Shorter telomere length in children with autism spectrum disorder is associated with oxidative stress

ObjectiveAutism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder caused by a complex interaction between genetic and environmental risk factors. The balance between antioxidant capacity and oxidative stress (OS) induced free radicals may be crucial during the pathophysiological development of ASD.MethodsIn this study, 96 children with ASD who met the diagnostic and statistical manual of mental disorders were collected, and the number of children in the typical development (TD) group was matched by 1:1. Digital PCR (dPCR) for telomere length (TL) expression in ASD in peripheral blood leukocytes. Urine levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) content were measured by tandem triple quadrupole mass spectrometry and corrected by urinary creatinine levels. The levels of superoxide dismutase (SOD), catalase (CAT), and capacity (AOC) were detected by kits.ResultsThe TL of the ASD group was shorter than the TD group (p < 0.01) and had some accurate predictive significance for the identification of ASD (AUC = 0.632, 95% CI: 0.533–0.710, p = 0.002). Both 8-OHdG content and SOD activity in the ASD group were significantly higher than those in the TD group (p < 0.05). Shortened TL (Monofactor: 2.20 (1.22, 3.96), p = 0.009; Multifactor: 2.22 (1.22, 4.00), p = 0.008) and reduced CAT activity (Monofactor: 2.31 (1.28, 4.17), p = 0.006; Multifactor: 2.31 (1.28, 4.18), p = 0.006) are risk factors for the development of ASD, while reduced 8-OHdG content (Monofactor: 0.29 (0.14, 0.60), p = 0.001; Multifactor: 0.27 (0.13, 0.57), p = 0.001) and reduced SOD activity (Monofactor: 0.55 (0.31, 0.98), p = 0.042; Multifactor: 0.54 (0.30, 0.98), p = 0.042) are protective factors for the development of ASD.ConclusionIn this study, TL and OS were significantly different between the ASD group and the TD group. As guanine-rich telomere sequences were likely damaged by oxygen free radicals, creating OS, which is a factor in the incidence and progression of ASDs. In conclusion, oxidative damage occurs in the bodies of children with ASD, which may lead to sustained disease progression and severe clinical manifestations. We assume that timely supplementation of antioxidants is very likely to be a potential treatment for early intervention in children with ASD. Identification and detection of OS-related biomarkers may contribute to early diagnosis and timely interventions in young patients with ASD

Research on Supporting Method for High Stressed Soft Rock Roadway in Gentle Dipping Strata of Red Shale

Red shale is widely distributed among the deep mine areas of Kaiyang Phosphate Mine, which is the biggest underground phosphate mine of China. Because of the effect of various factors, such as high stress, ground water and so on, trackless transport roadways in deep mine areas were difficult to effectively support for a long time by using traditional supporting design methods. To deal with this problem, some innovative works were carried out in this paper. First, mineral composition and microstructure, anisotropic, hydraulic mechanical properties and other mechanical parameters of red shale were tested in a laboratory to reveal its deformation and failure characteristics from the aspect of lithology. Then, some numerical simulation about the failure process of the roadways in layered red shale strata was implemented to investigate the change regulation of stress and strain in the surrounding rock, according to the real rock mechanical parameters and in-situ stress data. Therefore, based on the composite failure law and existing support problems of red shale roadways, some effective methods and techniques were adopted, especially a kind of new wave-type bolt that was used to relieve rock expansion and plastic energy to prevent concentration of stress and excess deformation. The field experiment shows the superiorities in new techniques have been verified and successfully applied to safeguard roadway stability

Ae-Based Failure Warning Mechanism During Cemented Paste Backfilling: Experimental Investigation

To research the AE warning mechanism of cemented paste backfilling (CPB), the uniaxial compression test with AE monitoring was carried out on CPB. The effects of different moisture content, cement proportion, and loading rate on AE characteristics of CPB were analyzed. And a damage model based on AE is established. The results show that the increase of water content, gypsum content, and loading rate can enhance the ductility of CPB and lengthen the AE warning area. However, the increase of moisture content will lead to the delay of AE signal peak, which is bad for the early warning. With the increase of loading rate, the failure mode of specimens gradually changes from splitting failure to shear failure. The cracks produced under different failure modes can correspond to the peaks of AE signals. The damage model based on AE shows that the damage process of CPB samples can be divided into three stages, linear-exponential-linear. The experimental results can further research the optimal conditions for ae monitoring of backfill, and provide a theoretical basis for ae monitoring and warning of backfill

Development and Application of Gas Production Measurement System of Coal-Rock under Temperature–Pressure Coupling

In this study, a measurement system for gas generation of coal-rock under temperature–pressure coupling was developed by adding gas extraction, collection, and flow-monitoring devices to the original stainless-steel liquid seepage pipeline of an MTS-815 rock triaxial testing machine, which can be used to study the production mechanism of coalbed methane in a real geological environment. The system has the functions of axial loading, confining pressure loading, continuous heating, gas gathering, etc., and has the advantages of good air tightness, high accuracy and stability, long-term loading and heating, and controllable single variables. The preliminary test for the gas production of anthracite in the Shaanxi Formation of the Qinshui Basin under temperature–pressure coupling was carried out by the developed test system. The results show that the test system can provide accurate and effective measurement means for the study of gas production by coal-rock deformation and is expected to provide effective help for the control and exploitation of coalbed methane

A Full-Aperture Image Synthesis Method for the Rotating Rectangular Aperture System Using Fourier Spectrum Restoration

The novel rotating rectangular aperture (RRA) system provides a good solution for space-based, large-aperture, high-resolution imaging tasks. Its imaging quality depends largely on the image synthesis algorithm, and the mainstream multi-frame deblurring approach is sophisticated and time-consuming. In this paper, we propose a novel full-aperture image synthesis algorithm for the RRA system, based on Fourier spectrum restoration. First, a numerical simulation model is established to analyze the RRA system’s characteristics and obtain the point spread functions (PSFs) rapidly. Then, each image is used iteratively to calculate the increment size and update the final restored Fourier spectrum. Both the simulation’s results and the practical experiment’s results show that our algorithm performs well in terms of objective evaluation and time consumption

A Full-Aperture Image Synthesis Method for the Rotating Rectangular Aperture System Using Fourier Spectrum Restoration

The novel rotating rectangular aperture (RRA) system provides a good solution for space-based, large-aperture, high-resolution imaging tasks. Its imaging quality depends largely on the image synthesis algorithm, and the mainstream multi-frame deblurring approach is sophisticated and time-consuming. In this paper, we propose a novel full-aperture image synthesis algorithm for the RRA system, based on Fourier spectrum restoration. First, a numerical simulation model is established to analyze the RRA system’s characteristics and obtain the point spread functions (PSFs) rapidly. Then, each image is used iteratively to calculate the increment size and update the final restored Fourier spectrum. Both the simulation’s results and the practical experiment’s results show that our algorithm performs well in terms of objective evaluation and time consumption

Neurobiological Mechanism of Acupuncture for Relieving Visceral Pain of Gastrointestinal Origin

It is currently accepted that the neural transduction pathways of gastrointestinal (GI) visceral pain include the peripheral and central pathways. Existing research on the neurological mechanism of electroacupuncture (EA) in the treatment of GI visceral pain has primarily been concerned with the regulation of relevant transduction pathways. The generation of pain involves a series of processes, including energy transduction of stimulatory signals in the sensory nerve endings (signal transduction), subsequent conduction in primary afferent nerve fibers of dorsal root ganglia, and transmission to spinal dorsal horn neurons, the ascending transmission of sensory signals in the central nervous system, and the processing of sensory signals in the cerebral cortex. Numerous peripheral neurotransmitters, neuropeptides, and cytokines participate in the analgesic process of EA in visceral pain. Although EA has excellent efficacy in the treatment of GI visceral pain, the pathogenesis of the disease and the analgesic mechanism of the treatment have not been elucidated. In recent years, research has examined the pathogenesis of GI visceral pain and its influencing factors and has explored the neural transduction pathways of this disease

Mirk/Dyrk1B mediates G0/G1 to S phase cell cycle progression and cell survival involving MAPK/ERK signaling in human cancer cells

Abstract Background Mirk/Dyrk1B contributes to G0 arrest by destabilization of cyclin D1 and stabilization of p27kip1 to maintain the viability of quiescent human cancer cells, and it could be negatively regulated by mitogenic-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling. This study was performed to investigate the effect of Mirk/Dyrk1B on cell cycle and survival of human cancer cells involving MAPK/ERK signaling. Methods The correlations between Mirk/Dyrk1B expression and active ERK1/2 detected by western blot in both ovarian cancer and non-small cell lung cancer (NSCLC) cells were analyzed by simple regression. Mirk/Dyrk1B unique phosphopeptides with sites associated with Mirk/Dyrk1B protein were isolated and quantitated by liquid chromatography coupled to tandem mass/mass spectrometry (LC-MS/MS) proteomics analysis. The human cancer cells were treated with small interfering RNAs (siRNAs) and/or U0126, an inhibitor of MEK for indicated duration, followed by investigating the alterations of cell cycle and apoptosis as well as related proteins examined by flow cytometry and Western blot, respectively. Results Our study demonstrated the widely expressed Mirk/Dyrk1B proteins in the human cancer cells were positively correlated with the levels of activated ERK1/2. Moreover, Mirk/Dyrk1B protein expressions consistent with the tyrosine autophosphorylated levels in the human cancer cells were increased by U0126 or growth factor-depleted culture. Conversely, knockdown of Mirk/Dyrk1B by siRNA led to up-regulated activation of c-Raf-MEK-ERK1/2 pathway and subsequent changes in cell cycle proteins (cyclin D1, p27kip1), accompanied by increased growth rate and cells from G0/G1 into S of cell cycle which could be blocked by U0126 in a dose-dependent manner, indicating Mirk/Dyrk1B may sequester MAPK/ERK pathway, and vice versa. Whereas, combined Mirk siRNA and U0126 induced cell apoptosis in the human cancer cells. Conclusions These data together show that Mirk/Dyrk1B mediates cell cycle and survival via interacting with MAPK/ERK signals and simultaneous inhibition of both pathways may be a novel therapeutic target for human cancer.</p