Structural basis of nucleosome recognition and modification by MLL methyltransferases.

Methyltransferases of the mixed-lineage leukaemia (MLL) family-which include MLL1, MLL2, MLL3, MLL4, SET1A and SET1B-implement methylation of histone H3 on lysine 4 (H3K4), and have critical and distinct roles in the regulation of transcription in haematopoiesis, adipogenesis and development1-6. The C-terminal catalytic SET (Su(var.)3-9, enhancer of zeste and trithorax) domains of MLL proteins are associated with a common set of regulatory factors (WDR5, RBBP5, ASH2L and DPY30) to achieve specific activities7-9. Current knowledge of the regulation of MLL activity is limited to the catalysis of histone H3 peptides, and how H3K4 methyl marks are deposited on nucleosomes is poorly understood. H3K4 methylation is stimulated by mono-ubiquitination of histone H2B on lysine 120 (H2BK120ub1), a prevalent histone H2B mark that disrupts chromatin compaction and favours open chromatin structures, but the underlying mechanism remains unknown10-12. Here we report cryo-electron microscopy structures of human MLL1 and MLL3 catalytic modules associated with nucleosome core particles that contain H2BK120ub1 or unmodified H2BK120. These structures demonstrate that the MLL1 and MLL3 complexes both make extensive contacts with the histone-fold and DNA regions of the nucleosome; this allows ease of access to the histone H3 tail, which is essential for the efficient methylation of H3K4. The H2B-conjugated ubiquitin binds directly to RBBP5, orienting the association between MLL1 or MLL3 and the nucleosome. The MLL1 and MLL3 complexes display different structural organizations at the interface between the WDR5, RBBP5 and MLL1 (or the corresponding MLL3) subunits, which accounts for the opposite roles of WDR5 in regulating the activity of the two enzymes. These findings transform our understanding of the structural basis for the regulation of MLL activity at the nucleosome level, and highlight the pivotal role of nucleosome regulation in histone-tail modification.

Serpentine-Inspired Strain Sensor with Predictable Cracks for Remote Bio-Mechanical Signal Monitoring.

Flexible strain sensors have attracted intense interest due to their application as intelligent wearable electronic devices. However, it is still a huge challenge to achieve a flexible sensor with simultaneous high sensitivity, excellent durability, and a wide sensing region. In this work, a crack-based strain sensor with a paired-serpentine conductive network is fabricated onto flexible film by screen printing. The innovative conductive network exhibits a controlled crack morphology during stretching, which endows the prepared sensor with outstanding sensing characteristics, including high sensitivity (gauge factor up to 2391.5), wide detection (rang up to 132%), low strain detection limit, a fast response time (about 40 ms), as well as excellent durability (more than 2000 stretching/releasing cycles). Benefiting from these excellent performances, full-range human body motions including subtle physiological signals and large motions are accurately detected by the prepared sensor. Furthermore, wearable electronic equipment integrated with a wireless transmitter and the prepared strain sensor shows great potential for remote motion monitoring and intelligent mobile diagnosis for humans. This work provides an effective strategy for the fabrication of novel strain sensors with highly comprehensive performance.

High-strength, anti-fatigue, cellulose nanofiber reinforced polyvinyl alcohol based ionic conductive hydrogels for flexible strain/pressure sensors and triboelectric nanogenerators.

Ionic conductive hydrogels (ICHs) have attracted great attention because of their excellent biocompatibility and structural similarity with biological tissues. However, it is still a huge challenge to prepare a high strength, conductivity and durability hydrogel-based flexible sensor with dual network structure through a simple and environmentally friendly method. In this work, a simple one-pot cycle freezing thawing method was proposed to prepare ICHs by dissolving polyvinyl alcohol (PVA) and ferric chloride (FeCl3) in cellulose nanofiber (CNF) aqueous dispersion. A dual cross-linked network was established in hydrogel through the hydrogen bonds and coordination bonds among PVA, CNF, and FeCl3. This structure endows the as-prepared hydrogel with high sensitivity (pressure sensitivity coefficient (S) = 5.326 in the pressure range of 0-5 kPa), wide response range (4511 kPa), excellent durability (over 3000 cycles), short response time (83 ms) and recovery time (117 ms), which can accurately detect various human activities in real time. Furthermore, the triboelectric nano-generator (TENG) made from PVA@CNF-FeCl3 hydrogel can not only supply power for commercial capacitors and LED lamps, but also be used as a self-powered sensor to detect human motion. This work provides a new approach for the development of the next generation of flexible wearable electronic devices.

Flexible and Anisotropic Strain Sensors with the Asymmetrical Cross-Conducting Network for Versatile Bio-Mechanical Signal Recognition.

Flexible strain sensors with high performance are actively and widely investigated for wearable electronic devices. However, the conventional sensors often suffer from a lack of detection of complex multidimensional strain, which severely limits their wide applications. To overcome this critical challenge, we propose a pattern design by screen printing to construct an asymmetrical cross-conductive network in the piezoresistive strain sensor, which can enhance the response to external stimuli in different directions. The unique network endows the prepared sensors with the excellent ability of instantaneous detection and accurate identification of multidimensional strains. Moreover, the sensor also demonstrates high sensitivity, fast response, an ultra-wide sensing range, and excellent stability and durability. Benefiting from the outstanding comprehensive performance of the prepared sensor, a full range of human actions (wink, smile, swallowing, and joint bending) and subtle bio-signals (pulse and breathing) are easily and accurately monitored. A wireless wearable device assembled by the sensor shows great potential applications in practical real-time physiological monitoring and intelligent mobile diagnosis for humans. This work provides an innovative and effective strategy for manufacturing flexible and multifunctional strain sensors to fully satisfy versatile applications of new-generation wearable electronic devices.

A Highly Sensitive and Broad-Range Pressure Sensor Based on Polyurethane Mesodome Arrays Embedded with Silver Nanowires.

The pressure sensor with high sensitivity and a broad pressure sensing range is highly desired for flexible electronics. Here, a high-performance pressure sensor based on a hybrid structure was facilely fabricated using the glass template method, which consists of polyurethane (PU) mesodomes embedded with gradient-distributed silver nanowire (AgNW). Such a novel hybrid architecture enables the as-prepared PU/AgNW pressure sensor to have high sensitivity as well as a wide detection range. Moreover, the obtained PU/AgNW pressure sensors have a fast response time (20 ms), good cycling stability, and excellent flexibility. The pressure sensor, benefiting from its outstanding comprehensive sensing performance, can be used for expression recognition and human activity monitoring, showing tremendous application potential in wearable devices. The proposed architecture and developed methodology in this work is promising for future flexible electronic applications.

Highly Sensitive and Stretchable Polyurethane Fiber Strain Sensors with Embedded Silver Nanowires.

Flexible strain sensors have attracted a great amount of attention for promising applications in next-generation artificially intelligent devices. However, it is difficult for conventional planar strain sensors to meet the requirements of miniature size and light weight for flexible electronics. Herein, a highly sensitive and stretchable fiber strain sensor with a millimeter diameter was innovatively fabricated by the capillary tube method to integrate silver nanowires (AgNWs) in polyurethane (PU) fibers. Scanning electron microscopy results demonstrate that AgNWs were embedded into the surface layer of PU fibers and formed completely conductive networks. The unique AgNW networks endow the PU/AgNW fibers with superior electrical conductivity of 3.1 S/cm, high elongation at break of 265%, wide response range of 43%, high gauge factor of 87.6 up to 22% strain, fast response time of 49 ms, and excellent reliability and stability. Such satisfactory stretchability and sensitivity is attributed to the combination of the highly stretchable PU matrix and the embedded architecture of the AgNW conductive network. Moreover, PU/AgNW fibers can be employed as wearable devices to detect various human motions and to drive light-emitting diodes at a lower voltage (2.7 V).