Wound healing has become one of the basic issues faced by the medical community because of the susceptibility of skin wounds to bacterial infection. As such, it is highly desired to design a nanocomposite hydrogel with excellent antibacterial activity to achieve high wound closure effectiveness. Here, based on ultrasound-triggered piezocatalytic therapy, a multifunctional hydrogel is designed to promote bacteria-infected wound healing. Under ultrasonic vibration, the surface of barium titanate (BaTiO₃, BT) nanoparticles embedded in the hydrogel rapidly generate reactive oxygen species (ROS) owing to the established strong built-in electric field, endowing the hydrogel with superior antibacterial efficacy. This modality shows intriguing advantages over conventional photodynamic therapy, such as prominent soft tissue penetration ability and the avoidance of serious skin phototoxicity after systemic administration of photosensitizers. Moreover, the hydrogel based on N-[tris(hydroxymethyl)methyl]acrylamide (THM), N-(3-aminopropyl)methacrylamide hydrochloride (APMH) and oxidized hyaluronic acid (OHA) exhibits outstanding self-healing and bioadhesive properties able to accelerate full-thickness skin wound healing. Notably, compared with the widely reported mussel-inspired adhesive hydrogels, OHA/THM-APMH hydrogel due to the multiple hydrogen bonds from unique tri-hydroxyl structure overcomes the shortage that catechol groups are easily oxidized, giving it long-term and repeatable adhesion performance. Importantly, this hybrid hydrogel confines BT nanoparticles to wound area and locally induced piezoelectric catalysis under ultrasound to eradicate bacteria, markedly improving the therapeutic biosafety and exhibits great potential for harmless treatment of bacteria-infected tissues.

Skeletal muscle depends on the precise orchestration of contractile and metabolic gene expression programs to direct fiber-type specification and to ensure muscle performance. Exactly how such fiber type–specific patterns of gene expression are established and maintained remains unclear, however. Here, we demonstrate that histone monomethyl transferase MLL4 (KMT2D), an enhancer regulator enriched in slow myofibers, plays a critical role in controlling muscle fiber identity as well as muscle performance. Skeletal muscle–specific ablation of MLL4 in mice resulted in downregulation of the slow oxidative myofiber gene program, decreased numbers of type I myofibers, and diminished mitochondrial respiration, which caused reductions in muscle fatty acid utilization and endurance capacity during exercise. Genome-wide ChIP-Seq and mRNA-Seq analyses revealed that MLL4 directly binds to enhancers and functions as a coactivator of the myocyte enhancer factor 2 (MEF2) to activate transcription of slow oxidative myofiber genes. Importantly, we also found that the MLL4 regulatory circuit is associated with muscle fiber–type remodeling in humans. Thus, our results uncover a pivotal role for MLL4 in specifying structural and metabolic identities of myofibers that govern muscle performance. These findings provide therapeutic opportunities for enhancing muscle fitness to combat a variety of metabolic and muscular diseases.

Background: Pelvic retroversion is one of the mechanisms for regulating sagittal balance in patients with a kyphotic deformity. This retroversion is limited by hip extension, which prevents the pelvis from becoming excessively retroverted, achieving a sacral slope of <0°. However, a negative sacral slope can be found in some patients with ankylosing spondylitis with thoracolumbar kyphosis. The purpose of this study was to analyze this finding. Methods: We performed a retrospective review of 106 consecutive Chinese Han patients with ankylosing spondylitis with thoracolumbar kyphosis treated at our center from October 2005 to October 2012. Forty-one patients in whom the upper third of the femur was clearly visualized on lateral radiographs were analyzed. Seventeen had a sacral slope of <0° (group A) and twenty-four had a sacral slope of ≥0° (group B). Eight sagittal parameters were measured and compared between the two groups. Correlations among sacral slope, the femoral obliquity angle, and the other sagittal parameters were analyzed. Results: Mean global kyphosis, lumbar lordosis, pelvic tilt, the sagittal vertical axis, and the femoral obliquity angle were significantly larger in group A than in group B, whereas mean pelvic incidence and sacral slope were significantly smaller in group A (p < 0.05 for all). Global kyphosis, lumbar lordosis, pelvic tilt, and the sagittal vertical axis were significantly negatively associated with sacral slope but positively associated with the femoral obliquity angle, whereas pelvic incidence was significantly positively associated with sacral slope but negatively associated with the femoral obliquity angle (p < 0.05 for all). The femoral obliquity angle was significantly negatively associated with sacral slope (p < 0.05). Conclusions: Negative sacral slope does exist in Chinese Han patients with ankylosing spondylitis with thoracolumbar kyphosis. This appears to be caused by severe kyphosis, an initially small sacral slope, and pronounced tilting of the femoral shaft as a result of knee flexion, resulting in the pelvis becoming further retroverted. Clinical Relevance: For spine surgeons, a comprehensive assessment of the complex comprising the spine, pelvis, and femoral shaft is mandatory for accurately evaluating sagittal alignment and for planning for surgical realignment.