), a multiple ...transmembrane protein located mainly on the ER, has been shown to promote cancer development, while the binding immunoglobulin protein (BiP) is a key regulator of cellular unfolded protein response (UPR) for the maintenance of ER protein homeostasis. In this study, we investigated the role of RHBDF1 in maintaining ER protein homeostasis in breast cancer cells. We showed that deleting or silencing RHBDF1 in breast cancer cell lines MCF-7 and MDA-MB-231 caused marked aggregation of unfolded proteins in proximity to the ER. We demonstrated that RHBDF1 directly interacted with BiP, and this interaction had a stabilizing effect on the BiP protein. Based on the primary structural motifs of RHBDF1 involved in BiP binding, we found a pentapeptide (PE5) targeted BiP and inhibited BiP ATPase activity. SPR assay revealed a binding affinity of PE5 toward BiP (K
= 57.7 μM). PE5 (50, 100, 200 μM) dose-dependently promoted ER protein aggregation and ER stress-mediated cell apoptosis in MCF-7 and MDA-MB-231 cells. In mouse 4T1 breast cancer xenograft model, injection of PE5 (10 mg/kg, s.c., every 2 days for 2 weeks) significantly inhibited the tumor growth with markedly increased ER stress and apoptosis-related proteins in tumor tissues. Our results suggest that the ability of RHBDF1 to maintain BiP protein stability is critical to ER protein homeostasis in breast cancer cells, and that the pentapeptide PE5 may serve as a scaffold for the development of a new class of anti-BiP inhibitors.
Summary
Genomics studies in wild species of wheat have been limited due to the lack of references; however, new technologies and bioinformatics tools have much potential to promote genomic research. ...The wheat–Haynaldia villosa translocation line T6VS·6AL has been widely used as a backbone parent of wheat breeding in China. Therefore, revealing the genome structure of translocation chromosome 6VS·6AL will clarify how this chromosome formed and will help to determine how it affects agronomic traits. In this study, chromosome flow sorting, NGS sequencing and Chicago long‐range linkage assembly were innovatively used to produce the assembled sequences of 6VS·6AL, and gene prediction and genome structure characterization at the molecular level were effectively performed. The analysis discovered that the short arm of 6VS·6AL was actually composed of a large distal segment of 6VS, a small proximal segment of 6AS and the centromere of 6A, while the collinear region in 6VS corresponding to 230–260 Mb of 6AS‐Ta was deleted when the recombination between 6VS and 6AS occurred. In addition to the molecular mechanism of the increased grain weight and enhanced spike length produced by the translocation chromosome, it may be correlated with missing GW2‐V and an evolved NRT‐V cluster. Moreover, a fine physical bin map of 6VS was constructed by the high‐throughput developed 6VS‐specific InDel markers and a series of newly identified small fragment translocation lines involving 6VS. This study will provide essential information for mining of new alien genes carried by the 6VS·6AL translocation chromosome.
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