RESUMEN
Osteoarthritis (OA) is a prevalent degenerative joint disease with a lack of effective therapeutic. Chondrocyte ferroptosis contributes to the progression of OA. PUM2 is shown to exacerbate ischemia-reperfusion-induced neuroinflammation by promoting ferroptosis, but its role in OA remains unexplored. Here, primary mouse chondrocytes were stimulated with IL-1ß to mimic OA chondrocyte injury in vitro. And PUM2 was upregulated in OA cartilage tissues and IL-1ß-induced chondrocytes. Silencing PUM2 alleviated IL-1ß-induced chondrocyte inflammation and ECM degradation. Mechanistically, PUM2 facilitated the degradation of NEDD4 mRNA by binding to the 3'UTR of NEDD4 mRNA, which in turn inhibited NEDD4 induced PTEN ubiquitination and degradation. Consistently, NEDD4 silencing reversed the ameliorative effect of PUM2 knockdown on chondrocyte injury, and overexpression of PTEN abolished the improved role of NEDD4 in chondrocyte injury. Moreover, PTEN aggravated IL-1ß-induced ferroptosis in chondrocytes through the Nrf2/HO-1 pathway by increasing the levels of Fe2+, ROS, MDA, and ACSL4 protein, decreasing the activity of SOD and the levels of GSH and GPX4 protein, and aggravating mitochondrial damage. Additionally, destabilized medial meniscus (DMM) were conducted to establish the OA mouse model, and adenovirus-mediated PUM2 shRNA was administered intra-articularly. Silencing PUM2 attenuated OA-induced cartilage damage in vivo. In conclusion, PUM2 promoted OA progression through PTEN-mediated chondrocyte ferroptosis by facilitating NEDD4 mRNA degradation.
Asunto(s)
Condrocitos , Ferroptosis , Ubiquitina-Proteína Ligasas Nedd4 , Osteoartritis , Fosfohidrolasa PTEN , Animales , Condrocitos/metabolismo , Condrocitos/efectos de los fármacos , Ubiquitina-Proteína Ligasas Nedd4/metabolismo , Ubiquitina-Proteína Ligasas Nedd4/genética , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Ferroptosis/efectos de los fármacos , Osteoartritis/patología , Osteoartritis/metabolismo , Ratones , Humanos , Masculino , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Ratones Endogámicos C57BL , Estabilidad del ARN , ARN Mensajero/metabolismo , ARN Mensajero/genéticaRESUMEN
To develop solution-processed and novel device structures is of great importance for achieving advanced and low-cost solar cells. In this paper, we report the solution-processed solar cells based on inorganic bulk heterojunctions (BHJs) featuring a bulk crystalline Sb2S3 absorbing layer interdigitated with a TiO2 nanoarray as an electron transporter. A solution-processed amorphous-to-crystalline transformation strategy is used for the preparation of Sb2S3/TiO2-BHJs. Steady-state and dynamic results demonstrate that the crystalline structure in the Sb2S3 absorbing layer is crucial for efficient devices, and a better Sb2S3 crystallization favors a higher device performance by increasing the charge collection efficiency for a higher short-circuit current, due to reduced interfacial and bulk charge recombinations, and enhancing the open-circuit voltage and fill factor with the reduced defect states in the Sb2S3 layer as well. Moreover, an evident contribution to photocurrent generation from the photogenerated holes in the Sb2S3 layer is revealed by experimental and simulated dynamic data. These results imply a kind of potential non-excitonic BHJ for energy conversion.
RESUMEN
OBJECTIVE: To investigate the prevalence of impaired glucose-insulin metabolism in obstructive sleep apnea hypopnea syndrome (OSAHS); to examine the relation between severity of OSAHS and impaired glucose metabolism; and to evaluate the effectiveness of continuous positive airway pressure (CPAP) on impaired glucose metabolism. METHODS: A total of 214 patients who were free of diabetes at baseline underwent both nocturnal polysomnography (PSG), and 2-h oral glucose-tolerance test, insulin and hemoglobin A1c test. CPAP treatment for glucose-insulin metabolism (+) was given to OSAHS group after informed consent had been obtained. RESULTS: Eighty-eight patients and 17 patients with impaired glucose-insulin metabolism were found in OSAHS group and the control group respectively. Impaired glucose-insulin metabolism was present in 54.3% of OSAHS group and 32.7% of control group. Logistic regression analysis showed a significant positive correlation with OSAHS (AHI ≥ 10 times/h) and impaired glucose-insulin metabolism in all patients (OR = 2.440, 95%CI 1.201 - 4.958). Plasma glucose level changes had no significant differences between before and after CPAP treatment (P > 0.05). CONCLUSION: OSAHS is associated with a high frequency of impaired glucose metabolism. The relationship between OSAHS and impaired glucose metabolism is independent of obesity. Longest apnea time (LAT) and AHI are important contributors to impaired glucose metabolism in OSAHS patients. Short-term CPAP therapy has no significant improvement on glucose metabolism in patients with OSAHS.
Asunto(s)
Trastornos del Metabolismo de la Glucosa/complicaciones , Glucosa/metabolismo , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/metabolismo , Adulto , Anciano , Estudios de Casos y Controles , Presión de las Vías Aéreas Positiva Contínua , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Persona de Mediana Edad , Apnea Obstructiva del Sueño/terapiaRESUMEN
We herein report a DNA sensor for the sequence-specific DNA detection by using glucose oxidase-based biocatalyzed electrochemiluminescence and non-fouling surfaces. In this design, a glucose oxidase-labeled sandwich-type DNA sensor was built on a non-fouling surfaces made of a mixed self-assembled monolayers (SAMs) incorporating thiolated oligonucleotides and oligo(ethylene glycol) (OEG) thiols (SH-DNA/OEG). The sequence-specific DNA sensing was accomplished by the electrochemiluminesce (ECL) signal of luminol with the in-situ generated H(2)O(2). The protein-resistant non-fouling surfaces significantly suppressed the non-specific adsorption of enzyme label on electrode and reduced the background noise of this sensor. This sensor was able to detect as little as 1 pM of target DNA in pure buffer matrix. In complicated biological fluids such as human serum, this non-fouling platform-based sensor also revealed superior performance over conventional sandwich-type DNA sensors with mercaptohexanol (MCH)-coated surfaces. This strategy combines the high sensitivity of enzymatic amplified ECL and protein-resistant non-fouling platform, which is expected to be extended to a range of biological detection.