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Image-based virtual try-on aims to fit a target garment to a reference person. Most existing methods are limited to solving the Garment-To-Person (G2P) try-on task that transfers a garment from a clean product image to the reference person and do not consider the Person-To-Person (P2P) try-on task that transfers a garment from a clothed person image to the reference person, which limits the practical applicability. The P2P try-on task is more challenging due to spatial discrepancies caused by different poses, body shapes, and views between the reference person and the target person. To address this issue, we propose a novel Keypoints-Driven Flow Based Virtual Try-On Network (KF-VTON) for handling both the G2P and P2P try-on tasks. Our KF-VTON has two key innovations: (1) We propose a new keypoints-driven flow based deformation model to warp the garment. This model establishes spatial correspondences between the target garment and reference person by combining the robustness of Thin-plate Spline (TPS) based deformation and the flexibility of appearance flow based deformation. (2) We investigate a powerful Context-aware Spatially Adaptive Normalization (CSAN) generative module to synthesize the final try-on image. Particularly, CSAN integrates rich contextual information with semantic parsing guidance to properly infer unobserved garment appearances. Extensive experiments demonstrate that our KF-VTON is capable of producing photo-realistic and high-fidelity try-on results for the G2P as well as P2P try-on tasks and surpasses previous state-of-the-art methods both quantitatively and qualitatively. Our code is available at https://github.com/OIUIU/KF-VTON. [ABSTRACT FROM AUTHOR]

Image-based virtual try-on aims at transferring a target in-shop garment onto a reference person, and has garnered significant attention from the research communities recently. However, previous methods have faced severe challenges in handling occlusion problems. To address this limitation, we classify occlusion problems into three types based on the reference person's arm postures: single-arm occlusion, two-arm non-crossed occlusion, and two-arm crossed occlusion. Specifically, we propose a novel Occlusion-Free Virtual Try-On Network (OF-VTON) that effectively overcomes these occlusion challenges. The OF-VTON framework consists of two core components: (i) a new Recurrent Appearance Flow based Deformation (RAFD) model that robustly aligns the in-shop garment to the reference person by adopting a multi-task learning strategy. This model jointly produces the dense appearance flow to warp the garment and predicts a human segmentation map to provide semantic guidance for the subsequent image synthesis model. (ii) a powerful Multi-mask Image SynthesiS (MISS) model that generates photo-realistic try-on results by introducing a new mask generation and selection mechanism. Experimental results demonstrate that our proposed OF-VTON significantly outperforms existing state-of-the-art methods by mitigating the impact of occlusion problems. Our code is available at https://github.com/gxl-groups/OF-VTON. [ABSTRACT FROM AUTHOR]

It is of significant theoretical and practical value to study the deposition process and deformation behavior of cold-sprayed particles to find the deposition mechanism of cold-sprayed coatings, further improve the coating performance, and expand its application scope. However, observing the deposition process and particle behavior through experiments is difficult due to the brief deposition duration of cold spray particles. Numerical simulation offers a means to slow the deposition process and predict the critical velocity, deformation behavior, bonding mechanism, and residual stress of cold-sprayed particles. This paper uses finite element analysis software, including ANSYS LS Dynamic-2022 R1 and ABAQUS-6.14, alongside various prevalent finite element methods for numerically simulating cold spray particle deposition. These methods involve the Lagrange, Euler, arbitrary Lagrange-Euler (ALE), and Smoothed Particle Hydrodynamics (SPH) to investigate the cold spray particle deposition process. The recent literature primarily summarizes the simulation outcomes achieved by applying these methodologies for simulating the deposition process and deformation characteristics of different particles under varying cold spraying conditions. In addition, the reliability of these simulation results is analyzed by comparing the consistency between the simulation results of single-particle and multi-particle and the actual experimental results. On this basis, these methods' advantages, disadvantages, and applicability are comprehensively analyzed, and the future simulation research work of particle deposition process and deformation behavior of cold spraying prospects is discussed. Future research is expected to provide a more in-depth study of the micro-mechanisms, such as the evolution of the inter-particle and internal organization of the particles, near the actual situation. [ABSTRACT FROM AUTHOR]

Graph Convolutional Networks (GCNs) have been widely used in skeleton‐based action recognition. Though significant performance has been achieved, it is still challenging to effectively model the complex dynamics of skeleton sequences. A novel position‐aware spatio‐temporal GCN for skeleton‐based action recognition is proposed, where the positional encoding is investigated to enhance the capacity of typical baselines for comprehending the dynamic characteristics of action sequence. Specifically, the authors' method systematically investigates the temporal position encoding and spatial position embedding, in favour of explicitly capturing the sequence ordering information and the identity information of nodes that are used in graphs. Additionally, to alleviate the redundancy and over‐smoothing problems of typical GCNs, the authors' method further investigates a subgraph mask, which gears to mine the prominent subgraph patterns over the underlying graph, letting the model be robust against the impaction of some irrelevant joints. Extensive experiments on three large‐scale datasets demonstrate that our model can achieve competitive results comparing to the previous state‐of‐art methods. [ABSTRACT FROM AUTHOR]

The recently developed pure transformer architectures have attained promising accuracy on point cloud learning benchmarks compared to convolutional neural networks. However, existing point cloud Transformers are computationally expensive because they waste a significant amount of time on structuring irregular data. To solve this shortcoming, we present the Sparse Window Attention module to gather coarse‐grained local features from nonempty voxels. The module not only bypasses the expensive irregular data structuring and invalid empty voxel computation, but also obtains linear computational complexity with respect to voxel resolution. Meanwhile, we leverage two different self‐attention variants to gather fine‐grained features about the global shape according to different scale of point clouds. Finally, we construct our neural architecture called point‐voxel transformer (PVT), which integrates these modules into a joint framework for point cloud learning. Compared with previous transformer‐based and attention‐based models, our method attains a top accuracy of 94.1% on the classification benchmark and 10× $10\times $ inference speedup on average. Extensive experiments also validate the effectiveness of PVT on semantic segmentation benchmarks. Our code and pretrained model are avaliable at https://github.com/HaochengWan/PVT. [ABSTRACT FROM AUTHOR]

We propose USTNet, a novel deep learning approach designed for learning shape‐to‐shape translation from unpaired domains in an unsupervised manner. The core of our approach lies in disentangled representation learning that factors out the discriminative features of 3D shapes into content and style codes. Given input shapes from multiple domains, USTNet disentangles their representation into style codes that contain distinctive traits across domains and content codes that contain domain‐invariant traits. By fusing the style and content codes of the target and source shapes, our method enables us to synthesize new shapes that resemble the target style and retain the content features of source shapes. Based on the shared style space, our method facilitates shape interpolation by manipulating the style attributes from different domains. Furthermore, by extending the basic building blocks of our network from two‐class to multi‐class classification, we adapt USTNet to tackle multi‐domain shape‐to‐shape translation. Experimental results show that our approach can generate realistic and natural translated shapes and that our method leads to improved quantitative evaluation metric results compared to 3DSNet. Codes are available at https://Haoran226.github.io/USTNet. [ABSTRACT FROM AUTHOR]

Traditional clinical diagnostic aid systems for medical images are facing challenges of reliability and interpretability. Artificial intelligence has the potential to bring driving changes to disease diagnosis methods through rapid traversal of medical images and efficient classification. However, the application of artificial intelligence in the field of medical image still faces challenges. Our method combines the multiple modalities of attention which consider the most discriminative part in the images. The proposed classification method is tested on the microscopic image dataset with 40 leukocyte categories, which achieves top-1 accuracy of 84.21% and top-5 accuracy of 99.44% during the testing procedure. And experiments on the dermoscopic image dataset show that our method has good generalization ability across multiple imaging modalities. [ABSTRACT FROM AUTHOR]

Accumulation of reactive oxygen species (ROS), which can be induced by inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), can significantly inhibit the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). This process can contribute to the imbalance of bone remodeling, which ultimately leads to osteoporosis. Therefore, reducing the ROS generation during osteogenesis of BMSCs may be an effective way to reverse the impairment of osteogenesis. Melatonin (MLT) has been reported to act as an antioxidant during cell proliferation and differentiation, but its antioxidant effect and mechanism of action during osteogenesis of MSCs in the inflammatory microenvironment, especially in the presence of TNF-α, remain unknown and need further study. In our study, we demonstrate that melatonin can counteract the generation of ROS and the inhibitory osteogenesis of BMSCs induced by TNF-α, by upregulating the expression of antioxidases and downregulating the expression of oxidases. Meanwhile, MLT can inhibit the phosphorylation of p65 protein and block the degradation of IκBα protein, thus decreasing the activity of the NF-κB pathway. This study confirmed that melatonin can inhibit the generation of ROS during osteogenic differentiation of BMSCs and reverse the inhibition of osteogenic differentiation of BMSCs in vitro, suggesting that melatonin can antagonize TNF-α-induced ROS generation and promote the great effect of osteogenic differentiation of BMSCs. Accordingly, these findings provide more evidence that melatonin can be used as a candidate drug for the treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

We present a novel active learning approach for shape cosegmentation based on graph convolutional networks (GCNs). The premise of our approach is to represent the collections of three-dimensional shapes as graph-structured data, where each node in the graph corresponds to a primitive patch of an oversegmented shape, and is associated with a representation initialized by extracting features. Then, the GCN operates directly on the graph to update the representation of each node based on a layer-wise propagation rule, which aggregates information from its neighbors, and predicts the labels for unlabeled nodes. Additionally, we further suggest an active learning strategy that queries the most informative samples to extend the initial training samples of GCN to generate more accurate predictions of our method. Our experimental results on the Shape COSEG dataset demonstrate the effectiveness of our approach. [ABSTRACT FROM AUTHOR]

Abstract: Bone marrow‐derived mesenchymal stem cells (BMSCs), with inherent chondrogenic differentiation potential appear to be ideally suited for therapeutic use in cartilage regeneration. Accumulating evidence has demonstrated that melatonin can promote chondrogenic differentiation in human BMSCs. However, little is known about the mechanism. MicroRNAs (miRNAs) have been shown to regulate the differentiation of BMSCs, but their roles in melatonin‐promoted chondrogenic differentiation have not been characterized. Here, we demonstrate that melatonin promoted chondrogenic differentiation of human BMSCs via upregulation of miR‐526b‐3p and miR‐590‐5p. Mechanistically, the elevated miR‐526b‐3p and miR‐590‐5p enhanced SMAD1 phosphorylation by targeting SMAD7. Additionally, administration of miR‐526b‐3p mimics or miR‐590‐5p mimics successfully promoted the chondrogenic differentiation of human BMSCs. Collectively, our study suggests that modification of BMSCs using melatonin or miRNA transduction could be an effective therapy for cartilage damage and degeneration. [ABSTRACT FROM AUTHOR]

Computer aided modeling and simulation of nanomaterials can describe the correlation between the material’s microstructure and its macroscopic properties quantitatively. In this paper, we propose an integrated modeling, simulation, and visualization approach for designing nanomaterials. Firstly, a fast parametric modeling method for important nanomaterials such as graphene, nanotubes, and MOFs is proposed; secondly, the material model could be edited adaptively without affecting the validity of the model on the physical level; thirdly a preliminary calculation for nanomaterials’ energy is implemented based on the theory of surface fitting; finally, an integrated framework of nanomaterials modeling, simulation, and visualization is designed and implemented. Experimental results show that the proposed approach is feasible and effective. [ABSTRACT FROM AUTHOR]

Adolescent idiopathic scoliosis (AIS) is a complex genetic disorder characterized by three-dimensional spinal curvatures, affecting 2%-3% of school age children, yet the causes underlying AIS are not well understood. Here, we first conducted a whole-exome sequencing and linkage analysis on a three-generation Chinese family with autosomal-dominant (AD) AIS, and then performed targeted sequencing in a discovery cohort comprising 20 AD AIS families and 86 simplex patients, and finally identified three disease-associated missense variants (c.886G> A, c.1943C> T, and c.1760C> T) in the MAPK7 gene (encoding mitogen-activated protein kinase 7). Genotyping of the three rare variants in a Chinese replication cohort comprising 1,038 simplex patients and 1,841 controls showed that their combined allele frequency was significantly over-represented in patients as compared with controls (2.0% [41/2,076] vs. 0.7% [27/3,682]; odds ratio = 2.7; P = 2.8 × 10−5). In vitro, we demonstrated that the three MAPK7 mutants disrupted nuclear translocation in cellular models, which is necessary for the normal function of MAPK7. In vivo, we also conducted CRISPR/Cas9-mediated deletion of mapk7 in zebrafish recapitulating the characteristic phenotype of idiopathic scoliosis. Taken together, our findings suggest that rare coding variants in MAPK7 predispose to AIS, providing clues to understanding the mechanisms of AIS. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-alpha ( TNFα) plays a pivotal role in inflammation-related osteoporosis through the promotion of bone resorption and suppression of bone formation. Numerous drugs have been produced to treat osteoporosis by inhibiting bone resorption, but they offer few benefits to bone formation, which is what is needed by patients with severe bone loss. Melatonin, which can exert both anti-inflammatory and pro-osteogenic effects, shows promise in overcoming TNFα-inhibited osteogenesis and deserves further research. This study demonstrated that melatonin rescued TNFα-inhibited osteogenesis of human mesenchymal stem cells and that the interactions between SMURF1 and SMAD1 mediated the crosstalk between melatonin signaling and TNFα signaling. Additionally, melatonin treatment was found to downregulate TNFα-induced SMURF1 expression and then decrease SMURF1-mediated ubiquitination and degradation of SMAD1 protein, leading to steady bone morphogenetic protein- SMAD1 signaling activity and restoration of TNFα-impaired osteogenesis. Thus, melatonin has prospects for treating osteoporosis caused by inflammatory factors due to its multifaceted functions on regulation of bone formation, bone resorption, and inflammation. Further studies will focus on unveiling the specific mechanisms by which melatonin downregulates SMURF1 expression and confirming the clinical therapeutic value of melatonin in the prevention and therapy of bone loss associated with inflammation. [ABSTRACT FROM AUTHOR]

Hybrid fillers of silicon carbide/glass fibres (SiC/GFs) are used to prepare SiC/GFs/bismaleimide (SiC/GFs/BMI) composites. Results show that the thermal conductivities of the SiC/GFs/BMI composites improved with the increasing content of SiC fillers, and the thermal conductivity coefficient is 1.64 W mK−1 with 60 wt% modified SiC fillers. The heat resistance properties and dielectric constant values of the SiC/GFs/BMI composites also improved with the increasing content of SiC fillers. Furthermore, surface modification of SiC fillers is beneficial for further improving the thermal conductivities of the composites. [ABSTRACT FROM AUTHOR]

Heparan sulfate (HS) interacts with growth factors and has been implicated in regulating chondrogenesis. However, the effect of HS on TGF-β-mediated mesenchymal stem cell (MSC) chondrogenesis and molecular mechanisms remains unknown. In this study, we explored the effects of exogenous HS alone and in combination with TGF-β3 on chondrogenic differentiation of human MSCs and possible signal mechanisms. The results indicated that HS alone had no obvious effects on chondrogenic differentiation of human MSCs and TGF-β/Smad2/3 signal pathways. However, the combined TGF-β3/HS treatment resulted in a significant increase in GAG synthesis, cartilage matrix protein secretion, and cartilage-specific gene expression compared to cells treated with TGF-β3 alone. Furthermore, HS inhibited type III TGF-β receptors (TβRIII) expression and increased TGF-β3-mediated ratio of the type II (TβRII) to the type I (TβRI) TGF-β receptors and phosphorylation levels of Smad2/3. The inhibitor of the TGF-β/Smad signal, SB431542, not only completely inhibited HS-stimulated TGF-β3-mediated Smad2/3 phosphorylation but also completely inhibited the effects of HS on TGF-β3-induced chondrogenic differentiation. These results demonstrate exogenous HS enhances TGF-β3-induced chondrogenic differentiation of human MSCs by activating TGF-β/Smad2/3 signaling. [ABSTRACT FROM AUTHOR]

The collagen type II alpha 1 (COL2A1) mutation causes severe skeletal malformations, but the pathogenic mechanisms of how this occurs are unclear. To understand how this may happen, a col2a1 p.Gly1170Ser mutated mouse model was constructed and in homozygotes, the chondrodysplasia phenotype was observed. Misfolded procollagen was largely synthesized and retained in dilated endoplasmic reticulum and the endoplasmic reticulum stress (ERS)-unfolded protein response (UPR)-apoptosis cascade was activated. Apoptosis occurred prior to hypertrophy, prevented the formation of a hypertrophic zone, disrupted normal chondrogenic signaling pathways, and eventually caused chondrodysplasia. Heterozygotes had normal phenotypes and endoplasmic reticulum stress intensity was limited with no abnormal apoptosis detected. Our results suggest that earlier chondrocyte death was related to the ERS-UPR-apoptosis cascade and that this was the chief cause of chondrodysplaia. The col2a1 p.Gly1170Ser mutated mouse model offered a novel connection between misfolded collagen and skeletal malformation. Further investigation of this mouse mutant model can help us understand mechanisms of type II collagenopathies. [ABSTRACT FROM AUTHOR]

Long noncoding RNA (lncRNAs) UCA1 has been known to be critical for the chondrogenic differentiation of marrow mesenchymal stem cells (MSCs). In this study, we explore the effects and mechanisms of UCA1 on the promotion of chondrogenesis of MSCs. During the processes of chondrogenic differentiation of MSCs, UCA1, miRNA-145-5p or miRNA-124-3p was overexpressed into MSCs. UCA1 substantially improved chondrogenesis of MSCs. Furthermore, UCA1 obviously down-regulated the expression of miRNA-145-5p and miRNA-124-3p, which attenuated the chondrogenic differentiation of MSCs. In addition, UCA1 significantly stimulated TGF-β pathway member SMAD5 and SMAD4, which is targeted by miRNA-145-5p and miRNA-124-3p. Collectively, these outcomes suggest that UCA1 enhances chondrogenic differentiation of MSCs via the miRNA-145-5p/SMAD5 and miRNA-124-3p/SMAD4 axis. • UCA1 promoted the chondrogenic differentiation of MSCs. • UCA1 down-regulated miRNA-145-5p/miRNA-124-3p during this process. • miRNA-145-5p targeted SMAD5 and miRNA-124-3p targeted SMAD4. [ABSTRACT FROM AUTHOR]

• Exosomes promoted the proliferation of chondrocytes and inhibited cells apoptosis. • Exosomes derived from BMSCs-miR-210 improve the proliferation of chondrocytes. • BMSCs-210-Exos prevented chondrocytes apoptosis via the NF-κB signal pathway. • BMSCs-210-Exos inhibited the NF-κB signal pathway by targeting Tnfrsf21. Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (Exos) have anti-inflammatory and anti-apoptotic functions. miRNA-210 has also been confirmed to play a role in inhibiting proinflammatory cytokines. Herein, we aimed to explore the effects of Exos derived from miRNA-210-overexpressing BMSCs (BMSCs-210-Exos) and the mechanisms by which they provide protection to chondrocytes from lipopolysaccharide (LPS)-induced injury. BMSCs were transfected with or without miRNA-210. Exos substantially improved the proliferation of chondrocytes and inhibited LPS-induced cell apoptosis. Furthermore, BMSCs-210-Exos promoted the proliferation of chondrocytes and prevented LPS-induced cell apoptosis better than BMSCs-Exos not overexpressing miRNA-210. In addition, tumor necrosis factor receptor superfamily member 21 (Tnfrsf21) expression was inhibited and the NF-κB pathway was attenuated by both BMSCs-Exos and BMSCs-210-Exos during LPS-induced chondrocyte injury. Collectively, these results suggest that BMSCs-210-Exos enhance the protection of chondrocytes from LPS-induced injury via the NF-κB pathway. [ABSTRACT FROM AUTHOR]

Introduction: Degenerative lumbar spinal stenosis is a common cause of low back or leg pain and disability in the elderly population. Patients with spinal stenosis who fail to respond to conservative treatment often require surgical interventions. Minimally invasive transforaminal lumbar interbody fusion (TLIF) with microscopic tubular technique (MT-TLIF) is a well-established procedure for lumbar spinal stenosis. Recently, a novel MIS technique, unilateral biportal endoscopic TLIF (UBE-TLIF), has been frequently performed to treat spinal stenosis. However, the efficacy and safety of using UBE-TLIF in this population have not been well examined., Methods and Analysis: A total of 96 patients with lumbar spinal stenosis will be randomly assigned to the UBE-TLIF group or the MT-TLIF group at a 1:1 ratio to receive UBE-TLIF or MT-TLIF treatment respectively. The primary outcome is the Oswestry Disability Index (ODI) score at 1 year after receiving the surgery. Secondary outcomes include the ODI scores at additional time points, Visual Analogue Scale score, 36-Item Short Form Survey questionnaire, EuroQol 5 Dimensions questionnaire, radiological measurements (disc height, lumbar lordosis angles and vertebral fusion rate) and general condition during hospitalisation., Ethics and Dissemination: This protocol is approved by the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University. All participants of the study will be well informed and written informed consent will be requested. Findings from this trial will be published in peer-reviewed publications, specifically in orthopedic and spinal journals. The completion of this study will not only examine the use of UBE-TLIF in lumbar spinal stenosis but also provide helpful clinical references., Trial Registration Number: ChiCTR2300069333., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Plasticulture, the practice of using plastic materials in agricultural applications, consumes about 6.7 million tons of plastics every year, which is about 2% of the overall global annual plastics production. For different reasons, plastic material used for agriculture is difficult to recycle. Therefore, most of it is either buried in fertile soils, thereby significantly causing deterioration of their properties, or, at best case, end in landfills where its half-life is measured in decades and even centuries. Hence, developing biodegradable plastic materials that are suitable for agricultural applications is a vital and inevitable need for the global human society. In our labs, two types of potentially biodegradable plastic polymer films were prepared and characterized imidazolium in terms of their bio-degradability. In the first approach, polymers made of ionic liquid monomers were prepared using photo radical induced polymerization. The second approach relies on formation of polyethylene-like n-alkane disulfide polymers from 1,ω-di-thiols through thermally activated air oxidation. These two families of materials were tested for their biodegradability in soils by using a simulation system that combines a controlled environment chamber equipped with a respirometer and a proton-transfer-reaction time of flight mass spectrometer (PTR-TOF-MS) system. This system provides a time-dependent and comprehensive fingerprint of volatiles emitted in the degradation process. The results obtained thus far indicate that whereas the ionic-liquid based polymer does not show significant bio-degradability under the test conditions, the building block monomer, 1,10-n-decane dithiol, as well as its disulfide-based polymer, are bio-degradable. The latter reaching, under basic soil conditions and in room temperature, ∼20% degradation within three months. These results suggest that by introduction of disulfide groups into the polyethylene backbone one may be able to render it biodegradable, thus considerably shortening its half-life in soils. Principal component analysis, PCA, of the data about the total volatiles produced during the degradation in soil indicates a distinctive volatile "fingerprint" of the disulfide-based bio-degradable products which comes from the volatile organic compounds portfolio as recorded by the PTR-TOF-MS. The biodegradation volatile fingerprint of this kind of film was different from the "fingerprint" of the soil background which served as a control. These results can help us to better understand and design biodegradable films for agricultural mulching practices., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dar, Wu, Zhang, Yu, Qin, Shen, Zou, Poh, Eichen and Achmon.)

Background : Intervertebral disc degeneration (IDD), the main cause of low back pain, is closely related to the inflammatory microenvironment in the nucleus pulposus (NP). Tumor necrosis factor-α (TNF-α) plays an important role in inflammation-related metabolic disturbance of NP cells. Melatonin has been proven to regulate the metabolism of NP cells, but whether it can protect NP cells from TNF-α-induced damage is still unclear. Therefore, this study aims to investigate the role and specific mechanism of melatonin on regulating the metabolism of NP cells in the inflammatory microenvironment. Methods: Western blotting, RT-qPCR and immunohistochemistry were used to detect the expression of melatonin membrane receptors (MTNR1A/B) and TNF-α in human NP tissues. In vitro , human primary NP cells were treated with or without vehicle, TNF-α and melatonin. And the metabolic markers were also detected by western blotting and RT-qPCR. The activity of NF-κB signaling and Hippo/YAP signaling were assessed by western blotting and immunofluorescence. Membrane receptors inhibitors, pathway inhibitors, lentiviral infection, plasmids transfection and immunoprecipitation were used to explore the specific mechanism of melatonin. In vivo , the rat IDD model was constructed and melatonin was injected intraperitoneally to evaluate its therapeutical effect on IDD. Results: The upregulation of TNF-α and downregulation of melatonin membrane receptors (MTNR1A/B) were observed in degenerative NP tissues. Then we demonstrated that melatonin could alleviate the development of IDD in a rat model and reverse TNF-α-impaired metabolism of NP cells in vitro . Further investigation revealed that the protective effects of melatonin on NP cells mainly rely on MTNR1B, which subsequently activates Gαi2 protein. The activation of Gαi2 could upregulate the yes-associated protein (YAP) level, resulting in anabolic enhancement of NP cells. In addition, melatonin-mediated YAP upregulation increased the expression of IκBα and suppressed the TNF-α-induced activation of the NF-κB pathway, thereby inhibiting the catabolism of NP cells. Conclusions: Our results revealed that melatonin can reverse TNF-α-impaired metabolism of NP cells via the MTNR1B/Gαi2/YAP axis and suggested that melatonin can be used as a potential therapeutic drug in the treatment of IDD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Degenerative disc disease (DDD) is a common degenerative condition initiated mainly within the nucleus pulposus (NP). To date, the etiopathogenesis of DDD remains unclear, and because no effective therapeutic strategies are available to target its pathological processes, DDD is still treated with symptomatic interventions that are far from adequate. Collagen type II is one of the major matrix components of the NP, and is considered to be essential to NP homeostasis. However, the specific mechanisms by which collagen type II influences NP cells remain unknown. In the present study, collagen type II expression was detected using immunohistochemistry analysis and quantitative polymerase chain reaction, and it was demonstrated to be significantly downregulated in NP tissues from patients with DDD compared with nondegenerative controls. To further explore the mechanism in vitro, interleukin (IL)‑1β stimulation was used to induce degeneration of a human NP cell line. IL‑1β stimulation upregulated both the mRNA and protein levels of the catabolic markers matrix metalloproteinase 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4), while it downregulated the anabolic makers aggrecan and collagen type II. However, addition of purified collagen type II prevented this IL‑1β‑induced metabolic disturbance of the NP cells. Furthermore, IL‑1β stimulation significantly promoted apoptosis in NP cells, while collagen type II treatment decreased the apoptotic rate and the protein levels of cleaved caspase‑3. In conclusion, collagen type II exhibited protective effects in suppressing NP cell degeneration through its anticatabolic, proanabolic and antiapoptotic effects, suggesting that it may be a promising therapeutic agent for the prevention and treatment of DDD.

Heparan sulfate (HS) interacts with growth factors and has been implicated in regulating chondrogenesis. However, the effect of HS on TGF-β-mediated mesenchymal stem cell (MSC) chondrogenesis and molecular mechanisms remains unknown. In this study, we explored the effects of exogenous HS alone and in combination with TGF-β3 on chondrogenic differentiation of human MSCs and possible signal mechanisms. The results indicated that HS alone had no obvious effects on chondrogenic differentiation of human MSCs and TGF-β/Smad2/3 signal pathways. However, the combined TGF-β3/HS treatment resulted in a significant increase in GAG synthesis, cartilage matrix protein secretion, and cartilage-specific gene expression compared to cells treated with TGF-β3 alone. Furthermore, HS inhibited type III TGF-β receptors (TβRIII) expression and increased TGF-β3-mediated ratio of the type II (TβRII) to the type I (TβRI) TGF-β receptors and phosphorylation levels of Smad2/3. The inhibitor of the TGF-β/Smad signal, SB431542, not only completely inhibited HS-stimulated TGF-β3-mediated Smad2/3 phosphorylation but also completely inhibited the effects of HS on TGF-β3-induced chondrogenic differentiation. These results demonstrate exogenous HS enhances TGF-β3-induced chondrogenic differentiation of human MSCs by activating TGF-β/Smad2/3 signaling.