Porcine platelet lysates exert the efficacy of chondroregeneration and SMAD2-mediated anti-chondrofibrosis on knee osteoarthritis.

BACKGROUND: The lack of self-repairability in cartilage and the formation of fibrocartilage pose significant challenges in treating knee osteoarthritis, and there is still no ideal solution. Autologous platelet lysates have been clinically applied to treat kOA and exert satisfactory cartilage-repair efficacy, but the preparation of human PL brings damage to patients and is hardly standardized. METHODS: In this study, porcine PL was developed to replace hPL, and its chondroregenerative and anti-chondrofibrosis effects were explored. Enzyme-Linked Immunosorbent Assay was applied to qualify the PL products. In vivo, partial-thickness cartilage defects were created on rats as a kOA model, and the von Frey test, histopathological observation, immunohistochemical analysis, and western blot analysis were conducted. In vitro, CCK-8 assay, real-time PCR analysis, immunofluorescence test, and WB analysis were conducted for the mechanism study of pPL. RESULTS: The in vivo data showed that pPL significantly repaired the cartilage defect by improving matrix synthesis and also ameliorated the pain response in the kOA model of rats. In addition, pPL exerted an anti-fibrosis effect on cartilage by suppressing the expressions of COL1, COL3, α-SMA, VIMENTIN, SMAD2, p-SMAD2, and CTGF in cartilage. The in vitro data verified these effects and indicated that the SMAD2 pathway mediated the anti-fibrosis mechanism of pPL. Moreover, the comparable effects between pPL and rat PL indicate that there is no immune rejection from pPL. CONCLUSIONS: This study firstly demonstrated the anti-kOA effects of pPL on both cartilage-repair and anti-chondrofibrosis. It developed pPL as a promising alternative to autologous PL for clinical applications.

Identification of five hub immune genes and characterization of two immune subtypes of osteoarthritis.

Background: Osteoarthritis (OA) is one of the most prevalent chronic diseases, leading to degeneration of joints, chronic pain, and disability in the elderly. Little is known about the role of immune-related genes (IRGs) and immune cells in OA. Method: Hub IRGs of OA were identified by differential expression analysis and filtered by three machine learning strategies, including random forest (RF), least absolute shrinkage and selection operator (LASSO), and support vector machine (SVM). A diagnostic nomogram model was then constructed by using these hub IRGs, with receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and clinical impact curve analysis (CICA) estimating its performance and clinical impact. Hierarchical clustering analysis was then conducted by setting the hub IRGs as input information. Differences in immune cell infiltration and activities of immune pathways were revealed between different immune subtypes. Result: Five hub IRGs of OA were identified, including TNFSF11, SCD1, PGF, EDNRB, and IL1R1. Of them, TNFSF11 and SCD1 contributed the most to the diagnostic nomogram model with area under the curve (AUC) values of 0.904 and 0.864, respectively. Two immune subtypes were characterized. The immune over-activated subtype showed excessively activated cellular immunity with a higher proportion of activated B cells and activated CD8 T cells. The two phenotypes were also seen in two validation cohorts. Conclusion: The present study comprehensively investigated the role of immune genes and immune cells in OA. Five hub IRGs and two immune subtypes were identified. These findings will provide novel insights into the diagnosis and treatment of OA.

Flow Regulation Performance Analysis of Microfluidic Passive Valve for High Throughput Liquid Delivery.

A microfluidic passive valve (MPV) is important for precise flow control, and it determines the reliability of the microfluidic system. In this paper, a novel MPV capable of delivering a constant flow rate independently of inlet pressure changes is proposed. The flow rate of the MPV is adjusted by the difference between the fluid force on the upper surface of the valve core and the spring force. The constant flow rate of the MPV is maintained by automatically changing the size of the gap channel formed by the groove on the valve core and the baffle on the valve body. The nearly constant flow rate of the MPV is 6.26 mL/min, with a variation of 6.5% under the inlet pressure varied from 1.25 kPa to 3.5 kPa. In addition, the flow characteristics of the MPV are analyzed by numerical simulation. With the increase in the inlet pressure, the maximum velocity gradually increases, while the increment of the maximum velocity decreases. In the movement process of the valve core, the region of pressure drop becomes larger. This work has a certain reference value for the design and research of the MPVs with high throughput liquid delivery.

Predictive value of using plasma long non-coding RNAs ANRIL and HOXA11-AS for in-stent restenosis.

In-stent restenosis (ISR) can pose serious challenges for cardiologists following coronary stent implantation. Early identification of patients at high risk of ISR is considered to be effective for its prevention. However, factors that can reliably predict the risk of ISR remain elusive at present. The present study aimed to investigate the possible association between plasma long non-coding RNA (lncRNA) levels and ISR. A total of 410 patients with single-vessel lesion who received drug-eluting stents (DES) were included in the present study. After 12-36 months of follow-up, coronary angiography was performed and ISR was defined as >50% diameter stenosis at follow-up. RT-qPCR was used to measure lncRNA expression. Expression of the lncRNA RNA antisense non-coding RNA at the INK4 locus (ANRIL) was found to be upregulated whereas the lncRNA homeobox A11 antisense (HOXA11-AS) was downregulated in the plasma of patients with ISR compared with that from patients without ISR (P<0.001). Logistic regression analysis revealed that ANRIL [odds ratio (OR)=2.95; 95% confidence interval (CI)=1.68-8.08] was an independent risk factor for ISR, whilst HOXA11-AS (OR=0.58; 95% CI=0.48-0.71) was found to be an independent protective factor for ISR. Receiver operating characteristic (ROC) analysis demonstrated that high ANRIL expression [area under the ROC (auROC)=0.755; 95% CI=0.702-0.803] and low HOXA11-AS levels (auROC=0.712; 95% CI=0.657-0.763) predicted a high risk for ISR, and the combined score of ANRIL and HOXA11-AS (auROC=0.844; 95% CI=0.798-0.884) was more efficient at predicting ISR than either ANRIL or HOXA11-AS alone (P<0.001). In conclusion, increased ANRIL and decreased HOXA11-AS expressions were associated with ISR. However, combined ANRIL and HOXA11-AS plasma levels proved to be more effective at predicting ISR compared with either ANRIL or HOXA11-AS alone, suggesting that the multiplex detection of lncRNAs could be used to predict ISR in the future.

A Novel Mutation of the KLK6 Gene in a Family With Knee Osteoarthritis.

To investigate the correlation between gene mutation and knee osteoarthritis (KOA), a whole-exome sequencing (WES) was applied to analyze blood samples of four KOA patients and two normal subjects in a family. Gene mutations were identified by gene-trapping and high-throughput sequencing analysis across the differences between the patients and normal subjects. The interactive gene network analysis on the retrieval of interacting genes (STRING) database and the KOA-related genes expression data sets was performed. A possibly detrimental and nonsynonymous mutation at the kallikrein-related peptidase 6 (KLK6) gene (rs201586262, c. C80A, P27H) was identified and attracted our attention. KLK6 belongs to the kallikrein family of serine proteases and its serum level is known as a prevalent biomarker in inflammatory and malignant diseases. KLK6 expresses in the extracellular compartment for matrix degradation, highlighting that KLK6 plays a role in the pathogenesis of KOA. By using the gene databases, the KOA-related genes were mined after de-duplication and IL6 was selected as the most relevant gene through interactive analysis of protein-protein interaction (PPI) network. The data suggested that KLK6 gene mutation and the related expression alteration of IL6 gene might determine the occurrence of hereditary KOA. The is the first study discovering the gene mutation of KLK6 as a factor of pathogenesis of KOA, especially the hereditary KOA.

Numerical Study of the Microflow Characteristics in a V-ball Valve.

V-ball valves are widely applied in many process industries to regulate fluid flow, and they have advantages of good approximately equal percentage flow characteristics and easy maintenance. However, in some applications, the V-ball valve needs to have good performance under both large and extremely small flow coefficients. In this paper, the improvement of the original V-ball valve is made and the flow characteristics between the original and the improved V-ball valve are compared. Two types of small gaps are added to the original V-ball, namely the gap with an approximately rectangular port and the gap with an approximately triangular port. The effects of the structure and the dimension of the gap on flow characteristics are investigated. Results show that within the gap, the flow coefficient increases but the loss coefficient decreases as the valve opening increases, and the flow coefficient has an approximately linear relationship with the flow cross-area of the added gap. Results also show that under the same flow cross-area, the flow coefficient has a higher value if the distance between the gap and the ball center is greater or if the gap is an approximately rectangular port, while the loss coefficient has an opposite trend.

Fluid-Structure Interaction Analysis on Membrane Behavior of a Microfluidic Passive Valve.

In this paper, the effect of membrane features on flow characteristics in the microfluidic passive valve (MPV) and the membrane behavior against fluid flow are studied using the fluid-structure interaction (FSI) analysis. Firstly, the microvalve model with different numbers of microholes and pitches of microholes are designed to investigate the flow rate of the MPV. The result shows that the number of microholes on the membrane has a significant impact on the flow rate of the MPV, while the pitch of microholes has little effect on it. The constant flow rate maintained by the microvalve (the number of microholes n = 4) is 5.75 mL/min, and the threshold pressure to achieve the flow rate is 4 kPa. Secondly, the behavior of the membrane against the fluid flow is analyzed. The result shows that as the inlet pressure increases, the flow resistance of the MPV increases rapidly, and the deformation of the membrane gradually becomes stable. Finally, the effect of the membrane material on the flow rate and the deformation of the membrane are studied. The result shows that changes in the material properties of the membrane cause a decrease in the amount of deformation in all stages the all positions of the membrane. This work may provide valuable guidance for the optimization of microfluidic passive valve in microfluidic system.

Cavitation Suppression of Bileaflet Mechanical Heart Valves.

PURPOSE: Mechanical heart valves (MHVs) are widely used to replace diseased heart valves, but it may suffer from cavitation due to the rapid closing velocity of the leaflets, resulting in the damage of red blood cells and platelets. The aim of this study is to apply computational fluid dynamics (CFD) method to investigate the cavitation in bileaflets mechanical heart valves (BMHVs) and discuss the effects of the conduit and leaflet geometries on cavitation intensity. METHODS: Firstly, CFD method together with moving-grid technology were applied and validated by comparing with experimental results obtained from other literature. Then the leaflets movement and the flow rate of BMHVs with different conduit geometries and leaflet geometries are compared. At last, the duration time of the saturated vapor pressure and the closing velocity of leaflets at the instant of valve closure were used to represent the cavitation intensity. RESULTS: Larger closing velocity of leaflets at the instant of valve closure means higher cavitation intensity. For BMHVs with different conduit geometries, the conduit with Valsalva sinuses has the maximum cavitation intensity and the straight conduit has the minimum cavitation intensity, but the leaflets cannot reach the fully opened state in a straight conduit. For BMHVs with different leaflet geometries, in order to minimize the cavitation intensity, the leaflets are better to have a large thickness and a small rotational radius. CONCLUSION: CFD method is a promising method to deal with cavitation in BMHVs, and the closing velocity of leaflets has the same trend with the cavitation intensity. By using CFD method, the effects of the conduit geometry and the leaflet geometry on cavitaion in BMHVs are found out.

Effects of throttling window on flow rate through feed-water valves.

Feed-water valves are widely used in nuclear power plants to regulate the flow rate of the water supplying to steam generators, and thus holding the water level in steam generators at desired values. The flow rate characteristics of feed-water valves have important effects on the management quality of the water level in steam generators and therefore influence the safety and the efficiency of nuclear power plants. In this paper, the effects of throttling window shapes on the flow rate characteristics through feed-water valves are investigated in two aspects, the overall performances and the fluid dynamics. First of all, a dimensionless parameter defining throttling window shapes is proposed for the quantitative assessment. Then, for the analysis of overall performances, the rated flow coefficient, the loss coefficient, and the inherent valve characteristics are investigated. A revised fitting function is obtained to predict the inherent valve characteristics with different throttling window shapes for engineering applications. Finally, for the observation of the fluid dynamics, the velocity characteristics and the pressure characteristics are both discussed. The wear conditions are predicted at different relative travels and throttling window shapes. This paper provides a reference for researchers dealing with the design work of feed-water valves and is beneficial for the improvement of the whole water level control system.

Actuation Mechanism of Microvalves: A Review.

The microvalve is one of the most important components in microfluidics. With decades of development, the microvalve has been widely used in many industries such as life science, chemical engineering, chip, and so forth. This paper presents a comprehensive review of the progress made over the past years about microvalves based on different actuation mechanisms. According to driving sources, plenty of actuation mechanisms are developed and adopted in microvalves, including electricity, magnetism, gas, material and creature, surface acoustic wave, and so on. Although there are currently a variety of microvalves, problems such as leakage, low precision, poor reliability, high energy consumption, and high cost still exist. Problems deserving to be further addressed are suggested, aimed at materials, fabrication methods, controlling performances, flow characteristics, and applications.

Cavitating Flow through a Micro-Orifice.

Microfluidic systems have witnessed rapid development in recent years. As one of the most common structures, the micro-orifice is always included inside microfluidic systems. Hydrodynamic cavitation in the micro-orifice has been experimentally discovered and is harmful to microfluidic systems. This paper investigates cavitating flow through a micro-orifice. A rectangular micro-orifice with a l/d ratio varying from 0.25 to 4 was selected and the pressure difference between the inlet and outlet varied from 50 to 300 kPa. Results show that cavitation intensity increased with an increase in pressure difference. Decreasing exit pressure led to a decrease in cavitation number and cavitation could be prevented by increasing the exit pressure. In addition, the vapor cavity also increased with an increase in pressure difference and l/d ratio. Results also show the pressure ratio at cavitation inception was 1.8 when l/d was above 0.5 and the cavitation number almost remained constant when l/d was larger than 2. Moreover, there was an apparent difference in cavitation number depending on whether l/d was larger than 1.

Collapse of Corroded Pipelines under Combined Tension and External Pressure.

In this work, collapse of corroded pipeline under combined external pressure and tension is investigated through numerical method. Axially uniform corrosion with symmetric imperfections is firstly considered. After verifying with existing experimental results, the finite element model is used to study the effect of tension on collapse pressure. An extensive parametric study is carried out using Python script and FORTRAN subroutine to investigate the influence of geometric parameters on the collapse behavior under combined loads. The results are used to develop an empirical equation for estimating the collapse pressure under tension. In addition, the effects of loading path, initial imperfection length, yielding anisotropy and corrosion defect length on the collapse behavior are also investigated. It is found that tension has a significant influence on collapse pressure of corroded pipelines. Loading path and anisotropic yielding are also important factors affecting the collapse behavior. For pipelines with relatively long corrosion defect, axially uniform corrosion models could be used to estimate the collapse pressure.

Numerical Simulation of Flow-Induced Noise in High Pressure Reducing Valve.

The main objective of this paper is to study the characteristics of flow-induced noise in high pressure reducing valve (HPRV) and to provide some guidance for noise control. Based on computational fluid dynamics (CFD), numerical method was used to compute flow field. Ffowcs Williams and Hawkings Model was applied to obtain acoustic signals. The unsteady flow field shows that noise sources are located at the bottom of plug for valve without perforated plate, and noise sources are behind the plate for valve with perforated plate. Noise directivity analysis and spectrum characteristics indicate that the perforated plate could help to reduce noise effectively. Inlet pressure has great effects on sound pressure level (SPL). The higher inlet pressure will lead to larger SPL at high frequency. When the maximum Ma is close to 1, SPL at low frequency becomes very high.