Human adipose-derived mesenchymal progenitor cells (haMPCs) are stem cells with multiple differentiation potential and immunomodulatory function. Re-Join® comprises in vitro expanded haMPCs from ...adipose tissue of patients combined with cell suspension solution. This study was undertaken to evaluate the efficacy and safety of Re-Join® in patients with symptomatic knee osteoarthritis (OA).
Patients with Kellgren-Lawrence grade 1-3 knee OA were recruited from two centers and randomized to receive intra-articular injection of Re-Join® or HA. Pain and function were assessed by using WOMAC score, VAS, and SF-36. Magnetic resonance imaging (MRI) analysis was performed to measure cartilage repair. Adverse events (AEs) were collected.
Fifty-three patients were randomized. Significant improvements in WOMAC, VAS, and SF-36 scores were observed in both groups at months 6 and 12 compared with baseline. Compared with the HA group, significantly more patients achieved 50% improvement of WOMAC and a trend of more patients achieved a 70% improvement rate in Re-Join® group after 12 months. Meanwhile, there was notably more increase in articular cartilage volume of both knees in the Re-Join® group than in the HA group after 12 months as measured by MRI. AEs were comparable between two groups. Most AEs were mild and moderate except one SAE of right knee joint infection in the HA group.
Significant improvements in joint function, pain, quality of life, and cartilage regeneration were observed in Re-Join®-treated knee OA patients with good tolerance in a period of 12 months.
ClinicalTrials.gov Identifier: NCT02162693 . Registered 13 June 2014.
Objective
Our previous studies revealed that normal synovial exosomes promoted chondrogenesis, and microRNA (miR)-19b-3p independently related to osteoarthritis (OA) risk. Subsequently, this study ...intended to further explore the effect of OA fibroblast-like synoviocyte (OA-FLS) exosomal miR-19b-3p on OA ferroptosis and its potential mechanisms.
Methods
Interleukin (IL)-1β-stimulated chondrocytes and medial meniscus surgery were used to construct the OA cellular model and the OA rat model, respectively. OA-FLS exosomes with/without miR-19b-3p modification were added to the IL-1β-stimulated chondrocytes and OA rat models, followed by direct miR-19b-3p mimic/inhibitor transfection with/without SLC7A11 overexpression plasmids. miR-19b-3p, ferroptosis-related markers (malondialdehyde (MDA), glutathione (GSH)/oxidized glutathione (GSSG), ferrous ion (Fe
2+
), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase long-chain family member 4 (ACSL4)), mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) levels were detected.
Results
Enhanced ferroptosis reflected by dysregulated ferroptosis-related markers, a reduced MMP, and an increased ROS was observed in cartilage tissues from OA patients vs. controls, IL-1β-stimulated chondrocytes vs. normal ones, and OA rat models vs. sham, so did miR-19b-3p. OA-FLS exosomes promoted MDA, Fe
2+
, ACSL4, and ROS but reduced cell viability, GSH/GSSG, GPX4, SLC7A11, and MMP in IL-1β-stimulated chondrocytes, whose effect was enhanced by miR-19b-3p mimics and attenuated by miR-19b-3p inhibitors. miR-19b-3p negatively regulated SLC7A11 and directly bound to SLC7A11 via luciferase reporter gene assay. Furthermore, SLC7A11 overexpression weakened miR-19b-3p mimics’ effect on ferroptosis-related markers, MMP, or ROS in IL-1β-stimulated chondrocytes. OA-FLS exosomes also induced cartilage damage and ferroptosis in OA rats whose influence was tempered by miR-19b-3p inhibitors.
Conclusion
OA-FLS exosomal miR-19b-3p enhances cartilage ferroptosis and damage by sponging SLC7A11 in OA, indicating a potential linkage among synovium, cartilage, and ferroptosis during the OA process.
This paper presents a speed up algorithm for real-time path planning based on massive trajectory data mining, which comprises three stages: preparatory work, preprocessing stage and the online ...fastest path query. At the preparatory stage, this algorithm constructs multi-level landmarks and divides the original road network into multiple levels accordingly. At the preprocessing stage, this algorithm first estimates the travel time of all road segments according to the real-time traffic information, then compares all taxi trajectories to extract the experiential fastest paths, and finally makes use of the multi-level landmarks to obtain the rough fastest paths for all landmark pairs. At the online fastest path query stage, the server side first responds by returning a rough fastest path based on the preprocessing result, and then refines it by iteratively introducing the experiential fastest paths. A series of experiments are made to compare the proposed algorithm with the other three algorithms. Experiments indicate that the proposed algorithm has the ability to find more time-saving paths in response to client requests. More importantly, because this algorithm is capable of ensuring the fast completion of pre-computation on the server side, it has an evident advantage in the time cost of the online fastest path query compared with the other three algorithms, which is particularly suitable for the online optimal path query from a larger number of end users.
Topography plays a critical role in soil migration and redistribution, but few studies have been conducted to quantify its effects on sediment deposition. In this study, we established a physical ...simulation and analysis framework to investigate the erosional and depositional impacts of two‐dimensional slope terrain, specifically applied to Xiannangou small watershed in the loess hilly region. The results showed that the slope gradient, slope length, and slope shape have significantly influence the distribution of soil erosion and deposition. The magnitude of the erosion/deposition rate (Yr) determines the relative intensity of slope erosion and deposition, where Yr < 0 indicates erosion and Yr > 0 signifies deposition. The erosion rate on straight slope exhibited a positive correlation with slope length, while the erosion/deposition rate on concave and convex slopes exhibited fluctuations with slope length. Soil erosion predominantly occurred along the main flow line and the middle slope, aligning with the observed distribution of gully and slope erosion in the field. The sediment deposition was primarily concentrated on the lower slope or the lowest outlet of the basin, notably in gullies and gentle slopes where the terrain slows, especially during transition from steep to gradual slopes. These results can effectively predict the relative erosion/sedimentation rate of two‐dimensional slopes, significantly contributing to a comprehensive understanding of how topography influences soil erosion and deposition. This study thoroughly considers the role of sediment deposition in the soil erosion process, providing a more accurate reflection of soil erosion/deposition in small watersheds. It addresses the existing deficiency in sediment consideration within soil erosion evaluation and supports the enhancement of soil erosion model.
In this study, we established a physical simulation and analysis framework to investigate the erosional and depositional impacts of two‐dimensional slope terrain, specifically applied to Xiannangou small watershed in the loess hilly region. The results showed that the slope gradient, slope length, and slope shape have significantly influence the distribution of soil erosion and deposition. The magnitude of the erosion/deposition rate (Yr) determines the relative intensity of slope erosion and deposition, where Yr < 0 indicates erosion and Yr > 0 signifies deposition.
As a typical application of geodesy, the GNSS/INS (Global Navigation Satellite System and Inertial Navigation System) integrated navigation technique was developed and has been applied for decades. ...For the integrated systems with multiple sensors, data fusion is one of the key problems. As a well-known data fusion algorithm, the Kalman filter can provide optimal estimates with known parameters of the models and noises. In the literature, however, the data fusion algorithm of the GNSS/INS integrated navigation and positioning systems is performed under a certain norm, and performance of the conventional filtering algorithms are improved only under this fixed and limited frame. The mixed norm-based data fusion algorithm is rarely discussed. In this paper, a mixed norm-based data fusion algorithm is proposed, and the hypothesis test statistics are constructed and adopted based on the chi-square distribution. Using the land vehicle data collected through the multi-GNSS and the IMU (Inertial Measurement Unit), the proposed algorithm is tested and compared with the conventional filtering algorithms. Results show that the influences of the outlying measurements and the uncertain noises are weakened with the proposed data fusion algorithm, and the precision of the estimates is further improved. Meanwhile, the proposed algorithm provides an open issue for geodetic applications with mixed norms.
With the popularity of various portable mobile devices with positioning functions, a large amount of spatial‐temporal trajectory data has emerged. To effectively compress large‐scale vehicle ...trajectory data and serve intelligent transportation system, we propose a spatial‐temporal trajectory data compression algorithm based on vehicle motion pattern recognition. The algorithm recognizes vehicles' turning behaviour and variable speed behaviour during the driving process through the analysis of vehicle motion patterns, and extracts the trajectory's turning feature points and variable speed feature points, so as to achieve online compression of the vehicle trajectory. By means of large‐scale experimental datasets, the authors compare this algorithm with representative trajectory compression algorithms in various performance metrics. The experimental results indicate that as an online vehicle trajectory compression algorithm, the proposed algorithm is superior to representative compression algorithms in compression accuracy and computational efficiency, and the compression results can reflect semantic motion information such as turning patterns and variable speed patterns in the trajectory. Therefore, this algorithm has comprehensive advantages, which is foundational for trajectory data mining in intelligent transportation systems.
Autoreactive T cell is one of the leading causes of immunological tolerance defects in the chronic inflammatory lesions of rheumatoid arthritis (RA). There have been several extracellular signals and ...intracellular pathways reported in regulating this process but largely remain unknown yet. In this study, we explored the roles of intestinal Wnt/β-catenin on disease severity during collagen-induced arthritis model (CIA), an animal model of RA. We first testified the activity pattern Wnt/β-catenin shifted by intragastric administration of LiCl and DKK-1 in the intestine by real-time PCR and WB analysis. The arthritis scores showing the disease severity in the DKK-1 group was significantly ameliorated compared with the control group at the late stage of the disease, while in the LiCl group, the scores were significantly elevated which was consistent with pathology score analysis of H&E staining. Next, ELISA was performed and showed that TNF-α and IL-17 in the LiCl group were significantly higher than that of the control group. IL-10 in the DKK-1 group was significantly higher than that in the LiCl-1 group and control group,
P
< 0.05. Flow cytometry of spleen T cells differentiation ratio showed that: Th1 from the DKK-1 and LiCl groups and Th17 from the LiCl group was significantly different from that of the blank model group,
P
< 0.05. Finally, we explored the effects of intestinal Wnt/β-catenin on T cell differentiation regulator ROR-
γt
and TCF1 and found that both transcription factors were up-regulated in the LiCl group. Together, these data suggested the pro-information role of Wnt/β-catenin pathway from the intestine in the CIA mouse, implying its use as a potential therapeutic target for the treatment of inflammatory diseases such as RA.
Primary Sjögren's syndrome is one of the most common autoimmune diseases. So far, genetic studies of Sjögren's syndrome have relied mostly on candidate gene approaches. To identify new genetic ...susceptibility loci for primary Sjögren's syndrome, we performed a three-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 556,134 autosomal SNPs in 542 cases and 1,050 controls. We then validated promising associations in 2 replication stages comprising 1,303 cases and 2,727 controls. The combined analysis identified GTF2I at 7q11.23 (rs117026326: Pcombined = 1.31 × 10(-53), combined odds ratio (ORcombined) = 2.20) as a new susceptibility locus for primary Sjögren's syndrome. Our analysis also confirmed previously reported associations in Europeans in the regions of STAT4, TNFAIP3 and the major histocompatibility complex (MHC). Fine mapping of the region around GTF2I showed that rs117026326 in GTF2I had the most significant association, with associated SNPs extending from GTF2I to GTF2IRD1-GTF2I.
Objective
Our objective was to explore the molecular pathogenesis of the onset of gout and the mechanism underlying the effect of interleukin (IL)-37 on PDZ domain-containing 1 (PDZK1) protein ...through the nuclear factor-κB signaling pathway.
Methods
Real-time PCR and western blotting were used to detect expression of PDZK1 mRNA and protein, respectively, in the HK-2 cell line. The inhibitors pyrrolidine dithiocarbamate (PDTC) and wortmannin were added to HK-2 cells stimulated by IL-37, and changes in PDZK1 protein were detected by western blotting.
Results
Based on our previous research, we used 10 µmol/L PDTC. We detected no significant change in PDZK1 at the mRNA level among the IL-37, PDTC+IL-37, and wortmannin+IL-37 groups. With increasing IL-37 concentration, the protein level of PDZK1 increased. After adding wortmannin, the protein level of PDZK1 increased with increasing concentration of IL-37, albeit not significantly, and the level of PDZK1 remained lower than that with IL-37 alone. After adding PDTC, the protein level of PDZK1 showed a trend to decrease with increasing concentrations of IL-37 up to 40 ng/mL. The immunofluorescence results supported the western blot results.
Conclusions
IL-37 can affect protein expression of PDZK1, but not at the translational level, in the pathogenesis of gout.
Abstract
Background
Diabetes increases the risk of hypertension morbidity, but whether this association is varied with glycemic control remains unknown. We aimed to examine the association of ...glycemic control with hypertension among individuals with diabetes.
Methods
Data was from the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2018. Participants were categorized as having adequate glycemic control (HbA1c < 7%) and inadequate glycemic uncontrol (HbA1c ≥ 7%) by combining blood glucose tests and physician’s diagnoses in 2011. Incident hypertension was ascertained through self-reported physician diagnoses from 2011 to 2018. Cox proportional hazards regression models were used to examine the effect of glycemic control on hypertension.
Results
Among 436 participants with diabetes in this study, 102 met the glycemic control standard, and 334 were insufficient glycemic control. During 7 years of follow-up, 141 individuals developed hypertension. Compared with adequate glycemic control, the hazard ratio of inadequate glycemic control on hypertension was 1.54 (95% CI, 1.07–2.21) in the multivariate model. Additionally, the influence of glycemic control on hypertension varied based on educational attainment and the presence of depressive symptoms (P for interaction < 0.05).
Conclusions
Insufficient glycemic control was associated with a higher risk of hypertension among individuals with diabetes. Notably, the effect of glycemic control on hypertension was more pronounced among those with lower educational attainment and those exhibiting depressive symptoms. These findings underscore the significance of vigilant glycemic monitoring, educational background considerations, and mental health assessments in managing diabetic individuals.
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