Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration

Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinicall

Characterization of Two New Apodemus Mitogenomes (Rodentia: Muridae) and Mitochondrial Phylogeny of Muridae

Apodemus is the most common small rodent species in the Palearctic realm and an ideal species for biogeographical research and understanding environmental changes. Elucidating phylogenetic relationships will help us better understand species adaptation and genetic evolution. Due to its stable structure, maternal inheritance, and rapid evolution, the mitogenome has become a hot spot for taxonomic and evolutionary studies. In this research, we determined the mitochondrial genome of Apodemus agrarius ningpoensis and Apodemus draco draco and studied the phylogeny of Muridae using ML and BI trees based on all known complete mitogenomes. The mitochondrial genome of Apodemus agrarius ningpoensis was 16,262 bp, whereas that of Apodemus draco draco was 16,222 bp, and both encoded 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes. Analysis of base composition showed a clear A-T preference. All tRNAs except tRNASer and tRNALys formed a typical trilobal structure. All protein-coding genes contained T- and TAA as stop codons. Phylogeny analysis revealed two main branches in the Muridae family. Apodemus agrarius ningpoensis formed sister species with Apodemus chevrieri, whereas Apodemus draco draco with Apodemus latronum. Our findings provide theoretical basis for future studies focusing on the mitogenome evolution of Apodemus

Association of human papillomavirus with Fanconi anemia promotes carcinogenesis in Fanconi anemia patients

Fanconi anemia (FA) is a rare recessive disorder associated with chromosomal fragility. FA patients are at very high risk of cancers, especially head and neck squamous cell carcinomas and squamous cell carcinomas caused by infection of human papillomaviruses (HPVs). By integrating into the host genome, HPV oncogenes E6 and E7 drive the genomic instability to promote DNA damage and gene mutations necessary for carcinogenesis in FA patients. Furthermore, E6 and E7 oncoproteins not only inhibit p53 and retinoblastoma but also impair the FANC/BRCA signaling pathway to prevent DNA damage repair and alter multiple signals including cell-cycle checkpoints, telomere function, cell proliferation, and interference of the host immune system leading to cancer development in FA patients. In this review, we summarize recent advances in unraveling the molecular mechanisms of FA susceptibility to HPV-induced cancers, which facilitate rational preventive and therapeutic strategies

Characterization of Two New <i>Apodemus</i> Mitogenomes (Rodentia: Muridae) and Mitochondrial Phylogeny of Muridae

Apodemus is the most common small rodent species in the Palearctic realm and an ideal species for biogeographical research and understanding environmental changes. Elucidating phylogenetic relationships will help us better understand species adaptation and genetic evolution. Due to its stable structure, maternal inheritance, and rapid evolution, the mitogenome has become a hot spot for taxonomic and evolutionary studies. In this research, we determined the mitochondrial genome of Apodemus agrarius ningpoensis and Apodemus draco draco and studied the phylogeny of Muridae using ML and BI trees based on all known complete mitogenomes. The mitochondrial genome of Apodemus agrarius ningpoensis was 16,262 bp, whereas that of Apodemus draco draco was 16,222 bp, and both encoded 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes. Analysis of base composition showed a clear A-T preference. All tRNAs except tRNASer and tRNALys formed a typical trilobal structure. All protein-coding genes contained T- and TAA as stop codons. Phylogeny analysis revealed two main branches in the Muridae family. Apodemus agrarius ningpoensis formed sister species with Apodemus chevrieri, whereas Apodemus draco draco with Apodemus latronum. Our findings provide theoretical basis for future studies focusing on the mitogenome evolution of Apodemus

Effect of storm events on riverine nitrogen dynamics in a subtropical watershed, southeastern China

Rain storms are predicted to increase in the subtropical region due to climate change. However, the effects of storm events on riverine nitrogen (N) dynamics are poorly understood. In this study, the riverine N dynamics and storm effects in a large subtropical river (North Jiulong River, southeastern China) were investigated through continuous sampling of two storm events which occurred in June 2010 and June 2011. The results disclosed a strong linkage between N dynamics and hydrological controls and watershed characteristics. The extreme storm in June 2010 resulted in more fluctuations in N concentrations, loads, and composition, compared with the moderate storm in June 2011. There were contrasting patterns (e.g., the hysteresis effect) between nitrate and ammonium behavior in storm runoff, reflecting their different supply source and transport mechanism. Overall, nitrate supply originated from subsurface runoff and was dominated by within-channel mobilization, while ammonium was mainly from over-land sources and flushed by surface runoff. Extreme storm runoff (2010) caused a four-fold increase in dissolved inorganic N fluxes (DIN), with a greater fraction of ammonium (up to 30% of DIN) compared with the moderate storm and background flow condition (less than 15%). Storm-driven sharp increases of N loads and changes in nutrient stoichiometry (more ammonium) might have been connected with algal blooms in the adjacent estuary and Xiamen Bay. Combined with the background flow measurement of N gradients along the main river and a stream together with anthropogenic N load information, the interactive effect of hydrological and biogeochemical process on riverine N was preliminarily revealed. Current results suggested that storm runoff N was controlled by rainfall, hydrological condition, antecedent soil moisture, spatial variability of land-based N source, and damming. These findings could be used as a reference for future water quality monitoring programs and the development of a pollution mitigation strategy. (C) 2012 Elsevier B.V. All rights reserved.National Natural Science Foundation of China [40810069004, 41076042]; Fundamental Research Funds for the Central Universities [2012121053]; Key Projects in the Science & Technology of Xiamen City [3502Z20091005

Four major factors regulate phosphatidylinositol 3-kinase signaling pathway in cancers induced by infection of human papillomaviruses

Epidemiological surveys and molecular studies have indicated that infection of human papillomavirus (HPV)itself is necessary but insufficient for completing transformation of the human epithelial cells in vivo to lead to different cancers. Mounting evidence exists that HPV E6/E7 oncoproteins indeed alter the cellular and molecular events in their transformed cells to induce cancers through a phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. The PI3K/AKT/mTOR signaling pathway is, nonetheless, of the central importance, which tightly modulates many cellular events that occur in cells to lead them to be cancerous under the action of oncogenic factors. The cancinogenic roles of the PI3K/AKT/mTOR signaling in HPV-induced cancers are generally regulated by different upstream signaling molecules such as upstream receptor tyrosine kinases. In this article, we review that the four major upstream signaling molecules (growth factor receptor, notch receptor, Ras and PI3KCA genes) regulate PI3K/AKT/mTOR pathway to confer oncogenicity in HPV-immortalized epithelial cells and various transformed phenotypes

Spatial-temporal variation of dissolved N-2 and denitrification in an agricultural river network, southeast China

National Natural Science Foundation of China [41076042, 41376082]; Fundamental Research Funds for the Central Universities [2012121053]The spatio-temporal pattern of excess N-2 production due to denitrification and gaseous nitrogen (N) removal via N-2 emission were investigated for a large agricultural river (the Jiulong River) in southeast China. During 2010-2011, direct measurement of excess dissolved N-2 (Delta N-2, denitrification product) using the N-2:Ar ratio method was carried out along the river network (North River and West River). The results showed that Delta N-2 ranged from 24 to 71 mu mol N-2 L-1 in the West River, and from 3 to 160 mu mol N-2 L-1 in the North River. Areal mean N-2 water-air flux was 8.66 kg N ha(-1) yr(-1) for the whole river network. "Hot spots" of denitrification were found in the upper North River and lower West River, where animal/human wastes dominated the riverine N source. Dissolved inorganic nitrogen (DIN) and dissolved oxygen are the key factors controlling the spatial variation of Delta N-2. Delta N-2 generally peaked in January and during the warm-wet season from May through October, indicating an interactive effect of water temperature and DIN concentration on denitrification. Gaseous N removal fraction (E-d = 22% of [DIN]; annual N removal = 24% of riverine N export) through net denitrification is comparable with other river-estuaries around the world. Gaseous N removal effectiveness generally decreased with N enrichment and was constrained in those hyper-N rich river reaches. Management of N loss should consider the terrestrial and aquatic systems, in order to reduce N export from watershed to coast and mitigate eutrophication in this region. (C) 2014 Elsevier B.V. All rights reserved

Identification of a 5-Gene-Based Scoring System by WGCNA and LASSO to Predict Prognosis for Rectal Cancer Patients

Background. Although accumulating evidence suggested that a molecular signature panel may be more effective for the prognosis prediction than routine clinical characteristics, current studies mainly focused on colorectal or colon cancers. No reports specifically focused on the signature panel for rectal cancers (RC). Our present study was aimed at developing a novel prognostic signature panel for RC. Methods. Sequencing (or microarray) data and clinicopathological details of patients with RC were retrieved from The Cancer Genome Atlas (TCGA-READ) or the Gene Expression Omnibus (GSE123390, GSE56699) database. A weighted gene coexpression network was used to identify RC-related modules. The least absolute shrinkage and selection operator analysis was performed to screen the prognostic signature panel. The prognostic performance of the risk score was evaluated by survival curve analyses. Functions of prognostic genes were predicted based on the interaction proteins and the correlation with tumor-infiltrating immune cells. The Human Protein Atlas (HPA) tool was utilized to validate the protein expression levels. Results. A total of 247 differentially expressed genes (DEGs) were commonly identified using TCGA and GSE123390 datasets. Brown and yellow modules (including 77 DEGs) were identified to be preserved for RC. Five DEGs (ASB2, GPR15, PRPH, RNASE7, and TCL1A) in these two modules constituted the optimal prognosis signature panel. Kaplan-Meier curve analysis showed that patients in the high-risk group had a poorer prognosis than those in the low-risk group. Receiver operating characteristic (ROC) curve analysis demonstrated that this risk score had high predictive accuracy for unfavorable prognosis, with the area under the ROC curve of 0.915 and 0.827 for TCGA and GSE56699 datasets, respectively. This five-mRNA classifier was an independent prognostic factor. Its predictive accuracy was also higher than all clinical factor models. A prognostic nomogram was developed by integrating the risk score and clinical factors, which showed the highest prognostic power. ASB2, PRPH, and GPR15/TCL1A were predicted to function by interacting with CASQ2/PDK4/EPHA67, PTN, and CXCL12, respectively. TCL1A and GPR15 influenced the infiltration levels of B cells and dendritic cells, while the expression of PRPH was positively associated with the abundance of macrophages. HPA analysis supported the downregulation of PRPH, RNASE7, CASQ2, EPHA6, and PDK4 in RC compared with normal controls. Conclusion. Our immune-related signature panel may be a promising prognostic indicator for RC

Spatial-temporal variation of dissolved N-2 and denitrification in an agricultural river network, southeast China

National Natural Science Foundation of China [41076042, 41376082]; Fundamental Research Funds for the Central Universities [2012121053]The spatio-temporal pattern of excess N-2 production due to denitrification and gaseous nitrogen (N) removal via N-2 emission were investigated for a large agricultural river (the Jiulong River) in southeast China. During 2010-2011, direct measurement of excess dissolved N-2 (Delta N-2, denitrification product) using the N-2:Ar ratio method was carried out along the river network (North River and West River). The results showed that Delta N-2 ranged from 24 to 71 mu mol N-2 L-1 in the West River, and from 3 to 160 mu mol N-2 L-1 in the North River. Areal mean N-2 water-air flux was 8.66 kg N ha(-1) yr(-1) for the whole river network. "Hot spots" of denitrification were found in the upper North River and lower West River, where animal/human wastes dominated the riverine N source. Dissolved inorganic nitrogen (DIN) and dissolved oxygen are the key factors controlling the spatial variation of Delta N-2. Delta N-2 generally peaked in January and during the warm-wet season from May through October, indicating an interactive effect of water temperature and DIN concentration on denitrification. Gaseous N removal fraction (E-d = 22% of [DIN]; annual N removal = 24% of riverine N export) through net denitrification is comparable with other river-estuaries around the world. Gaseous N removal effectiveness generally decreased with N enrichment and was constrained in those hyper-N rich river reaches. Management of N loss should consider the terrestrial and aquatic systems, in order to reduce N export from watershed to coast and mitigate eutrophication in this region. (C) 2014 Elsevier B.V. All rights reserved

Natural and human influences on dissolved silica export from watershed to coast in Southeast China

National Natural Science Foundation of China [41076042, 41376082]; Fundamental Research Funds for the Central Universities [2012121053]; Science Foundation of Fujian Province [2010Y0064]Natural and human factors controlling dissolved silica (DSi) export from the watershed were investigated for the Jiulong River watershed in Southeast China, which is a subtropical region where tectonic activity and high runoff combine to create a global hot spot for DSi flux. Results showed that river DSi was fairly high (24676 mu mol L-1) due to granite lithology and increased human perturbation. The percentage of granite, paddy soil, arable land, and forest land each explain 47-69% of the spatial variation in DSi level at the subwatershed scale. Land use change (deforestation for agriculture) and soil erosion increased DSi transfer from terrestrial systems towards the river. Discharge explains over 95% of the variation in DSi fluxes, and a discrepancy of up to 16% of watershed DSi export was observed between low and high flow conditions. DSi retention is more significant in the dry season, likely due to biological uptake by diatoms in reservoirs under low flow conditions and higher residence time. However, this may be offset by high runoff flush in the wet season, which might cause unfavorable conditions for diatom growth and DSi depletion. There has been little overall change in DSi in estuarine water in recent decades. However, seasonal variation and occasionally fluctuation of DSi during extreme hydrological events (rainstorms) does exist, with important implications for the coastal ecosystem. This research confirmed that human activities and land use change have substantially altered Si delivery, cycling and riverine export to the coast in this region. Key Points Land use/cover change explain most of stream DSi variation 16% reduction of DSi fluxes due to damming but offset by high runoff Human have altered riverine DSi delivery, cycling and seaward expor