Maternal dominance contributes to subgenome differentiation in allopolyploid fishes.

Teleost fishes, which are the largest and most diverse group of living vertebrates, have a rich history of ancient and recent polyploidy. Previous studies of allotetraploid common carp and goldfish (cyprinids) reported a dominant subgenome, which is more expressed and exhibits biased gene retention. However, the underlying mechanisms contributing to observed 'subgenome dominance' remains poorly understood. Here we report high-quality genomes of twenty-one cyprinids to investigate the origin and subsequent subgenome evolution patterns following three independent allopolyploidy events. We identify the closest extant relatives of the diploid progenitor species, investigate genetic and epigenetic differences among subgenomes, and conclude that observed subgenome dominance patterns are likely due to a combination of maternal dominance and transposable element densities in each polyploid. These findings provide an important foundation to understanding subgenome dominance patterns observed in teleost fishes, and ultimately the role of polyploidy in contributing to evolutionary innovations.

Association between ABCB1 (3435C>T) polymorphism and susceptibility of colorectal cancer: A meta-analysis.

Studies on the relationship between ABCB1 3435C>T polymorphism (rs1045642) and colorectal cancer (CRC)susceptibility have yielded inconclusive results. To clarify this issue, we undertook a meta-analysis to investigate the relationship between rs1045642 and CRC risk.Three electronic scientific publication databases (Cochrane Library, Pubmed, Embase) were screened using specific search terms. Relevant literature was identified using literature traceability methods. Selected publications were evaluated according to the inclusion and exclusion criteria. Effect size information (odds ratio and the corresponding 95% confidence interval [CI]) was obtained following quality assessment and data extraction from the included publications, and a meta-analysis conducted. Statistical analysis was performed with the Stata sofz (Version 13.0) software.Overall, 17 case-control studies involving 7129 CRC patients and 7710 healthy control subjects satisfied the criteria for inclusion in the meta-analysis. There was no significant association between ABCB1 3435C>T polymorphism and CRC risk in any of the genetic models. In the CC versus CT model (I = 20.9%, Pheterogeneity = .276), CC versus CT + TT model (I = 45.6%, Pheterogeneity = .102) and CT versus CC + TT model (I = 17.8%, Pheterogeneity = .298) analyses, between-study heterogeneities were detected as significant in Asian populations. In the CT versus TT model (I = 24%, Pheterogeneity = .254) and CC + CT versus TT model (I = 0, Pheterogeneity = .55), between-study heterogeneities were found to be significant in groups of different populations.The meta-analysis described here suggests that the ABCB1 3435C>T polymorphism is not related to CRC susceptibility.

FGFR1 Induces Acquired Resistance Against Gefitinib By Activating AKT/mTOR Pathway In NSCLC.

OBJECTIVE: As an epidermal growth factor, receptor-tyrosine kinase inhibitor (EGFR-TKI), gefitinib demonstrates a good therapeutic effect in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). However, an overwhelming majority of these patients inevitably develop resistance against gefitinib. Unfortunately, the mechanism underlying this phenomenon is still not fully understood. Here we aim to reveal the mechanism of gefitinib resistance in NSCLC induced by FGFR1. MATERIALS AND METHODS: We used high-throughput sequencing to compare the mRNA expression profiles of PC9 and PC9-GR (gefitinib-resistant) cells. The clinical significance of fibroblast growth factor receptor 1 (FGFR1) in NSCLC was also investigated using immunohistochemistry and Kaplan-Meier survival analysis. Finally, the in vitro molecular mechanisms were analyzed using confocal laser microscopy, Western blotting, transwell assay, colony formation assay, CCK-8 assay, and apoptosis assay. RESULTS: We observed that FGFR1 was highly expressed in NSCLC tissues and was closely associated with poor prognosis. Cytological experiments showed that FGFR1 promoted the proliferation and migration of PC9-GR cells and mediated their resistance to gefitinib. Furthermore, studies aimed at unraveling this mechanism revealed that FGFR1 activated the AKT/mTOR signaling pathway. These findings show that the FGFR1/AKT/mTOR signaling pathway plays a vital role in acquired resistance against gefitinib in NSCLC. CONCLUSION: This work provides new evidence that FGFR1 functions as a key regulator of gefitinib resistance, thereby demonstrating its potential as a novel biomarker and therapeutic target for NSCLC.

Long non-coding RNAs AC026904.1 and UCA1: a "one-two punch" for TGF-ß-induced SNAI2 activation and epithelial-mesenchymal transition in breast cancer.

Transforming growth factor-ß (TGF-ß) has received much attention as a major inducer of epithelial-mesenchymal transition (EMT) during cancer progression, mainly by activating a set of pleiotropic transcription factors including SNAI2/Slug. However, the involvement of long non-coding RNAs (lncRNAs) in TGF-ß-induced Slug activation and EMT remains largely unknown. Methods: In this study, we used microarray analysis to compare lncRNA expression profiles between TGF-ß treated and untreated breast cancer cells. Then, the clinical significance of lncRNAs in breast cancer was investigated by qPCR and Kaplan-Meier survival analysis. The molecular mechanisms and EMT-promoting effects in vitro were analyzed by confocal laser microscopy, Western blotting, chromosome conformation capture (3C), chromatin isolation by RNA purification (ChIRP), ChIP, luciferase reporter assay and transwell migration assay. Lastly, the pro-metastatic effects in vivo were evaluated by bioluminescent imaging and hematoxylin and eosin (H&E) staining. Results: We observed that TGF-ß induced genome-wide changes in lncRNA levels in breast cancer cells, among which AC026904.1 and UCA1 were highly expressed in metastatic breast cancer and closely associated with poor prognosis. Mechanistic study revealed that AC026904.1 and UCA1 were upregulated by non-canonical and canonical TGF-ß pathways, respectively. Further analysis showed that AC026904.1 functions as an enhancer RNA in the nucleus, whereas UCA1 exerts a competitive endogenous RNA (ceRNA) activity in the cytoplasm. In addition, the biological functions of these two lncRNAs converged on the activation and maintenance of Slug, constituting a one-two punch in promoting EMT and tumor metastasis. Conclusion: These findings uncover for the first time that AC026904.1 and UCA1 could cooperatively upregulate Slug expression at both transcriptional and post-transcriptional levels, exerting critical roles in TGF-ß-induced EMT. The present work provides new evidence that lncRNAs function as key regulators of EMT and hold great promise to be used as novel biomarkers and therapeutic targets for metastatic breast cancer.

Value of whole-body magnetic resonance imaging for screening multifocal osteonecrosis in patients with polymyositis/dermatomyositis.

OBJECTIVE: To assess the value of coronal short-tau inversion recovery whole-body MRI (STIR-WBMRI) for screening osteonecrosis in patients with polymyositis (PM)/dermatomyositis (DM). METHODS: The imaging and medical records of 129 patients with PM/DM who met the Bohan and Peter diagnostic criteria were retrospectively analyzed. STIR-WBMRI was performed in all patients. 18 patients had follow-up STIR-WBMRI. 12 patients underwent regional knee and/or hip MRI while 25 patients underwent radiography of the lower extremities. RESULTS: STIR-WBMRI detected osteonecrosis in 15 (11.6%) patients. 38 joints were affected (mean, 2.5 per patient; range, 1-5 joints). Of the 38 joints affected by osteonecrosis, 33 had no clinical symptoms. Among the 12 patients who underwent regional MRI, STIR-WBMRI detected all 10 osteonecrotic sites seen on the regional MRI. The location, shape and size of the osteonecrotic lesions revealed on regional MRI were in accordance with those displayed on STIR-WBMRI. Of the 15 patients with osteonecrosis, 6 performed routine radiography of the affected joints and revealed no osteonecrotic lesions. Follow-up WBMRI detected new osteonecrosis in two patients whose first WBMRI revealed that there was no osteonecrosis in any skeleton. CONCLUSION: In addition to displaying muscle inflammation, STIR-WBMRI can efficiently detect early multifocal osteonecrosis in the whole bodies of patients with PM/DM. Advances in knowledge: In patients with PM/DM, WBMRI which takes 12-15 min can display muscular involvement and detect early multisite osteonecrosis in the whole body at the same time. Osteonecrotic lesions revealed by WBMRI are in accordance with those displayed on regional WBMRI.

Horizontal transfer of a novel Helentron in insects.

Helentrons represent a novel subtype of Helitrons. However, the evolutionary history of Helentrons in organisms is not clearly understood. In this study, we performed structure and autonomous partner analyses, which revealed that bm_455, a TE obtained from the Bombyx mori TE database, BmTEdb, was a member of Helentrons but not a long-terminal repeat (LTR) retrotransposon. Further analyses showed that bm_455 was also present in a wide range of insects including lepidopterans, coleopterans and hymenopterans using a homology-based search strategy. Several lines of evidence (high sequence identity, discontinuous distribution and lack of intense purifying selection) suggested that these elements could have been transferred into these species in part by horizontal transfers (HTs). Because Helentrons can capture host gene fragments, HTs of Helentrons might have a huge impact on their host genome evolution.

TRT, a Vertebrate and Protozoan Tc1-Like Transposon: Current Activity and Horizontal Transfer.

We report a Danio rerio transposon named DrTRT, for D. rerio Transposon Related to Tc1 The complete sequence of the DrTRT transposon is 1,563 base pairs (bp) in length, and its transposase putatively encodes a 338-amino acid protein that harbors a DD37E motif in its catalytic domain. We present evidence based on searches of publicly available genomes that TRT elements commonly occur in vertebrates and protozoa. Phylogenetic and functional domain comparisons confirm that TRT constitutes a new subfamily within the Tc1 family. Hallmark features of having no premature termination codons within the transposase, the presence of all expected functional domains, and its occurrence in the bony fish transcriptome suggest that TRT might have current or recent activity in these species. Further analysis showed that the activity of TRT elements in these species might have arisen about between 4 and 19 Ma. Interestingly, our results also implied that the widespread distribution of TRT among fishes, frog, and snakes is the result of multiple independent HT events, probably from bony fishes to snakes or frog. Finally, the mechanisms underlying horizontal transfer of TRT elements are discussed.

DPYD*2A/*5A/*9A and UGT1A1*6/*28 polymorphisms in Chinese colorectal cancer patients.

AIM OF STUDY: Fluorouracil drugs and irinotecan are commonly used in the treatment of colorectal cancer (CRC), but some patients have severe toxic side effects in the conventional dose. DPYD*2A/*5A/*9A and UGT1A1 * 6/*28 polymorphisms are related to the toxicity of fluorouracil drugs and irinotecan, respectively. Herein, we investigated the frequencies of DPYD*2A/*5A/*9A and UGT1A1 * 6/*28 genotypes in Chinese CRC patients. MATERIALS AND METHODS: For this study, 117 CRC patients' tumor tissues were examined through sequencing technology of the first generation to explore the distribution of DPYD*2A/*5A/*9A and UGT1A1 * 6/*28 genotypes. RESULTS: DPYD*2A G/G genotype accounted for 100%. DPYD*5A A/A, A/G, and G/G genotypes accounted for 48.2, 37.5, and 14.3%, respectively. DPYD*9A T/T and T/C genotypes accounted for 85.7 and 14.3%, respectively. UGT1A1 * 6 G/G, G/A, and A/A genotypes accounted for 74.6, 21.8, and 3.6%, respectively. UGT1A1 * 28 TA6/TA6, TA6/TA7, and TA7/TA7 genotypes accounted for 71.8, 27.3, and 0.9%, respectively. The genotypes of DPYD*2A/*5A/*9A and UGT1A1 * 6/*28 were not associated with patient's sex, age, and primary tumor sites. Our findings showed that: (i) almost 57.1% of Chinese CRC patients had at least one variant of DPYD*5A and DPYD*9A; (ii) nearly 37.3% of Chinese CRC patients had at least one variant of UGT1A1 * 6 and UGT1A1 * 28. CONCLUSION: It suggests that it is necessary for Chinese CRC patients to detect the genotypes of DPYD*5A/*9A and UGT1A1 * 6/*28 before treating with fluorouracil drugs and irinotecan.

Surgical treatment and prognosis of octogenarians with non-small cell lung cancer

OBJECTIVE@#To explore the clinical characteristics, surgical treatment and prognosis of non-small cell lung cancer (NSCLC) among elderly patients over 80 years.@*METHODS@#The clinical data, surgical methods, perioperative management, postoperative complications and prognosis of 52 NSCLC patients aged over 80 years were retrospectively analyzed.@*RESULTS@#Out of 52 cases, 27 had a long-term smoking history (51.9%) and 44 were with other diseases (84.6%). Lobectomy was done in 32 cases (65.4%), sub-lobectomy in 20 cases (38.5%), including pulmonary wedge resection in 16 cases (30.8%) and lung segment resection in 4 cases (7.7%). The postoperative complication rate was 44.2% (23/52); the complication rate after lobectomy was 62.5% (20/32) and that after sub-lobectomy was 25% (5/20), with significant difference between lobectomy and sub-lobectomy (P0.05).@*CONCLUSIONS@#Octogenarians with NSCLC are often afflicted with comorbidity, so perioperative management is more complex. Strictly adhering to indications, surgery is still an important treatment of NSCLC patients over 80.

[A high-efficiency method of sorting and sequencing of functional genes].

The implementation of the Human Genome Project preludes the analyzing of biologic genomes. Following the successful analysis of diverse biologic genomes, it becomes more and more important to research the functions of genes and to find new functional genes. In this article, we use the techniques of Megaclone, Megasort and MPSS to sort and sequence effectively different functional genes.