Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

OBJECTIVE To investigate the potential of low-frequency, low-power ultrasound to enhance the transdermal absorption and efficacy of ketoprofen gel. METHODS Ketoprofen gel was used as a model drug to compare the in vitro transdermal permeation of ultrasound treated group and untreated group. Additionally, a rat model of collagen-induced inflammation provided a basis for evaluating pharmacodynamic differences. Pharmacokinetic studies further elucidated the effects of ultrasound on ketoprofen gel's penetration process. RESULTS Ultrasound treatment enhanced the cumulative transdermal permeation of ketoprofen gel by 3.5-fold over 24 hours compared to untreated. Significant pharmacokinetic improvements in AUC0-t from (4289.02±763.58)ng·h·mL−1 to (11301.10±3386.30)ng·h·mL−1 and a reduction in Tmax from (6.0±1.4)h to (3.0±2.0)h. Ultrasound notably improved the gel's anti-inflammatory effects in the rat model, effectively and rapidly reducing inflammation-induced swelling. CONCLUSION Low-frequency, low-power ultrasound can significantly improve the amount and rate of transdermal absorption of ketoprofen gel and enhance its pharmacological potency, from the aspects of skin permeation tests, pharmacodynamic evaluation, and pharmacokinetic studies, which is an effective penetration enhancer for transdermal administration of ketoprofen gel.

Objective To investigate tumor cell killing effect of superparamagnetic Fe3O4 nanoparticles with cubic phase through magneto-mechanical force under a low-frequency vibrating magnetic field ( VMF). Methods A kind of strong magnetic and irregular-shaped Fe3O4 nanoparticles with cubic phase was synthesized by coprecipitation method. The Fe3O4 nanoparticles were exposed to a self-developed VMF and cell killing efficiency of the Fe3O4-mediated magneto-mechanical force was investigated. Results VMF alone had no effects on cell viability. After Fe3O4 nanoparticles were added, the cell viability significantly decreased with prolonging the VMF treatment time and increasing the Fe3O4 nanoparticle concentration. Lactate dehydrogenase released by damaged cells also increased with prolonging the VMF exposure time. Conclusions The irregular-shaped Fe3O4 nanoparticles can transfer magneto-mechanical force to tumor cells under VMF, cause structural damage of cells and result in cell death. The VMF generator developed in this study has simple structure and it is safe for use and convenient for operation. The developed magnetic nanoparticles and the corresponding cancer cell killing technique have the potential for clinical transformation.

Objective To analyze the similarities and differences between four-point hand-knee position and hand-foot kneeling positions in trunk muscle activation and co-contraction, explore the possibility of hand-foot kneeling position as core stabilization exercises, so as to provide suggestions for actual training.Methods Nineteen healthy volunteers randomly performed exercises of four-point hand-knee position (4 motions) and hand-foot kneeling position (3 motions), while surface electromyography (sEMG) signals were collected from bilateral rectus abdominis, external oblique, erector spine, and multifidus muscles. The average sEMG and muscle co-contraction index (CCI) based on the sEMG signals were analyzed and compared.Results Significant differences were found in the sEMG and CCI within and between the two positions. Under four-point hand-knee position with the right hand and left leg lifting, the activation of all muscles was higher than that in the starting position. In four-point hand-knee position with the left leg lifting, the activation of ipsilateral multifidus muscle was significantly higher than that in hand-foot kneeling position. The activation degree of external oblique muscle and rectus abdominis was higher in hand-foot kneeling position with right hand lifting. A total of 28 muscle matching methods were obtained by pair-to-pair matching of 8 muscles. The starting posture in four-point hand-knee position fluctuated the least, indicating that the spine was the most stable, while the index of other exercises fluctuated in a larger range.Conclusions The possibility of hand-foot kneeling position as core stabilization exercises was proved from two aspects, namely, muscle activation and CCI. The hand-foot kneeling position and four-point hand-knee position can be used for strengthening abdominal muscles and back muscles, respectively. The four-point hand-knee position with contralateral upper and lower limbs lift is a more advanced exercise for trunk muscles, but sports injuries should be avoided.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unknown etiology and limited therapeutic options. Activation of fibroblasts is a prominent feature of pulmonary fibrosis. Here we report that lncRNA DACH1 (dachshund homolog 1) is downregulated in the lungs of IPF patients and in an experimental mouse model of lung fibrosis. LncDACH1 knockout mice develop spontaneous pulmonary fibrosis, whereas overexpression of LncDACH1 attenuated TGF-β1-induced aberrant activation, collagen deposition and differentiation of mouse lung fibroblasts. Similarly, forced expression of LncDACH1 not only prevented bleomycin (BLM)-induced lung fibrosis, but also reversed established lung fibrosis in a BLM model. Mechanistically, LncDACH1 binding to the serine/arginine-rich splicing factor 1 (SRSF1) protein decreases its activity and inhibits the accumulation of Ctnnb1. Enhanced expression of SRSF1 blocked the anti-fibrotic effect of LncDACH1 in lung fibroblasts. Furthermore, loss of LncDACH1 promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in mouse lung fibroblasts, whereas such effects were abolished by silencing of Ctnnb1. In addition, a conserved fragment of LncDACH1 alleviated hyperproliferation, ECM deposition and differentiation of MRC-5 cells driven by TGF-β1. Collectively, LncDACH1 inhibits lung fibrosis by interacting with SRSF1 to suppress CTNNB1 accumulation, suggesting that LncDACH1 might be a potential therapeutic target for pulmonary fibrosis.

Objective To explore the joint contact force, ligament tensile force and force transmission mode of foot internal structure in Down’s syndrome child (DSC) during standing. Methods The finite element models of foot were constructed based on CT image data from one DSC and one typically developing child (TDC). The models were validated by plantar pressure measurement during static standing. To simulate foot force during standing, the ground reaction force and the triceps surae force were applied as the loading condition. Contact pressure of the tibiotalar, talonavicular and calcaneocuboid joints, tensile force of the spring and plantar calcaneocuboid ligaments, and force transmission mode in transverse tarsal joints were calculated and analyzed. Results The finite element models of foot were validated to be reliable. Compared with the TDC, the DSC showed higher contact pressure at the tibiotalar joint and lower contact pressure at the talonavicular joint. The tensile force of spring and plantar calcaneocuboid ligaments of DSC was 10 times and 58 times of TDC, respectively. The forces transmitted through both mediate and lateral columns in DSC were lower than those in TDC. Conclusions Abnormal contact pressure of the tibiotalar joint, larger tensile force of midfoot ligaments and smaller force of the transverse tarsal joint were found in DSC during standing. The abnormal alteration of stress patterns in foot internal structure of DSC should be fully considered in clinical rehabilitation, so as to provide theoretical references for screening and making intervention plans for early rehabilitation, as well as designing individualized orthopedic insoles.

Objective To analyze the biomechanical feasibility of two-point fixation by distal radius plate for the treatment of SandersⅢ calcaneal fractures. Methods The three-dimensional (3D) finite element musculoskeletal foot model was established based on CT and MRI images, which comprised bones, muscles, plantar fascia, ligaments and soft tissues. After validation, the SandersⅢ calcaneal fracture models fixed by distal radial plate (two-point fixation) and calcaneal plate (three-point fixation) were established, so as to compare the biomechanical characteristics of two calcaneal models. Results The maximum stress of the two-point fixation and three-point fixation model was 324.70 and 407.90 MPa, respectively. The maximum displacements of the two models were 2.498 and 2.541 mm, respectively. There was no significant difference in the posterior articular surface displacement between the two models. In both models, the Bohler’s angle and Gissane’s angle were within the normal range. Conclusions The two-point fixation by distal radial plate can satisfy the biomechanical stability of calcaneal fracture treatment. Compared with traditional steel plate, the two-point fixation shows the advantage of smaller surgical trauma, more uniform overall stress distribution, early weight-bearing rehabilitation after surgery, which is a novel treatment recommended for treating calcaneal fractures.

In active health, biomechanics plays an irreplaceable role. Exercise creates mechanical stimulation to human tissues and organs. It promotes health, or causes injury and disease. In addition, biomechanics is involved in the design and evaluation of assistive devices, as well as in rehabilitation clinical diagnosis and treatment. The development of active health biomechanics requires the integration of sports and medicine. It includes more dynamics, fatigue and mechanical coupling issues. In the future research, on the one hand, the experience of other directions in biomechanics should be learnt from. On the other hand, it is necessary to combine the frontiers of scientific and technological development to develop new directions in biomechanics.

Objective To compare the differences in lower limb joint kinematics and muscle activation between Asian squat (AS) and Western squat (WS). Methods Eleven healthy adults were recruited to complete the biomechanical test of AS and WS. The 3D motion analysis system, force plates and surface electromyography (EMG) were used to collect kinematics, kinetics and muscle activation data of the subjects during two squats, and muscle force of the lower limb was also calculated by OpenSim. Results AS showed pelvis forward flexion, while WS showed pelvis backward extension at the time of peak knee flexion angle. Compared with the AS, a significant smaller hip flexion, larger knee flexion, larger hip abduction and hip rotation angles were found in WS at the time of peak knee flexion angle. Compared with AS, a significant greater peak force of soleus was found in WS during descent and ascent phases of squat. Additionally, a smaller peak force of anterior tibia was found in WS than that in AS during descent and ascent phases of the squat. No significant differences were found in other muscle peak force and the time of peak force between AS and WS. Conclusions The combined tibialis anterior activation and proximal joint flexion might be beneficial to stabilization during AS. The soleus muscle activation was significant in WS with heel lifting. The muscle activation pattern of proximal joint was similar between AS and WS. This study provides theoretical guidance for the design of clinical squat rehabilitation programs or the selection of squat training.

The purpose of this study is to analyze the biomechanics of ankle cartilage and ligaments during a typical Tai Chi movement-Brush Knee and Twist Step (BKTS). The kinematic and kinetic data were acquired in one experienced male Tai Chi practitioner while performing BKTS and in normal walking. The measured parameters were used as loading and boundary conditions for further finite element analysis. This study showed that the contact stress of the ankle joint during BKTS was generally less than that during walking. However, the maximum tensile force of the anterior talofibular ligament, the calcaneofibular ligament and the posterior talofibular ligament during BKTS was 130 N, 169 N and 89 N, respectively, while it was only 57 N, 119 N and 48 N during walking. Therefore, patients with arthritis of the ankle can properly practice Tai Chi. Practitioners with sprained lateral ligaments of the ankle joint were suggested to properly reduce the ankle movement range during BKTS.
Ankle ; Ankle Joint ; Biomechanical Phenomena ; Humans ; Knee Joint ; Lateral Ligament, Ankle ; Male ; Tai Ji