Articular cartilage is susceptible to damage but hard to self-repair due to its avascular nature. Traditional treatment methods are not able to produce satisfactory effects. Mesenchymal stem cells (MSCs) have shown great promise in cartilage repair. However, the therapeutic effect of MSCs is often unstable partly due to their heterogeneity. Understanding the heterogeneity of MSCs and the potential of different types of MSCs for cartilage regeneration will facilitate the selection of superior MSCs for treating cartilage damage. This review provides an overview of the heterogeneity of MSCs at the donor, tissue source and cell immunophenotype levels, including their cytological properties, such as their ability for proliferation, chondrogenic differentiation and immunoregulation, as well as their current applications in cartilage regeneration. This information will improve the precision of MSC-based therapeutic strategies, thus maximizing the efficiency of articular cartilage repair.

A case-control study was conducted on 1986 Hong Kong women to assess the risk of human papillomavirus (HPV) type 16 variants for cervical neoplasia. In total, 255 women were HPV-16 positive and were analyzed for E6 and E7 sequence variation. Two novel substitutions at E6 (T86I and Q116E) and 1 at E7 (R66W) were found. Most HPV-16 variants were of Asian (50.6%) or European (44.3%) lineage, and both lineages showed similar risk associations for high-grade and invasive cervical neoplasia. No increased risk was observed for the subclasses European variant and European 350G, which carry a higher risk for invasive cancer in some Western populations. The E7 N29S substitution, reported to have a higher risk in Korean women, was found equally distributed among normal and various degrees of neoplasia. The epidemiology and risk implication of HPV-16 variant infection in Hong Kong differ markedly from other parts of the world.

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Peripheral nerve injury is a challenging orthopedic condition that can be treated by autograft transplantation, a gold standard treatment in the current clinical setting. Nevertheless, limited availability of autografts and potential morbidities in donors hampers its widespread application. Bioactive scaffold‐based tissue engineering is a promising strategy to promote nerve regeneration. Additionally, magnesium (Mg) ions enhance nerve regeneration; however, an effectively controlled delivery vehicle is necessary to optimize their in vivo therapeutic effects. Herein, a bisphosphonate‐based injectable hydrogel exhibiting sustained Mg2+ delivery for peripheral nerve regeneration is developed. It is observed that Mg2+ promoted neurite outgrowth in a concentration‐dependent manner by activating the PI3K/Akt signaling pathway and Sema5b. Moreover, implantation of polycaprolactone (PCL) conduits filled with Mg2+‐releasing hydrogel in 10 mm nerve defects in rats significantly enhanced axon regeneration and remyelination at 12 weeks post‐operation compared to the controls (blank conduits or conduits filled with Mg2+‐absent hydrogel). Functional recovery analysis reveals enhanced reinnervation in the animals treated with the Mg2+‐releasing hydrogel compared to that in the control groups. In summary, the Mg2+‐releasing hydrogel combined with the 3D‐engineered PCL conduit promotes peripheral nerve regeneration and functional recovery. Thus, a new strategy to facilitate the repair of challenging peripheral nerve injuries is proposed.

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Injury of articular cartilage can cause osteoarthritis and seriously affect the physical and mental health of patients. Unfortunately, current surgical treatment techniques that are commonly used in the clinic cannot regenerate articular cartilage. Regenerative medicine involving stem cells has entered a new stage and is considered the most promising way to regenerate articular cartilage. In terms of theories on the mechanism, it was thought that stem cell-mediated articular cartilage regeneration was achieved through the directional differentiation of stem cells into chondrocytes. However, recent evidence has shown that the stem cell secretome plays an important role in biological processes such as the immune response, inflammation regulation, and drug delivery. At the same time, the stem cell secretome can effectively mediate the process of tissue regeneration. This new theory has attributed the therapeutic effect of stem cells to their paracrine effects. The application of stem cells is not limited to exogenous stem cell transplantation. Endogenous stem cell homing and in situ regeneration strategies have received extensive attention. The application of stem cell derivatives, such as conditioned media, extracellular vesicles, and extracellular matrix, is an extension of stem cell paracrine theory. On the other hand, stem cell pretreatment strategies have also shown promising therapeutic effects. This article will systematically review the latest developments in these areas, summarize challenges in articular cartilage regeneration strategies involving stem cells, and describe prospects for future development.

Articular cartilage (AC) lesions are fairly common but remain an obstacle for clinicians and researchers due to their poor self-healing capacity. Recently, a promising therapy based on the recruitment of autologous mesenchymal stem cells (MSCs) has been developed for the regeneration of full-thickness cartilage defects in the knee joint. In this study, a 3D-bioprinted difunctional scaffold was developed based on aptamer HM69mediated MSC-specific recruitment and growth factor-enhanced cell chondrogenesis. The aptamer, which can specifically recognize and recruit MSCs, was first chemically conjugated to the decellularized cartilage extracellular matrix and then mixed with gelatin methacrylate to form a photocrosslinkable bioink ready for 3D bioprinting. Together with the growth factor that promoted cell chondrogenic differentiation, the biodegradable polymer poly(ε-caprolactone) was further chosen to impart mechanical strength to the 3D bioprinted constructs. The difunctional scaffold specifically recruited MSCs, provided a favorable microenvironment for cell adhesion and proliferation, promoted chondrogenesis, and thus greatly improved cartilage repair in rabbit full-thickness defects.In conclusion, this study demonstrated that 3D bioprinting of difunctional scaffolds could be a promising strategy for in situ AC regeneration based on aptamer-directed cell recruitment and growth-factor-enhanced cell chondrogenesis.

Existing approaches for replay and synthetic speech detection still lack generalizability to unseen spoofing attacks. This work proposes to leverage a novel model structure, so-called Res2Net, to improve the anti-spoofing countermeasure's generalizability. Res2Net mainly modifies the ResNet block to enable multiple feature scales. Specifically, it splits the feature maps within one block into multiple channel groups and designs a residual-like connection across different channel groups. Such connection increases the possible receptive fields, resulting in multiple feature scales. This multiple scaling mechanism significantly improves the countermeasure's generalizability to unseen spoofing attacks. It also decreases the model size compared to ResNet-based models. Experimental results show that the Res2Net model consistently outperforms ResNet34 and ResNet50 by a large margin in both physical access (PA) and logical access (LA) of the ASVspoof 2019 corpus. Moreover, integration with the squeeze-and-excitation (SE) block can further enhance performance. For feature engineering, we investigate the generalizability of Res2Net combined with different acoustic features, and observe that the constant-Q transform (CQT) achieves the most promising performance in both PA and LA scenarios. Our best single system outperforms other state-of-the-art single systems in both PA and LA of the ASVspoof 2019 corpus.