3D Printing of Cobalt-Incorporated Chloroapatite Bioceramic Composite Scaffolds with Antioxidative Activity for Enhanced Osteochondral Regeneration.

Osteochondral defects are often accompanied by excessive reactive oxygen species (ROS) caused by osteoarthritis or acute surgical inflammation. An inflammatory environment containing excess ROS will not only hinder tissue regeneration but also impact the quality of newly formed tissues. Therefore, there is an urgent need to develop scaffolds with both ROS scavenging and osteochondral repair functions to promote and protect osteochondral tissue regeneration. In this work, by using 3D printing technology, a composite scaffold based on cobalt-incorporated chloroapatite (Co-ClAP) bioceramics, which possesses ROS-scavenging activity and can support cell proliferation, adhesion, and differentiation, is developed. Benefiting from the catalytic activity of Co-ClAP bioceramics, the composite scaffold can protect cells from oxidative damage under ROS-excessive conditions, support their directional differentiation, and simultaneously mediate an anti-inflammatory microenvironment. In addition, it is also confirmed by using rabbit osteochondral defect model that the Co-ClAP/poly(lactic-co-glycolic acid) scaffold can effectively promote the integrated regeneration of cartilage and subchondral bone, exhibiting an ideal repair effect in vivo. This study provides a promising strategy for the treatment of defects with excess ROS and inflammatory microenvironments.

A Multifunctional Hydrogel for Simultaneous Visible H2 O2 Monitoring And Accelerating Diabetic Wound Healing.

Diabetic wound is one of the chronic wounds that is difficult to heal, and effective treatment of it still confronts a great challenge. Monitoring the variation of diabetic wound microenvironment (such as hydrogen peroxide (H2 O2 )) can understand the wound state and guide the wound management. Herein, a multifunctional hydrogel with the abilities of monitoring the H2 O2 concentration, alleviating oxidative stress and promoting wound healing is developed, which is prepared by encapsulating manganese-containing bioactive glass (MnBG) and CePO4 :Tb in biocompatible gelatin methacryloyl (GelMA) hydrogel (CPT-MnBG-Gel). On the one hand, the H2 O2 -dependent fluorescence quenching effect of the CePO4 :Tb contributes to visible monitoring of the H2 O2 concentration of wounds via smartphone imaging, and the CPT-MnBG-Gel hydrogel can effectively monitor the H2 O2 level of 10.35-200 µmol L-1 . On the other hand, MnBG can alleviate oxidative stress and promote the proliferation, migration and differentiation of fibroblasts and endothelial cells in vitro owing to the bioactive Mn and Si ions, and in vivo evaluation also demonstrates that the CPT-MnBG-Gel hydrogels can effectively accelerate wound healing. Hence, such multifunctional hydrogel is promising for diabetic wound management and accelerating wound healing.

Metal-Organic Framework Functionalized Bioceramic Scaffolds with Antioxidative Activity for Enhanced Osteochondral Regeneration.

Osteoarthritis (OA) is a degenerative disease that often causes cartilage lesions and even osteochondral damage. Osteochondral defects induced by OA are accompanied by an inflammatory arthrosis microenvironment with overproduced reactive oxygen species (ROS), resulting in the exacerbation of defects and difficulty regenerating osteochondral tissues. Therefore, it is urgently needed to develop osteochondral scaffolds that can not only promote the integrated regeneration of cartilage and subchondral bone, but also possess ROS-scavenging ability to protect tissues from oxidative stress. Herein, zinc-cobalt bimetallic organic framework (Zn/Co-MOF) functionalized bioceramic scaffolds are designed for repairing osteochondral defects under OA environment. By functionalizing Zn/Co-MOF on the 3D-printed beta-tricalcium phosphate (ß-TCP) scaffolds, the Zn/Co-MOF functionalized ß-TCP (MOF-TCP) scaffolds with broad-spectrum ROS-scavenging ability are successfully developed. Benefiting from its catalytic active sites and degradation products, Zn/Co-MOF endows the scaffolds with excellent antioxidative and anti-inflammatory properties to protect cells from ROS invasion, as well as dual-bioactivities of simultaneously inducing osteogenic and chondrogenic differentiation in vitro. Furthermore, in vivo results confirm that MOF-TCP scaffolds accelerate the integrated regeneration of cartilage and subchondral bone in severe osteochondral defects. This study offers a promising strategy for treating defects induced by OA as well as other inflammatory diseases.

Chromosome-level genome and population genomics reveal evolutionary characteristics and conservation status of Chinese indigenous geese.

Geese are herbivorous birds that play an essential role in the agricultural economy. We construct the chromosome-level genome of a Chinese indigenous goose (the Xingguo gray goose, XGG; Anser cygnoides) and analyze the adaptation of fat storage capacity in the goose liver during the evolution of Anatidae. Genomic resequencing of 994 geese is used to investigate the genetic relationships of geese, which supports the dual origin of geese (Anser cygnoides and Anser anser). Chinese indigenous geese show higher genetic diversity than European geese, and a scientific conservation program can be established to preserve genetic variation for each breed. We also find that a 14-bp insertion in endothelin receptor B subtype 2 (EDNRB2) that determines the white plumage of Chinese domestic geese is a natural mutation, and the linkaged alleles rapidly increase in frequency as a result of genetic hitchhiking, leading to the formation of completely different haplotypes of white geese under strong artificial selection. These genomic resources and our findings will facilitate marker-assisted breeding of geese and provide a foundation for further research on geese genetics and evolution.

The ecological niche and terrestrial environment jointly influence the altitudinal pattern of aquatic biodiversity.

The altitudinal distribution of biodiversity in alpine ecosystems has captured academic attention, especially in streams because of their sensitivity to climate change. In the past years, research mainly focused on understanding the role played by alpine streams' internal factors such as aquatic environmental variables, as well as physical and hydrological conditions, on the shaping of benthic macroinvertebrate communities. More recently, external factors such as terrestrial environments were included in analyses worldwide. In particular, the inherent properties constituting the ecological niche of specific species were considered as factors regulating dispersal and influencing community construction. The objective of this study was to reveal the distribution pattern and the driving factors regulating aquatic biodiversity in alpine streams. We hypothesized that the altitudinal distribution of aquatic macroinvertebrates could be explained by the interaction of the aquatic environment with both species' ecological niche and the terrestrial environment surrounding their habitat, and that rare species display a more pronounced pattern than widespread dominant species. To test these hypotheses, samples were collected from two alpine streams situated on opposite slopes of Biluo Snow Mountain in Yunnan Province, China. Results of statistical analyses showed poor explanatory power from aquatic environmental factors, while the differences in vegetation type and the ecological niche of the species played an important role in determining the distribution pattern of aquatic biodiversity. Furthermore, we found that the altitudinal distribution pattern of aquatic biodiversity exhibits a bimodal type, with rare species fitting the bimodal peaks. These findings call for a better inclusion and further investigation on the effects of the terrestrial environment on aquatic ecosystems.

The Inhibition of Polysialyltranseferase ST8SiaIV Through Heparin Binding to Polysialyltransferase Domain (PSTD).

BACKGROUND: The polysialic acid (polySia) is a unique carbohydrate polymer produced on the surface Of Neuronal Cell Adhesion Molecule (NCAM) in a number of cancer cells, and strongly correlates with the migration and invasion of tumor cells and with aggressive, metastatic disease and poor clinical prognosis in the clinic. Its synthesis is catalyzed by two polysialyltransferases (polySTs), ST8SiaIV (PST) and ST8SiaII (STX). Selective inhibition of polySTs, therefore, presents a therapeutic opportunity to inhibit tumor invasion and metastasis due to NCAM polysialylation. Heparin has been found to be effective in inhibiting the ST8Sia IV activity, but no clear molecular rationale. It has been found that polysialyltransferase domain (PSTD) in polyST plays a significant role in influencing polyST activity, and thus it is critical for NCAM polysialylation based on the previous studies. OBJECTIVE: To determine whether the three different types of heparin (unfractionated hepain (UFH), low molecular heparin (LMWH) and heparin tetrasaccharide (DP4)) is bound to the PSTD; and if so, what are the critical residues of the PSTD for these binding complexes? METHODS: Fluorescence quenching analysis, the Circular Dichroism (CD) spectroscopy, and NMR spectroscopy were used to determine and analyze interactions of PSTD-UFH, PSTD-LMWH, and PSTD-DP4. RESULTS: The fluorescence quenching analysis indicates that the PSTD-UFH binding is the strongest and the PSTD-DP4 binding is the weakest among these three types of the binding; the CD spectra showed that mainly the PSTD-heparin interactions caused a reduction in signal intensity but not marked decrease in α-helix content; the NMR data of the PSTD-DP4 and the PSTDLMWH interactions showed that the different types of heparin shared 12 common binding sites at N247, V251, R252, T253, S257, R265, Y267, W268, L269, V273, I275, and K276, which were mainly distributed in the long α-helix of the PSTD and the short 3-residue loop of the C-terminal PSTD. In addition, three residues K246, K250 and A254 were bound to the LMWH, but not to DP4. This suggests that the PSTD-LMWH binding is stronger than the PSTD-DP4 binding, and the LMWH is a more effective inhibitor than DP4. CONCLUSION: The findings in the present study demonstrate that PSTD domain is a potential target of heparin and may provide new insights into the molecular rationale of heparin-inhibiting NCAM polysialylation.