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The present study was conducted to investigate the effectiveness of new, less toxic, less harmful, and nonmetallic graphite (G) and metallic iron oxide (Fe 2 O 3 ) nanofuel additives by analyzing experimentally their consequences on exhaust emissions and performance of an air cooled, single cylinder, 4-stroke gasoline engine. Fe 2 O 3 and graphite nanoparticles at 40, 80, and 120 mg/l of gasoline concentrations were mixed with gasoline by means of a magnetic stirrer. Brake power (BP), brake-specific fuel consumption (BSFC), torque (T), brake thermal efficiency (BTE), nitrogen oxides (NO x ), carbon monoxide (CO), hydrocarbons (HC), and carbon dioxide (CO 2 ) emissions were the investigated parameters. Experimental results indicated that G-blends showed a higher rise in brake power, brake thermal efficiency and torque and a greater reduction in the brake-specific fuel consumption as compared to that of Fe 2 O 3 fuel blends. Moreover, the G-blends produced less NO x and CO 2 than Fe 2 O 3 blends but produced more emissions of CO and HC than that of Fe 2 O 3 blends. On average, G-blends produced 0.46%, 0.71%, and 1.71% more torque, power, and BTE and 2.43%, 1.87%, and 13.39% less brake-specific fuel consumption (BSFC), NO x , and CO 2 than Fe 2 O 3 blends, respectively. So, in terms of the eight parameters, four performance parameters (i.e., T, BP, BSFC, BTE), and four engine emission exhaust indicators (i.e., CO, NO x , HC, CO 2 ), graphite nanoparticles showed more positive results for 6 parameters (T, BP, BSFC, BTE, NO x , CO 2 ), while two parameters HC and CO showed negative results with graphite as compared to that of Fe 2 O 3 nanoparticles. So, overall, we conclude that nanoparticles of graphite are more engine and environment friendly than that of iron oxide fuel additives., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Sinoatrial Node (SAN) is part of the cardiac conduction system, which controls the rhythmic contraction of the vertebrate heart. The SAN consists of a specialized pacemaker cell population that has the potential to generate electrical impulses. Although the SAN pacemaker has been extensively studied in mammalian and teleost models, including the zebrafish, their molecular nature remains inadequately comprehended., Results: To characterize the molecular profile of the zebrafish sinoatrial ring (SAR) and elucidate the mechanism of pacemaker function, we utilized the transgenic line sqet33mi59BEt to isolate cells of the SAR of developing zebrafish embryos and profiled their transcriptome. Our analyses identified novel candidate genes and well-known conserved signaling pathways involved in pacemaker development. We show that, compared to the rest of the heart, the zebrafish SAR overexpresses several mammalian SAN pacemaker signature genes, which include hcn4 as well as those encoding calcium- and potassium-gated channels. Moreover, genes encoding components of the BMP and Wnt signaling pathways, as well as members of the Tbx family, which have previously been implicated in pacemaker development, were also overexpressed in the SAR. Among SAR-overexpressed genes, 24 had human homologues implicated in 104 different ClinVar phenotype entries related to various forms of congenital heart diseases, which suggest the relevance of our transcriptomics resource to studying human heart conditions. Finally, functional analyses of three SAR-overexpressed genes, pard6a, prom2, and atp1a1a.2, uncovered their novel role in heart development and physiology., Conclusion: Our results established conserved aspects between zebrafish and mammalian pacemaker function and revealed novel factors implicated in maintaining cardiac rhythm. The transcriptome data generated in this study represents a unique and valuable resource for the study of pacemaker function and associated heart diseases., (© 2021. The Author(s).)

Cancer is a major stress for public well-being and is the most dreadful disease. The models used in the discovery of cancer treatment are continuously changing and extending toward advanced preclinical studies. Cancer models are either naturally existing or artificially prepared experimental systems that show similar features with human tumors though the heterogeneous nature of the tumor is very familiar. The choice of the most fitting model to best reflect the given tumor system is one of the real difficulties for cancer examination. Therefore, vast studies have been conducted on the cancer models for developing a better understanding of cancer invasion, progression, and early detection. These models give an insight into cancer etiology, molecular basis, host tumor interaction, the role of microenvironment, and tumor heterogeneity in tumor metastasis. These models are also used to predict novel cancer markers, targeted therapies, and are extremely helpful in drug development. In this review, the potential of cancer models to be used as a platform for drug screening and therapeutic discoveries are highlighted. Although none of the cancer models is regarded as ideal because each is associated with essential caveats that restraint its application yet by bridging the gap between preliminary cancer research and translational medicine. However, they promise a brighter future for cancer treatment., (© 2021 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Cancer cells go through a process known as epithelial-mesenchymal transition (EMT) during which they acquire the ability to migrate and invade extracellular matrix. Some cells also acquire the ability to move across a layer of endothelial cells to enter and exit the bloodstream; intra- and extravasation, respectively. The transcription factor PRH/HHEX (proline-rich homeodomain/haematopoietically expressed homeobox) controls cell proliferation and cell migration/invasion in a range of cell types. Our previous work showed that PRH activity is downregulated in prostate cancer cells owing to increased inhibitory PRH phosphorylation and that this increases cell proliferation and invasion. PRH inhibits migration and invasion by prostate and breast epithelial cells in part by activating the transcription of Endoglin, a transforming growth factor β (TGFβ) co-receptor. Here we show that depletion of PRH in immortalised prostate epithelial cells results in increased extravasation in vitro. We show that blood platelets stimulate extravasation of cells with depleted PRH and that inhibition of TGFβ signalling blocks the effects of platelets on these cells. Moreover, TGFβ induces changes characteristic of EMT including decreased E-Cadherin expression and increased Snail expression. We show that in prostate cells PRH regulates multiple genes involved in EMT and TGFβ signalling. However, both platelets and TGFβ increase PRH phosphorylation. In addition, TGFβ increases binding of its effector pSMAD3 to the PRH/HHEX promoter and downregulates PRH protein and mRNA levels. Thus, TGFβ signalling downregulates PRH activity by multiple mechanisms and induces an EMT that facilitates extravasation and sensitises cells to TGFβ.

PRH/HHEX (proline-rich homeodomain protein/haematopoietically expressed homeobox protein) is a transcription factor that controls cell proliferation, cell differentiation and cell migration. Our previous work has shown that in haematopoietic cells, Protein Kinase CK2-dependent phosphorylation of PRH results in the inhibition of PRH DNA-binding activity, increased cleavage of PRH by the proteasome and the misregulation of PRH target genes. Here we show that PRH and hyper-phosphorylated PRH are present in normal prostate epithelial cells, and that hyper-phosphorylated PRH levels are elevated in benign prostatic hyperplasia, prostatic adenocarcinoma, and prostate cancer cell lines. A reduction in PRH protein levels increases the motility of normal prostate epithelial cells and conversely, PRH over-expression inhibits prostate cancer cell migration and blocks the ability of these cells to invade an extracellular matrix. We show that CK2 over-expression blocks the repression of prostate cancer cell migration and invasion by PRH. In addition, we show that PRH knockdown in normal immortalised prostate cells results in an increase in the population of cells capable of colony formation in Matrigel, as well as increased cell invasion and decreased E-cadherin expression. Inhibition of CK2 reduces PRH phosphorylation and reduces prostate cell proliferation but the effects of CK2 inhibition on cell proliferation are abrogated in PRH knockdown cells. These data suggest that the increased phosphorylation of PRH in prostate cancer cells increases both cell proliferation and tumour cell migration/invasion.

PRH/HHex (proline-rich homeodomain protein) is a transcription factor that controls cell proliferation and cell differentiation in a variety of tissues. Aberrant subcellular localisation of PRH is associated with breast cancer and thyroid cancer. Further, in blast crisis chronic myeloid leukaemia, and a subset of acute myeloid leukaemias, PRH is aberrantly localised and its activity is downregulated. Here we show that PRH is involved in the regulation of cell migration and cancer cell invasion. We show for the first time that PRH is expressed in prostate cells and that a decrease in PRH protein levels increases the migration of normal prostate epithelial cells. We show that a decrease in PRH protein levels also increases the migration of normal breast epithelial cells. Conversely, PRH overexpression inhibits cell migration and cell invasion by PC3 and DU145 prostate cancer cells and MDA-MB-231 breast cancer cells. Previous work has shown that the transforming growth factor-β co-receptor Endoglin inhibits the migration of prostate and breast cancer cells. Here we show that PRH can bind to the Endoglin promoter in immortalised prostate and breast cells. PRH overexpression in these cells results in increased Endoglin protein expression, whereas PRH knockdown results in decreased Endoglin protein expression. Moreover, we demonstrate that Endoglin overexpression abrogates the increased migration shown by PRH knockdown cells. Our data suggest that PRH controls the migration of multiple epithelial cell lineages in part at least through the direct transcriptional regulation of Endoglin. We discuss these results in terms of the functions of PRH in normal cells and the mislocalisation of PRH seen in multiple cancer cell types.