Osteoarthritis is a major cause of disability worldwide, and understanding epidemiological trends in osteoarthritis is critical for public health planning and intervention strategies. This study analyzed the global, regional, and national burden on osteoarthritis utilizing the Global Burden of Disease Study 2021. Trends from 1990 to 2021 were primarily assessed, with projections to 2050 based on demographic changes and historical data. In 2021, 607 (95% UI: 538–671) million people worldwide suffered from osteoarthritis, including 46.6 (95% UI: 41.1–51.6) million new cases, and the DALYs was 21.3 (95% UI: 10.2–42.9) million. Age-standardized incidence, prevalence and DALYs rates increased to 535.00/100,000 (95% UI: 472.38–591.97), 6967.29/100,000 (95% UI: 6180.70–7686.06), and 244.50/100,000 (95% UI: 117.06–493.11), with knee osteoarthritis accounting for more than 56%. Age-standardized rates of osteoarthritis were higher in females than in males. East Asia, South Asia, and Western Europe were the regions and China, India, and the United States were the countries with the highest burdens. In addition, high body-mass index led to 4.43 (95% UI: -0.42–12.34) million DALYs, with an increase of 205.10%. Bayesian age-period cohort projections showed that the burden of osteoarthritis would continue to rise from 2021 to 2050. As an ageing population and rising obesity rates, the burden of osteoarthritis will continue to rise, with females and the middle-aged and older age groups being the current populations of concern. Awareness-raising, early detection, and effective management are essential to reduce the burden of osteoarthritis in the coming decades, especially among vulnerable groups.

As common pathogenic agents in the world and widely distributed globally, T-2 toxin and selenium deficiency might exacerbate toxic effects by combined exposure, posing a dramatic health hazard to humans and animals. In this study, we aim to elucidate the underlying mechanisms of renal fibrosis triggered by T-2 toxin and selenium deficiency exposure. A total of thirty-two rats are randomly divided into the normal control, T-2 toxin, selenium deficiency, and combined intervention groups. T-2 toxin (100 ng/g) is intragastric gavaged to the rats in compliance with the body weight. Both the standard (containing selenium 0.20 mg/Kg) and selenium-deficient (containing selenium 0.02 mg/Kg) diets were manufactured adhering to the AIN-93 formula. After 12 weeks of intervention, renal tissue ultrastructural and pathological changes, inflammatory infiltration, epithelial mesenchymal transition (EMT), and extracellular matrix (ECM) deposition are evaluated, respectively. Metabolomics analysis is conducted to explore the underlying pathology of renal fibrosis, followed by the validation of potential mechanisms at gene and protein levels. T-2 toxin and selenium deficiency exposure results in podocyte foot process elongation or fusion, tubular vacuolization and dilatation, and collagen deposition in the kidneys. Additionally, it also increases inflammatory infiltration, EMT conversion, and ECM deposition. Metabolomics analysis suggests that T-2 toxin and selenium deficiency influence amino acid and cholesterol metabolism, respectively, and the estrogen signaling pathway is probably engaged in renal fibrosis progression. Moreover, T-2 toxin and selenium deficiency are found to regulate the expressions of the ERα/PI3K/Akt signaling pathway. In conclusion, T-2 toxin and selenium deficiency synergistically exacerbate renal fibrosis through regulating the ERα/PI3K/Akt signaling pathway, and inflammatory infiltration, EMT and ECM deposition are involved in this process.

Kashin-Beck disease (KBD) is an endemic, environmentally associated cartilage disease. Previous studies have shown that the environmental suspected pathogenic factors of KBD, T-2 toxin and low selenium, are involved in the regulation of inflammation, oxidative stress and autophagy in some tissues and organs. In cartilage diseases, the level of cellular autophagy determines the fate of the chondrocytes. However, whether autophagy is involved in KBD cartilage lesions, and the role of low selenium and T-2 toxins in KBD cartilage injury and autophagy are still unclear. This work took the classical AMPK/mTOR/ULK1 autophagy regulatory pathway as the entry point to clarify the relationship between the environmental suspected pathogenic factors and chondrocyte autophagy. Transmission electron microscopy was used to observe the autophagy of chondrocytes in KBD patients. qRT-PCR and western blot were used to analyze the expression of AMPK/mTOR/ULK1 pathway and autophagy markers. The rat model of KBD was established by low selenium and T-2 toxin, the autophagy in rat cartilage was detected after 4- and 12-week interventions. Chondrocyte autophagy was found in KBD, and the AMPK/mTOR/ULK1 pathway was down-regulated. In the rat model, the pathway showed an up-regulated trend when low selenium and T-2 toxin, were treated for a short time or low concentration, and autophagy level increased. However, when low selenium and T-2 toxin were treated for a long time or at high concentrations, the pathway showed a down-regulated trend, and the autophagy level was reduced and even defective. In conclusion, in the process of KBD cartilage lesion, chondrocyte autophagy level may increase in the early stage, and decrease in the late stage with the progression of lesion. Low selenium and T-2 toxins may affect autophagy by AMPK/mTOR/ULK1 pathway.

This study investigates the associations between volatile organic compound (VOC) exposure and sarcopenia, focusing on independent and combined effects and exploring potential biological mechanisms. Utilizing data from the National Health and Nutrition Examination Survey, we applied logistic regression to examine associations between individual VOCs and sarcopenia, while restricted cubic splines (RCS) assessed dose-response relationships. Weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) evaluated mixed exposure effects. Mediation analyses explored the roles of potential mediators, alongside bioinformatic analyses to investigate the underlying mechanisms. Multivariable logistic regression identified significant associations between specific VOCs and sarcopenia, particularly for DHBMA (OR=2.71, 95 % CI: 1.62-4.55). RCS confirmed both linear and nonlinear associations of specific VOCs. WQS analysis corroborated a synergistic effect of mixed VOC exposures and increased sarcopenia risk (OR=1.64, 95 % CI: 1.14-2.36), and BKMR analysis further confirmed this positive relationship. Mediation analysis revealed that inflammation, oxidative stress, and renal function partially mediated these associations (mediated proportions: 4.67-11.00 %). Bioinformatic analyses highlighted apoptosis-related targets and pathways as key mechanisms underlying the observed associations. This study provides comprehensive evidence linking VOC exposure to sarcopenia, emphasizing the importance of reducing VOC exposure to prevent sarcopenia and associated health risks.