ZIF-8-Encapsulated Pexidartinib Delivery via Targeted Peptide-Modified M1 Macrophages Attenuates MDSC-Mediated Immunosuppression in Osteosarcoma.

Adoptive cellular therapy is a promising strategy for cancer treatment. However, the effectiveness of this therapy is limited by its intricate and immunosuppressive tumor microenvironment. In this study, a targeted therapeutic strategy for macrophage loading of drugs is presented to enhance anti-tumor efficacy of macrophages. K7M2-target peptide (KTP) is used to modify macrophages to enhance their affinity for tumors. Pexidartinib-loaded ZIF-8 nanoparticles (P@ZIF-8) are loaded into macrophages to synergistically alleviate the immunosuppressive tumor microenvironment synergistically. Thus, the M1 macrophages decorated with KTP carried P@ZIF-8 and are named P@ZIF/M1-KTP. The tumor volumes in the P@ZIF/M1-KTP group are significantly smaller than those in the other groups, indicating that P@ZIF/M1-KTP exhibited enhanced anti-tumor efficacy. Mechanistically, an increased ratio of CD4+ T cells and a decreased ratio of MDSCs in the tumor tissues after treatment with P@ZIF/M1-KTP indicated that it can alleviate the immunosuppressive tumor microenvironment. RNA-seq further confirms the enhanced immune cell function. Consequently, P@ZIF/M1-KTP has great potential as a novel adoptive cellular therapeutic strategy for tumors.

Multilayer Perceptron-Based Wearable Exercise-Related Heart Rate Variability Predicts Anxiety and Depression in College Students.

(1) Background: This study aims to investigate the correlation between heart rate variability (HRV) during exercise and recovery periods and the levels of anxiety and depression among college students. Additionally, the study assesses the accuracy of a multilayer perceptron-based HRV analysis in predicting these emotional states. (2) Methods: A total of 845 healthy college students, aged between 18 and 22, participated in the study. Participants completed self-assessment scales for anxiety and depression (SAS and PHQ-9). HRV data were collected during exercise and for a 5-min period post-exercise. The multilayer perceptron neural network model, which included several branches with identical configurations, was employed for data processing. (3) Results: Through a 5-fold cross-validation approach, the average accuracy of HRV in predicting anxiety levels was 89.3% for no anxiety, 83.6% for mild anxiety, and 74.9% for moderate to severe anxiety. For depression levels, the average accuracy was 90.1% for no depression, 84.2% for mild depression, and 82.1% for moderate to severe depression. The predictive R-squared values for anxiety and depression scores were 0.62 and 0.41, respectively. (4) Conclusions: The study demonstrated that HRV during exercise and recovery in college students can effectively predict levels of anxiety and depression. However, the accuracy of score prediction requires further improvement. HRV related to exercise can serve as a non-invasive biomarker for assessing psychological health.

Tai Chi Movement Recognition and Precise Intervention for the Elderly Based on Inertial Measurement Units and Temporal Convolutional Neural Networks.

(1) Background: The objective of this study was to recognize tai chi movements using inertial measurement units (IMUs) and temporal convolutional neural networks (TCNs) and to provide precise interventions for elderly people. (2) Methods: This study consisted of two parts: firstly, 70 skilled tai chi practitioners were used for movement recognition; secondly, 60 elderly males were used for an intervention study. IMU data were collected from skilled tai chi practitioners performing Bafa Wubu, and TCN models were constructed and trained to classify these movements. Elderly participants were divided into a precision intervention group and a standard intervention group, with the former receiving weekly real-time IMU feedback. Outcomes measured included balance, grip strength, quality of life, and depression. (3) Results: The TCN model demonstrated high accuracy in identifying tai chi movements, with percentages ranging from 82.6% to 94.4%. After eight weeks of intervention, both groups showed significant improvements in grip strength, quality of life, and depression. However, only the precision intervention group showed a significant increase in balance and higher post-intervention scores compared to the standard intervention group. (4) Conclusions: This study successfully employed IMU and TCN to identify Tai Chi movements and provide targeted feedback to older participants. Real-time IMU feedback can enhance health outcome indicators in elderly males.

Silencing eL31 suppresses the progression of colorectal cancer via targeting DEPDC1.

BACKGROUND: Colorectal cancer (CRC) is one of the most commonly diagnosed human malignancies. Ribosomal protein L31 (RPL31, aka eL31) is a component of the 60S large ribosomal subunit, and its expression pattern and functional role in CRC have not been reported. METHODS: Herein, we identified that eL31 protein level was dramatically increased in CRC tissues through using IHC analysis. More notably, elevated eL31 was associated with larger tumor size and shorter overall survival. Besides, we evaluated the effects of eL31 depletion on CRC cell phenotypes in vitro. RESULTS: The data indicated that eL31 knockdown restricted CRC cell proliferation, migration and colony formation whilst enhancing cell apoptosis. Importantly, eL31 was also essential for CRC tumor growth in vivo, as demonstrated by impaired tumor growth markers and reduced Ki67 levels in xenografts from eL31-depleted cells. In addition, our evidence indicated that DEP domain containing 1 (DEPDC1) was a potential downstream target of eL31 in regulating CRC. Consistently, DEPDC1 depletion restrained CRC cell proliferation and migration, as well as facilitated cell apoptosis. More interestingly, DEPDC1 depletion could reverse the promotion effects of eL31 elevation on CRC cells. CONCLUSIONS: Identification of eL31's function in CRC may pave the way for future development of more specific and more effective targeted therapy strategies against CRC.

Molecular mechanisms of mechanical load-induced osteoarthritis.

INTRODUCTION: Mechanical loading enhances the progression of osteoarthritis. However, its molecular mechanisms have not been established. OBJECTIVE: The aim of this review was to summarize the probable mechanisms of mechanical load-induced osteoarthritis. METHODS: A comprehensive search strategy was used to search PubMed and EMBASE databases (from the 15th of January 2015 to the 20th of October 2020). Search terms included "osteoarthritis", "mechanical load", and "mechanism". RESULTS: Abnormal mechanical loading activates the interleukin-1ß, tumour necrosis factor-α, nuclear factor kappa-B, Wnt, transforming growth factor-ß, microRNAs pathways, and the oxidative stress pathway. These pathways induce the pathological progression of osteoarthritis. Mechanical stress signal receptors such as integrin, ion channel receptors, hydrogen peroxide-inducible clone-5, Gremlin-1, and transient receptor potential channel 4 are present in the articular cartilages. CONCLUSION: This review highlights the molecular mechanisms of mechanical loading in inducing chondrocyte apoptosis and extracellular matrix degradation. These mechanisms provide potential targets for osteoarthritis prevention and treatment.

Role of the PGE2 receptor in ischemia-reperfusion injury of the rat retina.

Purpose: To investigate the function and expression of the PGE2 receptors EP1-4 in rat retinal ischemia-reperfusion (I/R) injury and to determine the regulatory role of resveratrol (RES) in this process. Methods: In vitro, we stimulated primary astrocytes extracted from the optic disc of rats with epidermal growth factor (EGF) and RES, and detected the location of EP1-4 expression with immunofluorescence. The expression of antiglial fibrillary acidic protein (GFAP), EGF receptor (EGFR), inducible NOS (iNOS), and EP1-4 in astrocytes was detected with western blotting. In vivo, we established an I/R injury model and RES treatment model with Sprague-Dawley rats. Changes in the thickness of the inner retina were observed with hematoxylin and eosin (H&E) staining. EP1-4 localization in the retina was observed with immunohistochemistry. The expression of COX-2, iNOS, and EP1-4 in the control and model groups was detected with western blotting. Results: In this study, immunofluorescence and immunohistochemistry showed that EP1-4 are expressed in astrocytes and the rat retina. EGF stimulation increased the expression of EGFR, iNOS, EP1, EP2, and EP4 in astrocytes. The expression of EP1-4 was statistically significantly increased on the third day after model induction, and EP1-4 expression decreased to normal levels on day 7. EGF and RES mediated the decrease in the expression of EP2. RES treatment significantly reduced retinal damage and RGC loss, as demonstrated by the relatively intact tissue structure on day 7 observed with H&E staining. Moreover, inflammation was associated with this I/R injury model, as demonstrated by the early induction of proinflammatory mediators, and this inflammation was significantly attenuated after RES treatment. Conclusions: These results indicate that the COX-2/PGE2/EPs pathway is involved in retinal damage and astrocyte inflammation. In addition, the results suggest that the neuroprotective effects of RES may be associated with decreased production of inflammatory mediators. These results suggest that the PGE2 receptor may be a key factor in the treatment of neurodegenerative diseases, and that RES may be used as a possible therapeutic strategy for glaucoma.

Resveratrol protects retinal ganglion cell axons through regulation of the SIRT1-JNK pathway.

It is reported that Ischemia and reperfusion damage (I/R damage) can lead to retinal ganglion cell (RGC) death and neurodegeneration, which in turn can lead to irreversible vision loss. In this study, we sought to understand the neuroprotective effect of resveratrol, the important activator of sirtuin1 (SIRT1), on RGC survival in I/R damage model and the molecular mechanism that mediate this effect. Our results show that resveratrol could reverse axonal swelling, holes, and the chaos of the nucleus in axons of RGCs caused by I/R. At the same time, resveratrol could also reverse the activation of retinal astrocytes and the loss of RGCs caused by I/R. Resveratrol increased the expression of SIRT1 while decreasing the phosphorylation of N-terminal kinase (JNK). SP600125(JNK inhibitor) decreased the phosphorylation of JNK while increasing the expression of SIRT1, indicating that SIRT1 and JNK can interact with each other. Simultaneous administration of resveratrol and sirtinol (SIRT1 inhibitor) neither increased the expression of SIRT1 nor decreased the phosphorylation of JNK, indicating that resveratrol affects the phosphorylation of JNK by SIRT1. In total, our research shows that resveratrol treatment significantly reduces apoptosis and axonal degeneration of RGCs, and this protection is partly mediated through the SIRT1-JNK pathway.

Doxycycline Attenuates Atrial Remodeling by Interfering with MicroRNA-21 and Downstream Phosphatase and Tensin Homolog (PTEN)/Phosphoinositide 3-Kinase (PI3K) Signaling Pathway.

BACKGROUND Atrial remodeling especially in the form of fibrosis is the most important substrate of atrial fibrillation (AF). The aim of this study was to investigate the effects of doxycycline on chronic intermittent hypoxia (CIH)-induced atrial remodeling and the pathophysiological mechanisms underlying such changes. MATERIAL AND METHODS A total of 30 Sprague-Dawley rats were randomized into 3 groups: Control group, CIH group, and CIH with doxycycline treatment group. CIH rats were subjected to CIH 6 h/d for 30 days and treatment rats were administrated doxycycline while they received CIH. After the echocardiography examination, rats were sacrificed at 31 days. The tissues of atria were collected for histological and molecular biological experiments, Masson staining was used to evaluate the extent of atrial fibrosis, microRNA-21, and its downstream target phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K) were assessed. RESULTS Compared to the control group, the CIH rats showed higher atrial interstitial collagen fraction, increased microRNA-21, PI3K levels, and decreased PTEN levels. Doxycycline treatment attenuated CIH-induced atrial fibrosis, reduced microRNA-21 and PI3K, and increased PTEN. CONCLUSIONS CIH induced significant atrial remodeling, which was attenuated by doxycycline in our rat model. These changes may be explained due to alterations in the microRNA-21-related signaling pathways by doxycycline.

Focus detection by shearing interference of vortex beams for non-imaging systems.

In focus detection of non-imaging systems, the common image-based methods are not available. Also, interference techniques are seldom used because only the degree with hardly any direction of defocus can be derived from the fringe spacing. In this paper, we propose a vortex-beam-based shearing interference system to do focus detection for a focused laser direct-writing system, where a vortex beam is already involved. Both simulated and experimental results show that fork-like features are added in the interference patterns due to the existence of an optical vortex, which makes it possible to distinguish the degree and direction of defocus simultaneously. The theoretical fringe spacing and resolution of this method are derived. A resolution of 0.79 µm can be achieved under the experimental combination of parameters, and it can be further improved with the help of the image processing algorithm and closed-loop controlling in the future. Finally, the influence of incomplete collimation and the wedge angle of the shear plate is discussed. This focus detection approach is extremely appropriate for those non-imaging systems containing one or more focused vortex beams.

HSP90B1 overexpression predicts poor prognosis in NSCLC patients.

Non-small cell lung cancer (NSCLC) accounts for 85 % of lung cancer-related mortality worldwide. The heat shock protein 90B1 (HSP90B1) and DNA damage-inducible transcript 3 (DDIT3) are endoplasmic reticulum stress-related proteins that are associated with many malignancies. However, the roles of two proteins on NSCLC remain uncovered. To investigate the correlation between the expressions of HSP90B1 and DDIT3 and clinicopathological parameters of NSCLC as well as the significance of prognosis in NSCLC, a total of 143 NSCLC tissue samples and 45 control tissues samples were assessed. NSCLC patients were followed up from the day of surgery and ended by March 2014. The expressions of HSP90B1 and DDIT3 proteins were detected in all paraffin-embedded biopsy samples by immunochemistry. The HSP90B1 was highly expressed (65.2 %) in the 143 NSCLC patients, and its high expression was correlated with clinical stages (P = 0.001) and lymph node metastasis (P = 0.016). Similarly, DDIT3 was highly expressed in 43 (30.1 %) of 143 NSCLC patients, but only correlated with lymph node metastasis. Furthermore, Log-rank test suggested that high HSP90B1 expression may predict shorter survival (overall survival (OS)) and disease-free survival (DFS) for NSCLC patients. Cox model multivariate analyses indicated that HSP90B1 overexpression was an independent poor prognostic factor for both of OS and DFS. Therefore, HSP90B1 and DDIT3 may the potential biomarker to predict the NSCLC clinicopathological progress. Meanwhile, high HSP90B1 expression means poor prognosis, and HSP90B1 can be a promising prognosis factor for NSCLC.

Magnesium status modulating the effect of serum vitamin D levels on retinopathy: National Health and Nutrition Examination Survey 2005 to 2008.

Aim: Magnesium levels may influence the effect of vitamin D levels on the body. This study aimed to assess the combined effect of magnesium status as reflected by magnesium depletion score (MDS) and vitamin D status on the risk of retinopathy. Methods: This cross-sectional study included participants aged 40 years and older with complete information on vitamin D, MDS, and retinopathy assessment from the 2005-2008 National Health and Nutrition Examination Survey (NHANES). Logistic regression analysis was utilized to analyze the relationship of MDS and vitamin D with retinopathy and expressed as odds ratio (OR) and 95% confidence interval (CI). Results: Of these 4,953 participants included, 602 (9.53%) participants had retinopathy. Serum vitamin D levels ≤30 nmol/L (vs. >30 nmol/L) (OR = 1.38, 95%CI: 1.05-1.81) and MDS >2 points (vs. ≤2 points) (OR = 1.47, 95%CI: 1.01-2.16) were associated with higher odds of retinopathy. There was an interaction between MDS and vitamin D on the increased odds of retinopathy (OR = 2.29, 95%CI: 1.12-4.68, P interaction = 0.025). In different MDS groups, serum vitamin D levels ≤30 nmol/L increased the odds of retinopathy only in the MDS >2 group (OR = 2.90, 95%CI: 1.16-7.24), but not in the MDS ≤2 group (p = 0.293). Subgroups analyses demonstrated that the interaction between MDS and serum vitamin D on retinopathy was observed in males (OR = 6.88, 95%CI: 1.41-33.66, P interaction = 0.019), people with diabetes (OR = 3.43, 95%CI: 1.78-6.63, P interaction < 0.001), and people with body mass index (BMI) ≥25 kg/m2 (OR = 2.46, 95%CI: 1.11-5.44, P interaction = 0.028). Conclusion: Magnesium plays a moderating role in the relationship between serum vitamin D and retinopathy. The protective effect of vitamin D against retinopathy was primarily present among those with inadequate magnesium levels.

pH-Responsive Mesoporous Silica Nanoparticles Loaded with Naringin for Targeted Osteoclast Inhibition and Bone Regeneration.

Background: It is well-established that osteoclast activity is significantly influenced by fluctuations in intracellular pH. Consequently, a pH-sensitive gated nano-drug delivery system represents a promising therapeutic approach to mitigate osteoclast overactivity. Our prior research indicated that naringin, a natural flavonoid, effectively mitigates osteoclast activity. However, naringin showed low oral availability and short half-life, which hinders its clinical application. We developed a drug delivery system wherein chitosan, as gatekeepers, coats mesoporous silica nanoparticles loaded with naringin (CS@MSNs-Naringin). However, the inhibitory effects of CS@MSNs-Naringin on osteoclasts and the underlying mechanisms remain unclear, warranting further research. Methods: First, we synthesized CS@MSNs-Naringin and conducted a comprehensive characterization. We also measured drug release rates in a pH gradient solution and verified its biosafety. Subsequently, we investigated the impact of CS@MSNs-Naringin on osteoclasts induced by bone marrow-derived macrophages, focusing on differentiation and bone resorption activity while exploring potential mechanisms. Finally, we established a rat model of bilateral critical-sized calvarial bone defects, in which CS@MSNs-Naringin was dispersed in GelMA hydrogel to achieve in situ drug delivery. We observed the ability of CS@MSNs-Naringin to promote bone regeneration and inhibit osteoclast activity in vivo. Results: CS@MSNs-Naringin exhibited high uniformity and dispersity, low cytotoxicity (concentration≤120 µg/mL), and significant pH sensitivity. In vitro, compared to Naringin and MSNs-Naringin, CS@MSNs-Naringin more effectively inhibited the formation and bone resorption activity of osteoclasts. This effect was accompanied by decreased phosphorylation of key factors in the NF-κB and MAPK signaling pathways, increased apoptosis levels, and a subsequent reduction in the production of osteoclast-specific genes and proteins. In vivo, CS@MSNs-Naringin outperformed Naringin and MSNs-Naringin, promoting new bone formation while inhibiting osteoclast activity to a greater extent. Conclusion: Our research suggested that CS@MSNs-Naringin exhibited the strikingly ability to anti-osteoclasts in vitro and in vivo, moreover promoted bone regeneration in the calvarial bone defect.

Intestinal Flora Imbalance Induced by Antibiotic Use in Rats.

Aim: This study aims to explore the effect of different doses of antibiotics on rats in order to observe alterations in their fecal microbiota, inflammatory changes in the colonic mucosa and four types of inflammatory markers in blood serum. Methods: Our methodology involved separating 84 female Sprague Dawley rats into groups A-G, with each group consisting of 12 rats. We collected the rat feces for analysis, using a distinct medium for bacterial cultivation and counting colonies under a microscope. On the 11th and 15th days of the experiment, half of the rats from each group were euthanized and 5 mL of abdominal aortic blood and colon tissues were collected. Inflammations changes of colon were observed and assessed by pathological Hematoxylin Eosin (HE) staining. Enzyme-linked immune sorbent assay (ELISA) was adopted for detecting C-reactive protein (CRP), IL-6, IL1-ß and TNF-α. Results: Our findings revealed that the initial average weight of the rats did not differ between groups (p>0.05); but significant differences were observed between stool samples, water intake, food intake and weight (p=0.009, <0.001, 0.016 and 0.04, respectively) within two hours after the experiment. Additionally, there were notable differences among the groups in nine tested microbiota before and after weighting methods (all p<0.001). There were no difference in nine microbiota at day 1 (all p>0.05); at day 4 A/B (p=0.044), A/D (p<0.001), A/E (p=0.029); at day 8, all p<0.01, at day 11, only A/F exist significant difference (p<0.001); at day 14 only A/D has difference (p=0.045). Inflammation changes of colon were observed between groups A-G at days 11 and 15. Significant differences between all groups can be observed for CRP, IL-6, IL1-ß and TNF-α (p<0.001). Conclusion: This study suggests that antibiotics administration can disrupt the balance of bacteria in the rat gut ecosystem, resulting in an inflammatory response in their bloodstream and inducing inflammation changes of colon.

A functional mineralized collagen hydrogel to promote angiogenic and osteogenic for osseointegration of 3D-printed titanium alloy microporous scaffolds.

Bone defects, resulting from trauma, inflammation, tumors, and various other factors, affect both health and quality of life. Although autologous bone transplantation is the gold-standard treatment for bone defects, it has disadvantages such as donor site limitations, prolonged surgical durations, and potential complications, necessitating the development of alternative bone tissue engineering materials. In this study, we used 3D printing technology to fabricate porous titanium implants characterized by superior biocompatibility and mechanical properties. Sodium alginate (SA) and strontium ions (Sr2+) were integrated into mineralized collagen matrices (MCs) to develop strontium-functionalized alginate-mineralized collagen hydrogels (SAMs) with high mechanical strength and sustained metal ion release ability. SAMs were seamlessly incorporated into the porous structures of 3D-printed titanium scaffolds, establishing a novel organic-inorganic bioactive interface. This composite system exhibited high biocompatibility in vitro and increased the expression of genes important for osteogenic differentiation and angiogenesis. In a rabbit model of femoral defect, the titanium implants effectively promoted bone and vascular regeneration on their surface, highlighting their potential in facilitating bone-implant integration.

Investigating the synergy of Shikonin and Valproic acid in inducing apoptosis of osteosarcoma cells via ROS-mediated EGR1 expression.

BACKGROUND: Osteosarcoma is the most prevalent malignant bone tumour with a poor prognosis. Shikonin (SHK) is derived from the traditional Chinese medicine Lithospermum that has been extensively studied for its notable anti-tumour effects, including for osteosarcoma. However, its application has certain limitations. Valproic acid (VPA) is a histone deacetylase inhibitor (HDACI) that has recently been employed as an adjunctive therapeutic agent that allows chromatin to assume a more relaxed state, thereby enhancing anti-tumour efficacy. PURPOSE: This study was aimed to investigate the synergistic anti-tumour efficacy of SHK in combination with VPA and elucidate its underlying mechanism. METHODS/STUDY DESIGN: CCK-8 assays were utilized to calculate the combination index. Additional assays, including colony formation, acridine orange/ethidium bromide double fluorescent staining, and flow cytometry, were employed to evaluate the effects on osteosarcoma cells. Wound healing and transwell assays were utilized to assess cell mobility. RNA sequencing, PCR, and Western blot analyses were conducted to uncover the underlying mechanism. Rescue experiments were performed to validate the mechanism of apoptotic induction. The impact of SHK and VPA combination treatment on primary osteosarcoma cells was also assessed. Finally, in vivo experiments were conducted to validate its anti-tumour effects and mechanism. RESULTS: The combination of SHK and VPA synergistically inhibited the proliferation and migration of osteosarcoma cells in vitro and induced apoptosis in these cells. Through a comprehensive analysis involving RNA sequencing, PCR, Western blot, and rescue experiments, we have substantiated our hypothesis that the combination of SHK and VPA induced apoptosis via the ROS-EGR1-Bax axis. Importantly, our in vivo experiments corroborated these findings, demonstrating the potential of the SHK and VPA combination as a promising therapeutic approach for osteosarcoma. CONCLUSION: The combination of SHK and VPA exerted an anti-tumour effect by inducing apoptosis through the ROS-EGR1-Bax pathway. Repurposing the old drug VPA demonstrated its effectiveness as an adjunctive therapeutic agent for SHK, enhancing its anti-tumour efficacy and revealing its potential value. Furthermore, our study expanded the application of natural compounds in the anti-tumour field and overcame some of their limitations through combination therapy. Finally, we enhanced the understanding of the mechanistic pathways linking reactive oxygen species (ROS) accumulation and apoptosis in osteosarcoma cells. Additionally, we elucidated the role of EGR1 in osteosarcoma cells, offering novel strategies and concepts for the treatment of osteosarcoma.

Strategy insight: Mechanical properties of biomaterials' influence on hydrogel-mesenchymal stromal cell combination for osteoarthritis therapy.

Osteoarthritis (OA) is a kind of degenerative joint disease usually found in older adults and those who have received meniscal surgery, bringing great suffering to a number of patients worldwide. One of the major pathological features of OA is retrograde changes in the articular cartilage. Mesenchymal stromal cells (MSCs) can differentiate into chondrocytes and promote cartilage regeneration, thus having great potential for the treatment of osteoarthritis. However, improving the therapeutic effect of MSCs in the joint cavity is still an open problem. Hydrogel made of different biomaterials has been recognized as an ideal carrier for MSCs in recent years. This review focuses on the influence of the mechanical properties of hydrogels on the efficacy of MSCs in OA treatment and compares artificial materials with articular cartilage, hoping to provide a reference for further development of modified hydrogels to improve the therapeutic effect of MSCs.

Newly compiled Tai Chi (Bafa Wubu) promotes lower extremity exercise: a preliminary cross sectional study.

Background: Tai Chi (Bafa Wubu) is a new type of simplified Tai Chi widely practiced by Tai Chi enthusiasts that has developed and perfected simplified Tai Chi movement and enriched Tai Chi practice methods. When practicing, Tai Chi athletes and enthusiasts can choose the Bafa Wubu movements to practice according to their physical conditions. The purpose of this article is to discuss the mechanism by which Bafa Wubu promotes lower extremity exercise from the perspective of exercise biomechanics. Objectives: This article aims to explore the scientific training methods and technical characteristics of Bafa Wubu, and its contribution to comprehensive exercise of the lower extremities, by analyzing the biomechanical characteristics of the lower extremities of participants who practice Bafa Wubu at different levels and by comparing their ground reaction force, lower limb joints, and muscles during Bafa Wubu. Methods: A total of 16 male participants were recruited and divided into an amateur group (N = 8) and a professional group (N = 8). The data were collected by a BTS 3D infrared-based motion capture system, and Kistler 3D force plate. The lower extremity joint forces and muscle strength were calculated by anybody simulation software with inverse dynamics. Results: During elbowing and leaning sideways with steps sideways (ELS), the ground reaction force of the professional group was significantly higher than that of the amateur group in the sagittal, vertical, and frontal axes (P < 0.01). While stepping forward, backward, and sideways, the professional group's joints loading at the hip, knee, and ankle was always higher in the vertical direction (P < 0.01). Furthermore, during warding off with steps forward (WOF), laying with steps forward (LF), and rolling back with steps backward (RBB), hip joint loading increased in the med-lat direction. During actions with steps backward and sideways, the professional group's ankle flexion/extension torque and hip abduction/rotation torque were significantly larger than those of the amateur group (P < 0.01). Different actions in Bafa Wubu activate muscles to different degrees, whereas the iliacus is mainly responsible for stabilizing postures when practitioners perform standing knee lifting motions. Conclusions: Professional groups who have been practicing Tai Chi (Bafa Wubu) for a long time have higher ground reaction force, and the force on the three joints of the lower extremities is different for various movements, which has positive significance for exercising the joints of the lower extremities. In addition, various motions activate muscles of different types at different levels. For amateurs to practice different movements to stimulate the muscles, targeted areas of practice promote the lower extremity muscles' synergistic force. In summary, the muscles and joints of the lower extremity can obtain comprehensive and balanced exercise through Bafa Wubu.

Umbilical cord mesenchymal stem cells relieve osteoarthritis in rats through immunoregulation and inhibition of chondrocyte apoptosis.

This study aims to investigate the effectiveness of umbilical cord mesenchymal stem cells (UCMSCs) in treating osteoarthritis (OA). Sprague-Dawley rats were used in in vivo experiments and divided into four groups: normal, OA model, saline, and UCMSC-treated groups (n = 6). An OA model was established by injecting iodoacetic acid into the joint cavity. The results indicate that UCMSC transplantation significantly reduced joint surface and articular cartilage damage, and the levels of IL-1ß, TNF-α, and MMP13 in the joint fluid were significantly reduced after UCMSC treatment. In vitro experiments showed that co-culturing UCMSCs and chondrocytes promoted the expression of aggrecan, COL2, SOX9, and BCL-2; downregulated the expression of BAX and BAD in chondrocytes; and promoted the expression of IL-10 and TGF-ß1 in UCMSCs. Additionally, the supernatant of UCMSCs inhibited the expression of IL-1ß and TNF-α in the articular cavity and promoted the expression of COL2 and aggrecan in vivo. These effects were impaired when IL-10 and TGF-ß1 were removed. Collectively, UCMSC transplantation appears to improve joint pathology, reduce inflammatory factors, and decrease chondrocyte apoptosis, likely through the involvement of IL-10 and TGF-ß1, thus providing a potential therapeutic option for patients with OA.

Biomimetic Intrafibrillar Mineralization of Native Tendon for Soft-Hard Interface Integration by Infiltration of Amorphous Calcium Phosphate Precursors.

Soft and hard tissues possess distinct biological properties. Integrating the soft-hard interface is difficult due to the inherent non-osteogenesis of soft tissue, especially of anterior cruciate ligament and rotator cuff reconstruction. This property makes it difficult for tendons to be mineralized and integrated with bone in vivo. To overcome this challenge, a biomimetic mineralization strategy is employed to engineer mineralized tendons. The strategy involved infiltrating amorphous calcium phosphate precursors into collagen fibrils, resulting in hydroxyapatite deposition along the c-axis. The mineralized tendon presented characteristics similar to bone tissue and induced osteogenic differentiation of mesenchymal stem cells. Additionally, the interface between the newly formed bone and tendon is serrated, suggesting a superb integration between the two tissues. This strategy allows for biomineralization of tendon collagen and replicating the hallmarks of the bone matrix and extracellular niche, including nanostructure and inherent osteoinductive properties, ultimately facilitating the integration of soft and hard tissues.