Identification of miRNAs and target genes associated with lymph node metastasis in cervical cancer using bioinformatics analysis.

This study was designed to identify the differentially expressed miRNAs (DEMs) and genes (DEGs) in metastatic cervical cancer using bioinformatic tools. In this study, fifty-seven DEMs (48 downregulated and 9 upregulated) were identified, among which miR-4459 and miR-3195 expression was negatively associated with overall survival of cervical cancer patients. Then, 476 target DEGs were determined, and protein-protein interaction (PPI) network was constructed. Seventeen hub genes (LONRF2, CCNE2, AURKA, SYT1, NEGR1, PPP1R12B, GABRP, RAD51, CDK1, FBLN5, PRKG1, CDC6, CACNA1C, MEOX2, ANLN, MYLK, and EDNRB) were finally selected to construct the miRNA-hub gene network. Overall, our study discovered the key miRNAs and mRNAs related to lymph node metastasis (LNM) in cervical cancer, which helps discover candidate therapeutic targets for cervical cancer.

Phosphorus recovery from urine using cooling water system effluent as a precipitant.

Phosphorus (P) recovery from wastewater has been recognized as a critical technology for solving the sustainable supply of this indispensable and non - renewable natural resource. In this study, the cost - free magnesium and calcium sources of using the cooling water system effluent (CWSE) in two thermal power plants were proposed (Z - CWSE and G - CWSE) and the P recovery performance from source - separated urine was investigated. About 90% P recovery efficiency was achieved from the hydrolyzed urine when Z - CWSE and G - CWSE were added at the Ca: Mg: P molar ratios of 3.1 : 4.0: 1 and 3.6 : 3.4: 1, respectively. More than 95% P recovery performance was obtained from the fresh urine as the initial pH of the CWSE - FU mixtures was adjusted to over 9.5 and 10.0, respectively. The precipitates obtained contain 10.84-17.04% Ca, 6.22-9.58% P, 0.75-3.76% Mg and 0.13-0.23% N. XRD analysis confirmed the presence of struvite in the precipitates. The reuse of precipitates is secure due to extremely low contents of heavy metals. The feasibility of using CWSEs as the flushing water in urinals and toilets was assessed. Besides, we proposed CWSEs could be invoked as precipitants in various wastewaters as long as it contains considerable phosphate, e.g. P concentration more than 100 mg/L and 50 mg/L for Z - CWSE and G - CWSE, respectively.

Effects of Pregnancy-Onset Asthma on Perinatal Outcomes: A Retrospective Cohort Study.

BACKGROUND: It is unknown whether women with pregnancy-onset asthma are predisposed to worse pregnancy outcomes compared with women with pre-pregnancy asthma. OBJECTIVE: To explore whether pregnancy-onset asthma leads to worse perinatal outcomes compared with pre-pregnancy asthma. METHODS: Women who were discharged with a diagnosis of asthma and gave birth to a live singleton were included in this retrospective cohort analysis. Women were separated into groups based on whether the asthma was diagnosed during or before pregnancy. We compared clinical characteristics, perinatal outcomes, and asthma exacerbations (AEs) between groups. RESULTS: A total of 335 women were included in this study, 39 of whom (11.6%) had pregnancy-onset asthma and 296 had pre-pregnancy asthma. All pregnant women in the pregnancy-onset group experienced AEs during pregnancy. The proportion of chronic hypertension, chronic hypertension with superimposed preeclampsia, and spontaneous preterm births in the pregnancy-onset group was significantly higher than that in the pre-pregnancy asthma group. After adjusting for age, body mass index, onset of asthma during pregnancy, and severity of AEs through multivariate analysis, pregnancy-onset asthma was an independent risk factor for spontaneous preterm birth (adjusted odds ratio = 7.71; 95% CI, 1.30-46.12) and severe AE was an independent risk factor for gestational hypertension and preeclampsia (adjusted odds ratio = 3.58; 95% CI, 1.30-9.87). CONCLUSIONS: During pregnancy, pregnancy-onset asthma in women is associated with an exacerbation of the condition. Obstetricians should be vigilant for signs of asthma onset during pregnancy. Other health care providers should watch for symptoms of gestational hypertension and preeclampsia in pregnant women with preexisting or new-onset asthma.

Deletion of Budding Yeast MAD2 Suppresses Clone-to-Clone Differences in Artificial Linear Chromosome Copy Numbers and Gives Rise to Higher Retention Rates.

Our goal was to investigate the changes in artificial short-linear chromosome average copy numbers per cell arising from partial or full loss of Mitotic Arrest-Deficient 2 (MAD2) spindle checkpoint function in budding yeast Saccharomyces cerevisiae. Average artificial linear chromosome copy numbers in a population of cells, as measured by quantitative polymerase chain reactions (qPCR), and retention rates, as measured by fluctuation analyses, were performed on a total of 62 individual wild type and mad2∆ mutant haploid and diploid clones. Wild type cells, both haploids and diploids, displayed phenotypically unique clone-to-clone differences: one group of 15 clones displayed low-copy numbers per cell and high retention rates, were 1 clone was found to have undergone a genomic integration event, and the second group of 15 clones displayed high copy numbers per cell and low retention rates, with the latter values being consistent with the previously published results where only a single clone had been measured. These chromosome states were observed to be unstable when propagated for 10 days under selection, where high copy-low retention rate clones evolved into low copy-high retention rate clones, but no evidence for integration events was observed. By contrast, mad2∆ haploid and mad2∆/mad2∆ diploids displayed a suppression of the clone-to-clone differences, where 20 out of 21 clones had mid-level artificial linear chromosome copy numbers per cell, but maintained elevated chromosome retention rates. The elevated levels in retention rates in mad2∆ and mad2∆/mad2∆ cells were also maintained even in the absence of selection during growth over 3 days. MAD2/mad2∆ heterozygous diploids displayed multiple clonal groups: 4 with low copy numbers, 5 with mid-level copy numbers, and 1 with a high copy number of artificial linear chromosomes, but all 10 clones uniformly displayed low retention rates. Our observations reveal that MAD2 function contributes to the ability of yeast cells to maintain a high number of artificial linear chromosomes per cell in some clones, but, counter-intuitively, mad2∆ suppresses clone-to-clone differences and leads to an improvement in artificial linear chromosome retention rates yielding a more uniform and stable clonal population with mid-level chromosome copy numbers per cell.

Peptide inhibitors of the anaphase promoting-complex that cause sensitivity to microtubule poison.

There is an interest in identifying Anaphase Promoting-Complex/Cyclosome (APC/C) inhibitors that lead to sensitivity to microtubule poisons as a strategy for targeting cancer cells. Using budding yeast Saccharomyces cerevisiae, peptides derived from the Mitotic Arrest Deficient 2 (Mad2)-binding motif of Cell Division Cycle 20 (Cdc20) were observed to inhibit both Cdc20- and CDC20 Homology 1 (Cdh1)-dependent APC/C activity. Over expression of peptides in vivo led to sensitivity to a microtubule poison and, in a recovery from a microtubule poison arrest, delayed degradation of yeast Securin protein Precocious Dissociation of Sisters 1 (Pds1). Peptides with mutations in the Cdc20 activating KILR-motif still bound APC/C, but lost the ability to inhibit APC/C in vitro and lost the ability to induce sensitivity to a microtubule poison in vivo. Thus, an APC/C binding and activation motif that promotes mitotic progression, namely the Cdc20 KILR-motif, can also function as an APC/C inhibitor when present in excess. Another activator for mitotic progression after recovery from microtubule poison is p31comet, where a yeast predicted open-reading frame YBR296C-A encoding a 39 amino acid predicted protein was identified by homology to p31comet, and named Tiny Yeast Comet 1 (TYC1). Tyc1 over expression resulted in sensitivity to microtubule poison. Tyc1 inhibited both APC/CCdc20 and APC/CCdh1 activities in vitro and bound to APC/C. A homologous peptide derived from human p31comet bound to and inhibited yeast APC/C demonstrating evolutionary retention of these biochemical activities. Cdc20 Mad2-binding motif peptides and Tyc1 disrupted the ability of the co-factors Cdc20 and Cdh1 to bind to APC/C, and co-over expression of both together in vivo resulted in an increased sensitivity to microtubule poison. We hypothesize that Cdc20 Mad2-binding motif peptides, Tyc1 and human hp31 peptide can serve as novel molecular tools for investigating APC/C inhibition that leads to sensitivity to microtubule poison in vivo.