Small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2.

Although bone morphogenetic protein-2 (BMP2) has demonstrated extraordinary potential in bone formation, its clinical applications require supraphysiological milligram-level doses that increase postoperative inflammation and inappropriate adipogenesis, resulting in well-documented life-threatening cervical swelling and cyst-like bone formation. Recent promising alternative biomolecular strategies are toward promoting pro-osteogenic activity of BMP2 while simultaneously suppressing its adverse effects. Here, we demonstrated that small molecular phenamil synergized osteogenesis and bone formation with BMP2 in a rat critical size mandibular defect model. Moreover, we successfully elicited the BMP2 adverse outcomes (i.e. adipogenesis and inflammation) in the mandibular defect by applying high dose BMP2. Phenamil treatment significantly improves the quality of newly formed bone by inhibiting BMP2 induced fatty cyst-like structure and inflammatory soft-tissue swelling. The observed positive phenamil effects were associated with upregulation of tribbles homolog 3 (Trib3) that suppressed adipogenic differentiation and inflammatory responses by negatively regulating PPARγ and NF-κB transcriptional activities. Thus, use of BMP2 along with phenamil stimulation or Trib3 augmentation may be a promising strategy to improve clinical efficacy and safety of current BMP therapeutics

Biogeographic Distribution Patterns of Bacteria in Typical Chinese Forest Soils

Microbes are widely distributed in soils and play a very important role in nutrient cycling and ecosystem services. To understand the biogeographic distribution of forest soil bacteria, we collected 115 soil samples in typical forest ecosystems across eastern China to investigate their bacterial community compositions using Illumina MiSeq high throughput sequencing based on 16S rRNA. We obtained 4,667,656 sequences totally and more than 70% of these sequences were classified into five dominant groups, i.e. Actinobacteria, Acidobacteria, Alphaproteobacteria, Verrucomicrobia and Planctomycetes (relative abundance > 5%). The bacterial diversity showed a parabola shape along latitude and the maximum diversity appeared at latitudes between 33.50°N and 40°N, an area characterized by warm-temperate zones and moderate temperature, neutral soil pH and high substrate availability (soil C and N) from dominant deciduous broad-leaved forests. Pairwise dissimilarity matrix in bacterial community composition showed that bacterial community structure had regional similarity and the latitude of 30°N could be used as the dividing line between southern and northern forest soils. Soil properties and climate conditions (MAT and MAP) greatly accounted for the differences in the soil bacterial structure. Among all soil parameters determined, soil pH predominantly affected the diversity and composition of the bacterial community, and soil pH = 5 probably could be used as a threshold below which soil bacterial diversity might decline and soil bacterial community structure might change significantly. Moreover, soil exchangeable cations, especially Ca2+ (ECa2+) and some other soil variables were also closely related to bacterial community structure. The selected environmental variables (21.11%) explained more of the bacterial community variation than geographic distance (15.88%), indicating that the edaphic properties and environmental factors played a more important role than geographic dispersal limitation in determining the bacterial community structure in Chinese forest soils

Enhanced Osteogenesis of Adipose-Derived Stem Cells by Regulating Bone Morphogenetic Protein Signaling Antagonists and Agonists.

UnlabelledAlthough adipose-derived stem cells (ASCs) are an attractive cell source for bone tissue engineering, direct use of ASCs alone has had limited success in the treatment of large bone defects. Although bone morphogenetic proteins (BMPs) are believed to be the most potent osteoinductive factors to promote osteogenic differentiation of ASCs, their clinical applications require supraphysiological dosage, leading to high medical burden and adverse side effects. In the present study, we demonstrated an alternative approach that can effectively complement the BMP activity to maximize the osteogenesis of ASCs without exogenous application of BMPs by regulating levels of antagonists and agonists to BMP signaling. Treatment of ASCs with the amiloride derivative phenamil, a positive regulator of BMP signaling, combined with gene manipulation to suppress the BMP antagonist noggin, significantly enhanced osteogenic differentiation of ASCs through increased BMP-Smad signaling in vitro. Furthermore, the combination approach of noggin suppression and phenamil stimulation enhanced the BMP signaling and bone repair in a mouse calvarial defect model by adding noggin knockdown ASCs to apatite-coated poly(lactic-coglycolic acid) scaffolds loaded with phenamil. These results suggest novel complementary osteoinductive strategies that could maximize activity of the BMP pathway in ASC bone repair while reducing potential adverse effects of current BMP-based therapeutics.SignificanceAlthough stem cell-based tissue engineering strategy offers a promising alternative to repair damaged bone, direct use of stem cells alone is not adequate for challenging healing environments such as in large bone defects. This study demonstrates a novel strategy to maximize bone formation pathways in osteogenic differentiation of mesenchymal stem cells and functional bone formation by combining gene manipulation with a small molecule activator toward osteogenesis. The findings indicate promising stem cell-based therapy for treating bone defects that can effectively complement or replace current osteoinductive therapeutics

A novel small-scale self-focusing suppression method for ultrahigh peak power lasers

We proposed a novel method, using an asymmetric four grating compressor (AFGC) to improve the spatial uniformity of laser beams, to suppress the small-scale self-focusing (SSSF) during the post-compression of ultrahigh peak power lasers. The spatial uniformity is an important factor in performing post-compression, due to the spatial intensity nonuniformity will be enhanced while going through a nonlinear process. And what's more, the strong intensity spikes induced during nonlinear process can seriously damage the subsequent optical components. Moreover, the three-dimensional numerical simulations of the post-compression are implemented based on a petawatt (PW) class laser with a standard compressor and an AFGC. The results show that the post-compression with AFGC can shorten the laser pulses from 30fs to sub-10fs and meanwhile efficiently suppress SSSF. This work provides a promising scheme for the post-compression scaling to PW and even 10PW lasers

Genipin-cross-linked collagen/chitosan biomimetic scaffolds for articular cartilage tissue engineering applications

This was the first study to use genipin to cross-link collagen and chitosan.In this study, genipin-cross-linked collagen/chitosan biodegradable porous scaffolds were prepared for articular cartilage regeneration. The influence of chitosan amount and genipin concentration on the scaffolds physicochemical properties was evaluated. The morphologies of the scaffolds were characterized by scanning electron microscope (SEM) and cross-linking degree was investigated by ninhydrin assay. Additionally, the mechanical properties of the scaffolds were assessed under dynamic compression. To study the swelling ratio and the biostability of the collagen/chitosan scaffold, in vitro tests were also carried out by immersion of the scaffolds in PBS solution or digestion in collagenase, respectively. The results showed that the morphologies of the scaffolds underwent a fiber-like to a sheet-like structural transition by increasing chitosan amount. Genipin cross-linking remarkably changed the morphologies and pore sizes of the scaffolds when chitosan amount was less than 25%. Either by increasing the chitosan ratio or performing cross-linking treatment, the swelling ratio of the scaffolds can be tailored. The ninhydrin assay demonstrated that the addition of chitosan could obviously increase the cross-linking efficiency. The degradation studies indicated that genipin cross-linking can effectively enhance the biostability of the scaffolds. The biocompatibility of the scaffolds was evaluated by culturing rabbit chondrocytes in vitro. This study demonstrated that a good viability of the chondrocytes seeded on the scaffold was achieved. The SEM analysis has revealed that the chondrocytes adhered well to the surface of the scaffolds and contacted each other. These results suggest that the genipin-cross-linked collagen/chitosan matrix may be a promising formulation for articular cartilage scaffolding.Key Projects in the National Science and Technology Pillar Program in the Eleventh Five-year Plan Period. Grant Number: 2006BA116B04Guangdong Natural Science Foundation. Grant Number: 07300602Natural Science Foundation Team Project of Guangdong. Grant Number: 4205786State Key Program of National Natural Science of China. Grant Number: 50732003National Basic Research Program of China. Grant Number: 2005CB62390

Knowledge, attitudes and practices (KAP) relating to avian influenza in urban and rural areas of China

<p>Abstract</p> <p>Background</p> <p>Studies have revealed that visiting poultry markets and direct contact with sick or dead poultry are significant risk factors for H5N1 infection, the practices of which could possibly be influenced by people's knowledge, attitudes and practices (KAPs) associated with avian influenza (AI). To determine the KAPs associated with AI among the Chinese general population, a cross-sectional survey was conducted in China.</p> <p>Methods</p> <p>We used standardized, structured questionnaires distributed in both an urban area (Shenzhen, Guangdong Province; n = 1,826) and a rural area (Xiuning, Anhui Province; n = 2,572) using the probability proportional to size (PPS) sampling technique.</p> <p>Results</p> <p>Approximately three-quarters of participants in both groups requested more information about AI. The preferred source of information for both groups was television. Almost three-quarters of all participants were aware of AI as an infectious disease; the urban group was more aware that it could be transmitted through poultry, that it could be prevented, and was more familiar with the relationship between AI and human infection. The villagers in Xiuning were more concerned than Shenzhen residents about human AI viral infection. Regarding preventative measures, a higher percentage of the urban group used soap for hand washing whereas the rural group preferred water only. Almost half of the participants in both groups had continued to eat poultry after being informed about the disease.</p> <p>Conclusions</p> <p>Our study shows a high degree of awareness of human AI in both urban and rural populations, and could provide scientific support to assist the Chinese government in developing strategies and health-education campaigns to prevent AI infection among the general population.</p

Influence of Beijing Winter Olympic Games Construction on Vegetation Coverage around Zhangjiakou Competition Zone

There is a rising concern that Olympic venue construction may affect the surrounding environment. The construction of Winter Olympic venues and competition zones is more likely to degrade the surrounding natural environment than the summer counterpart, considering the prominent land use change and extensive vegetation disturbance during the construction of ski trails in mountainous areas. Scientific assessment of the impact of this Winter Olympic Games construction on the surrounding ecological environment can be of significance for the construction of a Green Olympics. At this stage, the main framework of venue and competition construction in Zhangjiakou for the Beijing Winter Olympic Games is essentially completed, so we assessed the vegetation coverage change conditions based on the Normalized Difference Vegetation Index (NDVI) and the Enhanced Vegetation Index (EVI) from 2000 to 2020. Our results show that the construction of venues, roads, and other facilities for the 2022 Olympic Games led to a remarkable change in land use, but the impacts on vegetation coverage were negligible in the surrounding area. Due to the intensive reforestation activities since the year that Beijing won the race to host the Winter Olympics, vegetation coverage continued to increase in the Zhangjiakou area, even in the core area of Winter Olympic Games construction zones. This study provides support to the belief in hosting a Green Olympics