The spatial organization of the genome is intimately linked to its biological function, yet our understanding of higher order genomic structure is coarse, fragmented and incomplete. In the nucleus of eukaryotic cells, interphase chromosomes occupy distinct chromosome territories (CT), and numerous models have been proposed for how chromosomes fold within CTs1. These models, however, provide only few mechanistic details about the relationship between higher order chromatin structure and genome function. Recent advances in genomic technologies have led to rapid revolutions in the study of 3D genome organization. In particular, Hi-C has been introduced as a method for identifying higher order chromatin interactions genome wide2. In the present study, we investigated the 3D organization of the human and mouse genomes in embryonic stem cells and terminally differentiated cell types at unprecedented resolution. We identify large, megabase-sized local chromatin interaction domains, which we term “topological domains”, as a pervasive structural feature of the genome organization. These domains correlate with regions of the genome that constrain the spread of heterochromatin. The domains are stable across different cell types and highly conserved across species, suggesting that topological domains are an inherent property of mammalian genomes. Lastly, we find that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, tRNAs, and SINE retrotransposons, suggesting that these factors may play a role in establishing the topological domain structure of the genome.

PurposeThe aim of this study was to evaluate the therapeutic efficacy and safety of mesenchymal stem cells (MSCs) for the treatment of patients with knee osteoarthritis (OA).MaterialsWe performed a meta-analysis of relevant published clinical studies. An electronic search was conducted for randomized controlled trials (RCTs) of MSC-based therapy in knee OA. The visual analogue scale (VAS), International Knee Documentation Committee (IKDC) form, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne algofunctional indices (Lequesne), Lysholm knee scale (Lysholm), Tegner activity scale (Tegner) and adverse events (AEs) were evaluated.ResultsEleven eligible trials with 582 knee OA patients were included in the present meta-analysis. We demonstrated that MSC treatment could significantly decrease VAS and increase IKDC scoresafter a 24-month follow-up compared with controls (P<0.05). MSC therapy also showed significant decreases in WOMAC and Lequesne scores after the 12-month follow-up (P<0.01). Analysis of Lysholm (24-month) and Tegner (12- and 24-month) scores also demonstrated favorable results for MSC treatment (P<0.05).ConclusionOverall, MSC transplantation treatment was shown to be safe and has great potential as an efficacious clinical therapy for patients with knee OA.

Intrinsically stretchable electronics represent an attractive platform for next-generation implantable devices by reducing the mechanical mismatch and the immune responses with biological tissues. Despite extensive efforts, soft implantable electronic devices often exhibit an obvious trade-off between electronic performances and mechanical deformability because of limitations of commonly used compliant electronic materials. Here, we introduce a scalable approach to create intrinsically stretchable and implantable electronic devices featuring the deployment of liquid metal components for ultrahigh stretchability up to 400% tensile strain and excellent durability against repetitive deformations. The device architecture further shows long-term stability under physiological conditions, conformal attachments to internal organs, and low interfacial impedance. Successful electrophysiological mapping on rapidly beating hearts demonstrates the potential of intrinsically stretchable electronics for widespread applications in health monitoring, disease diagnosis, and medical therapies.

Ala92-D2 accumulates in the Golgi, where its presence and/or ensuing oxidative stress disrupts basic cellular functions and increases pre-apoptosis. These findings are reminiscent to disease mechanisms observed in other neurodegenerative disorders such as Huntington's disease, and could contribute to the unresolved neurocognitive symptoms of affected carriers.

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Liquid metal confined in the elastomer represents an ideal platform for stretchable electronics with ultimate deformability. To enable facile and scalable patterning of conductive features, bulk liquid metal is typically dispersed into fine particles to formulate printable inks. The presence of native oxide or organic ligands stabilizing these liquid metal particles unfortunately inhibits their direct coalescence to recover the metallic conductivity and liquid-state deformability. Here, we report a chemical sintering process that converts printed liquid metal microparticles into a highly deformable conductor. The process involves the removal of surface passivating oxide by a short exposure to acid fume and subsequent selective wetting of liquid metal microparticles onto copper nanoplates present in the ink formulation. The chemical reaction provides the basis for a facile and scalable procedure to print conductive features over a large area with exceptional conductivity (>104 S cm–1) and ultrahigh stretchability (∼1000% strain). Their practical suitability is demonstrated by the fabrication of an ultrastretchable ribbon cable and an epidermal heater.

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Acetohydroxyacid synthase, a thiamine diphosphate-dependent enzyme, can condense either two pyruvate molecules to form acetolactate for synthesizing L-valine and L-leucine or pyruvate with 2-ketobutyrate to form acetohydroxybutyrate for synthesizing L-isoleucine. Because the key reaction catalyzed by acetohydroxyacid synthase in the biosynthetic pathways of branched-chain amino acids exists in plants, fungi, archaea, and bacteria, but not in animals, acetohydroxyacid synthase becomes a potential target for developing novel herbicides and antimicrobial compounds. In this article, the evolution, structure, and catalytic mechanism of acetohydroxyacid synthase are summarized.