Identification of polyunsaturated fatty acids as potential biomarkers of osteoarthritis after sodium hyaluronate and mesenchymal stem cell treatment through metabolomics

Introduction: Osteoarthritis (OA) is a prevalent joint disorder worldwide. Sodium hyaluronate (SH) and mesenchymal stem cells (MSCs) are promising therapeutic strategies for OA. Previous studies showed they could improve knee function and clinical symptoms of OA. However, the mechanism of the therapeutic effects on the improvement of OA has not been clearly explained.Methods: In our study, we used a technique called 5-(diisopropylamino)amylamine derivatization liquid chromatography coupled with mass spectrometry to find the metabolites in OA synovial fluid under different treatments.Results and Discussion: After looking into the metabolomics, we discovered that SH and MSC treatment led to the downregulation of ω-6 polyunsaturated fatty acids (PUFAs) and the upregulation of ω-3 PUFAs. Significantly, the contents of 5(S)-HETE, PGA2, PGB2, and PGJ2 were lower in the MSC group than in the SH group after quantification using 5-(diisopropylamino)amylamine derivatization–UHPLC–QQQ-MS. This is the first report on the relationship of 11(S)-HETE, PGA2, PGB2, PGF2β, 11β-PGF2α, and DK-PGE2 with OA. Moreover, the correlation analysis of metabolites and inflammation factors showed the positive association of ω-6 PUFAs with pro-inflammation cytokines, and of ω-3 PUFAs with anti-inflammation cytokines. Our results indicated the therapeutic effect of SH and MSCs in patients with OA. In addition, this reliable metabolic approach could uncover novel biomarkers to treat OA

Shengui Sansheng San Ameliorates Cerebral Energy Deficiency via Citrate Cycle After Ischemic Stroke

Cerebral energy deficiency is a key pathophysiologic cascade that results in neuronal injury and necrosis after ischemic stroke. Shengui Sansheng San (SSS) has been used to treat stroke for more than 300 years. In present study, we investigated the therapeutic efficacy and mechanism of SSS extraction on cerebral energy deficiency post-stroke. In permanent middle cerebral artery occlusion (pMCAo) model of rats, it suggested that SSS extraction in dose-dependent manner improved neurological function, cerebral blood flow (CBF), 18F-2-deoxy-glucose uptake and the density and diameter of alpha smooth muscle actin (α-SMA) positive vasculature in ipsilateral area, as well as decreased infarcted volume. Meanwhile, the metabolomics study in cerebrospinal fluid (CSF) was performed by using 5-(diisopropylamino)amylamine (DIAAA) derivatization-UHPLC-Q-TOF/MS approach. Eighty-eight endogenous metabolites were identified, and mainly involved in citrate cycle, fatty acid biosynthesis, aminoacyl-tRNA biosynthesis, amino acids metabolism and biosynthesis, etc. The remarkable increase of citrate in CSF after treatment with three dosages indicated that the therapeutic mechanism of SSS extraction might be related with citrate cycle. Simultaneously, it showed that high dosage group significantly increased peripheral blood glucose level, the expressions of glucose transporter (GLUT) 1, GLUT3, and monocarboxylic acid transporter 1 (MCT1), which contributed to the transportation of glucose and lactate. By the regulations of phosphorylated pyruvate dehydrogenase E1-alpha (p-PDHA1), acetyl CoA synthetase and citrate synthetase (CS), the levels of citrate and its upstream molecules (pyruvate and acetyl CoA) in peri-infarction zone further enhanced, which ultimately caused the massive yield of adenosine triphosphate (ATP). Our study first demonstrated that SSS extraction could ameliorate cerebral energy deficiency after ischemia by citrate cycle, which is characterized by the enhancements of glucose supply, transportation, utilization, and metabolism

Hypoxic acclimatization training improves the resistance to motion sickness

ObjectiveVestibular provocation is one of the main causes of flight illusions, and its occurrence is closely related to the susceptibility of motion sickness (MS). However, existing training programs have limited effect in improving the resistance to motion sickness. In this study, we investigated the effects of hypoxia acclimatization training (HAT) on the resistance to motion sickness.MethodsHealthy military college students were identified as subjects according to the criteria. MS model was induced by a rotary chair. Experimental groups included control, HAT, 3D roller training (3DRT), and combined training.ResultsThe Graybiel scores were decreased in the HAT group and the 3DRT group and further decreased in the combined training group in MS induced by the rotary chair. Participants had a significant increase in blood pressure after the rotary chair test and a significant increase in the heart rate during the rotary chair test, but these changes disappeared in all three training groups. Additionally, LFn was increased, HFn was decreased, and LF/HF was increased accordingly during the rotary chair test in the control group, but the changes of these three parameters were completely opposite in the three training groups during the rotary chair test. Compared with the control group, the decreasing changes in pupillary contraction velocity (PCV) and pupillary minimum diameter (PMD) of the three training groups were smaller. In particular, the binocular PCV changes were further attenuated in the combined training group.ConclusionOur research provides a possible candidate solution for training military pilots in the resistance to motion sickness

An intelligent weighted clustering algorithm (IWCA) for Ad Hoc

Intelligent management to the large scale Ad Hoc network has already become a kind of trend, and the clustering algorithm is the key. This article examines formula factors and their mutual relations of EWCA algorithm weights. After considering complex external environment of nodes, digging factors of network, it proposes an algorithn that calculates, sets and adjusts these weights by comparing weights, efficent-weights and expecting-weights, so as to fit for all kinds of application environment. The algorithm does not only guarantee the rational and effective weights, but also run in a human friendly manner.E

Discrete Optimization of Internal Part Structure via SLM Unit Structure-Performance Database

The structural optimization of the internal structure of parts based on three-dimensional (3D) printing has been recognized as being important in the field of mechanical design. The purpose of this paper is to present a creation of a unit structure-performance database based on the selective laser melting (SLM), which contains various structural units with different functions and records their structure and performance characteristics so that we can optimize the internal structure of parts directly, according to the database. The method of creating the unit structure-performance database was introduced in this paper and several structural units of the unit structure-performance database were introduced. The bow structure unit was used to show how to create the structure-performance database of the unit as an example. Some samples of the bow structure unit were designed and manufactured by SLM. These samples were tested in the WDW-100 compression testing machine to obtain their performance characteristics. After this, the paper collected all data regarding unit structure parameters, weight, performance characteristics, and other data; and, established a complete set of data from the bow structure unit for the unit structure-performance database. Furthermore, an aircraft part was reconstructed conveniently to be more lightweight according to the unit structure-performance database. Its weight was reduced by 36.8% when compared with the original structure, while the strength far exceeded the requirements

Artificial neural network models for forecasting the combustion and emission characteristics of ethanol/gasoline DFSI engines with combined injection strategy

Ethanol was a viable alternative and renewable fuel for spark ignition engines, and ethanol/gasoline dual-fuel combustion with combined injection strategy can strengthen the benefits of using ethanol in engines. However, delicate calibration and optimization were required for ethanol/gasoline DFSI engines due to their higher control complexity and flexibility. Therefore, Artificial Neural Network (ANN) models were developed to represent the performance of DFSI engines. This study established the architecture for the ANN models of ethanol/gasoline DFSI engines, and the topology of 8-36-24-3, 8-64-70-6, 8-48-48-3, and 8-36-16-2 were suggested for the modeling of performance, combustion characteristics, gaseous and PN emissions, respectively. The non-linear relationship between the core control variables and performance, combustion, and emission characteristics of ethanol/gasoline engines can be accurately mapped by the proposed ANN models. The regression values were within the range of 0.9387–0.9962, and the mean square relative errors were within the range of 0.000184–0.03935 between the ANN predicted and experimentally measured results. Moreover, the ANN models had the advantages of high accuracy, sound model completeness, superior robustness, and satisfied reliability, which were desirable for the calibration and optimization of engines

Achieving enhanced toughness of a nanocomposite coating by lattice distortion at the variable metallic oxide interface

Ceramic coatings are in general a kind of brittle material because they are predominantly made up of ionic crystals that avoid dislocation motion caused by lattice distortion. In this regard, a remarkable toughened ZrO2/MgO nanocomposite coating is obtained by the plasma electrolytic oxidation (PEO) process and in-situ synthesized ZrO2 with quantitative control approach. It is revealed that the toughening behavior of the ZrO2/MgO coating is related to the coordination and diversion of lattice distortion at the metallic oxide interface, which induces distinct dislocation motion at the interface. The semicoherent interface between m-ZrO2 and MgO is verified to act as a buffer to realize toughening of the nanocomposite coating through dislocation slipping induced by lattice coordinated distortion. Simultaneously, significant interfacial lattice distortion transfer and dislocation pinning are discovered at the semicoherent interface between t-ZrO2 and MgO, which are beneficial to toughness enhancement of the nanocomposite coating. The results indicate that the toughening effect occurs along with dislocation slipping and pinning caused by lattice distortion of the ZrO2/MgO semicoherent interface, which enables the toughness of novel nanocomposite coating to reach 2.7 times of the traditional PEO coating.</p

Table1_Exploring the causality between ankylosing spondylitis and atrial fibrillation: A two-sample Mendelian randomization study.XLSX

Objective: To study whether ankylosing spondylitis (AS) has a causal effect on the risk of atrial fibrillation (AF) using two-sample Mendelian randomization (MR) analysis.Methods: Single nucleotide polymorphisms (SNPs) were selected as independent instrumental variables (IVs) from a GWAS study of AS. Summary data from a large-scale GWAS meta-analysis of AF was utilized as the outcome dataset. Inverse-variance weighted (IVW) model was used for the primary analysis. Multiple sensitivity and heterogeneity tests were conducted to confirm the robustness of the results.Results: In total, 18 SNPs were identified as IVs for MR analysis. Five MR methods consistently found that ankylosing spondylitis was not causally associated with atrial fibrillation (IVW: OR = 0.983 (0.894, 1.080), p = 0.718; MR-Egger: OR = 1.190 (0.973, 1.456), p = 0.109; Simple mode: OR = 0.888 (0.718, 1.098), p = 0.287; Weighted mode: OR = 0.989 (0.854, 1.147), p = 0.890; Weight median: OR = 0.963 (0.852, 1.088), p = 0.545). Leave-one-out analysis supported the stability of MR results. Both the MR-Egger intercept and MR-PRESSO method revealed the absence of horizontal pleiotropy.Conclusion: The two-sample MR analysis did not support a causal relationship between AS and the risk of AF.</p