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Transposable elements (TEs) are abundant in the human genome, and some are capable of generating new insertions through RNA intermediates. In cancer, the disruption of cellular mechanisms that normally suppress TE activity may facilitate mutagenic retrotranspositions. We performed single-nucleotide resolution analysis of TE insertions in 43 high-coverage whole-genome sequencing data sets from five cancer types. We identified 194 high-confidence somatic TE insertions, as well as thousands of polymorphic TE insertions in matched normal genomes. Somatic insertions were present in epithelial tumors but not in blood or brain cancers. Somatic L1 insertions tend to occur in genes that are commonly mutated in cancer, disrupt the expression of the target genes, and are biased toward regions of cancer-specific DNA hypomethylation, highlighting their potential impact in tumorigenesis.

Homology and structure-based approaches were used to identify Helitrons in the genome of maize inbred B73. A total of 1,930 intact Helitrons from eight families (62 subfamilies) and >20,000 Helitron fragments were identified, accounting for [almost equal to]2.2% of the B73 genome. Transposition of at least one of these families is ongoing, but the most prominent burst of amplification activity was [almost equal to]250,000 years ago. Sixty percent of maize Helitrons were found to have captured fragments of nuclear genes ([almost equal to]840 different fragment acquisitions, with tens of thousands of predicted gene fragments inside Helitrons within the B73 assembly). Most acquired gene fragments are undergoing random drift, but 4% were calculated to be under purifying selection, whereas another 4% exhibit apparent adaptive selection, suggesting beneficial effects for the host or Helitron transposition/retention. Gene fragment capture is frequent in some Helitron subfamilies, with as many as 10 unlinked genes providing DNA inserts within a single element. Gene fragment acquisition appears to positively influence element survival and/or ability of the Helitron to acquire additional gene fragments. Helitrons with gene fragment captures in the antisense orientation have a lesser chance of survival. Helitron distribution in maize exhibits severe biases, including preferential accumulation in relatively gene-rich regions. Insertions, however, are not usually found inside genes. Rather, Helitrons preferentially insert near (but not into) other HELITRONS: This biased accumulation is not caused by a preference for cis or nearby transposition, suggesting a specific association between Helitron integration functions and unknown chromatin characteristics that specifically mark HELITRONS:

To systematically evaluate the efficacy and safety of tenofovir and entecavir in chronic hepatitis B-related cirrhosis. A comprehensive search was conducted in databases including PubMed, Web of Science, Embase and Cochrane Library from the inception until June 2024. Studies on the use of tenofovir and entecavir for chronic hepatitis B-related cirrhosis were collected. A total of 14 studies involving 14,208 patients were included. The meta-analysis revealed that tenofovir significantly reduced the cumulative incidence of hepatocellular carcinoma and cumulative mortality compared to entecavir in East Asian popupation, while in non East Asian populations, the two groups are roughly equivalent. After 48 weeks, the hepatitis B virus-deoxyribonucleic acid clearance rate in the tenofovir group were comparable to the entecavir group. Both tenofovir and entecavir showed similar effect in reducing the incidence of hepatic encephalopathy. Compared with the entecavir group, patients in the tenofovir group, including tenofovir disoproxil fumarate and tenofovir alafenamide fumarate showed a significant increase in estimated glomerular filtration rate after 48 weeks of treatment. Compared to entecavir, tenofovir significantly reduced the cumulative incidence of hepatocellular carcinoma and cumulative mortality in chronic hepatitis B-related cirrhosis in East Asian population. However, both drugs were comparable in terms of hepatitis B virus-deoxyribonucleic acid clearance and hepatic encephalopathy. Tenofovir did not significantly cause renal dysfunction, but instead improved estimated glomerular filtration rate levels compared with entecavir. Randomized controlled trials with larger sample size are still needed for validation. https://www.crd.york.ac.uk/prospero/, identifier CRD42024588432.

The “Forest Village” model utilizes forests as a central medium, leveraging rural forest resources as a key asset for rural revitalization. Taking 1140 national forest villages in Southwest China as the research object, the spatial distribution characteristics of national forest villages in southwest China were analyzed from two dimensions, nature and village nature, using ArcGIS 10.8 tools with watersheds as the research unit. The two dimensions of nature and society and their influencing factors were identified by using a combination of methods such as spatial autocorrelation, the closest neighbor index, the standard deviation ellipse, kernel density analysis and OPGD. The results revealed the following: (1) It is sparsely in the west and densely in the east, featuring four high—density cores that radiate outward to the surrounding areas. (2) The most significant among these factors are socio—economic ones, such as GDP density and population density, which demonstrate the notable impact of human disturbances on rural distribution. (3) Among the natural factors, topography and climate exert the most significant influence. Among the remaining factors, the densities of the river network and road network are strongly influenced by urban development, showing a high degree of alignment with the distribution of other social factors.

Helitrons are recently discovered eukaryotic transposons that are predicted to amplify by a rolling-circle mechanism. They are present in most plant and animal species investigated, but were previously overlooked partly because they lack terminal repeats and do not create target site duplications. Hetitrons are particularly abundant in flowering plants, where they frequently acquire, and sometimes express, 1 or more gene fragments. A structure-based search protocol was developed to find Helitrons and was used to analyze several plant and animal genomes, leading to the discovery of hundreds of new Helitrons. Analysis of these Helitrons has uncovered mechanisms of element evolution, including end creation and sequence acquisition. Preferential accumulation in genepoor regions and target site specificities were also identified. Overall, these studies provide insights into the transposition and evolution of Helitrons and their contributions to evolved gene content and genome structure.

Background Gene fusions have been studied extensively, as frequent drivers of tumorigenesis as well as potential therapeutic targets. In many well-known cases, breakpoints occur at two intragenic positions, leading to in-frame gene-gene fusions that generate chimeric mRNAs. However, fusions often occur with intergenic breakpoints, and the role of such fusions has not been carefully examined. Results We analyze whole-genome sequencing data from 268 patients to catalog gene-intergenic and intergenic-intergenic fusions and characterize their impact. First, we discover that, in contrast to the common assumption, chimeric oncogenic transcripts—such as those involving ETV4 , ERG , RSPO3 , and PIK3CA— can be generated by gene-intergenic fusions through splicing of the intervening region. Second, we find that over-expression of an upstream or downstream gene by a fusion-mediated repositioning of a regulatory sequence is much more common than previously suspected, with enhancers sometimes located megabases away. We detect a number of recurrent fusions, such as those involving ANO3 , RGS9 , FUT5 , CHI3L1 , OR1D4 , and LIPG in breast; IGF2 in colon; ETV1 in prostate; and IGF2BP3 and SIX2 in thyroid cancers. Conclusion Our findings elucidate the potential oncogenic function of intergenic fusions and highlight the wide-ranging consequences of structural rearrangements in cancer genomes.

Background The classical genetic model of colorectal cancer presents APC mutations as the earliest genomic alterations, followed by KRAS and TP53 mutations. However, the timing and relative order of clonal expansion and other types of genomic alterations, such as genomic rearrangements, are still unclear. Results Here, we perform comprehensive bioinformatic analysis to dissect the relative timing of somatic genetic alterations in 63 colorectal cancers with whole-genome sequencing data. Utilizing allele fractions of somatic single nucleotide variants as molecular clocks while accounting for the presence of copy number changes and structural alterations, we identify key events in the evolution of colorectal tumors. We find that driver point mutations, gene fusions, and arm-level copy losses typically arise early in tumorigenesis; different mechanisms act on distinct genomic regions to drive DNA copy changes; and chromothripsis—clustered rearrangements previously thought to occur as a single catastrophic event—is frequent and may occur multiple times independently in the same tumor through different mechanisms. Furthermore, our computational approach reveals that, in contrast to recent studies, selection is often present on subclones and that multiple evolutionary models can operate in a single tumor at different stages. Conclusion Combining these results, we present a refined tumor progression model which significantly expands our understanding of the tumorigenic process of human colorectal cancer.

Background Genomic rearrangements exert a heavy influence on the molecular landscape of cancer. New analytical approaches integrating somatic structural variants (SSVs) with altered gene features represent a framework by which we can assign global significance to a core set of genes, analogous to established methods that identify genes non-randomly targeted by somatic mutation or copy number alteration. While recent studies have defined broad patterns of association involving gene transcription and nearby SSV breakpoints, global alterations in DNA methylation in the context of SSVs remain largely unexplored. Results By data integration of whole genome sequencing, RNA sequencing, and DNA methylation arrays from more than 1400 human cancers, we identify hundreds of genes and associated CpG islands (CGIs) for which the nearby presence of a somatic structural variant (SSV) breakpoint is recurrently associated with altered expression or DNA methylation, respectively, independently of copy number alterations. CGIs with SSV-associated increased methylation are predominantly promoter-associated, while CGIs with SSV-associated decreased methylation are enriched for gene body CGIs. Rearrangement of genomic regions normally having higher or lower methylation is often involved in SSV-associated CGI methylation alterations. Across cancers, the overall structural variation burden is associated with a global decrease in methylation, increased expression in methyltransferase genes and DNA damage response genes, and decreased immune cell infiltration. Conclusion Genomic rearrangement appears to have a major role in shaping the cancer DNA methylome, to be considered alongside commonly accepted mechanisms including histone modifications and disruption of DNA methyltransferases.

The development of some central cities tends to be saturated, so some mega cities try to adopt the express and local mode of the metro. Suburban lines with imbalanced passenger flow between stations will lead to extremely crowded passenger flow in some stations, while scarce passenger flow in other stations. To balance the train’s carrying capacity with the imbalanced passenger flow, this study explores the collaborative optimization of train operation under the new mode of express and local. First, a time-stamped data cropping strategy based on fine-grained time zones as the grid index is developed, which is used to deeply explore the OD spatiotemporal representation of passenger flow correlation mapping mechanism based on multisource data; then, the calculation model of the proportion of trains matching with the OD temporal and spatial characteristics of suburban passenger flow are constructed, and an efficient solution algorithm is developed to solve the problem of interest. Finally, a set of numerical experiments with operation data from Shanghai Metro Line 16 are conducted to verify the performance and effectiveness of the proposed model and algorithm. The experimental results show that the proposed approach can effectively realize the collaborative optimization of passenger OD prediction, train proportion, stop scheme, and travel time, so as to provide decision-making support and method guidance for the optimization of metro organizations in megacities.

Traditional models of timetable generation for last trains do not account for the fact that decision-maker (DM) often incorporates transfer demand variability within his/her decision-making process. This study aims to develop such a model with particular consideration of the decision-makers’ risk preferences in subway systems under uncertainty. First, we formulate an optimization model for last-train timetabling based on mean-variance (MV) theory that explicitly considers two significant factors including the number of successful transfer passengers and the running time of last trains. Then, we add the mean-variance risk measure into the model to generate timetables by adjusting the last trains’ departure times and running times for each line. Furthermore, we normalize two heterogeneous terms of the risk measure to provide assistance in getting reasonable results. Due to the complexity of MV model, we design a tabu search (TS) algorithm with specifically designed operators to solve the proposed timetabling problem. Through computational experiments involving the Beijing subway system, we demonstrate the computational efficiency of the proposed MV model and the heuristic approach.