Small extracellular vesicles derived from human mesenchymal stem cells prevent Th17-dominant neutrophilic airway inflammation via immunoregulation on Th17 cells.

Type 17 helper T cells (Th17)-dominant neutrophilic airway inflammation is critical in the pathogenesis of steroid-resistant airway inflammation such as severe asthma. Small extracellular vesicles (sEV) derived from human mesenchymal stem cells (MSCs) display extensive therapeutic effects and advantages in many diseases. However, the role of MSC-sEV in Th17-dominant neutrophilic airway inflammation and the related mechanisms are still poorly studied. Here we found that MSC-sEV significantly alleviated the infiltration of inflammatory cells in peribronchial interstitial tissues and reduced levels of inflammatory cells, especially neutrophils, in bronchoalveolar lavage fluids (BALF) of mice with neutrophilic airway inflammation. Consistently, MSC-sEV significantly decreased levels of IL-17A in BALF and Th17 in lung tissues. Furthermore, we found that labelled MSC-sEV were taken up by human CD4+ T cells most obviously at 12 h after incubation, and distributed mostly in mouse lungs. More importantly, potential signaling pathways involved in the MSC-sEV mediated inhibition of Th17 polarization were found using RNA sequencing. Using Western blot, JAK2-STAT3 pathway was identified as an important role in the inhibition of Th17 polarization by MSC-sEV. We found that proteins in MSC-sEV were mostly involved in the therapeutic effects of MSC-sEV. In total, our study suggested that MSC-sEV could be a potential therapeutic strategy for the treatment of neutrophilic airway inflammation.

Mesenchymal stem cells overexpressing interleukin-10 prevent allergic airway inflammation.

BACKGROUNDS: Allergic airway inflammation is prevalent worldwide and imposes a considerable burden on both society and affected individuals. This study aimed to investigate the therapeutic advantages of mesenchymal stem cells (MSCs) overexpressed interleukin-10 (IL-10) for the treatment of allergic airway inflammation, as both IL-10 and MSCs possess immunosuppressive properties. METHODS: Induced pluripotent stem cell (iPSC)-derived MSCs were engineered to overexpress IL-10 via lentiviral transfection (designated as IL-10-MSCs). MSCs and IL-10-MSCs were administered intravenously to mice with allergic inflammation induced by ovalbumin (OVA), and the features of allergic inflammation including inflammatory cell infiltration, Th cells in the lungs, and T helper 2 cell (Th2) cytokine levels in bronchoalveolar lavage fluid (BALF) were examined. MSCs and IL-10-MSCs were co-cultured with CD4+ T cells from patients with allergic rhinitis (AR), and the levels of Th2 cells and corresponding type 2 cytokines were studied. RNA-sequence was performed to further investigate the potential effects of MSCs and IL-10-MSCs on CD4+ T cells. RESULTS: Stable IL-10-MSCs were established and characterised by high IL-10 expression. IL-10-MSCs significantly reduced inflammatory cell infiltration and epithelial goblet cell numbers in the lung tissues of mice with allergic airway inflammation. Inflammatory cell and cytokine levels in BALF also decreased after the administration of IL-10-MSCs. Moreover, IL-10-MSCs showed a stronger capacity to inhibit the levels of Th2 after co-cultured with CD4+ T cells from patients with AR. Furthermore, we elucidated lower levels of IL-5 and IL-13 in IL-10-MSCs treated CD4+ T cells, and blockade of IL-10 significantly reversed the inhibitory effects of IL-10-MSCs. We also reported the mRNA profiles of CD4+ T cells treated with IL-10-MSCs and MSCs, in which IL-10 played an important role. CONCLUSION: IL-10-MSCs showed positive effects in the treatment of allergic airway inflammation, providing solid support for the use of genetically engineered MSCs as a potential novel therapy for allergic airway inflammation.

The causality between gut microbiome and liver cirrhosis: a bi-directional two-sample Mendelian randomization analysis.

Background and aim: Previous studies have reported an association between gut microbiota and cirrhosis. However, the causality between intestinal flora and liver cirrhosis still remains unclear. In this study, bi-directional Mendelian randomization (MR) analysis was used to ascertain the potential causal effect between gut microbes and cirrhosis. Methods: Large-scale Genome Wide Association Study (GWAS) data of cirrhosis and gut microbes were obtained from FinnGen, Mibiogen consortium, and a GWAS meta-analysis of Alcoholic cirrhosis (ALC). Two-sample MR was performed to determine the causal relationship between gut microbiota and cirrhosis. Furthermore, a bi-directional MR analysis was employed to examine the direction of the causal relations. Result: In MR analysis, we found that 21 gut microbiotas were potentially associated with cirrhosis. In reverse MR analysis, 11 gut microbiotas displayed potentially associations between genetic liability in the gut microbiome and cirrhosis. We found that the family Lachnospiraceae (OR: 1.59, 95% CI:1.10-2.29) might be harmful in cirrhotic conditions (ICD-10: K74). Furthermore, the genus Erysipelatoclostridium might be a protective factor for cirrhosis (OR:0.55, 95% CI:0.34-0.88) and PBC (OR:0.68, 95% CI:0.52-0.89). Combining the results from the MR analysis and reverse MR analysis, we firstly identified the Genus Butyricicoccus had a bi-directional causal effect on PBC (Forward: OR: 0.37, 95% CI:0.15-0.93; Reverse: OR: 1.03, 95% CI:1.00-1.05). Conclusion: We found a new potential causal effect between cirrhosis and intestinal flora and provided new insights into the role of gut microbiota in the pathological progression of liver cirrhosis.

Prediction of In-Flight Particle Properties and Mechanical Performances of HVOF-Sprayed NiCr-Cr3C2 Coatings Based on a Hierarchical Neural Network.

High-velocity oxygen fuel (HVOF) spraying is a promising technique for depositing protective coatings. The performances of HVOF-sprayed coatings are affected by in-flight particle properties, such as temperature and velocity, that are controlled by the spraying parameters. However, obtaining the desired coatings through experimental methods alone is challenging, owing to the complex physical and chemical processes involved in the HVOF approach. Compared with traditional experimental methods, a novel method for optimizing and predicting coating performance is presented herein; this method involves combining machine learning techniques with thermal spray technology. Herein, we firstly introduce physics-informed neural networks (PINNs) and convolutional neural networks (CNNs) to address the overfitting problem in small-sample algorithms and then apply the algorithms to HVOF processes and HVOF-sprayed coatings. We proposed the PINN and CNN hierarchical neural network to establish prediction models for the in-flight particle properties and performances of NiCr-Cr3C2 coatings (e.g., porosity, microhardness, and wear rate). Additionally, a random forest model is used to evaluate the relative importance of the effect of the spraying parameters on the properties of in-flight particles and coating performance. We find that the particle temperature and velocity as well as the coating performances (porosity, wear resistance, and microhardness) can be predicted with up to 99% accuracy and that the spraying distance and velocity of in-flight particles exert the most substantial effects on the in-flight particle properties and coating performance, respectively. This study can serve as a theoretical reference for the development of intelligent HVOF systems in the future.

Research on path planning of autonomous manganese nodule mining vehicle based on lifting mining system.

Deep-sea manganese nodules are abundant in the ocean, with high exploitation potential and commercial value, and have become mineral resources that coastal countries compete to develop. The pipeline-lifting mining system is the most promising deep-sea mining system at present. A deep-sea mining vehicle is the core equipment of this system. Mining quality and efficiency rely on mining vehicles to a great extent. According to the topographic and geomorphic environmental characteristics of deep-sea manganese nodules at the bottom of the ocean, a new deep-sea mining system based on an autonomous manganese nodule mining vehicle is proposed in this paper. According to the operating environment and functional requirements of the seabed, a new mining method is proposed, and the global traverse path planning research of the autonomous manganese nodule mining vehicle based on this mining method is carried out. The arc round-trip acquisition path planning method is put forward, and the simulation verification shows that the method effectively solves the problems of low efficiency of mining vehicle traversing acquisition and obstacle avoidance.

Numerical and Experimental Investigations of Cold-Sprayed Basalt Fiber-Reinforced Metal Matrix Composite Coating.

The aluminum-basalt fiber composite coating was prepared for the first time with basalt fiber as the spraying material by cold-spraying technology. Hybrid deposition behavior was studied by numerical simulation based on Fluent and ABAQUS. The microstructure of the composite coating was observed on the as-sprayed, cross-sectional, and fracture surfaces by SEM, focusing on the deposited morphology of the reinforcing phase basalt fibers in the coating, the distribution of basalt fibers, and the interaction between basalt fibers and metallic aluminum. The results show that there are four main morphologies of the basalt fiber-reinforced phase, i.e., transverse cracking, brittle fracture, deformation, and bending in the coating. At the same time, there are two modes of contact between aluminum and basalt fibers. Firstly, the thermally softened aluminum envelops the basalt fibers, forming a seamless connection. Secondly, the aluminum that has not undergone the softening effect creates a closed space, with the basalt fibers securely trapped within it. Moreover, the Rockwell hardness test and the friction-wear test were conducted on Al-basalt fiber composite coating, and the results showed that the composite coating has high wear resistance and high hardness.

Efficacy and Safety of Drug-Eluting Beads Bronchial Arterial Chemoembolization in Treating Patients with Lung Cancer Who Were Complicated with Hemoptysis.

Background: This study explored the effectiveness and safety of drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) in patients with lung cancer who were complicated with hemoptysis. Materials and Methods: In total, 11 patients with lung cancer who were complicated with hemoptysis and underwent DEB-BACE treatment were analyzed. Clinical success was defined as no hemoptysis or reduction of hemoptysis volume >50% after treatment. Hemoptysis recurrence was recorded, and overall survival (OS) was calculated. Results: After DEB-BACE treatment, the clinical and technical success was 100%: in detail, 10 (90.0%) patients presented with no hemoptysis and 1 (9.1%) patient exhibited a reduction of hemoptysis volume >50%. Regarding the prognosis, 1 (9.1%) patient had hemoptysis recurrence at 46 d after DEB-BACE treatment. Furthermore, 4 (36.4%) patients died (1 [9.1%] patient died of nonhemoptysis asphyxia; 1 [9.1%] patient died of massive gastrointestinal hemorrhage; 1 [9.1%] patient died of respiratory failure; and 1 [9.1%] patient died of hemoptysis recurrence). Additionally, the mean OS in total patients was 14.2 (95% confidence interval: 8.2-20.3) months. As to adverse events, 1 (9.1%) patient showed high fever, 2 (18.2%) patients exhibited low fever, and 1 (9.1%) patient suffered from chest pain. Conclusions: DEB-BACE can be considered an effective and safe treatment in treating hemoptysis in patients with lung cancer.

Highly selective and easily regenerated porous fibrous composite of PSF-Na2.1Ni0.05Sn2.95S7 for the sustainable removal of cesium from wastewater.

The removal of 137Cs from radioactive wastewater remains a huge challenge due to the interference of many coexisting ions. Several tin chalcogenides (X2Sn3Y7, XNa, K; YTe, Se, S) were synthesized and screened for highly selective cesium removal from radioactive wastewater. It was found that Na2Sn3S7 showed the best adsorption performance for low cesium concentrations. Especially after nickel doping, the adsorption capacity and thermal stability of the adsorbent were significantly enhanced. Its maximum adsorption capacity reached 436.72 mg·g-1 within only 5 min and adsorption performance kept active in the pH range of 2-12. After being coated with a porous polysulfone (PSF) fiber, the developed PSF-Na2.1Ni0.05Sn2.95S7 was applied to natural complex water with cesium concentration of 17.58 mg·L-1. The separation factors between Cs+ and competitive ions ranged from 625.21 to 13123.21. It is noteworthy that NaNO3 was an efficient regenerating agent and can be easily separated from the CsNO3 mixture for cyclic utilization. Remarkably, only 45 min in each cycle of adsorption and desorption toward cesium was realized, and the adsorption properties hardly decreased even after 50 consecutive cycles. The above advantages make the proposed material an excellent candidate for efficient Cs+ removal and enrichment from wastewater.

Current Implementation Status of Cold Spray Technology: A Short Review.

In recent years, cold spray technology has attracted more and more attentions. After more than 30 years of rapid development, research focus of cold spray technology is gradually shifting from fundamental and theoretical studies to application developments, some of which have been industrialized and mass-produced. In this paper, the characteristics of cold spray technology, cold spray materials perspectives and cold spray system developments were briefly introduced. Besides, the recent developments of cold spray applications in different fields including aerospace, biomedical, energy, electronics, semiconductor fields were discussed. Although cold spray technology is in the early stages of implementation, it has demonstrated a great potential to reduce costs and improve performance. World-wide awareness of ongoing and planned cold spray programs is critical to expand its applications and benefits.

Time-Frequency Distribution Map-Based Convolutional Neural Network (CNN) Model for Underwater Pipeline Leakage Detection Using Acoustic Signals.

Detection technology of underwater pipeline leakage plays an important role in the subsea production system. In this paper, a new method based on the acoustic leak signal collected by a hydrophone is proposed to detect pipeline leakage in the subsea production system. Through the pipeline leakage test, it is found that the radiation noise is a continuous spectrum of the medium and high-frequency noise. Both the increase in pipe pressure and the diameter of the leak hole will narrow the spectral structure and shift the spectrum center towards the low frequencies. Under the same condition, the pipe pressure has a greater impact on the noise; every 0.05 MPa increase in the pressure, the radiation sound pressure level increases by 6-7 dB. The time-frequency images were obtained by processing the acoustic signals using the Ensemble Empirical Mode Decomposition (EEMD) and Hilbert-Huang transform (HHT), and fed into a two-layer Convolutional Neural Network (CNN) for leakage detection. The results show that CNN can correctly identify the degree of pipeline leakage. Hence, the proposed method provides a new approach for the detection of pipeline leakage in underwater engineering applications.

The Analysis of Biomimetic Caudal Fin Propulsion Mechanism with CFD.

In nature, fish not only have extraordinary ability of underwater movement but also have high mobility and flexibility. The low energy consumption and high efficiency of fish propulsive method provide a new idea for the research of bionic underwater robot and bionic propulsive technology. In this paper, the swordfish was taken as the research object, and the mechanism of the caudal fin propulsion was preliminarily explored by analyzing the flow field structure generated by the swing of caudal fin. Subsequently, the influence of the phase difference of the heaving and pitching movement, the swing amplitude of caudal fin, and Strouhal number (St number) on the propulsion performance of fish was discussed. The results demonstrated that the fish can obtain a greater propulsion force by optimizing the motion parameters of the caudal fin in a certain range. Lastly, through the mathematical model analysis of the tail of the swordfish, the producing propulsive force principle of the caudal fin and the caudal peduncle was obtained. Hence, the proposed method provided a theoretical basis for the design of a high-efficiency bionic propulsion system.

Dislocation Evaluation of Fe Twist Grain Boundary Based on Molecular Dynamics.

The grain boundary and dislocation motion characteristics on the atomic scale are significant for the study of material failure mechanisms. In the present work, by theoretical analysis and numerical simulation, the most stable phase of Fe crystal under given conditions is confirmed. Distribution of dislocation potential under different torsion angles is studied for BCC-Fe (001) twist grain boundary. The dislocation motion in Fe (001), Fe (110) and Fe (111) twist grain boundary under tension, compression and shear loading are also investigated.

Damage detection of offshore platforms using acoustic emission analysis.

This paper aims to detect the structure damage in KT type jacket offshore platforms using acoustic emission analysis. Experimental investigation has been implemented to analyze the transmission characteristics, attenuation law, and source localization of the acoustic emission signals. The range of energy attenuation coefficient α and the signal amplitude attenuation law were obtained from experimental data. Hence, the layout of acoustic emission sensors was optimized based on the energy attenuation to achieve online damage monitoring for KT-jacket platforms. In order to validate the performance of the optimized sensor layout, another experimental test was conducted on the designed KT-jacket offshore platform to locate the acoustic emission sources. The test results demonstrate that a positioning error of 8 mm or below can be obtained using the optimized sensor layout, and the number of sensors can be reduced by 80% compared with that of the theoretical layout. As a result, the optimized sensor layout enables efficient and effective damage detection for KT-jacket offshore platforms.

Optimization of phenoxazinone synthase production by response surface methodology and its application in Congo red decolourization

Background: Enzymatic decolourization has been recently proposed as a promising and eco-friendly method for treatment of synthetic dye-contaminated wastewaters. However, the processes require large quantities of enzymes, attracting significant attention in developing efficient methods for mass production of multifunctional enzymes. Several methods such as response surface methodology (RSM) and orthogonal experiment have been applied to optimize the parameters in bioprocesses for enzyme production. Results: In the present study, a laccase-like enzyme, phenoxazinone synthase (PHS) originated from Streptomyces antibioticus was recombinantly expressed in Escherichia coli BL21 (DE3). The production of PHS in E. coli BL21 was optimized by response surface methodology based on Box-Behnken design. A full third-order polynomial model was generated by data analysis with Statistica 8.0 in which the optimal conditions for PHS production were calculated to be 1.525 mM CuSO4 and 16.096 hrs induction at temperature of 29.88ºC. The highest PHS production under optimal conditions was calculated to be 4098.51 U/l using the established model. Average PHS production obtained from actual production processes carried out under the calculated optimal conditions was 4052.00 U/l, very close to the value predicted by the model. Crude PHS was subsequently tested in Congo red decolourization which exhibited a low decolourization rate of 27% without mediator. Several mediators were found to improve PHS-catalyzed Congo red decolourization, with the highest rate of 73.89% obtained with 2,2’-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) as mediator under optimized conditions of 4000 U/l PHS activity, 10 μM ABTS, 100 μM Congo red, and 8 hrs reaction time. Conclusion: Our results indicated that PHS recombinantly produced in E. coli BL21 was a prospective enzyme for decolorizing reactive dye Congo red.

Safety of telaprevir for chronic hepatitis C virus infection: a meta-analysis of randomized controlled trials.

BACKGROUND: Previous studies have reported telaprevir is effective for chronic hepatitis C virus infection, but the safety of a telaprevir-based regimen remains uncertain. OBJECTIVE: A meta-analysis was performed to assess the safety of the addition of telaprevir to a standard regimen of pegylated interferon (peginterferon) plus ribavirin (combination telaprevir with peginterferon plus ribavirin, the TPR group) compared with the standard regimen group (peginterferon plus ribavirin, the PR group). METHODS AND RESULTS: Seven randomized controlled trials involving a total of 2808 patients were included in the meta-analysis. The addition of telaprevir to the standard regimen was associated with a significantly increased risk of serious adverse events compared with the standard PR group (relative risk [RR] = 1.56; 95% confidence interval [CI] 1.21, 2.03; p = 0.0007; I2 = 0%). Telaprevir was also associated with increased risk of treatment discontinuation (RR = 2.10; 95% CI 1.56, 2.83; p < 0.0001; I2 = 42%). In addition, telaprevir was more likely to cause nausea (RR = 1.39; p < 0.0001), diarrhoea (RR = 1.32; p = 0.004), pruritus (RR = 1.56; p = 0.0006), rash (RR = 1.60; p < 0.0001) and anaemia (RR = 1.55; p = 0.007). There was no difference in the other kinds of adverse events between the two groups. Sensitivity analysis further validated the credibility of the above outcomes. CONCLUSION: Our meta-analysis raises safety concerns about the potential for an increased risk of serious adverse events associated with the use of telaprevir among patients with chronic hepatitis C virus infection, and cautious use of telaprevir is warranted.