Identification of Piwil2-Like (PL2L) Proteins that Promote Tumorigenesis

PIWIL2, a member of PIWI/AGO gene family, is expressed in the germline stem cells (GSCs) of testis for gametogenesis but not in adult somatic and stem cells. It has been implicated to play an important role in tumor development. We have previously reported that precancerous stem cells (pCSCs) constitutively express Piwil2 transcripts to promote their proliferation. Here we show that these transcripts de facto represent Piwil2-like (PL2L) proteins. We have identified several PL2L proteins including PL2L80, PL2L60, PL2L50 and PL2L40, using combined methods of Gene-Exon-Mapping Reverse Transcription Polymerase Chain Reaction (GEM RT-PCR), bioinformatics and a group of novel monoclonal antibodies. Among them, PL2L60 rather than Piwil2 and other PL2L proteins is predominantly expressed in various types of human and mouse tumor cells. It promotes tumor cell survival and proliferation in vitro through up-regulation of Stat3 and Bcl2 gene expressions, the cell cycle entry from G0/1 into S-phase, and the nuclear expression of NF-κB, which contribute to the tumorigenicity of tumor cells in vivo. Consistently, PL2L proteins rather than Piwil2 are predominantly expressed in the cytoplasm or cytoplasm and nucleus of euchromatin-enriched tumor cells in human primary and metastatic cancers, such as breast and cervical cancers. Moreover, nuclear PL2L proteins are always co-expressed with nuclear NF-κB. These results reveal that PL2L60 can coordinate with NF-κB to promote tumorigenesis and might mediate a common pathway for tumor development without tissue restriction. The identification of PL2L proteins provides a novel insight into the mechanisms of cancer development as well as a novel bridge linking cancer diagnostics and anticancer drug development

Precancerous Stem Cells Have the Potential for both Benign and Malignant Differentiation

Cancer stem cells (CSCs) have been identified in hematopoietic and solid tumors. However, their precursors—namely, precancerous stem cells (pCSCs) —have not been characterized. Here we experimentally define the pCSCs that have the potential for both benign and malignant differentiation, depending on environmental cues. While clonal pCSCs can develop into various types of tissue cells in immunocompetent mice without developing into cancer, they often develop, however, into leukemic or solid cancers composed of various types of cancer cells in immunodeficient mice. The progress of the pCSCs to cancers is associated with the up-regulation of c-kit and Sca-1, as well as with lineage markers. Mechanistically, the pCSCs are regulated by the PIWI/AGO family gene called piwil2. Our results provide clear evidence that a single clone of pCSCs has the potential for both benign and malignant differentiation, depending on the environmental cues. We anticipate pCSCs to be a novel target for the early detection, prevention, and therapy of cancers

Prediction model of critical liquid‐carrying gas velocity for high gas‐to‐liquid ratio gathering pipelines

As the pressure and temperature of natural gas pipelines decreases during operation, water and condensate accumulates form in the low areas of the pipelines, affecting the operational efficiency of the pipelines and even corroding them. The critical gas velocity is a key factor in predicting liquid loading onset in the pipeline, so that appropriate measures can be taken in advance and hazards can be reduced. This paper proposes a model for predicting pipeline liquid loading onset based on the liquid film and wall shear stress of zero, and applicable to different pipe diameters and different inclination angles. This model provides a more simplified and comprehensive prediction of pipeline fluid loading than other models with complex calculations. The critical gas velocity in this model is a function of the liquid holding rate rather than the liquid film thickness, and the critical gas velocity prediction in a phase-inclined pipe is carried out by an improved Belfroid angle correction term. The experimental data, field data and seven models in the published literature were compared and validated, and the errors were judged. The results showed that the new model outperformed the other models in terms of absolute mean error at full inclination angle, and was able to predict the pipeline liquid loading accurately

Copper-Mediated Aerobic Oxidative Synthesis of 3‑Bromo-imidazo[1,2‑<i>a</i>]pyridines with Pyridines and Enamides

A conversion of pyridines and enamides for the synthesis of 3-bromo-imidazo­[1,2-<i>a</i>]­pyridines was developed by copper-mediated aerobic oxidative coupling in a one-pot manner. This procedure tolerates various functional groups and affords a series of 3-bromo-imidazo­[1,2-<i>a</i>]­pyridines under mild conditions