Exosomes from osteoarthritic fibroblast-like synoviocytes promote cartilage ferroptosis and damage via delivering microRNA-19b-3p to target SLC7A11 in osteoarthritis

ObjectiveOur 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.MethodsInterleukin (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 (Fe2+), 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.ResultsEnhanced 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, Fe2+, 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.ConclusionOA-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

Genetic causal relationship between gut microbiome and psoriatic arthritis: a bidirectional two-sample Mendelian randomization study

BackgroundSeveral observational studies have suggested a potential relationship between gut microbiome and psoriatic arthritis (PsA). However, the causality of this relationship still remains unclear. We aim to explore if the specific gut microbiome is causally associated with PsA at the genetic level and offer valuable insights into the etiology of PsA.MethodsIn this study, we employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal effects of the gut microbiome on PsA. Publicly accessible genome-wide association study summary data of gut microbiome were obtained from the MiBioGen consortium (n = 14,306), while the summary statistics of psoriatic arthropathies were sourced from the FinnGen consortium R8 release data (2,776 cases and 221,323 controls). The primary analytical method employed was inverse variance weighted (IVW), complemented by supplementary methods including MR-Egger, weighted median, weighted mode, maximum likelihood, MR-PRESSO, and cML-MA. Reverse MR analysis was performed on the bacteria that were found to be causally associated with PsA in forward MR analysis. Cochran’s IVW Q statistic was utilized to assess the heterogeneity of instrumental variables among the selected single nucleotide polymorphisms.ResultsIVW estimates revealed that Ruminococcaceae_UCG-002 (odds ratio (OR) = 0.792, 95% confidence interval (CI), 0.643–0.977, p = 0.029) exhibited a protective effect on PsA. Conversely, Blautia (OR = 1.362, 95% CI, 1.008–1.842, p = 0.044), Eubacterium_fissicatena_group (OR = 1.28, 95% CI, 1.075–1.524, p = 0.006), and Methanobrevibacter (OR = 1.31, 95% CI, 1.059–1.621, p = 0.013) showed a positive correlation with the risk of PsA. No significant heterogeneity, horizontal pleiotropy, or outliers were observed, and the results of the MR analysis remained unaffected by any single nucleotide polymorphisms. According to the results of reverse MR analysis, no significant causal effect of PsA was found on gut microbiome.ConclusionThis study establishes for the first time a causal relationship between the gut microbiome and PsA, providing potential valuable strategies for the prevention and treatment of PsA. Further randomized controlled trials are urgently warranted to support the targeted protective mechanisms of probiotics on PsA

X-Ray Repair Cross-Complementing Group 1 (XRCC1) Genetic Polymorphisms and Risk of Childhood Acute Lymphoblastic Leukemia: A Meta-Analysis

Background: Recently, there have been a number of studies on the association between XRCC1 polymorphisms and childhood acute lymphoblastic leukemia (ALL) risk. However, the results of previous reports are inconsistent. Thus, we performed a meta-analysis to clarify the effects of XRCC1 variants on childhood ALL risk. Methods: A meta-analysis was performed to examine the association between XRCC1 polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) and childhood ALL risk. We critically reviewed 7 studies with a total of 880 cases and 1311 controls for Arg399Gln polymorphism, 3 studies with a total of 345 cases and 554 controls for Arg280His polymorphism, and 6 studies with a total of 783 cases and 1180 controls for Arg194Trp polymorphism, respectively. Odds ratio (OR) and its 95% confidence interval (CI) were used. Results: Significant association between XRCC1 Arg399Gln polymorphism and childhood ALL risk was observed in total population analyses (OR additive model = 1.501, 95 % CI 1.112–2.026, P OR = 0.008; OR dominant model = 1.316, 95 % CI = 1.104–1.569, POR = 0.002) and Asian subgroup analyses (ORadditive model = 2.338, 95%CI = 1.254–4.359, POR = 0.008; ORdominant model = 2.108, 95%CI = 1.498–2.967, POR = 0.000). No association was detected in Caucasians, Metizo and mixed populations. Ethnicity was considered as a significant source of heterogeneity in the meta-regression model. For the other two XRCC1 polymorphisms, no association with childhood ALL risk was found

A Multi-GNSS/IMU Data Fusion Algorithm Based on the Mixed Norms for Land Vehicle Applications

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

Design and Control of a Series–Parallel Elastic Actuator for a Weight-Bearing Exoskeleton Robot

Weight-bearing exoskeletons are robots that need to carry loads and interact with humans frequently. Therefore, the actuators of these exoskeletons are supposed to be capable of outputting sufficient force with high compliance and little weight. A series–parallel elastic actuator (SPEA) is designed, in this work, to meet the demanding requirements of an exoskeleton robot called PALExo. A gas spring is installed in parallel with an electric cylinder to adjust the force output range of the actuator according to the needs of the exoskeleton. A series elastic module (SEM) is installed in series with the electric cylinder and gas spring to improve the compliance of the actuator, the stiffness of which is variable to adapt to the different stiffness requirements of the exoskeleton’s legs in the standing phase and swinging phase. A force controller combining dynamic compensation and a cascade control with an inner velocity loop and a disturbance observer is designed for the SPEA. The performance of the force controller is verified by experiments and the results demonstrate that the controller has good adaptability to the stiffness of the SEM

Modular Robotic Limbs for Astronaut Activities Assistance

In order to meet the assist requirements of extravehicular activity (EVA) for astronauts, such as moving outside the international space station (ISS) or performing on-orbit tasks by a single astronaut, this paper proposes an astronaut robotic limbs system (AstroLimbs) for extravehicular activities assistance. This system has two robotic limbs that can be fixed on the backpack of the astronaut. Each limb is composed of several basic module units with identical structure and function, which makes it modularized and reconfigurable. The robotic limbs can work as extra arms of the astronaut to assist them outside the space station cabin. In this paper, the robotic limbs are designed and developed. The reinforcement learning method is introduced to achieve autonomous motion planning capacity for the robot, which makes the robot intelligent enough to assist the astronaut in unstructured environment. In the meantime, the movement of the robot is also planned to make it move smoothly. The structure scene of the ISS for extravehicular activities is modeled in a simulation environment, which verified the effectiveness of the proposed method

The Response Mechanisms of Topographic Changes in Small Loess Watershed under Rainstorm

This paper uses a small watershed entity model to simulate the rainfall experiment and combines traditional water and sediment observation and terrain three-dimensional laser scanning technology to reveal the characteristics of erosion and sediment yield in small watersheds and the law of channel sediment transport and quantitatively describe the response mechanism of terrain changes in small watersheds to the layout of silt dams and rainfall intensity. Rainfall intensity with three types (30, 60, and 120 mm/h) under three soil conservation measure types (none dam, single dam, and double dams) was simulated, and a small watershed entity model was adopted. The changes in topography were recorded by a Focus 3D laser scanner (Faro) for each experiment. The main results were as follows: (1) Soil erosion under the effect of rainfall occurs on the slope of the watershed and in the gully, while deposition usually occurs on the gentle slope of the gully or in low-lying areas. (2) When the runoff volume is small, deposition occurs easily in the gully, and vice versa. (3) The increase in the number of silt dams deployed has a small effect on the rate of runoff yield on the small watershed, but the limitation on the rate of sand production is especially obvious. Silt dam measures have a good flood and sand reduction effect on small- and medium-intensity rain, but for high-intensity rain, their runoff and sand reduction effect will be reduced, so rainfall is the dominant factor in the formation of soil erosion. Our results provide the scientific basis for identifying key parts of soil erosion and for the rational arrangement of soil and water conservation measures in loess areas

Adverse events of anti-tumor necrosis factor α therapy in ankylosing spondylitis.

This study aims to investigate the prevalence of short-term and long-term adverse events associated with tumor necrosis factor-α (TNF-α) blocker treatment in Chinese Han patients suffering from ankylosing spondylitis (AS).The study included 402 Chinese Han AS patients treated with TNF-α blockers. Baseline data was collected. All patients were monitored for adverse events 2 hours following administration. Long-term treatment was evaluated at 8, 12, 52 and 104 weeks follow-up for 172 patients treated with TNF-α blockers.Short-term adverse events occurred in 20.15% (81/402), including rash (3.5%; 14/402), pruritus (1.2%; 5/402), nausea (2.2%; 9/402), headache (0.7%; 3/402), skin allergies (4.0%; 16/402), fever (0.5%; 2/402), palpitations (3.0%; 12/402), dyspnea (0.5%; 2/402), chest pain (0.2%; 1/402), [corrected] abdominal pain (1.0%; 4/402), hypertension (2.2%; 9/402), papilledema (0.5%; 2/402), laryngeal edema (0.2%; 1/402) and premature ventricular contraction (0.2%; 1/402). Long-term adverse events occurred in 59 (34.3%; 59/172) patients, including pneumonia (7.6%; 13/172), urinary tract infections (9.9%; 17/172), otitis media (4.7%; 8/172), tuberculosis are (3.5%; 6/172) [corrected], abscess (1.2%; 2/172), oral candidiasis (0.6%; 1/172), elevation of transaminase (1.7%; 3/172), anemia (1.2%; 2/172), hematuresis (0.6%; 1/172), constipation (2.3%; 4/172), weight loss (0.6%; 1/172), exfoliative dermatitis (0.6%; 1/172). CRP, ESR and disease duration were found to be associated with an increased risk of immediate and long-term adverse events (P<0.05). Long-term treatment with Infliximab was associated with more adverse events than rhTNFR-Fc (P<0.01).This study reports on the prevalence of adverse events in short-term and long-term treatment with TNF-α blocker monotherapy in Chinese Han AS patients. Duration of disease, erythrocyte sedimentation rate, and c-reactive protein serum levels were found to be associated with increased adverse events with anti-TNF-α therapy. Long-term treatment with Infliximab was associated with more adverse events than rhTNFR-Fc

Economic Burden of Depressive Symptoms Conditions among Middle-Aged and Elderly People with Hypertension in China

People with hypertension are more prone to incur depressive symptoms, while depressive symptoms have an obvious influence on the healthy functioning, treatment, and management of hypertensive patients. However, there have been limited studies on the association between depression and the economic burden of hypertension. We used data from the 2018 China Health and Retirement Longitudinal Study (CHARLS) to estimate the additional annual direct and indirect economic burden of depressive symptoms among middle-aged and elderly hypertensive patients with a multivariable regression model. The depressive symptoms were associated with substantial additional direct and indirect economic burden. Compared with non-co-MHDS (non-co-morbid hypertension and depressive symptoms) patients, the direct economic burden of lower co-MHDS (co-morbid hypertension and depressive symptoms) patients and higher co-MHDS patients increased 1887.4 CNY and 5508.4 CNY, respectively. For indirect economic burden, the lower co-MHDS patients increased 331.2 CNY and the higher co-MHDS patients increased 636.8 CNY. Both direct and indirect economic burden were incremental with the aggravation of depressive symptoms. The results showed depressive symptoms increased total healthcare costs by increasing the utilization and expenditure of primary healthcare services. Depressive symptoms also led to economic loss of productivity, especially for agricultural workers. This study highlights the importance of mental healthcare for hypertensive patients

Association of glycemic control with hypertension in patients with diabetes: a population-based longitudinal study

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