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Acquired genomic structural variants (SVs) are major hallmarks of cancer genomes, but they are challenging to reconstruct from short-read sequencing data. Here we exploited the long reads of the nanopore platform using our customized pipeline, Picky (https://github.com/TheJacksonLaboratory/Picky), to reveal SVs of diverse architecture in a breast cancer model. We identified the full spectrum of SVs with superior specificity and sensitivity relative to short-read analyses, and uncovered repetitive DNA as the major source of variation. Examination of genome-wide breakpoints at nucleotide resolution uncovered micro-insertions as the common structural features associated with SVs. Breakpoint density across the genome is associated with the propensity for interchromosomal connectivity and was found to be enriched in promoters and transcribed regions of the genome. Furthermore, we observed an over-representation of reciprocal translocations from chromosomal double-crossovers through phased SVs. We demonstrate that Picky analysis is an effective tool for comprehensive detection of SVs in cancer genomes from long-read data.

Exosomes are secreted into the extracellular space by most cell types and contain various molecular constituents, which play roles in many biological processes. Adipose‐derived mesenchymal stem cells (ADSCs) can differentiate into a variety of cell types and secrete a series of paracrine factors through exosomes. ADSC‐derived exosomes have shown diagnostic and therapeutic potential in many clinical diseases. The molecular components are critical for their mechanisms. Several methods have been developed for exosome purification, including ultracentrifugation, ultrafiltration, density gradient purification, size‐based isolation, polymer precipitation and immuno‐affinity purification. Thus, we employed four methods to isolate exosomes from the hADSC culture medium, including ultracentrifugation, size exclusion chromatography, ExoQuick‐TC precipitation and ExoQuick‐TC ULTRA isolation. Following exosome isolation, we performed quantitative proteomic analysis of the exosome proteins using isobaric tags for relative and absolute quantification (iTRAQ) labelling, combined with 2D‐LC‐MS/MS. There were 599 universal and 138 stably expressed proteins in hADSC‐derived exosomes. We proved that these proteins were potential hADSC‐derived exosomes markers, including CD109, CD166, HSPA4, TRAP1, RAB2A, RAB11B and RAB14. From the quantitative proteomic analysis, we demonstrated that hADSC‐derived exosome protein expression varied, with lipopolysaccharide (LPS) treatment, in the different isolation methods. Pathway analysis and proliferation, migration and endothelial tube formation assays showed varying effects in cells stimulated with hADSC‐derived exosomes from different isolation methods. Our study revealed that different isolation methods might introduce variations in the protein composition in exosomes, which reflects their effects on biological function. The pros and cons of these methods are important points to consider for downstream research applications.

Sound signals have been widely applied in various fields. One of the popular applications is sound localization, where the location and direction of a sound source are determined by analyzing the sound signal. In this study, two microphone linear arrays were used to locate the sound source in an indoor environment. The TDOA is also designed to deal with the problem of delay in the reception of sound signals from two microphone arrays by using the generalized cross-correlation algorithm to calculate the TDOA. The proposed microphone array system with the algorithm can successfully estimate the sound source’s location. The test was performed in a standardized chamber. This experiment used two microphone arrays, each with two microphones. The experimental results prove that the proposed method can detect the sound source and obtain good performance with a position error of about 2.0~2.3 cm and angle error of about 0.74 degrees. Therefore, the experimental results demonstrate the feasibility of the system.

Chia-Lin Wei, Yijun Ruan and colleagues used chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) to determine the CTCF-chromatin interactome in mouse embryonic stem cells. Mammalian genomes are viewed as functional organizations that orchestrate spatial and temporal gene regulation. CTCF, the most characterized insulator-binding protein, has been implicated as a key genome organizer. However, little is known about CTCF-associated higher-order chromatin structures at a global scale. Here we applied chromatin interaction analysis by paired-end tag (ChIA-PET) sequencing to elucidate the CTCF-chromatin interactome in pluripotent cells. From this analysis, we identified 1,480 cis - and 336 trans -interacting loci with high reproducibility and precision. Associating these chromatin interaction loci with their underlying epigenetic states, promoter activities, enhancer binding and nuclear lamina occupancy, we uncovered five distinct chromatin domains that suggest potential new models of CTCF function in chromatin organization and transcriptional control. Specifically, CTCF interactions demarcate chromatin-nuclear membrane attachments and influence proper gene expression through extensive cross-talk between promoters and regulatory elements. This highly complex nuclear organization offers insights toward the unifying principles that govern genome plasticity and function.

RPThe wheel condition monitoring when the train in operation is significant task to prevent the occurrence of unexpected event. In this study, the piezoelectric sensors were installed on the railway track to collect the dynamic voltage-and-strain signals when the train wheels pressed them. These one-dimensional time series signals were transformed to the two-dimensional Recurrence Plots (RP) images as an input data sets for two deep learning models, Xception and EfficientNet-B7. The binary classification, Normal or Faulty as the diagnostical output to indicate the health state of the train wheels in that time. Five metrics were selected to evaluate the performance of two models, namely Accuracy, Precision, Recall, Miss Rate, and AUC. The results show that both models perform the high accuracy of 91.1% to the wheel condition classification. Furthermore, EfficientNet-B7 shows better performance in Recall, Miss-rate, and AUC metrics than those of Xception to express the premium ability in defective wheel identification, which is crucial for this application. Therefore, the efficientNet-B7 is selected as a favorable machine learning classifier for the fault diagnosis of rolling stock wheels. It is significant contribution to train wheel condition monitoring and health management since it provides the effective diagnostic information for maintenance decision to decrease the occurrence of unexpected event.

Background Promoting physical activity (PA) in different populations experiencing sleep disturbance may increase population PA levels and improve sleep. This scoping review aimed to examine the effect of various PA intervention strategies on sleep across different populations, identify key sleep outcomes, and analyze knowledge gaps by mapping the relevant literature. Methods For this study, we systematically searched articles published till March 2022 from PubMed, Web of Science, Cochrane Library, and Embase databases for randomized clinical trials (RCTs) regarding the effect of physical activity on sleep. Two authors extracted key data and descriptively analyzed the data. Thematic analysis was used to categorize the results into themes by all authors. Arksey and O’Malley’s scoping review framework was used to present the findings. Results Twenty-one randomized controlled trials out of 3052 studies were finally included with 3677 participants (2852 females (78%)). Five trials were conducted in healthy working-age adults with sleep disturbance but without the diagnosis of insomnia, five in healthy older adults, two in perinatal women, four in patients with cancer, three in mental illness related subjects, and another two in other disease-related areas. PA interventions were diverse, including walking, resistance training, aerobic exercise, housework, water exercise, basketball, smartphone/tablet \"apps\", web, online videos or wearable actigraphy, and self-determined exercise. Three major themes were identified: (1) Sleep environment may be important to address prior to instituting PA interventions, (2) All types of PA were effective for improving sleep in all populations studied, (3) Self-tolerated PA is safe for improving sleep in the elderly and in co-morbid or perinatal populations. Conclusions PA is effective and safe for improving sleep in both healthy and co-morbid populations with sleep disturbance by increasing daily activity levels using a variety of strategies, even low intensity, such as housekeeping, sit-to-stand repetitions, along with encouraging PA through web pages, videos, and self-goal setting apps. In addition, this scoping review identifies the need for further therapeutic research and future exploration in populations with sleep initiation or sleep maintenance disturbance.

Jmjd3, a JmjC family histone demethylase, is induced by the transcription factor NF‐kB in response to microbial stimuli. Jmjd3 erases H3K27me3, a histone mark associated with transcriptional repression and involved in lineage determination. However, the specific contribution of Jmjd3 induction and H3K27me3 demethylation to inflammatory gene expression remains unknown. Using chromatin immunoprecipitation‐sequencing we found that Jmjd3 is preferentially recruited to transcription start sites characterized by high levels of H3K4me3, a marker of gene activity, and RNA polymerase II (Pol_II). Moreover, 70% of lipopolysaccharide (LPS)‐inducible genes were found to be Jmjd3 targets. Although most Jmjd3 target genes were unaffected by its deletion, a few hundred genes, including inducible inflammatory genes, showed moderately impaired Pol_II recruitment and transcription. Importantly, most Jmjd3 target genes were not associated with detectable levels of H3K27me3, and transcriptional effects of Jmjd3 absence in the window of time analysed were uncoupled from measurable effects on this histone mark. These data show that Jmjd3 fine‐tunes the transcriptional output of LPS‐activated macrophages in an H3K27 demethylation‐independent manner.

Mammalian genomes are pervasively transcribed outside mapped protein-coding genes. One class of extragenic transcription products is represented by long non-coding RNAs (lncRNAs), some of which result from Pol_II transcription of bona-fide RNA genes. Whether all lncRNAs described insofar are products of RNA genes, however, is still unclear. Here we have characterized transcription sites located outside protein-coding genes in a highly regulated response, macrophage activation by endotoxin. Using chromatin signatures, we could unambiguously classify extragenic Pol_II binding sites as belonging to either canonical RNA genes or transcribed enhancers. Unexpectedly, 70% of extragenic Pol_II peaks were associated with genomic regions with a canonical chromatin signature of enhancers. Enhancer-associated extragenic transcription was frequently adjacent to inducible inflammatory genes, was regulated in response to endotoxin stimulation, and generated very low abundance transcripts. Moreover, transcribed enhancers were under purifying selection and contained binding sites for inflammatory transcription factors, thus suggesting their functionality. These data demonstrate that a large fraction of extragenic Pol_II transcription sites can be ascribed to cis-regulatory genomic regions. Discrimination between lncRNAs generated by canonical RNA genes and products of transcribed enhancers will provide a framework for experimental approaches to lncRNAs and help complete the annotation of mammalian genomes.

The systematic review and meta‐analysis aimed to examine the dose‐response relationship between isometric handgrip (IHG) training and blood pressure outcomes in normotensive and hypertensive populations. Three databases (EMBASE, MEDLINE/PubMed, and Cochrane CENTRAL) were searched from inception to June 2025. Thirty‐one studies with 905 participants (51% male) met the criteria. Primary outcomes were resting systolic (SBP) and diastolic blood pressure (DBP). Study quality was assessed using the PEDro scale and RoB‐2. Meta‐regression was used to evaluate dose‐response effects on SBP and DBP. The included studies demonstrated fair to good methodological quality (5.9 ± 1.0). Moderate evidence indicated that IHG reduced SBP (–5.38 mmHg, 95% CI –6.91 to –3.85; p < 0.001; I2 = 86% and DBP (–2.71 mmHg, 95% CI –3.75 to –1.66; p < 0.001; I2 = 90%), with greater effects observed in hypertensive compared to normotensive groups. For meta‐regression, lower training intensity protocols (<30% of maximal voluntary isometric contraction [MVIC]) yield smaller blood pressure‐lowering effects in both SBP (p = 0.043) and DBP (p = 0.032). Higher weekly frequency (e.g., >3 to 7 days/week) was associated with a diminished effect in SBP (p = 0.032). In conclusion, the IHG training significantly lowers SBP and DBP in both normotensive and hypertensive individuals, offering preventive benefits for normotensive individuals at risk for hypertension and therapeutic potential for hypertensive patients. The evidence‐informed protocol might appear to be four sets of 2‐min unilateral contractions at ≥30 MVIC, performed ≤3 times per week for a minimum of 8 weeks. These findings support IHG as a practical non‐pharmacological strategy for blood pressure management. Registration: PROSPERO number: CRD420251154235

A chromatin interaction analysis with paired-end tagging (ChIA-PET) approach is used to delineate chromatin interactions mediated by RNA polymerase II in several different stem-cell populations; putative long-range promoter–enhancer interactions are inferred, indicating that linear juxtaposition does not necessarily guide enhancer target selection and prevalent cell-specific enhancer usage. Chromatin and gene expression Gene transcription requires dynamic chromatin connectivity between promoters bound by RNA polymerase II and their corresponding distal-acting enhancers. In this paper the authors use the ChIA-PET (chromatin interaction analysis with paired-end tagging) approach to delineate chromatin interactions mediated by RNA polymerase II in embryonic stem cells, neural stem cells and neurosphere progenitor cells. Putative enhancer–promoter interactions can be inferred, and many enhancers associate with promoters located beyond their nearest active genes, indicating that linear juxtaposition does not necessarily guide enhancer target selection. This work illustrates the possible importance of underlying chromatin structures in nuclear function. In multicellular organisms, transcription regulation is one of the central mechanisms modelling lineage differentiation and cell-fate determination 1 . Transcription requires dynamic chromatin configurations between promoters and their corresponding distal regulatory elements 2 . It is believed that their communication occurs within large discrete foci of aggregated RNA polymerases termed transcription factories in three-dimensional nuclear space 3 . However, the dynamic nature of chromatin connectivity has not been characterized at the genome-wide level. Here, through a chromatin interaction analysis with paired-end tagging approach 3 , 4 , 5 using an antibody that primarily recognizes the pre-initiation complexes of RNA polymerase II 6 , we explore the transcriptional interactomes of three mouse cells of progressive lineage commitment, including pluripotent embryonic stem cells 7 , neural stem cells 8 and neurosphere stem/progenitor cells 9 . Our global chromatin connectivity maps reveal approximately 40,000 long-range interactions, suggest precise enhancer–promoter associations and delineate cell-type-specific chromatin structures. Analysis of the complex regulatory repertoire shows that there are extensive colocalizations among promoters and distal-acting enhancers. Most of the enhancers associate with promoters located beyond their nearest active genes, indicating that the linear juxtaposition is not the only guiding principle driving enhancer target selection. Although promoter–enhancer interactions exhibit high cell-type specificity, promoters involved in interactions are found to be generally common and mostly active among different cells. Chromatin connectivity networks reveal that the pivotal genes of reprogramming functions are transcribed within physical proximity to each other in embryonic stem cells, linking chromatin architecture to coordinated gene expression. Our study sets the stage for the full-scale dissection of spatial and temporal genome structures and their roles in orchestrating development.