wgd v2: a suite of tools to uncover and date ancient polyploidy and whole-genome duplication.

MOTIVATION: Major improvements in sequencing technologies and genome sequence assembly have led to a huge increase in the number of available genome sequences. In turn, these genome sequences form an invaluable source for evolutionary, ecological, and comparative studies. One kind of analysis that has become routine is the search for traces of ancient polyploidy, particularly for plant genomes, where whole-genome duplication (WGD) is rampant. RESULTS: Here, we present a major update of a previously developed tool wgd, namely wgd v2, to look for remnants of ancient polyploidy, or WGD. We implemented novel and improved previously developed tools to (a) construct KS age distributions for the whole-paranome (collection of all duplicated genes in a genome), (b) unravel intragenomic and intergenomic collinearity resulting from WGDs, (c) fit mixture models to age distributions of gene duplicates, (d) correct substitution rate variation for phylogenetic placement of WGDs, and (e) date ancient WGDs via phylogenetic dating of WGD-retained gene duplicates. The applicability and feasibility of wgd v2 for the identification and the relative and absolute dating of ancient WGDs is demonstrated using different plant genomes. AVAILABILITY AND IMPLEMENTATION: wgd v2 is open source and available at https://github.com/heche-psb/wgd.

Seagrass genomes reveal ancient polyploidy and adaptations to the marine environment.

We present chromosome-level genome assemblies from representative species of three independently evolved seagrass lineages: Posidonia oceanica, Cymodocea nodosa, Thalassia testudinum and Zostera marina. We also include a draft genome of Potamogeton acutifolius, belonging to a freshwater sister lineage to Zosteraceae. All seagrass species share an ancient whole-genome triplication, while additional whole-genome duplications were uncovered for C. nodosa, Z. marina and P. acutifolius. Comparative analysis of selected gene families suggests that the transition from submerged-freshwater to submerged-marine environments mainly involved fine-tuning of multiple processes (such as osmoregulation, salinity, light capture, carbon acquisition and temperature) that all had to happen in parallel, probably explaining why adaptation to a marine lifestyle has been exceedingly rare. Major gene losses related to stomata, volatiles, defence and lignification are probably a consequence of the return to the sea rather than the cause of it. These new genomes will accelerate functional studies and solutions, as continuing losses of the 'savannahs of the sea' are of major concern in times of climate change and loss of biodiversity.

Inference of Ancient Polyploidy from Genomic Data.

Whole-genome sequence data have revealed that numerous eukaryotic organisms derive from distant polyploid ancestors, even when these same organisms are genetically and karyotypically diploid. Such ancient whole-genome duplications (WGDs) have been important for long-term genome evolution and are often speculatively associated with important evolutionary events such as key innovations, adaptive radiations, or survival after mass extinctions. Clearly, reliable methods for unveiling ancient WGDs are key toward furthering understanding of the long-term evolutionary significance of polyploidy. In this chapter, we describe a set of basic established comparative genomics approaches for the inference of ancient WGDs from genomic data based on empirical age distributions and collinearity analyses, explain the principles on which they are based, and illustrate a basic workflow using the software "wgd," geared toward a typical exploratory analysis of a newly obtained genome sequence.

Revisiting ancient polyploidy in leptosporangiate ferns.

Ferns, and particularly homosporous ferns, have long been assumed to have experienced recurrent whole-genome duplication (WGD) events because of their substantially large genome sizes, surprisingly high chromosome numbers, and high degrees of polyploidy among many extant members. As the number of sequenced fern genomes is limited, recent studies have employed transcriptome data to find evidence for WGDs in ferns. However, they have reached conflicting results concerning the occurrence of ancient polyploidy, for instance, in the lineage of leptosporangiate ferns. Because identifying WGDs in a phylogenetic context is the foremost step in studying the contribution of ancient polyploidy to evolution, we here revisited earlier identified WGDs in leptosporangiate ferns, mainly the core leptosporangiate ferns, by building KS -age distributions and applying substitution rate corrections and by conducting statistical gene tree-species tree reconciliation analyses. Our integrative analyses not only identified four ancient WGDs in the sampled core leptosporangiate ferns but also identified false positives and false negatives for WGDs that recent studies have reported earlier. In conclusion, we underscore the significance of substitution rate corrections and uncertainties in gene tree-species tree reconciliations in calling WGD events and advance an exemplar workflow to overcome such often-overlooked issues.

The genome of homosporous maidenhair fern sheds light on the euphyllophyte evolution and defences.

Euphyllophytes encompass almost all extant plants, including two sister clades, ferns and seed plants. Decoding genomes of ferns is the key to deep insight into the origin of euphyllophytes and the evolution of seed plants. Here we report a chromosome-level genome assembly of Adiantum capillus-veneris L., a model homosporous fern. This fern genome comprises 30 pseudochromosomes with a size of 4.8-gigabase and a contig N50 length of 16.22 Mb. Gene co-expression network analysis uncovered that homospore development in ferns has relatively high genetic similarities with that of the pollen in seed plants. Analysing fern defence response expands understanding of evolution and diversity in endogenous bioactive jasmonates in plants. Moreover, comparing fern genomes with those of other land plants reveals changes in gene families important for the evolutionary novelties within the euphyllophyte clade. These results lay a foundation for studies on fern genome evolution and function, as well as the origin and evolution of euphyllophytes.

Adjuvant chemotherapy in patients with recurrence after completely resected stage IB lung adenocarcinoma: Propensity-matched analysis in a cohort of 147 recurrences.

BACKGROUND: Adjuvant chemotherapy (ACT) is considered for high-risk patients in stage IB lung adenocarcinoma (LUAD). However, these risk factors are recognized as negative prognostic factors, not as predictors of ACT efficacy. This study aimed to analyze the efficacy of ACT in stage IB patients by retrospectively examining patients who had recurrence. METHODS: We reviewed 1399 patients with stage IB (American Joint Committee on Cancer 7th edition) LUAD from 2012 to 2017 in our institution and found 147 patients with recurrence. The last follow-up date was December 30, 2021. One-to-one propensity-score matching (PSM) was used to reduce the potential selection bias. RESULTS: Fifty-five (37.4%) patients had received ACT and 92 (62.6%) had not (non-ACT). Patients with ACT were younger (p < 0.001), had larger tumors (p < 0.001) and more lymphovascular invasion (p = 0.02), and seemed to have less distant recurrence (p = 0.001). After PSM, 110 patients were matched and baseline characteristics were balanced. ACT was not associated with improved disease-free survival (DFS) after matching (mDFS = 23.5 m for ACT vs. 29.5 m for non-ACT, p = 0.13). ACT failed to prolong DFS of patients in the extracranial recurrence subgroup and EGFR mutation subgroups, and was even associated with shorter DFS in intracranial relapsed patients (mDFS = 30.3 m vs. 33.5 m, p = 0.083) and patients with tumor ≤30 mm (mDFS = 21.9 m vs. 30.8 m, p = 0.076). CONCLUSION: In patients who were destined to develop recurrence after completely resected stage IB LUAD, ACT might not be associated with improved DFS. Further large multicenter studies are warranted to validate these findings.

27-hydroxycholesterol linked high cholesterol diet to lung adenocarcinoma metastasis.

Dietary cholesterol has been implicated to promote lung cancer. Lung adenocarcinoma (LAC) is a main type of lung cancer, whereas the functional mechanism of cholesterol in LAC remained largely unknown. In the present study, we evidenced that cholesterol promoted cell proliferation and invasion of LAC in vitro as well as LAC metastasis in vivo. Cyp27A1 knockdown reduced the cholesterol-induced LAC cells proliferation and invasion. In contrast, Cyp7B1 knockdown enhanced the effect of cholesterol on LAC cells proliferation and invasion. Furthermore, Cyp27A1 deficiency remarkably reduced high cholesterol-induced LAC metastasis in vivo. Mechanism investigation demonstrated that exposure of LAC cells to 27-hydroxycholesterol induced the phosphorylation of AKT and NFκB p65, and promoted the expression of peptidylprolyl isomerase B (PPIB), especially in the coculture with THP1-derived macrophage. Meanwhile, 27-hydroxycholesterol induced the secretion of FGF2 and IL-6, which contributed to the expression of snail and vimentin. Luciferase report assay and ChIP assay confirmed that NFκB p65 controlled the transcription of PPIB. Inhibiting NFκB p65 activation reduced PPIB expression. PPIB inhibition reduced 27-hydroxycholesterol-induced expression of snail and vimentin. These results indicated that 27-hydroxycholesterol linked high cholesterol and LAC metastasis by regulating NFκB/PPIB axis and the secretion of FGF2 and IL-6.

Clinical and pathological characteristics of patients with pulmonary inflammatory pseudotumors: An 18-year retrospective study of 31 cases.

ABSTRACT: To investigate the clinical and pathological characteristics in patients with pulmonary inflammatory pseudotumors (PIP).This retrospective study included 31 patients with PIP from 2001 to 2019. Preoperative computed tomography scan was performed in all patients. Clinical and pathological characteristics were collected and analyzed.Thirty-one patients (16 female and 15 male) were recruited, with a median age of 57 years (range, 11-72 years). Eight (25.8%) patients were asymptomatic, and the others had symptoms characterized by cough with sputum, chest and back pain, dry cough, fever and blood in sputum, or hemoptysis. All cases were single lesions, including 23 cases in the right lung, and 8 cases in the left lung. Computed tomography scan demonstrated irregular lobulated nodules or masses in 14 patients, and regular round or oval nodules or masses in 11 cases. The blurred edge of tumors and spiculation was found in 12 cases. Microscopic results were characterized by the collection of inflammatory mesenchymal cells. Immunohistochemical examination showed vimentin, smooth muscle actin, and anaplastic lymphoma kinase positive. Complete tumor resection was obtained in all cases. No recurrence or metastasis was observed during the follow-up period.PIP has a variety of manifestations. Preoperative diagnosis is difficult to reach. The final diagnosis still depends on the pathological and immunohistochemical examination. Complete surgical resection is the main treatment at present, and the overall prognosis is good.

Silencing of CD276 suppresses lung cancer progression by regulating integrin signaling.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the cancers with the highest morbidity and mortality among the world. Studies have shown that the invasion and metastasis of tumor are biological characteristics of lung cancer, and also the main cause of treatment failure and patient death. In-depth study of lung cancer invasion related genes will help to explore the etiology of lung cancer, molecular typing and individualized treatment of lung cancer. Studies have shown that CD276 molecules are closely related to the prognosis of tumors, but the exact mechanism remains to be unclear. METHODS: We used the UALCAN and KM-plotter databases to investigate the expression of CD276 in human NSCLC and adjacent normal tissues, and its correlation with clinicopathology. In addition, we analyzed the function of CD276 in NSCLC cell by suppressing the expression of CD276 in A549 and H460 cells. RESULTS: In this study, we found that CD276 expression was significantly up-regulated in NSCLC tissues, and its expression was positively correlated with tumor stage in NSCLC. Silencing in CD276 inhibited cell invasion and migration by reducing integrin-associated protein expression. CONCLUSIONS: Our results indicate functional role of CD276 in the progression of NSCLC.

Characteristics and prognosis of primary malignant melanoma of the esophagus.

Primary malignant melanoma of esophagus (PMME) is a rare malignant tumor of esophagus. This study aimed to investigate the clinic pathologic characteristics and analyze the factors that might affect the prognosis of PMME patients.A total of 20 PMME patients who underwent surgical treatment in our hospital from 1975 to 2017 were analyzed. The clinical data, surgical and pathologic features of all patients were collected.For 20 PMME patients, the average age was 57.3 ±â€Š10.7 years, and the male patients account for 75%. Most of the tumors (95%) were located in the middle and lower of the esophagus. There were 7 patients with primary tumor invasion beyond the muscular layer (T3 + T4) and 10 patients with lymph node metastasis (LNM). The median survival time of 20 patients was 12 months, and the 1-year and 5-year survival rates were 50% and 16.9%, respectively. The probability of LNM in tumors confined to submucosa (T1) and myometrium (T2) was lower than that in tumors with deeper invasion (T3, T4) (P = .035). Multivariate analysis showed that tumor node metastasis (TNM) staging was the independent prognostic factor for survival of PMME patients (hazard ratio [95% confidence interval], 4.15 [1.36-12.67]; P = .012).For PMME patients, tumors with deeper invasion were more likely to have LNM, and TNM staging was an independent predictor of prognosis for survival. Early detection of the disease and radical resection of the tumor are critical for better survival of the PMME patients.

Efficacy and prognosis analysis of surgical treatment for bilateral synchronous multiple primary non-small cell lung cancer.

Colorectal cancer (CRC) is the third most common cancer and the second cause of cancer-related deaths worldwide. Despite early diagnosis and treatment improvement, the majority of patients will still suffer from metastatic disease (mCRC), which has a poor prognosis. Molecular diversity of CRC requires personalized targeted approach for improving patient outcomes. Antiangiogenic agents proved to be beneficial in the continuum of mCRC treatment. For efficient epidermal growth factor receptor (EGFR) directed therapy, subtle molecular selection and better strategies to overcome resistance are needed. BRAF mutant and HER-2 positive mCRC will soon be provided with approved targeted treatments and check-point inhibitors demonstrated effectiveness in microsatellite instability (MSI) - high mCRC. Moreover, numeorous promising agents are entering clinical trial arena. This review summarizes actual and possible targets and current and promising agents for mCRC treatment. With broader accessibility of liquid biopsy we could track molecular evolution of CRC and target genetic alterations as they emerge.