Activation of GDNF-ERK-Runx1 signaling contributes to P2X3R gene transcription and bone cancer pain.

Bone cancer pain is a common symptom in cancer patients with bone metastases and its underlying mechanisms remain unknown. Here, we report that Runx1 directly upregulates the transcriptional activity of P2X3 receptor (P2X3R) gene promoter in PC12 cells. Knocking down Runx1 in dorsal root ganglion (DRG) neurons suppresses the functional upregulation of P2X3R, attenuates neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats, whereas overexpressing Runx1 promotes P2X3R gene transcription in DRG neurons, induces neuronal hyperexcitability and pain hypersensitivity in naïve rats. Activation of GDNF-GFRα1-Ret-ERK signaling is required for Runx1-mediated P2X3R gene transcription in DRG neurons, and contributes to neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats. These findings indicate that the Runx1-mediated P2X3R gene transcription resulted from activation of GDNF-GFRα1-Ret-ERK signaling contributes to the sensitization of DRG neurons and pathogenesis of bone cancer pain. Our findings identify a potentially targetable mechanism that may cause bone metastasis-associated pain in cancer patients.

Whole exome sequencing is an alternative method in the diagnosis of mitochondrial DNA diseases.

BACKGROUND: Mitochondrial disease (MD) is genetically a heterogeneous group of disorders with impairment in respiratory chain complexes or pathways associated with the mitochondrial function. Nowadays, it is still a challenge for the genetic screening of MD due to heteroplasmy of mitochondrial genome and the complex model of inheritance. This study was designed to investigate the feasibility of whole exome sequencing (WES)-based testing as an alternative option for the diagnosis of MD. METHODS: A Chinese Han cohort of 48 patients with suspect MD features was tested using nanoWES, which was a self-designed WES technique that covered the complete mtDNA genome and 21,019 nuclear genes. Fourteen patients were identified with a single genetic variant and three with single deletion in mtDNA. RESULTS: The heteroplasmy levels of variants in mitochondrial genome range from 11% to 100%. NanoWES failed to identify multiple deletions in mtDNA compared with long range PCR and massively parallel sequencing (LR-PCR/MPS). However, our testing showed obvious advantages in identifying variations in nuclear DNA. Based on nanoWES, we identified two patients with nuclear DNA variation. One of them showed Xp22.33-q28 duplication, which indicated a possibility of Klinefelter syndrome. CONCLUSION: NanoWES yielded a diagnostic rate of 35.4% for MD. With the rapid advances of next generation sequencing technique and decrease in cost, we recommend the usage of nanoWES as a first-line method in clinical diagnosis.

Improving the removal of fine particles by chemical agglomeration during the limestone-gypsum wet flue gas desulfurization process.

Coal-fired power plants are considered a major source of fine particle emissions in China. Aimed to improve the removal efficiency of fine particles during the limestone-gypsum wet flue gas desulfurization (WFGD) process, a novel technology using chemical agglomeration to abate the emission of fine particles is presented herein. The relationship between fine particle emission and the proportion of fine particles in the desulfurization slurry was studied. Additionally, the influence of chemical agglomeration on fine particle size distribution, both in the flue gas and slurry was experimentally investigated. When chemical agglomeration agents were added to the desulfurization slurry, the fine particle removal performance as well as the effects of the operation parameters was also explored via the simulated experimental facility. The results revealed that the fine particles in both the desulfurization slurry and flue gas were significantly enlarged after the addition of the agglomeration agents. This was more marked in the submicron particles. Thus, the proportion of fine particles (< 10 µm) in the slurry decreased from 31.1% to 22.6%. An increase in the desulfurization slurry temperature and liquid-to-gas ratio aided the reduction in fine particle emission. Moreover, the addition of an agglomeration agent in the slurry did not affect the desulfurization efficiency of the desulfurization tower and even promoted the WFGD process. Thus, the proposed chemical agglomeration technique reduced the fine particle emission of the WFGD system by ~30%, while a desulfurization efficiency >90% was maintained.