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DNA methylation plays key roles in diverse biological processes such as X chromosome inactivation, transposable element repression, genomic imprinting, and tissue-specific gene expression. Sequencing-based DNA methylation profiling provides an unprecedented opportunity to map and compare complete DNA methylomes. This includes one of the most widely applied technologies for measuring DNA methylation: methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq), coupled with a complementary method, methylation-sensitive restriction enzyme sequencing (MRE-seq). A computational approach that integrates data from these two different but complementary assays and predicts methylation differences between samples has been unavailable. Here, we present a novel integrative statistical framework M&M (for integration of MeDIP-seq and MRE-seq) that dynamically scales, normalizes, and combines MeDIP-seq and MRE-seq data to detect differentially methylated regions. Using sample-matched whole-genome bisulfite sequencing (WGBS) as a gold standard, we demonstrate superior accuracy and reproducibility of M&M compared to existing analytical methods for MeDIP-seq data alone. M&M leverages the complementary nature of MeDIP-seq and MRE-seq data to allow rapid comparative analysis between whole methylomes at a fraction of the cost of WGBS. Comprehensive analysis of nineteen human DNA methylomes with M&M reveals distinct DNA methylation patterns among different tissue types, cell types, and individuals, potentially underscoring divergent epigenetic regulation at different scales of phenotypic diversity. We find that differential DNA methylation at enhancer elements, with concurrent changes in histone modifications and transcription factor binding, is common at the cell, tissue, and individual levels, whereas promoter methylation is more prominent in reinforcing fundamental tissue identities.

Three-dimensional (3D) cell culture has been reported to increase the therapeutic potentials of mesenchymal stem cells ( MSCs). In this study, we aimed to investigate the therapeutic effects of 3D spheroids of human adipose-derived MSCs for acute kidney injury ( AKI). In vitro studies indicated that 3D spheroids of MSCs produced higher levels of extracellular matrix proteins (including collagen I, fibronectin and laminin), and exhibited stronger anti-apoptotic and anti-oxidative capacities than two-dimensional (2D) cultured cells. Furthermore, 3D culture increased the paracrine secretion of cytokines by MSCs, including angiogenic factors ( VEGF and basic fibroblast growth factor), anti-apoptotic factors (epidermal growth factor and hepatocyte growth factor), the anti-oxidative factor insulin-like growth factor and the anti-inflammatory protein tumour necrosis factor-alpha stimulated gene/protein 6. Consistent with in vitro experiments, 3D spheroids of MSCs showed enhanced survival and paracrine effects in vivo. More importantly, when injected into the kidney of model rats with ischemia-reperfusion (I/R)-induced AKI, 3D spheroids were more beneficial in protecting the I/R kidney against apoptosis, reducing tissue damage, promoting vascularization and ameliorating renal function compared with 2D cultured cells. Therefore, the 3D culture strategy improved the therapeutic effects of MSCs, and might be promising for AKI treatment. [ABSTRACT FROM AUTHOR]

Background: Telesurgery has the potential to overcome spatial limitations for surgeons, which depends on surgical robot and the quality of network communication. However, the influence of network latency and bandwidth on telesurgery is not well understood., Methods: A telesurgery system capable of dynamically adjusting image compression ratios in response to bandwidth changes was established between Beijing and Sanya (Hainan province), covering a distance of 3000 km. In total, 108 animal operations, including 12 surgical procedures, were performed. Total latency ranging from 170 ms to 320 ms and bandwidth from 15-20 Mbps to less than 1 Mbps were explored using designed surgical tasks and hemostasis models for renal vein and internal iliac artery rupture bleeding. Network latency, jitter, frame loss, and bit rate code were systemically measured during these operations. National Aeronautics and Space Administration Task Load Index (NASA-TLX) and a self-designed scale measured the workload and subjective perception of surgeons., Results: All 108 animal telesurgeries, conducted from January 2023 to June 2023, were performed effectively over a total duration of 3866 min. The operations were completed with latency up to 320 ms and bandwidths as low as 1-5 Mbps. Hemostasis for vein and artery rupture bleeding models was effectively achieved under these low bandwidth conditions. The NASA-TLX results indicated that latency significantly impacted surgical performance more than bandwidth and image clarity reductions., Conclusions: This telesurgery system demonstrated safety and reliability. A total of 320 ms latency is acceptable for telesurgery operations. Reducing image clarity can effectively mitigate the potential latency increase caused by decreased bandwidth, offering a new method to reduce the impact of latency on telesurgery., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)