Highlights • Discussing several key characters of lncRNAs to well understand the lncRNAs. • Broad functions of lncRNAs are more adapted to explain the complexity of CNS. • lncRNAs in ...neurodegenerative disease have the potential as therapeutic targets.
In recent years, long noncoding RNAs (lncRNAs) have been shown to have critical roles in a broad range of cell biological processes. However, the activities of lncRNAs during ischemic stroke remain ...largely unknown. In this study, we carried out a genome-wide lncRNA microarray analysis in rat brains with ischemia/reperfusion (I/R) injury. The results revealed the differential expression of a subset of lncRNAs. Through the construction of lncRNA-mRNA co-expression networks, we identified lncRNA-N1LR as a novel I/R-induced lncRNA. The functions of lncRNA-N1LR were assessed by silencing and overexpressing this lncRNA in vitro and in vivo. We found that lncRNA-N1LR enhanced cell cycle progression and cell proliferation, and inhibited apoptosis in N2a cells subjected to in vitro ischemia (oxygen-glucose deprivation/reoxygenation, OGD/R). Furthermore, we showed that lncRNA-N1LR reduced neuronal apoptosis and neural cell loss in I/R-induced mouse brains. Mechanistically, we discovered that lncRNA-N1LR promoted neuroprotection probably through the inhibition of
p53
phosphorylation on serine 15 in a manner that was independent of its location-associated gene
Nck1
. In summary, our results indicated that lncRNA-N1LR promoted neuroprotection against ischemic stroke probably by inactivating
p53
. Thus, we propose that lncRNA-N1LR may serve as a potential target for therapeutic intervention following ischemic brain injury.
Radiotherapy is essential to treat breast cancer and microRNA (miRNA) miR-200c is considered as a radiosensitizer of breast cancer. However, the molecular mechanisms by which miR-200c regulates ...radiosensitivity remain largely unknown. In the present study, we showed that induction of miR-200c led to widespread alteration in long noncoding RNA (lncRNA) expression in breast cancer cells. We identified lncRNA LINC02582 as a target of miR-200c. Inhibition of LINC02582 expression increased radiosensitvity, while overexpression of LINC02582 promoted radioresistance. Mechanistically, LINC02582 interacts with deubiquitinating enzyme ubiquitin specific peptidase 7 (USP7) to deubiquitinate and stabilize checkpoint kinase 1 (CHK1), a critical effector kinase in DNA damage response, thus promoting radioresistance. Furthermore, we detected an inverse correlation between the expression of miR-200c vs. LINC02582 and CHK1 in breast cancer samples. These findings identified LINC02582 as a downstream target of miR-200c linking miR-200c to CHK1, in which miR-200c increases radiosensitivity by downregulation of CHK1.
Radiotherapy is one of the standard treatments for glioma patients; however, its clinical efficacy is limited by radioresistance. We identified a mechanism of such resistance mediated by linc-RA1 ...(radioresistance-associated long intergenic noncoding RNA 1). Linc-RA1 was upregulated in radioresistant glioma cells and glioma tissue samples, compared with radiosensitive cells and nontumor tissues. Linc-RA1 was associated with inferior overall survival and advanced clinical stage of glioma. Linc-RA1 promoted glioma radioresistance in vitro and in vivo. Mechanistically, linc-RA1 stabilized the level of H2B K120 monoubiquitination (H2Bub1) by combining with H2B and inhibiting the interaction between H2Bub1 and ubiquitin-specific protease 44 (USP44), which inhibited autophagy, thus contributing to glioma radioresistance. These results reveal that linc-RA1-mediated autophagy is a key mechanism of radioresistance and is an actionable target for improving radiotherapy efficacy in patients with glioma.
In response to the unclear impact of header vibration on cutting performance (stalk cutting quality and cutting energy consumption) during field operations of industrial hemp harvesters, this study ...utilized a vibration recorder to collect information on header vibration during the operation of industrial hemp harvesters. Through data processing, the dominant range for the resonant frequency and amplitude of the cutting platform is primarily concentrated between 5–45 Hz and 0–35 mm, respectively. Using numerical simulation techniques, a quadratic orthogonal rotation combination experiment was conducted with vibration frequency and amplitude as experimental factors and stalk cutting quality and cutting energy consumption as indicators. Regression equations were established to reveal the relationships between indicators and factors, elucidating the influence of each factor and its interactions on the indicators. Specifically, for the crack length indicator, the amplitude has a highly significant influence on the model, and there is a significant interaction effect between vibration frequency and amplitude on the model. As for the cutting energy consumption indicator, frequency and the interaction between frequency and amplitude significantly affect the model, while amplitude has an extremely significant impact on the model. Through comprehensive fuzzy evaluation, the optimal vibration parameter combination satisfying comprehensive cutting performance indicators was determined as a vibration frequency of 37.86 Hz and an amplitude of 5.34 mm. Furthermore, the reliability of the model has been further validated. This research can provide a reference for improving the field performance of industrial hemp harvesters.
Hexapod robots have attracted attention for their excellent terrain adaptabilities. When a robot walks on soft soil, dynamic subsidence and slippage greatly reduce its walking performance. The ...influence of foot’s shape is usually ignored or simply studied without considering the multibody dynamics of the robot. This study is focused on the influence of the foot shape on the walking performance of a robot by coupling the sinkage with multibody dynamics. A composite contact model based on the Bekker, spring-damping, and Janosi-Hanamoto models was used to model the interaction of the robot and soft soil. Non-uniform rational B-spline (NURBS) surface and mesh were used to describe the geometries of foot and soft soil, respectively. The influences of three foot shapes on the sinkage and walking stability of the robot were analyzed by comparsion. The improved X-shaped foot reduced the robot’s sinkage and improved its walking stability.
The excellent mechanical properties of graphyne (GY) have made it an appealing candidate in the field of impact protection. We assessed the deformation mechanisms of monolayer GY nanosheets of ...different morphologies, including α-GY, β-GY, γ-GY and 6612-GY, under supersonic-velocity impacts (from 1 to 6 km/s) based on in silico studies. Generally, cracks initiate at the geometry center and the nanosheet experiences significant out-of-plane deformation before the propagation of cracks. Tracking the atomic von Mises stress distribution, it is found that its cumulative density function has a strong correlation with the magnitude of the Young's modulus of the GYs. For nanosheets with a higher Young's modulus, it tends to transfer momentum at a faster rate. Thus, a better energy dissipation or delocalization is expected during impact. This study provides a fundamental understanding of the deformation and penetration mechanisms of monolayer GY nanosheets under impact, which is crucial in order to facilitate their emerging applications for impact protection.
The epidermal growth factor receptor (EGFR) is an important anti-tumor target. The development of novel molecular-targeted anti-tumor drugs that can target the interior of tumor cells and ...specifically silence EGFR expression is valuable and promising. In this work, a promising anti-tumor conjugate comprising methoxy-modified EGFR siRNA and cyclic arginine-glycine-aspartic acid (cRGD) peptides, which selectively bind to αvβ3 integrins, was synthesized and examined. To prepare cRGD-EGFR siRNA (cRGD-siEGFR), cRGD was covalently conjugated to the 5′-end of an siRNA sense strand using a thiol-maleimide linker. The cellular uptake and cytotoxicity of cRGD-siEGFR in vitro were tested using an αvβ3-positive U87MG cell line. In vivo bio-distribution, anti-tumor activity, immunogenicity and toxicity were investigated in a nude mouse tumor model through repeated i.v. administration of cRGD-siEGFR (7 times over a 48 h interval). Analyses of in vitro data showed that cRGD-siEGFR silenced EGFR expression effectively, with high tumor targeting ability. Administration of cRGD-siEGFR to tumor-bearing nude mice led to significant inhibition of tumor growth, obvious reduction of EGFR expression and down-regulation of EGFR mRNA and protein in tumor tissue. Furthermore, serum biochemistry and pathological section evaluation did not indicate any serious toxicity of cRGD-siEGFR in vivo. cRGD-siEGFR is likely a promising candidate with high targeting ability, substantial anti-tumor effects and low toxicity in vitro and in vivo.
In response to the unclear issue of whether the dynamic cutting performance and structural parameters of an industrial hemp blade, which was developed earlier based on the bionic prototype of the ...batocera horsfieldi, can be optimized in actual working conditions, this paper analyzes the effective clamping conditions of a reciprocating double-acting cutting blade for stalks and the cutting motion. To investigate the effect of different structural and motion parameters, as well as their interactions, of the bionic blade on cutting energy consumption, bionic blades with different combinations of tooth pitch and tooth angle were designed. A Box–Behnken response surface method with three factors and three levels was used to design an experimental scheme. Utilizing rigid-flexible coupling numerical simulation technology, numerical simulation experiments were conducted to investigate the cutting performance of industrial hemp stalks using the blade. A regression model for cutting energy consumption was established, and variance analysis indicated that tooth angle, speed ratio, and the interaction between tooth angle and speed ratio had an extremely significant effect on the regression model. The primary and secondary orders of factors affecting cutting energy consumption were determined to be: speed ratio > tooth angle > tooth pitch. Through optimization, the optimal parameter combination was found to be a blade tooth pitch of 6.61 mm, a tooth angle of 30°, and a speed ratio of 1.62. Under these conditions, the cutting energy consumption was 3947.99 mJ. The optimized parameters were verified through numerical simulation cutting experiments, and the results showed that the error compared with the optimization results was only 8.16%. This indicates that the optimization results have high credibility and further verifies the reliability of the model. This study can provide a reference for the development of cutting devices for industrial hemp harvesters and the selection of motion parameters.
Finite element numerical simulations provide a visual and quantitative approach to studying the interaction between rigid mechanical components and flexible agricultural crops. This method is an ...important tool for the design of modern agricultural production equipment. Obtaining accurate material model parameters for crops is a prerequisite for ensuring the reliability and accuracy of numerical simulations. To address the issue of unclear mechanical constitutive model parameters for industrial hemp stalks, this study utilized the theory of composite materials to establish a mechanical constitutive relationship model for industrial hemp stalks. Compression, tensile, and bending tests on different components of the stalk were conducted, using a computer-controlled universal testing machine, to obtain their elastic parameters. Combined with the measured basic material parameters and contact parameters of industrial hemp stalks, a finite-element numerical simulation model of industrial hemp stalks was established. By conducting Plackett–Burman and central composite experiments, it was determined that among the six measured parameters, the anisotropic plane Poisson’s ratio of the phloem and the isotropic plane Poisson’s ratio of the xylem have a significant influence on the maximum bending force of the stalk. Parameter optimization was carried out, using the relative error of the maximum bending force as the optimization objective, resulting in an anisotropic plane Poisson’s ratio of 0.054 for the phloem and an isotropic plane Poisson’s ratio of 0.28 for the xylem of industrial hemp stalks. To validate the accuracy and reliability of the optimized parameters, a numerical simulation was conducted and compared with the physical experiments. The simulated value obtained was 405.81 N while the actual measured value was 392.55 N. The error between the simulated and measured values was only 3.4%, confirming the effectiveness of the model. The precise parameters for the mechanical characteristics of industrial hemp stalk material obtained in this study can provide a parameter basis for future research on the numerical simulation of mechanized industrial hemp harvesting and retting.
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