Silk-based hydrogel incorporated with metal-organic framework nanozymes for enhanced osteochondral regeneration

Osteochondral defects(OCD)cannot be efficiently repaired due to the unique physical architecture and the pathological microenvironment including enhanced oxidative stress and inflammation.Conventional strategies,such as the control of implant microstructure or the introduction of growth factors,have limited functions failing to manage these complex environments.Here we developed a multifunctional silk-based hydrogel incorporated with metal-organic framework nanozymes(CuTA@SF)to provide a suitable microenvironment for enhanced OCD regeneration.The incorporation of CuTA nanozymes endowed the SF hydrogel with a uniform microstructure and elevated hydrophilicity.In vitro cultivation of mesenchymal stem cells(MSCs)and chondrocytes showed that CuTA@SF hydrogel accelerated cell proliferation and enhanced cell viability,as well as had antioxidant and antibacterial properties.Under the inflammatory environment with the stimulation of IL-1β,CuTA@SF hydrogel still possessed the potential to promote MSC osteogenesis and deposition of cartilage-specific extracellular matrix(ECM).The proteomics analysis further confirmed that CuTA@SF hydrogel promoted cell proliferation and ECM synthesis.In the full-thickness OCD model of rabbit,CuTA@SF hydrogel displayed successfully in situ OCD regeneration,as evidenced by micro-CT,histology(HE,S/O,and toluidine blue staining)and immunohistochemistry(Col I and aggrecan immunostaining).Therefore,CuTA@SF hydrogel is a promising biomaterial targeted at the regeneration of OCD.

Global seismic tomography reveals remnants of subducted Tethyan oceanic slabs in the deep mantle

The Tethyan evolution depicts the continuous process of landmasses separating from the Gondwana continent in the south,drifting northwards,and subsequently colliding with the continents in the north over the past 500 million years.In this process,the Tethyan oceans that formed between the landmass and the southern or northern continents underwent growth,evolution,and eventual closure with the early Cenozoic India-Eurasia collision.However,the Tethyan lithosphere did not disappear but rather continued to evolve after entering into the deep Earth.The current position,morphology,and volume of the subducted Tethyan oceanic slabs in the deep mantle record the latest moment of this continuous evolution,providing critical constraints for Tethyan studies.This paper summarizes and analyzes the results of global-scale whole-mantle seismic tomography in the past nearly two decades,revealing a northwest-southeast seismically high-velocity anomaly,which is linearly distributed at depths of 1000–2000 km beneath the Tethyan realm and referred to as the Tethyan anomaly.By searching for an optimal linear combination of previous global seismic tomographic models to best match the known subducted slabs in the upper mantle,we observe that the Tethyan anomaly extends approximately 8700 km in length and 2600 km in width,exhibiting a parallel structure with northern and southern branches.Combining geological records of oceanic subduction initiation and previous geodynamic studies,this study suggests that the main body of the Tethyan anomaly represents the remnants of the subducted Neo-Tethyan oceanic slabs,which subducted from the Late Jurassic to the early Cenozoic.The northern branch consists of subducted slabs from the Neo-Tethys beneath the southern margin of Eurasia,while the southern branch likely reflects the intra-oceanic subducted slabs of Neo-Tethys during the Cretaceous.The western portion of the Tethyan anomaly may reflect remnants of Paleo-Tethys,while the eastern portion,towards India and the Bay of Bengal,shows signs of subduction towards the core-mantle boundary.Finally,this study discusses the future prospects of whole-mantle seismic tomographic studies focusing on the Tethyan realm.

APOBEC3B and IL-6 form a positive feedback loop in hepatocellular carcinoma cells

APOBEC3 protein families, a DNA cytidine deaminase, were up-regulated in multiple tumors. However, the relationship between Hepatocellular carcinoma(HCC) and APOBEC3B(A3B) remains unknown. It has been confirmed that interleukin-6(IL-6)has significant impacts on oncogenesis of HCC. Here, we reported that the expression of IL-6 was substantially up-regulated by A3 B in HepG2 cells. A3 B induced IL-6 expression through relocating HuR to enhance the IL-6 mRNA stability. Further analysis indicated that IL-6 also increased the expression of A3 B through JAK1/STAT3 signaling pathway, which formed a positive feedback to maintain the continuous expression of A3 B and IL-6, and thereby promoted the prolonged non-resolving inflammation. Collectively, these findings suggest that A3 B is essential for oncogenesis of HCC, and is a potential target for preventive intervention.