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Abstract Background Z-DNA binding protein 1 (ZBP1) is a nucleic acid sensor that is involved in multiple inflammatory diseases, but whether and how it contributes to osteoarthritis (OA) are unclear. Methods Cartilage tissues were harvested from patients with OA and a murine model of OA to evaluate ZBP1 expression. Subsequently, the functional role and mechanism of ZBP1 were examined in primary chondrocytes, and the role of ZBP1 in OA was explored in mouse models. Results We showed the upregulation of ZBP1 in articular cartilage originating from OA patients and mice with OA after destabilization of the medial meniscus (DMM) surgery. Specifically, knockdown of ZBP1 alleviated chondrocyte damage and protected mice from DMM-induced OA. Mechanistically, tumor necrosis factor alpha induced ZBP1 overexpression in an interferon regulatory factor 1 (IRF1)-dependent manner and elicited the activation of ZBP1 via mitochondrial DNA (mtDNA) release and ZBP1 binding. The upregulated and activated ZBP1 could interact with receptor-interacting protein kinase 1 and activate the transforming growth factor-beta-activated kinase 1-NF-κB signaling pathway, which led to chondrocyte inflammation and extracellular matrix degradation. Moreover, inhibition of the mtDNA-IRF1-ZBP1 axis with Cyclosporine A, a blocker of mtDNA release, could delay the progression of DMM-induced OA. Conclusions Our data revealed the pathological role of the mtDNA-IRF1-ZBP1 axis in OA chondrocytes, suggesting that inhibition of this axis could be a viable therapeutic approach for OA.

Summary: Osteoarthritis (OA) is a progressive degenerative joint disease, and the underlying molecular mechanisms of OA remain poorly understood. This study aimed to elucidate the relationship between mitochondrial autophagy and OA by identifying key regulatory genes and their biological functions. Utilizing bioinformatics analyses of RNA expression profiles from the GSE55235 dataset, we identified 2,136 differentially expressed genes, leading to the discovery of hub genes associated with mitochondrial autophagy and OA. Gene set enrichment analysis (GSEA) revealed their involvement in critical pathways, highlighting their potential roles in OA pathogenesis. Furthermore, our study explored the immunological landscape of OA, identifying distinct immune cell infiltration patterns that contribute to the disease’s inflammatory profile. We also evaluated the therapeutic potential of drugs targeting these hub genes, suggesting potential approaches for OA treatment. Collectively, this study advances our knowledge of mitochondrial autophagy in OA and proposes promising biomarkers and therapeutic targets.

Aims: Osteoarthritis (OA) is the most common chronic pathema of human joints. The pathogenesis is complex, involving physiological and mechanical factors. In previous studies, we found that ferroptosis is intimately related to OA, while the role of Sat1 in chondrocyte ferroptosis and OA, as well as the underlying mechanism, remains unclear. Methods: In this study, interleukin-1β (IL-1β) was used to simulate inflammation and Erastin was used to simulate ferroptosis in vitro. We used small interfering RNA (siRNA) to knock down the spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15), and examined damage-associated events including inflammation, ferroptosis, and oxidative stress of chondrocytes. In addition, a destabilization of the medial meniscus (DMM) mouse model of OA induced by surgery was established to investigate the role of Sat1 inhibition in OA progression. Results: The results showed that inhibition of Sat1 expression can reduce inflammation, ferroptosis changes, reactive oxygen species (ROS) level, and lipid-ROS accumulation induced by IL-1β and Erastin. Knockdown of Sat1 promotes nuclear factor-E2-related factor 2 (Nrf2) signalling. Additionally, knockdown Alox15 can alleviate the inflammation-related protein expression induced by IL-1β and ferroptosis-related protein expression induced by Erastin. Furthermore, knockdown Nrf2 can reverse these protein expression alterations. Finally, intra-articular injection of diminazene aceturate (DA), an inhibitor of Sat1, enhanced type II collagen (collagen II) and increased Sat1 and Alox15 expression. Conclusion: Our results demonstrate that inhibition of Sat1 could alleviate chondrocyte ferroptosis and inflammation by downregulating Alox15 activating the Nrf2 system, and delaying the progression of OA. These findings suggest that Sat1 provides a new approach for studying and treating OA. Cite this article: Bone Joint Res 2024;13(3):110–123.

Temperature swing adsorption is one of most important means of the enrichment of xenon, and temperature is an important factor affecting adsorbent performance for xenon. In this paper, the dynamic adsorption experimental platform at ultra-low temperatures was designed, based on which the adsorption characteristics of carbon molecular sieve for xenon was studied within the temperature range of -110 ℃ to -60 ℃. The effects of xenon volume fraction, gas flow rate, inlet pressure, and inner diameter of the adsorption column on xenon adsorption performance were analyzed at -110 ℃. The results show that at -110 ℃, the volume fraction of xenon and flow rate have the most significant effects on the dynamic adsorption coefficient of xenon, while the effects of the inlet pressure and the inner diameter of the adsorption column are less than the above two factors within a certain range.

Abstract Fraxinus hubeiensis is a plant endemic to China and widely used as folk medicine to treat various diseases. However, its chemical constituents have never been reported sufficiently. Thus, the primary objective of this study was to investigate the phytochemical constituents and biological activities of F. hubeiensis leaves. Hence, combined column chromatographic and spectroscopic techniques were used to identify and characterize the secondary metabolites such as a pair of 3-keto-glycoside epimers (1) and (2), along with five known compounds (3 ~ 7). The results of α-glucosidase inhibitory activity exhibited that 1 and 2 had moderate activity with IC50 values of 359.50 and 468.43 µM, respectively, compared to a positive control acarbose with the IC50 value of 164.08 µM. However, Compounds 1–6 were shown to be inactive against the tested microbes.

Background: Tubulointerstitial fibrosis (TIF) is a critical pathological feature of chronic renal failure (CRF), with oxidative stress (OS) and hypoxic responses in renal proximal tubular epithelial cells playing pivotal roles in disease progression. This study explores the effects of Modified Zhenwu Tang (MZWT) on these processes, aiming to uncover its potential mechanisms in slowing CRF progression. Methods: We used adenine (Ade) to induce CRF in rats, which were then treated with benazepril hydrochloride (Lotensin) and MZWT for 8 weeks. Assessments included liver and renal function, electrolytes, blood lipids, renal tissue pathology, OS levels, the hypoxia-inducible factor (HIF) pathway, inflammatory markers, and other relevant indicators. In vitro, human renal cortical proximal tubular epithelial cells were subjected to hypoxia and lipopolysaccharide for 72 h, with concurrent treatment using MZWT, FM19G11, and N-acetyl-l-cysteine. Measurements taken included reactive oxygen species (ROS), HIF pathway activity, inflammatory markers, and other relevant indicators. Results: Ade treatment induced significant disruptions in renal function, blood lipids, electrolytes, and tubulointerstitial architecture, alongside heightened OS, HIF pathway activation, and inflammatory responses in rats. In vivo, MZWT effectively ameliorated proteinuria, renal dysfunction, lipid and electrolyte imbalances, and renal tissue damage; it also suppressed OS, HIF pathway activation, epithelial-mesenchymal transition (EMT) in proximal tubular epithelial cells, and reduced the production of inflammatory cytokines and collagen fibers. In vitro findings demonstrated that MZWT decreased apoptosis, reduced ROS production, curbed OS, HIF pathway activation, and EMT in proximal tubular epithelial cells, and diminished the output of inflammatory cytokines and collagen. Conclusion: OS and hypoxic responses significantly contribute to TIF development. MZWT mitigates these responses in renal proximal tubular epithelial cells, thereby delaying the progression of CRF.

Currently, the spectra-based physical models and deep learning methods are frequently used to detect wildfires from remote sensing data. However, physical algorithms mainly rely on radiative transfer processes, which limit their effectiveness in detecting small and weak fires. On the other hand, deep learning methods usually lack mechanism constraints, thus generally resulting in false alarms of bright surfaces. It is promising to combine the advantages of them and correspondingly reduce the inherent error of a single algorithm. To this end, in this paper, both the local contextual and the global index method based on physical mechanisms are optimized, simultaneously, a new U-Net model is also establish to accurately detect fires. Moreover, YOLO v5 is incorporated for the first time to extract and remove the false alarms of objects with high exposure. Based on the above series of novel works, a self-adaptive fusing algorithm is finally proposed. Our results reveal that: (1) Short-wave infrared band of about 2.15 μm is crucial in fire detection for data with moderate-to-high resolutions. Taking Landsat 8 as an example, the band combinations of 7, 6, 2(SWIR + VI), 7, 6, 5(SWIR + NIR), and 7, 5, 3(SWIR + VI + NIR) show reasonable accuracy, with recall rate of greater than 81 %. The thermal infrared band can be used to assist in detecting the general location of the fire and serve as alternative choice in extreme cases. (2) The optimized physical algorithm can reduce false alarms and predict more accurate fire positions. (3) It is very effective to introduce the YOLO v5 framework to remove false alarms with high exposure in urban and suburban regions. (4) The proposed self-adaptive fusion algorithm integrates the advantages of various schemes, proving its better performance in terms of robustness, stability and generality compared to any single method. Even in extreme situations such as the Gobi Desert, thin cloud edges, and mountain shadow areas, the fusion algorithm still works well. The generality tests based on Sentinel-2A, WorldView-3, and SPOT-4 reveal the potential applicability of the newly proposed fusing algorithm, especially for data with fine spatial and spectral resolutions.