RNF43 is a novel tumor-suppressor and prognostic indicator in clear cell renal cell carcinoma

Identifying prognostic indicators of clear cell renal cell carcinoma(ccRCC)and elucidating the mechanisms underlying ccRCC progression are crucial for improving ccRCC patient prognosis.This study investigated the clinical significance and biological role of Ring finger protein 43(RNF43)in ccRCC.Two independent cohorts of patients with ccRCC were employed to determine the prognostic significance of RNF43 by immunohistochemistry and statistical analyses.In vitro and in vivo experiments,RNA-seq,and other techniques were used to determine the biological role of RNF43 in ccRCC and related molecular mechanisms.RNF43 expression was commonly decreased in ccRCC specimens,and low expression of RNF43 indicated a higher TNM stage,SSIGN score,and WHO/ISUP grade and short survival in patients with ccRCC.Additionally,RNF43 overexpression suppressed the proliferation,migration,and targeted drug resistance of ccRCC cells,while the knockdown of RNF43 enhanced these characteristics of ccRCC.RNF43 knockdown activated YAP signaling by decreasing YAP phosphorylation by p-LATS1/2 and increasing the transcription and nuclear distribution of YAP.By contrast,RNF43 overexpression showed the opposite effects.Decreasing YAP abolished the effect of RNF43 knockdown in promoting the malignant features of ccRCC.Additionally,restoring RNF43 expression suppressed the resistance of the targeted drug pazopanib in in vivo orthotopic ccRCC.Furthermore,combining the expression of RNF43 and YAP with TNM stage or the SSIGN score exhibited greater accuracy than any of these indicators alone in assessing the postoperative prognosis of ccRCC patients.In summary,our study identified a novel tumor suppressor,RNF43,which is also a prognostic indicator and potential target for ccRCC.

Research on Protection of Tuning Area Equipment Disconnection in the ZPW-2000A Track Circuit

To overcome the problem of tuning area faults influencing the normal operation of the ZPW-2000A track circuit,protector models are established to protect the track circuit from interference.First,the parameters of the protector models are calculated according to the circuit resonance principle.Second,a four-terminal network model of the track circuit in a normal state is established according to transmission-line theory and the transmission equations are derived.Third,the rail voltage is simulated,and an experimental platform is built to verify the models.Finally,the transmission equations of the protectors are derived,and the variation of the rail voltage is analyzed.The results indicate that tuning area faults have significant influence on the rail voltage.However,the installation of protectors can effectively reduce the influence,and not bear on the normal operation and maintenance of the track circuit,which significantly improves the protection ability of the track circuit against tuning area faults.