Esophageal cancer is among the most deadly malignant diseases. However, the genetic factors contributing to its occurrence are poorly understood. Multiple studies with large clinic-based cohorts revealed that variations of the phospholipase C epsilon (PLCE1) gene were associated with esophageal cancer susceptibility. However, the causative role of PLCE1 in esophageal cancer is not clear. We inactivated the functional alleles of PLCE1 by CRISPR/Cas9 genome editing technology. The resultant PLCE1 inactivated cells were analyzed both in vitro and in vivo. Our results showed that loss of PLCE1 dramatically decreased the invasion and proliferation capacity of esophageal carcinoma cells in vitro. Moreover, such PLCE1 inactivated tumor grafts exhibited significantly decreased tumor size in mice. We found that PLCE1 was required to maintain protein level of snail a key transcription factor responsible for invasion. Our further transcriptomic data revealed that deficient cells were significantly decreased in expression of genes enriched as targets of Snail. Strikingly, recovery of Snail protein at least partially rescued the invasion and proliferation capacity in PLCE1 inactivated cells. In ESCC clinical specimens, PLCE1 was correlated with tumor stage (P < .0001). Interestingly, PLCE1 expression was positively correlated Snail by immunohistochemistry in such specimens (P < .0001). Therefore, our functional experiments showed the essential roles of PLCE1 in esophageal carcinoma cells and provided evidences that targeting PLCE1 and its downstream molecules could be effective therapies for esophageal cancer.
Stable triggering of acquisition devices is critical to accurately measure electromagnetic transients, especially for very fast transient overvoltages (VFTOs). A highly stable and lowcos t self-trigger method for transient measurement is proposed. An integrated low-voltage arm module was developed to synchronously realise the triggering and VFTO measurement. The trigger branch was developed using a high-pass filter. This component obtained the high-frequency component of the VFTO to trigger the oscilloscope. The trigger branch was integrated with the measurement branch through an impedance converter. An attenuator was implemented before the impedance converter to avoid overvoltage damage to the chip. The circuit parameters of the attenuator were optimised to alleviate the disturbance of the measurement branch. The calibration results demonstrated that the �1 dB bandwidth of the measurement branch in this system ranged from 11.8 Hz to 105 MHz. The low cutoff frequency of the trigger branch was 710 Hz. The VFTO waveforms generated by the operation of a disconnector in a real 252 kV gas insulated switchgear were measured using the proposed system. The test results verified that the self-trigger measurement system can provide stable trigger signals and accurately measure the VFTO waveforms.
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