Nicotine promotes Staphylococcus aureus-induced osteomyelitis by activating the Nrf2/Slc7a11 signaling axis.

Although smoking is a significant risk factor for osteomyelitis, there is limited experimental evidence that nicotine, a key tobacco constituent, is associated with this condition, leaving its mechanistic implications uncharacterized. This study revealed that nicotine promotes Staphylococcus aureus-induced osteomyelitis by increasing Nrf2 and Slc7a11 expression in vivo and in vitro. Inhibition of Slc7a11 using Erastin augmented bacterial phagocytosis/killing capabilities and fortified antimicrobial responses in an osteomyelitis model. Moreover, untargeted metabolomic analysis demonstrated that Erastin mitigated the effects of nicotine on S. aureus-induced osteomyelitis by altering glutamate/glutathione metabolism. These findings suggest that nicotine aggravates S. aureus-induced osteomyelitis by activating the Nrf2/Slc7a11 signaling pathway and that Slc7a11 inhibition can counteract the detrimental health effects of nicotine.

Stress and strain changes of the anterior cruciate ligament at different knee flexion angles: A three-dimensional finite element study.

OBJECTIVE: This study aimed to analyze the stress and strain changes of the anterior cruciate ligament (ACL) at different knee flexion angles using a three-dimensional finite element model. METHODS: Computed tomography and magnetic resonance imaging scans were performed on the right knee of 30 healthy adult volunteers. The imaging data were used to construct a three-dimensional finite element model of the knee joint. The magnitude and concentration area of stress and strain of ACL at knee flexion angles 0°, 30°, 60° and 90° were assessed. RESULTS: The magnitude of stress remained consistent at 0-30° (P > 0.999) and decreased at 30-90° (P < 0.001, P = 0.005, respectively), while the magnitude of strain increased between 0° and 30° (P = 0.004) and decreased between 30° and 90° (P < 0.001, P = 0.004, respectively). The stress concentration area remained consistent at the proximal end, midsubstance, and distal end between 0° and 60° (P > 0.05). The concentration area of strain increased at the proximal end, decreased at the midsubstance between 0° and 30°, and remained consistent between 30° and 90° (P < 0.001). CONCLUSION: At the low knee flexion angle, ACL's magnitude of stress and strain reached the peak, and the concentration area of ACL strain gradually shifted from midsubstance to the proximal end.

TWIST1 rescue calcium overload and apoptosis induced by inflammatory microenvironment in S. aureus-induced osteomyelitis.

Currently, there is no effective therapy for Staphylococcus aureus-induced osteomyelitis. It is widely recognized that the inflammatory microenvironment around abscess plays an essential role in protracting the course of S. aureus-induced osteomyelitis. In this study, we found TWIST1 was highly expressed in macrophages around abscesses but less related to local S. aureus in the later stages of Staphylococcus aureus-infected osteomyelitis. Mouse bone marrow macrophages show apoptosis and elevated TWIST1 expression when treated with the inflammatory medium. Knockdown of TWIST1 induced macrophage apoptosis, impaired the bacteria phagocytosis/killing abilities, and promoted cell apoptosis markers expression in inflammatory microenvironment stimulation. Furthermore, inflammatory microenvironments were responsible for inducing calcium overload in macrophage mitochondrial while calcium overload inhibition significantly rescued macrophage apoptosis, bacteria phagocytosis/killing abilities and improved the mice's antimicrobial ability. Our findings indicated that TWIST1 is a crucial molecule that protects macrophages from calcium overload induced by inflammatory microenvironments.

A case report of early unilateral external fixation by 3D printing and computer-assisted and secondary bone graft internal fixation in pseudarthrosis of the tibia surgery.

Congenital pseudarthrosis of the tibia (CPT) is a rare congenital malformation. It is characterized by a tibial anterior bowing deformity or specific types of non-union, which typically result from abnormal development of the tibia, leading to the formation of local pseudarthrosis. The treatment of CPT is very challenging. The advent of 3D printing and computer-assisted techniques in recent years has provided a new ancillary technique for treatment planning and implementation. This case report describes the successful surgical treatment of a 14-year-old male that presented with a shortened limb deformity. Ahead of elective surgery, 3D printing and computer-assisted techniques were used to provide a 1:1 model of his left tibia, fibula and ankle joint to precisely determine the surgical procedure. The first surgery did not result in complete calcification of the tibial extension area, so a second proximal tibia iliac bone graft and internal fixation surgery was undertaken. Following regular follow-up and rehabilitation, by the 18-month follow-up, the proximal tibial bone graft had healed and the patient had resumed walking with a normal gait. This case report describes in detail the successful use of unilateral external fixation using the Ilizarov technique, 3D printing and computer-assisted orthopaedic surgery in the planning of treatment for CPT.

Transfection of neurotrophin-3 into neural stem cells using ultrasound with microbubbles to treat denervated muscle atrophy.

Neurotrophin-3 (NT-3) has potential as a therapeutic agent for the treatment of patients with denervated muscle atrophy. However, the endogenous secretion of NT-3 is low and exogenous NT-3 lacks sufficient time to accumulate due to its short half-life. The transfection of NT-3 has been demonstrated to have a beneficial effect on denervated muscle and motor endplates. Neural stem cells (NSCs) differentiate into neurons and form motor endplate nerve-muscle connections. It has been previously demonstrated that local and noninvasive transfection can be performed using ultrasound with microbubbles (MBs). In the current study, hematoxylin and eosin, acetylcholinesterase and gold chloride staining, as well as transmission electron microscopy, were performed to verify the effects of this treatment strategy. The results demonstrated that using ultrasound with MBs for the transfection of NT-3 into NSCs, and their subsequent transplantation in vivo, attenuated the atrophy of denervated muscle and reduced motor endplate degeneration. This noninvasive, efficient and targeted treatment strategy may therefore be a potential treatment for patients with denervated muscle atrophy.