Comprehensive bulk and single-cell transcriptome profiling give useful insights into the characteristics of osteoarthritis associated synovial macrophages

BackgroundOsteoarthritis (OA) is a common chronic joint disease, but the association between molecular and cellular events and the pathogenic process of OA remains unclear.ObjectiveThe study aimed to identify key molecular and cellular events in the processes of immune infiltration of the synovium in OA and to provide potential diagnostic and therapeutic targets.MethodsTo identify the common differential expression genes and function analysis in OA, we compared the expression between normal and OA samples and analyzed the protein–protein interaction (PPI). Additionally, immune infiltration analysis was used to explore the differences in common immune cell types, and Gene Set Variation Analysis (GSVA) analysis was applied to analyze the status of pathways between OA and normal groups. Furthermore, the optimal diagnostic biomarkers for OA were identified by least absolute shrinkage and selection operator (LASSO) models. Finally, the key role of biomarkers in OA synovitis microenvironment was discussed through single cell and Scissor analysis.ResultsA total of 172 DEGs (differentially expressed genes) associated with osteoarticular synovitis were identified, and these genes mainly enriched eight functional categories. In addition, immune infiltration analysis found that four immune cell types, including Macrophage, B cell memory, B cell, and Mast cell were significantly correlated with OA, and LASSO analysis showed that Macrophage were the best diagnostic biomarkers of immune infiltration in OA. Furthermore, using scRNA-seq dataset, we also analyzed the cell communication patterns of Macrophage in the OA synovial inflammatory microenvironment and found that CCL, MIF, and TNF signaling pathways were the mainly cellular communication pathways. Finally, Scissor analysis identified a population of M2-like Macrophages with high expression of CD163 and LYVE1, which has strong anti-inflammatory ability and showed that the TNF gene may play an important role in the synovial microenvironment of OA.ConclusionOverall, Macrophage is the best diagnostic marker of immune infiltration in osteoarticular synovitis, and it can communicate with other cells mainly through CCL, TNF, and MIF signaling pathways in microenvironment. In addition, TNF gene may play an important role in the development of synovitis

Characterization of the Transcriptome of Hair Cell Regeneration in the Neonatal Mouse Utricle

Background/Aims: Hearing and balance deficits are mainly caused by loss of sensory inner ear hair cells. The key signals that control hair cell regeneration are of great interest. However, the molecular events by which the cellular signals mediate hair cell regeneration in the mouse utricle are largely unknown. Methods: In the present study, we investigated gene expression changes and related molecular pathways using RNA-seq and qRT-PCR in the newborn mouse utricle in response to neomycin-induced damage. Results: There were 302 and 624 genes that were found to be up-regulated and down-regulated in neomycin-treated samples. GO and KEGG pathway analyses of these genes revealed many deregulated cellular components, molecular functions, biological processes and signaling pathways that may be related to hair cell development. More importantly, the differentially expressed genes included 9 transcription factors from the zf-C2H2 family, and eight of them were consistently down-regulated during hair cell damage and subsequent regeneration. Conclusion: Our results provide a valuable source for future studies and highlighted some promising genes, pathways or processes that may be useful for therapeutic applications

Persistent sulfate formation from London Fog to Chinese haze

Sulfate aerosols exert profound impacts on human and ecosystem health, weather, and climate, but their formation mechanism remains uncertain. Atmospheric models consistently underpredict sulfate levels under diverse environmental conditions. From atmospheric measurements in two Chinese megacities and complementary laboratory experiments, we show that the aqueous oxidation of SO2 by NO2 is key to efficient sulfate formation but is only feasible under two atmospheric conditions: on fine aerosols with high relative humidity and NH3 neutralization or under cloud conditions. Under polluted environments, this SO2 oxidation process leads to large sulfate production rates and promotes formation of nitrate and organic matter on aqueous particles, exacerbating severe haze development. Effective haze mitigation is achievable by intervening in the sulfate formation process with enforced NH3 and NO2 control measures. In addition to explaining the polluted episodes currently occurring in China and during the 1952 London Fog, this sulfate production mechanism is widespread, and our results suggest a way to tackle this growing problem in China and much of the developing world

Predicting Adolescent Idiopathic Scoliosis among Chinese Children and Adolescents

Objective. Adolescent idiopathic scoliosis (AIS) affects 1%-4% of adolescents in the early stages of puberty, but there is still no effective prediction method. This study aimed to establish a prediction model and validated the accuracy and efficacy of this model in predicting the occurrence of AIS. Methods. Data was collected from a population-based school scoliosis screening program for AIS in China. A sample of 884 children and adolescents with the radiological lateral Cobb angle≥10° was classified as an AIS case, and 895 non-AIS subjects with a Cobb angle<10° were randomly selected from the screening system. All selected subjects were screened by visual inspection of clinical signs, the Adam’s forward-bending test (FBT), and the measurement of angle of trunk rotation (ATR). LR and receiver operating characteristic (ROC) curves were used to preliminarily screen the influential factors, and LR models with different adjusted weights were established to predict the occurrence of AIS. Results. Multivariate LR and ROC curves indicated that angle of thoracic rotation (adjusted odds ratios AOR=5.18−10.06), angle of thoracolumbar rotation (AOR=4.67−7.22), angle of lumbar rotation (AOR=6.97−8.09), scapular tilt (area under the curve AUC=0.77, 95% CI: 0.75-0.80), shoulder-height difference, lumbar concave, and pelvic tilt were the risk predictors for AIS. LR models with different adjusted weights (by AOR, AUC, and AOR+AUC) performed similarly in predicting the occurrence of AIS compared with multivariate LR. The sensitivity (82.55%-83.27%), specificity (82.59%-83.33%), Youden’s index (0.65-0.67), positive predictive value (82.85%-83.58%), negative predictive value (82.29%-83.03%), and total accuracy (82.57%-83.30%) manifested that LR could accurately identify patients with AIS. Conclusions. LR model is a relatively high accurate and feasible method for predicting AIS. Increased performance of LR models using clinically relevant variables offers the potential to early identify high-risk groups of AIS

Biomarkers in patients with myocardial fibrosis

Myocardial fibrosis is observed in many cardiovascular diseases including hypertension, heart failure and cardiomyopathy. Myocardial fibrosis has been proved to be reversible and treatable only under timely intervention, which makes early detection and assessment of fibrosis crucial. Aside from tissue biopsy as the gold standard for the diagnosis of myocardial fibrosis, circulating biomarkers have been adopted as noninvasive assessment of this lesion. Dysregulated collagen deposition is thought to be the major cause of myocardial fibrosis. Collagens, procollagens, TGF-β, TIMP, galectin-3, and microRNAs are thought to be indicators of myocardial fibrosis. In this review, we summarize the molecules that are frequently used as biomarkers in diagnosis of cardiac fibrosis. Mechanisms of fibrosis that they take part in are also introduced

Durability investigation of fractured coal-gasified ash slag concrete eroded by sulfate and chlorine salts

The combined action of sulfate and chlorine salts erodes concrete structures in coastal and saline-alkali zones. The induced fractures under load also accelerate the deterioration of concrete. In this study, ion erosion tests of fractured coal-gasified ash slag (FC-GAS) concrete under dry-wet cyclic conditions were performed using ordinary concrete as the reference. The mass loss rates, the relative dynamic moduli of elasticity, and the distribution patterns of chlorine and sulfate ions of specimens in erosive environments of single sulfate salt, single chlorine salt, and mixed sulfate and chlorine salts were measured. The deterioration mechanism of FC-GAS concrete under coupled erosion by sulfate and chlorine salts was explored with SEM and XRD techniques. By introducing the influence coefficient and deterioration coefficient of the fracture width of FC-GAS concrete, a modified model describing the diffusion behavior of chlorine ions in FC-GAS concrete was established. The results show that for the concrete specimens after erosion in sulfate salt and the mixture of sulfate and chlorine salts, the mass and the relative dynamic modulus of elasticity first increased and then dropped. The deterioration of the concrete performance after soaking in the mixed solution was significantly lower than that of the specimen after dry-wet cycles in the single solution. The formation of fractures accelerated ion erosion. Chlorine and sulfate ions in the mixed solution could inhibit the diffusion of other ions. The diffraction peak strengths of the erosion products of the specimen after dry-wet cycles in the mixed solution were significantly reduced. The results calculated by the proposed modified model on the diffusion of chlorine ions in FC-GAS concrete agreed with the experimental results

Liproxstatin-1 Protects Hair Cell-Like HEI-OC1 Cells and Cochlear Hair Cells against Neomycin Ototoxicity

Ferroptosis is a recently discovered iron-dependent form of oxidative programmed cell death distinct from caspase-dependent apoptosis. In this study, we investigated the effect of ferroptosis in neomycin-induced hair cell loss by using selective ferroptosis inhibitor liproxstatin-1 (Lip-1). Cell viability was identified by CCK8 assay. The levels of reactive oxygen species (ROS) were determined by DCFH-DA and cellROX green staining. The mitochondrial membrane potential (ΔΨm) was evaluated by TMRM staining. Intracellular iron and lipid peroxides were detected with Mito-FerroGreen and Liperfluo probes. We found that ferroptosis can be induced in both HEI-OC1 cells and neonatal mouse cochlear explants, as evidenced by Mito-FerroGreen and Liperfluo staining. Further experiments showed that pretreatment with Lip-1 significantly alleviated neomycin-induced increased ROS generation and disruption in ΔΨm in the HEI-OC1 cells. In parallel, Lip-1 significantly attenuated neomycin-induced hair cell damage in neonatal mouse cochlear explants. Collectively, these results suggest a novel mechanism for neomycin-induced ototoxicity and suggest that ferroptosis inhibition may be a new clinical intervention to prevent hearing loss