CCAT2 contributes to hepatocellular carcinoma progression via inhibiting miR-145 maturation to induce MDM2 expression.

Long noncoding RNA colon cancer-associated transcript 2 (CCAT2) has been recently found to function as an oncogene in hepatocellular carcinoma (HCC). However, the mechanisms of CCAT2 in HCC development remain to be further explored. In the present study, we found that CCAT2 was abnormally upregulated in HCC cells and tissue specimens, exhibiting an inverse correlation with microRNA (miR)-145 expression. Mechanistic investigation showed that CCAT2 selectively blocked miR-145 processing, leading to decreased mature miR-145 presence. Both the in vitro and in vivo effects of CCAT2 knockdown on the proliferation and metastasis of HCC cells were reversed by miR-145 inhibitor, indicating that miR-145 modulation accounts for CCAT2-meditated HCC progression. Furthermore, miR-145 mimic dramatically suppressed HCC cells' proliferation and metastasis, revealing a tumor suppressor role of miR-145 in HCC. Mechanistically, MDM2 was predicted to be a potential target of miR-145. The luciferase and western blot assay demonstrated that miR-145 mimic largely inhibited MDM2 3'-untranslated region luciferase activity and MDM2 expression, followed by the upregulation of p53/p21 expression. Finally, the coexpression of MDM2 in miR-145 mimic-transfected HCC cells was able to largely compromise the inhibitory effects of miR-145 mimic on HCC cells' proliferation and metastasis in vitro and tumor formation in a xenograft model, confirming MDM2 is the critical mediator of miR-145 in HCC. In summary, our findings indicated that CCAT2 selectively blocks the miR-145 maturation process and plays an oncogene in HCC. Furthermore, a novel CCAT2/miR-145/MDM2 axis was revealed in HCC development and might provide a new target in the molecular treatment of HCC.

Phase-field study of the effects of the multi-controlling parameters on columnar dendrite during directional solidification in hexagonal materials.

The growth of hexagonal columnar dendrite during directional solidification with respect to the multi-controlling parameters such as anisotropy, cooling rate, temperature gradient and orientation angle were investigated by a quantitative phase-field method, respectively. The simulation results show that the increase of anisotropy, cooling rate and temperature gradient can accelerate the solidification velocity of columnar dendrites. Among them, the cooling rate has the most significant effect on the solidification velocity of columnar dendrite. In contrast, the solidification velocity of columnar dendrite slows down with the increase of the orientation angle. Meanwhile, the primary dendrite spacing decreases with the increase of cooling rates and temperature gradient, and the primary dendrite arms are smooth. The primary dendrite spacing increases with the increase of anisotropy and orientation angle, which provides space for the development of secondary dendrite arms. In addition, the effects of cooling rate and temperature gradient on the solid volume fraction were also studied.

The treatment of congenital pyriform sinus fistula: a single-center experience.

PURPOSE: Congenital pyriform sinus fistula (CPSF) often presents diagnosis and treatment challenges. This study aimed to explore the treatment principles and to evaluate the effectiveness of the hypothermia plasma cauterization with suspension laryngoscopy for CPSF. METHODS: The medical records of 56 patients with CPSF from January 2000 to December 2019 were retrospectively reviewed. RESULTS: Of the 56 cases, the lesions were predominantly located on the left side (95%), and the accuracy of the first diagnosis was 30%. Ultrasound showed an abnormal rate of 86%, while CT or MRI displayed an abnormal anatomic lesion of 92%. The 3D visual reconstruction enabled the analysis of morphological characteristics of CPSF. The positive predictive value of barium esophagography was 89%, whereas the positive rate of the internal opening in CPSF under local anesthesia laryngoscopy was 33%. Nine cases of sinus type underwent open resection, and the recurrence rate was 33%. Interestingly, ten patients with sinus type underwent hypothermia plasma cauterization with suspension laryngoscopy, leading to a success rate of 100% without apparent complications. CONCLUSIONS: Hypothermia plasma cauterization with suspension laryngoscopy alongside 3D imaging is both minimally invasive and repeatable with neglectable complications, which has the potential to serve as the first-line treatment for CPSF in the future.

Different triggers for the two pulses of mass extinction across the Permian and Triassic boundary.

Widespread ocean anoxia has been proposed to cause biotic mass extinction across the Permian-Triassic (P-Tr) boundary. However, its temporal dynamics during this crisis period are unclear. The Liangfengya section in the South China Block contains continuous marine sedimentary and fossil records. Two pulses of biotic extinction and two mass extinction horizons (MEH 1 & 2) near the P-Tr boundary were identified and defined based on lithology and fossils from the section. The data showed that the two pulses of extinction have different environmental triggers. The first pulse occurred during the latest Permian, characterized by disappearance of algae, large foraminifers, and fusulinids. Approaching the MEH 1, multiple layers of volcanic clay and yellowish micritic limestone occurred, suggesting intense volcanic eruptions and terrigenous influx. The second pulse occurred in the earliest Triassic, characterized by opportunist-dominated communities of low diversity and high abundance, and resulted in a structural marine ecosystem change. The oxygen deficiency inferred by pyrite framboid data is associated with biotic declines above the MEH 2, suggesting that the anoxia plays an important role.

Dexmedetomidine impairs P­glycoprotein­mediated efflux function in L02 cells via the adenosine 5'­monophosphate­activated protein kinase/nuclear factor­κB pathway.

Dexmedetomidine (DEX) a type of the anaesthetic that has been widely used in anaesthesia and intensive care. However, whether DEX affects the pharmacokinetics of drugs remains elusive. As hepatic P­glycoprotein (P­gp) serves a critical role in the disposition of drugs, the present study aimed to address whether P­gp function could be affected by DEX in vitro. In the present study, L02 cells (a normal human liver cell line) were exposed to DEX for 24 h and P­gp function was evaluated by the intracellular accumulation of Rhodamine 123. The results indicated that P­gp function was significantly impaired by DEX treatment and that the mRNA levels and protein levels of P­gp were downregulated in a dose­ and time­dependent manner. Importantly, DEX­induced downregulation of P­gp was associated with adenosine 5'­monophosphate-activated protein kinase (AMPK) activation, as it was significantly attenuated by AMPK inhibition using dorsomorphin. Furthermore, the results revealed that changes in the subcellular localisation of nuclear factor (NF)­κB following AMPK activation were involved in the P­gp regulation in response to DEX treatment. Collectively, these results suggested that DEX impairs P-glycoprotein­mediated efflux function in L02 cells via the AMPK/NF­κB pathway, which provided direct evidence that the hepatic disposition of drugs may be affected by DEX through the downregulation of P­gp.