Although systemic or local inflammation, commonly featured by cytokine activation, is implicated in patients with bone loss, the underlying mechanisms are still elusive. As microRNAs (miR), a class of small non-coding RNAs involved in essential physiological processes, have been found in bone cells, we aimed to investigate the role of miR for modulating osteogenesis in inflammatory milieu using human bone marrow mesenchymal stem cells (hBM-MSCs). Induced by proinflammatory cytokine TNF-α, miR-150-3p was identified as a key player in suppressing osteogenic differentiation through downregulating β-catenin, a transcriptional co-activator promoting bone formation. TNF-α treatment increased the levels of miR-150-3p, which directly targeted the 3′-UTR of β-catenin mRNA and in turn repressed its expression. In addition, we observed that miR-150-3p expression was increased by TNF-α via IKK-dependent NF-κB signalling. There are three putative NF-κB binding sites in the promoter region of miR-150, and we identified −686 region as the major NF-κB binding site for stimulation of miR-150 expression by TNF-α. Finally, the osteogenic differentiation of hBM-MSCs was inhibited by either miR-150-3p overexpression or TNF-α treatment, which was prevented by anti-miR-150-3p oligonucleotides. Taken together, our data suggested that miR-150-3p integrated inflammation signalling and osteogenic differentiation and may contribute to the inhibition effects of inflammation on bone formation, thus expanding the pathophysiological functions of microRNAs in bone diseases.

Implant-related infections (IRIs) which led to a large amount of medical expenditure were caused by bacteria and fungi that involve the implants in the operation or in ward. Traditional treatments of IRIs were comprised of repeated radical debridement, replacement of internal fixators, and intravenous antibiotics. It needed a long time and numbers of surgeries to cure, which meant a catastrophe to patients. So how to prevent it was more important than to cure it. As an excellent local release system, coating is a good idea by its local drug infusion and barrier effect on resisting biofilms which were the main cause of IRIs. So in this review, materials used for coatings and evidences of prevention were elaborated.

Cold stress is a major factor limiting rice () production worldwide, especially at the seedling and booting stages. The identification of genes associated with cold tolerance (CT) in rice is important for sustainable food production. Here, we report the results of a genome-wide association study to identify the genetic loci associated with CT by using a 1,033-accession diversity panel. We identified five CT-related genetic loci at the booting stage. Accessions carrying multiple cold-tolerant alleles displayed a higher seed-setting rate than did accessions that had no cold-tolerant alleles or carried a single allele. At the seedling stage, eight genetic loci related to CT have been identified. Among these, was identified as the candidate gene for the genetic locus that is associated with CT in rice seedlings. A single-nucleotide polymorphism (SNP), SNP2, at position 343 in is responsible for conferring CT at the seedling stage in rice. Further analysis of the haplotype network revealed that SNP2 was present in 80.08% of the temperate accessions but only 3.8% of the ones. We used marker-assisted selection to construct a series of BCF near-isogenic lines possessing the cold-tolerant allele SNP2 When subjected to cold stress, plants carrying SNP2 survived better as seedlings and showed higher grain weight than plants carrying the SNP2 allele. The CT-related loci identified here and the functional verification of will provide genetic resources for breeding cold-tolerant varieties and for studying the molecular basis of CT in rice.

Sheath blight (SB), caused by Rhizoctonia solani kühn, is one of the most serious global rice diseases. No major resistance genes to SB have been identified so far. All discovered loci are quantitative resistance to rice SB. The qSB-11(LE) resistance quantitative trait locus (QTL) has been previously reported on chromosome 11 of Lemont (LE). In this study, we report the precise location of qSB-11 (LE) . We developed a near isogenic line, NIL-qSB11(TQ), by marker-assisted selection that contains susceptible allele(s) from Teqing (TQ) at the qSB-11 locus in the LE genetic background. NIL-qSB11(TQ) shows higher susceptibility to SB than LE in both field and greenhouse tests, suggesting that this region of LE contains a QTL contributing to SB resistance. In order to eliminate the genetic background effects and increase the accuracy of phenotypic evaluation, a total of 112 chromosome segment substitution lines (CSSLs) with the substituted segment specific to the qSB-11 (LE) region were produced as the fine mapping population. The genetic backgrounds and morphological characteristics of these CSSLs are similar to those of the recurrent parent LE. The donor TQ chromosomal segments in these CSSL lines contiguously overlap to bridge the qSB-11 (LE) region. Through artificial inoculation, all CSSLs were evaluated for resistance to SB in the field in 2005. For the recombinant lines, their phenotypes were evaluated in the field for another 3 years and during the final year were also evaluated in a controlled greenhouse environment, showing a consistent phenotype in SB resistance across years and conditions. After comparing the genotypic profile of each CSSL with its phenotype, we are able to localize qSB-11 (LE) to the region defined by two cleaved-amplified polymorphic sequence markers, Z22-27C and Z23-33C covering 78.871 kb, based on the rice reference genome. Eleven putative genes were annotated within this region and three of them were considered the most likely candidates. The results of this study will greatly facilitate the cloning of the genes responsible for qSB-11 (LE) and marker-assisted breeding to incorporate qSB-11 (LE) into other rice cultivars.

The detrimental effects of oxidative stress on the skeletal system have been documented, and understanding the mechanisms is important to design a therapeutic strategy. As an antioxidant and anti-inflammatory agent, the active ingredient of turmeric curcumin has been used as medication for numerous complications including bone loss. However, it is unclear if curcumin could influence the osteogenic potential of mesenchymal stem cells (MSCs), particularly in oxidative injuries. Here we demonstrate that curcumin treatment protects cell death caused by hydrogen peroxide (HO) exposure in human adipose-derived MSCs in vitro. Importantly, curcumin is able to enhance the osteoblast differentiation of human adipose-derived MSCs that is inhibited by HO. Notably, both oxidative stress and the inhibition of Wnt/β-catenin signaling are attenuated by curcumin treatment. These results suggest that curcumin can promote osteoblast differentiation of MSCs and protect the inhibitory effect elicited by oxidative injury. The findings support potential use of curcumin or related antioxidants in MSC-based bone regeneration for disease related with oxidative stress-induced bone loss.

Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is a major constraint to rice production worldwide. In this study, we developed monogenic near-isogenic lines (NILs) NILPi9, NILPizt, and NILPi54 carrying genes Pi9, Pizt, and Pi54, respectively, by marker assisted backcross breeding using 07GY31 as the japonica genetic background with good agronomic traits. Polygene pyramid lines (PPLs) PPLPi9+Pi54 combining Pi9 with Pi54, and PPLPizt+Pi54 combining Pizt with Pi54 were then developed using corresponding NILs with genetic background recovery rates of more than 97%. Compared to 07GY31, the above NILs and PPLs exhibited significantly enhanced resistance frequencies (RFs) for both leaf and panicle blasts. RFs of both PPLs for leaf blast were somewhat higher than those of their own parental NILs, respectively, and PPLPizt+Pi54 exhibited higher RF for panicle blast than NILPizt and NILPi54 (P < 0.001), hinting an additive effect on the resistance. However, PPLPi9+Pi54 exhibited lower RF for panicle blast than NILPi9 (P < 0.001), failing to realize an additive effect. PPLPizt+Pi54 showed higher resistant level for panicle blast and better additive effects on the resistance than PPLPi9+Pi54. It was suggested that major R genes interacted with each other in a way more complex than additive effect in determining panicle blast resistance levels. Genotyping by sequencing analysis and extreme-phenotype genome-wide association study further confirmed the above results. Moreover, data showed that pyramiding multiple resistance genes did not affect the performance of basic agronomic traits. So the way to enhance levels of leaf and panicle blast resistances for rice breeding in this study is effective and may serve as a reference for breeders.Key Message: Resistant levels of rice blast is resulted from different combinations of major R genes, PPLPizt+Pi54 showed higher resistant level and better additive effects on the panicle blast resistance than PPLPi9+Pi54.

BackgroundPelvic floor dysfunction (PFD) is a group of clinical conditions including stress urinary incontinence (SUI) and pelvic organ prolapse (POP). The abnormality of collagen and elastin metabolism in pelvic connective tissues is implicated in SUI and POP.MethodsTo reconstitute the connective tissues with normal distribution of collagen and elastin, we transduced elastin to bone marrow-derived mesenchymal stem cells (BMSC). Elastin-expressing BMSCs were then differentiated to fibroblasts using bFGF, which produced collagen and elastin. To achieve the sustained release of bFGF, we formulated bFGF in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP).ResultsIn an in vitro cell culture system of 7 days, when no additional bFGF was administrated, the initial PLGA-loaded bFGF NP induced prolonged production of collagen and elastin from elastin-expressing BMSCs. In vivo, co-injection of PLGA-loaded bFGF NP and elastin-expressing BMSCs into the PFD rats significantly improved the outcome of urodynamic tests. Together, these results provided an efficient model of connective tissue engineering using BMSC and injectable PLGA-loaded growth factors.ConclusionsOur results provided the first instance of a multidisciplinary approach, combining both stem cell and nanoparticle technologies, for the treatment of PFD.

Rice blast caused by Magnaporthe oryzae is the most devastating disease of rice and poses a serious threat to world food security. In this study, the distribution and effectiveness of 18 R genes in 277 accessions were investigated based on pathogenicity assays and molecular markers. The results showed that most of the accessions exhibited some degree of resistance (resistance frequency, RF >50%). Accordingly, most of the accessions were observed to harbor two or more R genes, and the number of R genes harbored in accessions was significantly positively correlated with RF. Some R genes were demonstrated to be specifically distributed in the genomes of rice sub-species, such as Pigm, Pi9, Pi5 and Pi1, which were only detected in indica-type accessions, and Pik and Piz, which were just harbored in japonica-type accessions. By analyzing the relationship between R genes and RF using a multiple stepwise regression model, the R genes Pid3, Pi5, Pi9, Pi54, Pigm and Pit were found to show the main effects against M. oryzae in indica-type accessions, while Pita, Pb1, Pik, Pizt and Pia were indicated to exhibit the main effects against M. oryzae in japonica-type accessions. Principal component analysis (PCA) and cluster analysis revealed that combination patterns of major R genes were the main factors determining the resistance of rice varieties to M. oryzae, such as ‘Pi9+Pi54’, ‘Pid3+Pigm’, ‘Pi5+Pid3+Pigm’, ‘Pi5+Pi54+Pid3+Pigm’, ‘Pi5+Pid3’ and ‘Pi5+Pit+Pid3’ in indica-type accessions and ‘Pik+Pib’, ‘Pik+Pita’, ‘Pik+Pb1’, ‘Pizt+Pia’ and ‘Pizt+Pita’ in japonica-type accessions, which were able to confer effective resistance against M. oryzae. The above results provide good theoretical support for the rational utilization of combinations of major R genes in developing rice cultivars with broad-spectrum resistance.