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

The Variation of Nasal Microbiota Caused by Low Levels of Gaseous Ammonia Exposure in Growing Pigs

Exposure to gaseous ammonia, even at low levels, can be harmful to pigs and human health. However, less is known about the effects of sustained exposure to gaseous ammonia on nasal microbiota colonization in growing pigs. A total of 120 Duroc×Landrace×Yorkshire pigs were housed in 24 separate chambers and continuously exposed to gaseous ammonia at 0,5, 10, 15, 20, and 25 ppm (four groups per exposure level) for 4 weeks. Then, we used high-throughput sequencing to perform 16S rRNA gene analysis in nasal swabs samples from 72 pigs (n = 12). The results of the nasal microbiota analysis showed that an increase in ammonia concentration, especially at 20 and 25 ppm, decreased the alpha diversity and relative abundance of nasal microbiota. Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, and Chloroflexi were the most abundant phyla. In addition, the relative abundances of 24 microbial genera significantly changed as the ammonia level increased. Four microbial genera (Pseudomonas, Lactobacillus, Prevotella, and Bacteroides) were significantly decreased at 25 ppm, while only two genera (Moraxella and Streptococcus) were increased at 25 ppm. PICRUSt analyses showed that the relative abundances of the nasal microbiota involved in cell motility, signal transduction, the nervous system, environmental adaptation, and energy and carbohydrate metabolism were significantly decreased, while genes involved in the immune system, endocrine system, circulatory system, immune system diseases and metabolism of vitamins, lipid, and amino acids were increased with increased ammonia levels. The results of in vivo tests showed that an increase in ammonia levels, especially an ammonia level of 25 ppm, caused respiratory tract injury and increase the number of Moraxella and Streptococcus species, while simultaneously decreasing respiratory immunity and growth performance, consistent with the increased presence of harmful bacteria identified by nasal microbiota analysis. Herein, this study also indicted that the threshold concentration of ammonia in pig farming is 20 ppm

The Effect of Social Exclusion on Trust Among Youth Orphaned by HIV/AIDS: Evidence From an Event-Related Potentials Study

Grounded in a follow-up study among children who lost one or both parents to HIV in central China in the early 2000s, we conducted an event-related potentials (ERPs) experiment to explore the effect of social exclusion on trust and the corresponding neurophysiological mechanism among youth orphaned by HIV/AIDS (“AIDS orphans”). A sample of 31 AIDS orphans (26.16 ± 3.34 years old; 15 female) and 32 age and development status matched controls (25.02 ± 3.45 years old; 14 female) participated in the study. They were all assigned to play Cyberball, a virtual ball-tossing game that reliably induced social exclusion (15 orphans, 16 controls) and inclusion (16 orphans, 16 controls). Then, they played the Trust Game by taking the role of trustor with their electroencephalograms (EEGs) being recorded during the game. In the Trust Game, each participant was required to decide whether to trust their partners in over 150 trials (decision-making stage). The partner’s reciprocation strategies were pre-programmed by the experimenter (with an overall reciprocating rate of 50%). All participants were provided with post-decision feedback about the outcome of their decisions (gain or loss of game points) in each trial (outcome evaluation stage). We analyzed their behavioral responses at the decision-making stage and ERP components at the outcome evaluation stage. Behavioral results showed that the proportion of orphans choosing trust was significantly higher than the controls, and the trust ratio of the orphan exclusion (OE) group was significantly higher than that of the orphan inclusion (OI) group, control exclusion (CE) group, and control inclusion (CI) group. Furthermore, the response time of the OE group was significantly shorter than that of other groups. ERP results indicated that the amplitude of the feedback-related negativity (FRN) in the OI group was significantly more negative than that in the CI group with loss feedback, while there was no significant difference between the OE and OI groups. Similarly, the P300 amplitudes following outcome feedback were larger in the CI group than that in the OI group with gain feedback and had no significant difference between OE and OI

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Study on Stability of Round Tunnel Surrounding Rock

Tunnel excavation will lead to the immediate surrounding rock unloading caused by the surrounding rock stress release, the stability of the surrounding rock have a certain impact. In this paper, finite element software ANSYS and finite difference software FLAC3D are used to simulate the excavation and lining process of circular tunnel. The influence of excavation on the rock stability around circular tunnel is analyzed, and the effect of applying lining on the stability of surrounding rock is analyzed. Evaluation criteria selection hole displacement, stress and plastic area of three factors

Multiple Vehicle Tracking Based on Labeled Multiple Bernoulli Filter Using Pre-Clustered Laser Range Finder Data

1967-2012 IEEE. Multiple vehicle tracking (MVT) system is a prerequisite to path planning and decision making of self-driving cars as it can provide positions of surrounding vehicles. Most of the available approaches belonging to the so called tracking-by-detection approach inevitably bring detection errors into the tracking result. In this study, we proposed a laser range finder (LRF) based track-before-detect MVT algorithm without detection procedure. Moreover, different from the state of the art in track-before-detect approaches using raw data, we applied a pre-clustering procedure to segment the raw data into disjoint clusters to reduce computation demand. Specifically, a clustering algorithm named iterative nearest point search (INPS) which can even handle the partial occlusion situations that are challenging for traditional clustering algorithms was designed for the pre-clustering procedure. Furthermore, a detailed cluster-to-target measurement model was proposed to describe the difference between cluster and hypothesis vehicle. Finally, we integrated the measurement model into the labeled multi-Bernoulli filter with particle implementation. Simulations and experiments show that the proposed MVT algorithm provides more accurate estimates of vehicle number and position in comparison with conventional methods

Study on Misalignment Angle Compensation during Scale Factor Matching for Two Pairs of Accelerometers in a Gravity Gradient Instrument

A method for automatic compensation of misalignment angles during matching the scale factors of two pairs of the accelerometers in developing the rotating accelerometer gravity gradient instrument (GGI) is proposed and demonstrated in this paper. The purpose of automatic scale factor matching of the four accelerometers in GGI is to suppress the common mode acceleration of the moving-based platforms. However, taking the full model equation of the accelerometer into consideration, the other two orthogonal axes which is the pendulous axis and the output axis, will also sense the common mode acceleration and reduce the suppression performance. The coefficients from the two axes to the output are δO and δP respectively, called the misalignment angles. The angle δO, coupling with the acceleration along the pendulous axis perpendicular to the rotational plane, will not be modulated by the rotation and gives little contribution to the scale factors matching. On the other hand, because of coupling with the acceleration along the centripetal direction in the rotating plane, the angle δP would produce a component with 90 degrees phase delay relative to the scale factor component. Hence, the δP component coincides exactly with the sensitive direction of the orthogonal accelerometers. To improve the common mode acceleration rejection, the misalignment angle δP is compensated by injecting a trimming current, which is proportional to the output of an orthogonal accelerometer, into the torque coil of the accelerometer during the scale factor matching. The experimental results show that the common linear acceleration suppression achieved three orders after the scale factors balance and five orders after the misalignment angles compensation, which is almost down to the noise level of the used accelerometers of 1~2 × 10−7 g/√Hz (1 g ≈ 9.8 m/s2)