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Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage loss that causes disability worldwide. The accumulation of senescent chondrocytes in aging human cartilage contributes to the high incidence of OA. Heterochromatin instability, the hallmark and driving factor of senescence, regulates the expression of the senescence-associated secretory phenotype that induces inflammation and cartilage destruction. However, the role of heterochromatin instability in OA progression remains unclear. In this work, we identified AURKB as a key senescence-associated chromatin regulator using bioinformatics methods. We found that AURKB was upregulated in OA cartilage and chondrocytes exposed to abnormal mechanical strain. Overexpression of AURKB could cause senescence and heterochromatin instability. Furthermore, the AURKB inhibitor Barasertib reversed senescence and heterochromatin instability in chondrocytes and alleviated OA in a rat model. Mechanistically, abnormal mechanical strain increased AURKB levels through the Piezo1/Ca2+ signaling axis. Blocking Piezo1/Ca2+ signaling by short interfering RNA against Piezo1 and Ca2+ chelator BAPTA could reduce the expression of AURKB and alleviate senescence in chondrocytes exposed to abnormal mechanical strain. In conclusion, our data confirmed that abnormal mechanical strain increases the expression of AURKB by activating the Piezo1/Ca2+ signaling axis, leading to destabilized heterochromatin and senescence in chondrocytes, whereas Barasertib consolidates heterochromatin, counteracts senescence and alleviates OA.

Abstract Background Osteoarthritis (OA) is a common chronic disease characterized by chronic inflammation and extracellular matrix degradation. Indole-3-propionic acid (IPA) is a tryptophan metabolite secreted by intestinal flora, which can exert anti-inflammatory effects in a variety of diseases. In this study, we further investigated the potential therapeutic role of IPA in OA and the underlying mechanism. Methods IL-1β was utilized to induce chondrocyte inflammation. Then, the cytotoxicity of IPA on rat chondrocytes was assessed. Meanwhile, RT-qPCR, Griess reaction, ELISA, Western blot and immunofluorescence were performed to evaluate the expression of inflammatory factors and stromal proteins, and the NF-κB pathway in chondrocytes treated with IL-1β alone, with IPA or with aryl hydrocarbon receptor (AhR) knockdown. An OA rat model was established by anterior cruciate ligament transection, and hematoxylin-eosin staining, Safranin-O/Fast Green staining and immunochemistry were applied to estimate OA severity. Results IPA did not affect cellular viability at concentrations up to 80 µM. IPA significantly inhibited the IL-1β-induced expression of inflammatory factors (Nitric oxide, PGE2, TNF-α, IL-6, iNOS and COX-2) and matrix-degrading enzymes (MMP-3, MMP-13 and ADAMTS-5), upregulated the expression of anabolic markers (aggrecan and collagen-II) and inactivated the NF-κB pathway. However, AhR knockdown could abolish the above protection capabilities and the suppression of the NF-κB pathway induced by IPA. Furthermore, IPA significantly reduced serum inflammatory cytokines expression, cartilage destruction and synovitis in vivo, demonstrating its protective role in OA progression. Conclusion IPA improved IL-1β-induced chondrocyte inflammation and extracellular matrix degradation through the AhR/NF-κB axis, which provides an innovative therapeutic strategy for OA.

Osteoarthritis (OA) is a common and disabling disease. For advanced OA, surgical treatment is still the main treatment. Human umbilical cord mesenchymal stem cells (hUC-MSCs) are self-regenerative pluripotent cells, that coordinate cartilage regeneration by secreting various trophic factors, which adjust the injured tissue environment. hUC-MSCs secret extracellular vesicles and participates in OA treatment by transmitting bioactive molecules related to migration, proliferation, apoptosis, inflammatory reaction, extracellular matrix synthesis and cartilage repair. In addition, the combination of multiple substances represented by cartilage matrix and hUC-MSCs also have a significant synergistic effect on OA treatment. Because hUC-MSCs have shown considerable promise in cartilage repair, some scholars have proposed transplanting mesenchymal stem cells into damaged cartilage to delay OA progression. This article reviews the application of hUC-MSCs as a treatment for OA. With the continuous development of routine clinical applications, more reliable intervention modalities for hUC-MSCs in OA treatment will be discovered for the time to come.

Abstract Airborne SARS‐CoV‐2 virus surveillance faces challenges in complicated biomarker enrichment, interferences from various non‐specific matters and extremely low viral load in the urban ambient air, leading to difficulties in detecting SARS‐CoV‐2 bioaerosols. This work reports a highly specific bioanalysis platform, with an exceptionally low limit‐of‐detection (≤1 copy m−3) and good analytical accordance with RT‐qPCR, relying on surface‐mediated electrochemical signaling and enzyme‐assisted signal amplification, enabling gene and signal amplification for accurate identification and quantitation of low doses human coronavirus 229E (HCoV‐229E) and SARS‐CoV‐2 viruses in urban ambient air. This work provides a laboratory test using cultivated coronavirus to simulate the airborne spread of SARS‐CoV‐2, and validate that the platform could reliably detect airborne coronavirus and reveal the transmission characteristics. This bioassay conducts the quantitation of real‐world HCoV‐229E and SARS‐CoV‐2 in airborne particulate matters collected from road‐side and residential areas in Bern and Zurich (Switzerland) and Wuhan (China), with resultant concentrations verified by RT‐qPCR.

AS1411 aptamer can function as a recognition probe to detect the cell surface nucleolin overexpressed in cancer cells, however, little is known about their binding process. This study proposed a feasible binding mode for the first time and provided atomic-level descriptions for the high affinity and specific binding of AS1411. The binding pose predicted by docking was screened using knowledge-based criteria, and a microsecond molecular dynamics (MD) simulation showed the stable existence of the predicted structure in the solution. Structural analysis shows that the unique capping of the 5′ end of AS1411 provides the specific binding with RBD1, and the interactions of hydrogen bond, salt bridge, and water-mediated network between AS1411 and RBD1,2 stabilize the binding. The calculation of per-residue decomposition emphasizes the dominant contribution of van der Waals energy and critical residues are screened. Our study provides the molecular basis of this specific binding and can guide rational AS1411-based aptamers design. Further insights require tight collaborations between the experiments and in silico studies.

Accumulation of senescent cells is the prominent risk factor for osteoarthritis (OA), accelerating the progression of OA through a senescence-associated secretory phenotype (SASP). Recent studies emphasized the existence of senescent synoviocytes in OA and the therapeutic effect of removing senescent synoviocytes. Ceria nanoparticles (CeNP) have exhibited therapeutic effects in multiple age-related diseases due to their unique capability of ROS scavenging. However, the role of CeNP in OA remains unknown. Our results revealed that CeNP could inhibit the expression of senescence and SASP biomarkers in multiple passaged and hydrogen-peroxide-treated synoviocytes by removing ROS. In vivo, the concentration of ROS in the synovial tissue was remarkably suppressed after the intra-articular injection of CeNP. Likewise, CeNP reduced the expression of senescence and SASP biomarkers as determined by immunohistochemistry analysis. The mechanistic study showed that CeNP inactivated the NFκB pathway in senescent synoviocytes. Finally, safranin O–fast green staining showed milder destruction of articular cartilage in the CeNP-treated group compared with the OA group. Overall, our study suggested that CeNP attenuated senescence and protected cartilage from degeneration via scavenging ROS and inactivating the NFκB signaling pathway. This study has potentially significant implications in the field of OA as it provides a novel strategy for OA treatment.

Atomization and spraying are well-established methods for the production of submicrometer- and micrometer- sized powders. In addition, they could be of interest to the immobilization of photocatalytic nanoparticles onto supports because they enable the formation of microporous films with photocatalytic activity. Here, we provide a comparison of aerosol-assisted immobilization methods, such as spray-drying (SD), spray atomization (SA), and spray gun (SG), which were used for the deposition of TiO2 dispersions onto fibrous filter media. The morphology, microstructure, and electronic properties of the structures with deposited TiO2 were characterized by SEM and TEM, BET and USAXS, and UV-Vis spectrometry, respectively. The photocatalytic performances of the functionalized filters were evaluated and compared to the benchmark dip-coating method. Our results showed that the SG and SA immobilization methods led to the best photocatalytic and operational performance for the degradation of toluene, whereas the SD method showed the lowest degradation efficiency and poor stability of coating. We demonstrated that TiO2 sprays using the SG and SA methods with direct deposition onto filter media involving dispersed colloidal droplets revealed to be promising alternatives to the dip-coating method owing to the ability to uniformly cover the filter fibers. In addition, the SA method allowed for fast and simple control of the coating thickness as the dispersed particles were continuously directed onto the filter media without the need for repetitive coatings, which is common for the SG and dip-coating methods. Our study highlighted the importance of the proper immobilization method for the efficient photocatalytic degradation of VOCs.

Excessive mechanical strain is the prominent risk factor for osteoarthritis (OA), causing cartilage destruction and degeneration. However, the underlying molecular mechanism contributing to mechanical signaling transduction remains unclear in OA. Piezo type mechanosensitive ion channel component 1 (Piezo1) is a calcium-permeable mechanosensitive ion channel and provides mechanosensitivity to cells, but its role in OA development has not been determined. Herein, we found up-regulated expression of Piezo1 in OA cartilage, and that its activation contributes to chondrocyte apoptosis. The knockdown of Piezo1 could protect chondrocytes from apoptosis and maintain the catabolic and anabolic balance under mechanical strain. In vivo, Gsmtx4, a Piezo1 inhibitor, markedly ameliorated the progression of OA, inhibited the chondrocyte apoptosis, and accelerated the production of the cartilage matrix. Mechanistically, we observed the elevated activity of calcineurin (CaN) and the nuclear transfection of nuclear factor of activated T cells 1 (NFAT1) under mechanical strain in chondrocytes. Inhibitors of CaN or NFAT1 rescued the pathologic changes induced by mechanical strain in chondrocytes. Overall, our findings revealed that Piezo1 was the essential molecule response to mechanical signals and regulated apoptosis and cartilage matrix metabolism via the CaN/NFAT1 signaling axis in chondrocytes, and that Gsmtx4 could be an attractive therapeutic drug for OA treatment.

The soluble fraction of atmospheric transition metals is particularly associated with health effects such as reactive oxygen species compared to total metals. However, direct measurements of the soluble fraction are restricted to sampling and detection units in sequence burdened with a compromise between time resolution and system bulkiness. Here, we propose the concept of aerosol-into-liquid capture and detection, which allowed one-step particle capture and detection via the Janus-membrane electrode at the gas–liquid interface, enabling active enrichment and enhanced mass transport of metal ions. The integrated aerodynamic/electrochemical system was capable of capturing airborne particles with a cutoff size down to 50 nm and detecting Pb(II) with a limit of detection of 95.7 ng. The proposed concept can pave the way for cost-effective and miniaturized systems, for the capture and detection of airborne soluble metals in air quality monitoring, especially for abrupt air pollution events with high airborne metal concentrations (e.g., wildfires and fireworks). [ABSTRACT FROM AUTHOR]