Circular RNA SLTM as a miR-421-competing endogenous RNA to mediate HMGB2 expression stimulates apoptosis and inflammation in arthritic chondrocytes.

Osteoarthritis (OA) is the most common age-related joint disease characterized by chronic inflammation, progressive articular cartilage destruction, and subchondral sclerosis. Accumulating evidence suggests that circular RNAs (circRNAs) play key roles in OA, but the function of circSLTM in OA remains greatly unknown. Therefore, this study focused on interleukin-1ß (IL-1ß)-treated primary human chondrocytes as well as a rat model to investigate the expression pattern and functional role of circSLTM in OA in vitro and in vivo. CircSLTM and high mobility group protein B2 (HMGB2) were upregulated in IL-1ß-induced chondrocytes, whereas miR-421 was downregulated. Knockdown of circSLTM or overexpression of miR-421 ameliorated IL-1ß-induced chondrocyte apoptosis and inflammation. The regulatory relationship between circSLTM and miR-421, as well as that between miR-421 and HMGB2, was predicted by bioinformatics and then verified by the RNA immunoprecipitation experiment and dual-luciferase reporter gene assay. Furthermore, silencing of circSLTM increased cartilage destruction and decreased cartilage tissue apoptosis rate and inflammation in a rat model of OA. Taken together, our findings demonstrate the fundamental role of circSLTM in OA progression and provide a potential molecular target for OA therapy.

Cajaninstilbene acid inhibits osteoporosis through suppressing osteoclast formation and RANKL-induced signaling pathways.

Osteoporosis is a form of osteolytic disease caused by an imbalance in bone homeostasis, with reductions in osteoblast bone formation, and augmented osteoclast formation and resorption resulting in reduced bone mass. Cajaninstilbene acid (CSA) is a natural compound derived from pigeon pea leaves. CSA possesses beneficial properties as an anti-inflammatory, antibacterial, antihepatitis, and anticancer agent; however, its potential to modulate bone homeostasis and osteoporosis has not been studied. We observed that CSA has the ability to suppress RANKL-mediated osteoclastogenesis, osteoclast marker gene expression, and bone resorption in a dose-dependent manner. Mechanistically, it was revealed that CSA attenuates RANKL-activated NF-κB and nuclear factor of activated T-cell pathways and inhibited phosphorylation of key signaling mediators c-Fos, V-ATPase-d2, and ERK. Moreover, in osteoclasts, CSA blocked RANKL-induced ROS activity as well as calcium oscillations. We further evaluated the therapeutic effect of CSA in a preclinical mouse model and showed that in vivo treatment of ovariectomized C57BL/6 mice with CSA protects the mice from osteoporotic bone loss. Thus, this study demonstrates that osteolytic bone diseases can potentially be treated by CSA.

MiR-214 is an important regulator of the musculoskeletal metabolism and disease.

MiR-214 belongs to a family of microRNA (small, highly conserved noncoding RNA molecules) precursors that play a pivotal role in biological functions, such as cellular function, tissue development, tissue homeostasis, and pathogenesis of diseases. Recently, miR-214 emerged as a critical regulator of musculoskeletal metabolism. Specifically, miR-214 can mediate skeletal muscle myogenesis and vascular smooth muscle cell proliferation, migration, and differentiation. MiR-214 also modulates osteoblast function by targeting specific molecular pathways and the expression of various osteoblast-related genes; promotes osteoclast activity by targeting phosphatase and tensin homolog (Pten); and mediates osteoclast-osteoblast intercellular crosstalk via an exosomal miRNA paracrine mechanism. Importantly, dysregulation in miR-214 expression is associated with pathological bone conditions such as osteoporosis, osteosarcoma, multiple myeloma, and osteolytic bone metastasis of breast cancer. This review discusses the cellular targets of miR-214 in bone, the molecular mechanisms governing the activities of miR-214 in the musculoskeletal system, and the putative role of miR-214 in skeletal diseases. Understanding the biology of miR-214 could potentially lead to the development of miR-214 as a possible biomarker and a therapeutic target for musculoskeletal diseases.

The emerging role of NPNT in tissue injury repair and bone homeostasis.

Nephronectin (NPNT), a highly conserved extracellular matrix protein, plays an important role in regulating cell adhesion, differentiation, spreading, and survival. NPNT protein belongs to the epidermal growth factor (EGF)-like superfamily and exhibits several common structural determinants; including EGF-like repeat domains, MAM domain (Meprin, A5 Protein, and Receptor Protein-Tyrosine Phosphatase µ), RGD motif (Arg-Gly-Asp) and a coiled-coil domain. It regulates integrins-mediated signaling pathways via the interaction of its RGD motif with integrin α8ß1. Recent studies revealed that NPNT is involved in kidney development, renal injury repair, atrioventricular canal differentiation, pulmonary function, and muscle cell niche maintenance. Moreover, NPNT regulates osteoblast differentiation and mineralization, as well as osteogenic angiogenesis. Altered expression of NPNT has been linked with the progression of certain types of cancers, such as spontaneous breast tumor metastasis and malignant melanoma. Interestingly, NPNT gene expression can be regulated by a range of external factors such as tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-ß), oncostatin M (OSM), bone morphogenic protein 2 (BMP2), Wnt3a, Vitamin D3 , and microRNA-378 (miR378). Further understanding the cellular and molecular mechanisms by which NPNT regulates tissue homeostasis in an organ-specific manner is critical in exploring NPNT as a therapeutic target for tissue regeneration and tissue engineering.

Achyranthes bidentata polysaccharide suppresses osteoclastogenesis and bone resorption via inhibiting RANKL signaling.

Osteoclasts are highly differentiated multinucleated giant cells that play fundamental roles in bone resorption and in the pathogenesis of osteolytic conditions, such as osteoporosis and cancer-induced bone loss. Achyranthes bidentata polysaccharide (ABP) is a hydrophilic compound with anti-oxidation and anti-aging characteristics. The impact of ABP on RANKL-induced osteoclast formation and bone resorption has not been assessed, hence, in this study we investigated the effect of ABP on osteoclast formation and resorption in murine bone marrow derived osteoclasts. We found that ABP was able to suppress RANKL-induced osteoclast differentiation and bone resorption activity at concentrations above 6.5 µM, while demonstrating no cytotoxicity at concentrations up to 10 µM. The actions of ABP were mediated through inhibition of RANKL-induced c-Fos and NFATc1 gene and protein expression. Furthermore, we found that ABP suppressed NFATc1 transcriptional activity, and the phosphorylation of MAPK pathways induced by RANKL. Collectively, ABP attenuates RANKL-mediated osteoclast activity and signaling, and might serve as a potential therapeutic candidate for preventing bone loss related diseases.

Mutual learning with memory for semi-supervised pest detection.

Effectively monitoring pest-infested areas by computer vision is essential in precision agriculture in order to minimize yield losses and create early scientific preventative solutions. However, the scale variation, complex background, and dense distribution of pests bring challenges to accurate detection when utilizing vision technology. Simultaneously, supervised learning-based object detection heavily depends on abundant labeled data, which poses practical difficulties. To overcome these obstacles, in this paper, we put forward innovative semi-supervised pest detection, PestTeacher. The framework effectively mitigates the issues of confirmation bias and instability among detection results across different iterations. To address the issue of leakage caused by the weak features of pests, we propose the Spatial-aware Multi-Resolution Feature Extraction (SMFE) module. Furthermore, we introduce a Region Proposal Network (RPN) module with a cascading architecture. This module is specifically designed to generate higher-quality anchors, which are crucial for accurate object detection. We evaluated the performance of our method on two datasets: the corn borer dataset and the Pest24 dataset. The corn borer dataset encompasses data from various corn growth cycles, while the Pest24 dataset is a large-scale, multi-pest image dataset consisting of 24 classes and 25k images. Experimental results demonstrate that the enhanced model achieves approximately 80% effectiveness with only 20% of the training set supervised in both the corn borer dataset and Pest24 dataset. Compared to the baseline model SoftTeacher, our model improves mAP @0.5 (mean Average Precision) at 7.3 compared to that of SoftTeacher at 4.6. This method offers theoretical research and technical references for automated pest identification and management.

Cyasterone has a protective effect on steroid-induced Osteonecrosis of the femoral head.

CONTEXT: Cyasterone alleviated the apoptosis of BMSCs induced by Dexamethasone via the PI3K/AKT signaling pathway. In addition, Cyasterone had a protective effect on SIONFH model rats by reducing the percentage of empty bone lacunae. OBJECTIVE: To study the effect of Cyasterone on apoptosis of rat BMSCs and its function on the SIONFH rat model. METHODS: Rat BMSCs were cultured and divided into Control, DXM and Cyasterone (DXM+Cyasterone) groups. The apoptosis of each group was detected by flow cytometry, the expressions of Caspase-3 and Caspase-9 were detected by immunofluorescence staining, and the mRNA and protein expressions of AKT, BAX, P53, P85, Bcl-2 and Cytochrome C were detected by qPCR and WB. In animal experiments, the femoral head of rats were subjected to HE staining and Micro-CT to observe the necrosis and repair conditions. RESULTS: The apoptosis rate of DXM and Cyasterone groups increased compared with Control group, and the apoptosis rate of Cyasterone group decreased compared with DXM group. Compared with DXM group, the mRNA expression of BAX, P53, P85 and Cytochrome C in Cyasterone group were increased, while the protein expression of AKT and Bcl-2 decreased. The histopathological and morphological analysis showed that Cyasterone promoted the trabecular bone structure in rat, which evenly benefit for the repair of SIONFH. CONCLUSION: Cyasterone can reduce the apoptosis of rat BMSCs induced by Dexamethasone, and help promoting the bone repair in SIONFH rats.

AgriPest-YOLO: A rapid light-trap agricultural pest detection method based on deep learning.

Light traps have been widely used for automatic monitoring of pests in the field as an alternative to time-consuming and labor-intensive manual investigations. However, the scale variation, complex background and dense distribution of pests in light-trap images bring challenges to the rapid and accurate detection when utilizing vision technology. To overcome these challenges, in this paper, we put forward a lightweight pest detection model, AgriPest-YOLO, for achieving a well-balanced between efficiency, accuracy and model size for pest detection. Firstly, we propose a coordination and local attention (CLA) mechanism for obtaining richer and smoother pest features as well as reducing the interference of noise, especially for pests with complex backgrounds. Secondly, a novel grouping spatial pyramid pooling fast (GSPPF) is designed, which enriches the multi-scale representation of pest features via fusing multiple receptive fields of different scale features. Finally, soft-NMS is introduced in the prediction layer to optimize the final prediction results of overlapping pests. We evaluated the performance of our method on a large scale multi pest image dataset containing 24 classes and 25k images. Experimental results show that AgriPest-YOLO achieves end-to-end real-time pest detection with high accuracy, obtaining 71.3% mAP on the test dataset, outperforming the classical detection models (Faster RCNN, Cascade RCNN, Dynamic RCNN,YOLOX and YOLOv4) and lightweight detection models (Mobilenetv3-YOLOv4, YOLOv5 and YOLOv4-tiny), meanwhile our method demonstrates better balanced performance in terms of model size, detection speed and accuracy. The method has good accuracy and efficiency in detecting multi-class pests from light-trap images which is a key component of pest forecasting and intelligent pest monitoring technology.

[The causes of Latarjet surgery failure and the revision surgeries].

OBJECTIVE: To review the causes of Latarjet surgery failure and various revision surgeries, in order to provide the reference for the revision of treatment options for Latarjet surgery failure. METHODS: Literature on the causes of Latarjet surgery failure and revision surgeries was extensively reviewed and analyzed. RESULTS: Latarjet surgery is widely used in clinical practice for recurrent anterior dislocation of shoulder with glenoid defects, especially for the defects of more than 25%. The main reasons for its failure are ununion, bone resorption, graft dislocation, trauma, and graft fracture, etc. The revision surgeries are diverse, the standard treatment has not yet been formed. The revision surgeries include open iliac bone grafting, microscopic Eden-Hybinette surgery, soft tissue reconstruction, open or arthroscopic bone grafting, etc. The differences among the revisions are mainly reflected in grafts, complications, and their costs. CONCLUSION: Latarjet surgery is difficult to operate and requires high technical requirements for the surgeons. It is necessary to continuously improve the surgical technology to reduce the complications related to Latarjet surgery and its revision surgery.

Relation classification via BERT with piecewise convolution and focal loss.

Recent relation extraction models' architecture are evolved from the shallow neural networks to natural language model, such as convolutional neural networks or recurrent neural networks to Bert. However, these methods did not consider the semantic information in the sequence or the distance dependence problem, the internal semantic information may contain the useful knowledge which can help relation classification. Focus on these problems, this paper proposed a BERT-based relation classification method. Compare with the existing Bert-based architecture, the proposed model can obtain the internal semantic information between entity pair and solve the distance semantic dependence better. The pre-trained BERT model after fine tuning is used in this paper to abstract the semantic representation of sequence, then adopt the piecewise convolution to obtain semantic information which influence the extraction results. Compare with the existing methods, the proposed method can achieve a better accuracy on relational extraction task because of the internal semantic information extracted in the sequence. While, the generalization ability is still a problem that cannot be ignored, and the numbers of the relationships are difference between different categories. In this paper, the focal loss function is adopted to solve this problem by assigning a heavy weight to less number or hard classify categories. Finally, comparing with the existing methods, the F1 metric of the proposed method can reach a superior result 89.95% on the SemEval-2010 Task 8 dataset.

Tert-butylhydroquinone attenuates osteoarthritis by protecting chondrocytes and inhibiting macrophage polarization.

AIMS: Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA. METHODS: OA animal model was induced by destabilization of the medial meniscus (DMM). Different concentrations of tBHQ (25 and 50 mg/kg) were intraperitoneally injected in ten-week-old female mice. Chondrocytes were isolated from articular cartilage of mice and treated with 5 ng/ml lipopolysaccharide (LPS) or 10 ng/ml interleukin 1 beta (IL-1ß) for 24 hours, and then treated with different concentrations of tBHQ (10, 20, and 40 µM) for 12 hours. The expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured. The expression levels of interleukin 6 (IL-6), IL-1ß, and tumour necrosis factor alpha (TNF-α) leptin in plasma were measured using enzyme-linked immunoabsorbent assay (ELISA) kits. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathway proteins, and macrophage repolarization-related markers, were detected by western blot. RESULTS: Tert-butylhydroquinone significantly attenuated cartilage destruction in DMM-induced mice in vivo. It demonstrated clear evidence of inhibiting IL-1ß-induced chondrocyte apoptosis, inflammation, and differentiation defect in vitro. Meanwhile, tBHQ inhibited LPS-induced activation of NF-κB and MAPK signalling pathways, and also inhibited LPS-induced reactive oxygen species production and macrophages repolarization in vitro. CONCLUSION: Taken together, tBHQ might be a potential therapeutic strategy for protecting against OA development. Cite this article: Bone Joint Res 2021;10(11):704-713.

Fumitremorgin C Attenuates Osteoclast Formation and Function via Suppressing RANKL-Induced Signaling Pathways.

Excessive bone resorption conducted by osteoclasts is considered as the main cause of osteoclast-related bone diseases such as osteoporosis. Therefore, the suppression of excessive osteoclast formation and function is one of the strategies to treat osteoclast-related bone diseases. Fumitremorgin C (Fum) is a mycotoxin extracted from Aspergillus fumigatus. It has been shown to have extensive pharmacological properties, but its role in the treatment of osteoclast-related bone diseases remains unclear. In this study, we aim to find out whether Fum can inhibit the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and function. The results showed that Fum could significantly attenuate osteoclast formation and function at concentrations from 2.5 to 10 µM. The protein expression of bone resorption factors such as NFATc1, cathepsin K, V-ATPase-d2, and c-Fos was suppressed with the treatment of Fum at a concentration of 10 µM. In addition, Fum was also shown to suppress the activity of NF-κB, intracellular reactive oxygen species level, and MAPK pathway. Taken together, the present study showed that Fum could attenuate the formation and function of osteoclast via suppressing RANKL-induced signaling pathways, suggesting that Fum might be a potential novel drug in the treatment of osteoclast-related bone diseases.

Loureirin B suppresses RANKL-induced osteoclastogenesis and ovariectomized osteoporosis via attenuating NFATc1 and ROS activities.

Rationale: Osteoporosis is a severe bone disorder that is a threat to our aging population. Excessive osteoclast formation and bone resorption lead to changes in trabecular bone volume and architecture, leaving the bones vulnerable to fracture. Therapeutic approaches of inhibiting osteoclastogenesis and bone resorption have been proven to be an efficient approach to prevent osteoporosis. In our study, we have demonstrated for the first time that Loureirin B (LrB) inhibits ovariectomized osteoporosis and explored its underlying mechanisms of action in vitro. Methods: We examined the effects of LrB on RANKL-induced osteoclast differentiation and bone resorption, and its impacts on RANKL-induced NFATc1 activation, calcium oscillations and reactive oxygen species (ROS) production in osteoclasts in vitro. We assessed the in vivo efficacy of LrB using an ovariectomy (OVX)-induced osteoporosis model, which was analyzed using micro-computed tomography (micro-CT) and bone histomorphometry. Results: We found that LrB represses osteoclastogenesis, bone resorption, F-actin belts formation, osteoclast specific gene expressions, ROS activity and calcium oscillations through preventing NFATc1 translocation and expression as well as affecting MAPK-NFAT signaling pathways in vitro. Our in vivo study indicated that LrB prevents OVX-induced osteoporosis and preserves bone volume by repressing osteoclast activity and function. Conclusions: Our findings confirm that LrB can attenuate osteoclast formation and OVX-induced osteoporosis. This novel and exciting discovery could pave the way for the development of LrB as a potential therapeutic treatment for osteoporosis.

Minimally invasive versus extensile lateral approach for sanders type II and III calcaneal fractures: A meta-analysis of randomized controlled trials.

BACKGROUND: The use of less-invasive techniques in the treatment of displaced intra-articular calcaneal fractures (DIACFs) remains controversial. No prior meta-analysis has considered the influence of differences in the fracture type. Thus, our meta-analysis aimed to investigate the efficacy and safety of minimally invasive (MI) in Sanders type II and III fractures. MATERIALS AND METHODS: A comprehensive search was performed to identify RCTs comparing MI using sinus tarsi approach (STA) or percutaneous reduction (PR) to open reduction (OR) via extensile lateral approach (ELA) from the Cochrane Library, PubMed, Embase and CNKI. Dichotomous and continuous data were pooled using risk ratio (RR) and mean difference (MD), respectively, with 95% confidence intervals (CIs). The data were analysed using Review Manager 5.3. RESULTS: Eight RCTs (495 participants) were selected in our meta-analysis. Based on the American Orthopaedic Foot and Ankle Society score (AOFAS), both general pooled data and subgroup analysis of Sanders type II fractures indicated that MI improves functional outcomes, while in the Sanders type III subgroup, the advantage disappeared. Additionally, the pooled results showed that MI reduces the rate of wound complications; lowers the VAS score; and shortens the time to surgery, duration of surgery and length of hospital stay. There was no statistical significance with respect to recovery of calcaneus length and width or improvement of Gissane's angle and Bohler's angle. CONCLUSION: Our meta-analysis suggests that MI and ELA are equally effective treating Sanders type II and III fractures. However, MI is effective in improving the AOFAS score (Sanders type II); reducing the rate of wound complications; and shortening the time to surgery, duration of surgery and length of hospital stay.

Is percutaneous pinning needed for the treatment of displaced distal radius metaphyseal fractures in children?: A systematic review.

BACKGROUND: Distal radius metaphyseal (DRM) fractures are very frequent childhood fractures. Whether additional percutaneous pinning improves the outcome remains controversial. In this review, we tried to systematically evaluate the effect of percutaneous pinning on re-displacement, secondary reduction, radiographs, function, and complications in children with displaced DRM fractures. METHODS: PubMed, Medline, Embase, Cochrane Library, and Web of Science databases were explored systematically to identify randomized controlled trials (RCTs) and clinical controlled trials (CCTs) comparing cast immobilization alone or following reduction to additional percutaneous pinning in the treatment of pediatric displaced DRM fractures. Two reviewers independently screened eligible articles and extracted relevant information from each article. The methodological quality of eligible articles was evaluated using the Cochrane Collaboration risk assessment tool (RCTs) and modified Jadad scale (CCTs). RESULTS: A total of 4 RCTs and 3 CCTs met the inclusion criteria, with a total patient count of 1144 children. The results showed that additional percutaneous pinning significantly reduced the rate of re-placement (Chi-square tests, P < .001) and complications (Chi-square tests, P = .030). The superior results, both radiographically and functionally seemed to be temporary. No difference was found between the 2 groups after longer-term follow-up. CONCLUSIONS: This systematic review suggested that compared with casting following reduction, percutaneous pinning had a positive effect on maintaining the initial reduction and reducing fracture complication rate of displaced DRM fractures in children, but with no significant improvement in function and radiographic outcome at the long-term follow-up. We suggest clinicians think twice before percutaneous pinning of displaced pediatric DRM fractures.

[A summary of hip-preservation surgery based on peri-collapse stage of osteonecrosis of femoral head].

Objective: To summarize surgical procedures of hip-preservation based on peri-collapse stage of osteonecrosis of the femoral head (ONFH). Methods: The basic points of peri-collapse stage theory was expounded. The related literature on surgical procedures was summarized and analyzed based on the theory. Results: Surgical procedures of hip-preservation tend to emphasize on mechanical repair, giving consideration to biological repair. It is consistent with the essence of peri-collapse stage theory, which attaches great importance to biomechanical stability. Conclusion: Peri-collapse stage theory has a guiding significance to the choice of surgical timing and approach, and it is one of the important theoretical basis for hip-preservation treatment.