E6 Protein Expressed by High-Risk HPV Activates Super-Enhancers of the EGFR and c-MET Oncogenes by Destabilizing the Histone

The high-risk (HR) human papillomaviruses (HPV) are causative agents of anogenital tract dysplasia and cancers and a fraction of head and neck cancers. The HR HPV E6 oncoprotein possesses canonical oncogenic functions, such as p53 degradation and telomerase activation. It is also capable of stimulating expression of several oncogenes, but the molecular mechanism underlying these events is poorly understood. Here, we provide evidence that HPV16 E6 physically interacts with histone H3K4 demethylase KDM5C, resulting in its degradation in an E3 ligase E6AP- and proteasome-dependent manner. Moreover, we found that HPV16-positive cancer cell lines exhibited lower KDM5C protein levels than HPV-negative cancer cell lines. Restoration of KDM5C significantly suppressed the tumorigenicity of CaSki cells, an HPV16-positive cervical cancer cell line. Whole genome ChIP-seq and RNA-seq results revealed that CaSki cells contained super-enhancers in the proto-oncogenes EGFR and c-MET. Ectopic KDM5C dampened these super-enhancers and reduced the expression of proto-oncogenes. This effect was likely mediated by modulating H3K4me3/H3K4me1 dynamics and decreasing bidirectional enhancer RNA transcription. Depletion of KDM5C or HPV16 E6 expression activated these two super-enhancers. These results illuminate a pivotal relationship between the oncogenic E6 proteins expressed by HR HPV isotypes and epigenetic activation of super-enhancers in the genome that drive expression of key oncogenes like EGFR and c-MET. Significance: This study suggests a novel explanation for why infections with certain HPV isotypes are associated with elevated cancer risk by identifying an epigenetic mechanism through which E6 proteins expressed by those isotypes can drive expression of key oncogenes.</p

Model-Based Fault Diagnosis of Actuators in Electronically Controlled Air Suspension System

The air suspension adjusts the height of the vehicle body through charging and bleeding air to meet the high performance of the vehicle, which needs a reliable electronic control system. Through fault tree analysis of the electronically controlled air suspension (ECAS) system and considering the correlation between the duty cycle and flow rate of the air spring solenoid valve, the fault model of the solenoid valve is constructed, and the fault diagnosis design method of the ECAS system solenoid valve based on multiple extended Kalman filter banks (EKFs) is proposed. An adaptive threshold is used to realize fault diagnosis, and active fault-tolerant control is carried out based on an analytical model. The real controller based on d2p rapid prototyping technology and the vehicle model based on AMESim are further verified on the hardware-in-the-loop (HiL) simulation test platform and compared with the pure simulation results. The test results show that the fault diagnosis and fault-tolerant control algorithm can work normally in the actual controller, and can effectively realize the fault diagnosis and fault-tolerant control of the actuator in the vehicle ECAS system

Effective Way to Control the Performance of a Ceria-Based DeNO_<i>x</i> Catalyst with Improved Alkali Resistance: Acid–Base Adjusting

Compared with V₂O₅–WO₃/TiO₂, the ceria catalyst supported on sulfated zirconia (referred to as CeSZ) shows a superior alkali resistance for selective catalytic reduction of NO in flue gases. It reveals an unexpected result that a moderate amount of potassium (normally considered as SCR poisons) could even enhance the activity of CeSZ catalyst. To investigate this exceptional phenomenon, we studied the surface acid–base properties of CeSZ catalysts with different amounts of K and their influences on SCR performances. Although K resulted in a sharp decrease in Brønsted acid sites, the total acidity, especially strong acidity, barely changed when K/Ce was less than 0.4. It was proposed that a small amount of potassium could initially alter some Brønsted acid sites to Lewis ones, therefore retaining the majority of total acidity. Moreover, increased surface basicity due to K depositing led to an enhancement in NO chemisorption and oxidation, which is beneficial to the SCR process via the reaction of NO₂ and NO_<i>x</i> ad-species with adsorbed NH₃ species. This explains why the SCR catalytic activity was improved at lower temperature for CeSZ catalysts after K depositing. Therefore, the catalytic activity and reaction temperature window of CeSZ catalyst could be controlled by simply tuning the surface acid/base sites, which may give some inspiration to improve the catalytic activity and poisoning tolerance

Insight into the Mechanism of Selective Catalytic Reduction of NO by CO over a Bimetallic IrRu/ZSM‑5 Catalyst in the Absence/Presence of O₂ by Isotopic C¹³O Tracing Methods

The development of efficient catalysts for the selective catalytic reduction of NO by CO (CO-SCR) in the presence of O2 is highly desirable for controlling the emission of toxic gases from tailpipes. Here, a bimetallic IrRu/ZSM-5 catalyst was prepared for the selective catalytic reduction of NO by CO in the presence of O2 (5%) for the low-temperature treatment of exhaust gas. IrRu/ZSM-5 afforded 90% NOx conversion in the range of 225–250 °C and maintained 90% NOx conversion after 12 h of reaction. Ru addition inhibited agglomeration of the Ir particles during the reduction process and provided more active sites for NO adsorption. Isotopic C13O tracing and in situ diffuse reflectance infrared Fourier-transform spectroscopy experiments were used to elucidate the CO-SCR mechanism in the absence or presence of O2. NCO could easily form on the surface of catalysts in the absence of O2, whereas NCO formation has been inhibited owing to the quick consumption of CO in the presence of O2. Moreover, some byproducts such as N2O and NO2 are generated in the presence of O2. Finally, a possible mechanism for CO-SCR under different conditions was proposed based on in situ experiments and physicochemical analyses