Research models and mesenchymal/epithelial plasticity of osteosarcoma

Most osteosarcomas (OSs) develop from mesenchymal cells at the bone with abnormal growth in young patients. OS has an annual incidence of 3.4 per million people and a 60–70% 5-year surviving rate. About 20% of OS patients have metastasis at diagnosis, and only 27% of patients with metastatic OS survive longer than 5 years. Mutation of tumor suppressors RB1, TP53, REQL4 and INK4a and/or deregulation of PI3K/mTOR, TGFβ, RANKL/NF-κB and IGF pathways have been linked to OS development. However, the agents targeting these pathways have yielded disappointing clinical outcomes. Surgery and chemotherapy remain the main treatments of OS. Recurrent and metastatic OSs are commonly resistant to these therapies. Spontaneous canine models, carcinogen-induced rodent models, transgenic mouse models, human patient-derived xenograft models, and cell lines from animal and human OSs have been developed for studying the initiation, growth and progression of OS and testing candidate drugs of OS. The cell plasticity regulated by epithelial-to-mesenchymal transition transcription factors (EMT-TFs) such as TWIST1, SNAIL, SLUG, ZEB1 and ZEB2 plays an important role in maintenance of the mesenchymal status and promotion of cell invasion and metastasis of OS cells. Multiple microRNAs including miR-30/9/23b/29c/194/200, proteins including SYT-SSX1/2 fusion proteins and OVOL2, and other factors that inhibit AMF/PGI and LRP5 can suppress either the expression or activity of EMT-TFs to increase epithelial features and inhibit OS metastasis. Further understanding of the molecular mechanisms that regulate OS cell plasticity should provide potential targets and therapeutic strategies for improving OS treatment.

Forest Changes by Precipitation Zones in Northern China after the Three-North Shelterbelt Forest Program in China

China launched the Three-North Shelterbelt Forest Program (TNSFP) in 1978 in northern China to combat desertification and dust storms, but it is still controversial in ecologically fragile arid and semi-arid areas, which is partly due to the uncertainties of monitoring of the spatial-temporal changes of forest distribution. In this study, we aim to provide an overall retrospect of the forest changes (i.e., forest gain and forest loss) in northern China during 2007–2017, and to analyze the forest changes in different precipitation zones. We first generated annual forest maps at 30 m spatial resolution during 2007–2017 in northern China through integrating Landsat and PALSAR/PALSAR-2 data. We found the PALSAR/Landsat-based forest maps outperform other four existing products (i.e., JAXA F/NF, FROM-GLC, GlobeLand30, and NLCD-China) from either PALSAR or Landsat data, with a higher overall accuracy 96% ± 1%. The spatial-temporal analyses of forests showed a substantial forest expansion from 316,898 ± 34,537 km2 in 2007 to 384,568 ± 35,855 km2 in 2017 in the central and eastern areas. We found a higher forest loss rate (i.e., 35%) in the precipitation zones with the annual mean precipitation less than 400 mm (i.e., the arid and semi-arid areas) comparing to that (i.e., 25%) in the zones with more than 400 mm (i.e., the humid areas), which suggests the lower surviving rate in the drylands. This study provides satellite-based evidence for the forest changes in different precipitation zones, and suggests that the likely impacts of precipitation on afforestation effectiveness should be considered in future implementation of ecological restoration projects like TNSFP.

Enhancing the antibacterial activities of sow milk via site-specific knock-in of a lactoferrin gene in pigs using CRISPR/Cas9 technology

Colostrum quality is a vital factor in mortality and growth performance for piglets. Lactoferrin is an immuno-active milk protein that contributes to the formation of a protective layer above intestinal mucosa, possesses the antibacterial and antiviral activities that are favorable for piglet development. However, there is a notable reduction in lactoferrin in sow milk during lactation after the first few days, which causes many piglets to fail to ingest enough colostrum thereby leading to an increase in piglet mortality. In this study, we successfully constructed genome-edited Large-White pigs with marker-free site-specific knock-in of lactoferrin gene in the 3′-end of Casein alpha-s1 via CRISPR/Cas9 mediated homologous recombination. Thus, the lactoferrin protein can be expressed in the mammary gland in the control of Casein alpha-s1 promoter. As expected, the lactoferrin protein in genetically modified pigs sustained high expression in both colostrum and milk when compared with wild-type pigs. Moreover, the bacterial plate assay indicated that the milk from genetically modified pigs showed bacteriostatic effects when compared with control pigs. Taken together, our study demonstrated that the milk from genetically modified pigs had antibacterial activity which may reduce the costs of veterinary drug and improve the surviving rate of piglets, which is promising for pig breeding.

PHENOLOGY OF BUSH-FORAGE SPECIES ESTABLISHED IN A SILVOPASTORAL SYSTEM IN TWO SOIL TYPES IN YUCATAN, MEXICO

Silvopastoral systems represent a sustainable alternative for livestock production. Such systems are part of agroforestry and represent an agroecosystem which can be designed chronological and topological by an arboreal and herbaceous component. It has been demonstrated that silvopastoral systems can improve the forage production, add firewood and reduce temperature in grassland what generating animal wellness. However, to obtain the benefits of a silvopastoral system, it is important to know the phenology of forage bushes in a multi-associated system. The objective of this work was to evaluate a multi-associated silvopastoral system accord of the phenological behavior of four bushes with forage potential in two types of soil (Leptosol and Lithosol). The study was carried out in a plot of 130 x 25 m. Around the plot was intercalated Hibiscus rosa-sinensis(Tulipan)species at 25 cm between plant, Gliricidiasepium(Cocoite)and Guazumaulmifolia(Pixoy)at 2 m, and inside of the plot Leucaenaleucocephala(Huaxin) at 50 cmbetween plants and3 m between rows. Evaluated treatments were Leptosol or Lithosol soils, the variables measured were plant height, basal diameter, diameter at 35 cm, branches number, flowering date and pods number, growth rate and surviving. The analysis of variance and Duncan test were carried out to detect differences between treatments in plant age. The 100% of surviving was observed in Huaxin, Pixoy and Tulipan species in both soil types at 10,7 and 10 months of age respectively, furthermore, Cocoite showed 69 and 81 % of surviving in Leptosol and Lithosol soil respectively at the 6 months of transplant. Plant height of Huaxin at ten months of age was (P<0.05) 145.5±38.70 cm with growth rate (GR) of 0.66±0.19 cm d-1 in Leptosol soil and 138.2±46.71 cm for Lithosol with GR of 0.62±0.16 cm d-1. Flowering was in winter at 5 age months. Pods productions differences (P<0.05) were observed in Leptosol with 56.3±49.41 pods and in Lithosol with 45±43.74 pods. The growth rate of Pixoy at seven months of age was (P<0.05) 133.0±29.00 cm in Leptosol with 0.68±14 cm d-1 and 101.0±27.33 cm in Lithosol soil with 0.52±138 cm d-1. The highest Tulipan plants at ten mons age were (P<0.05) 163±36.10 cm with 0.68±0.12 cm d-1 of GR in Leptosol soil and 147.7±20.38 cm with 0.62±0.07 cm d-1 of GR in Lithosol soil. For all variables in soil treatment were detected differences (P<0.05), in which, Leptosol showed be the best soil for growth. Furthermore, this type soil showed positive influence in forage bushes growth due to plants showed the best growth, except Cocoite which the surviving rate was higher in Lithosol soil.

Nifurtimox hampered the progression of astroglioma in vivo via manipulating the AKT-GSK3βaxis

: Astroglioma, one major form of brain tumors, has remained principally tough to handle for decades, due to the complexity of tumor pathology and the poor response to chemo‐ and radio‐therapies. Our previous study demonstrated that nifurtimox could regulate the signaling axis of AKT‐GSK3β in vari ous tumor types including the astroglioma U251 cells. Intriguingly, earlier case studies suggested that nifurtimox could possibly permeate the blood brain barrier and arrest neuroblastoma in the brain. These observations jointly encouraged us to explore whether nifurtimox would hinder the growth of astroglioma in vivo. Our results exhibited that nifurtimox could competently hinder the development of astroglioma in mouse brain as compared to temozolomide, the first line of drug for brain tumors. Meanwhile the surviving rate, as well as the body weight was dramatically upregulated upon nifurtimox treatment, as compared to that of temozolomide. These findings offered nifurtimox as a better alternative drug in treating astroglioma in vivo. Persistently, the manipulation of the signaling axis of AKT‐GSK3β in astroglioma was found in line with earlier findings in neuroblastoma when treated with nifurtimox.

Effects of low temperature on Chrysanthemum shiwogiku var. kinokuniense in vitro conservation

The effect of low temperature condition on wild Chrysanthemum shiwogiku var. in vitro conservation was investigated, and its plant regeneration hereditary stability was detected using its sterile seedling. The results show that the test tube young plant grows rapidly, and its preservation time is short at a temperature at 25±2°C, at condition of 12 h/d, photoperiod at 2000 ~ 3000 lx, and all die after 180 days. However, the sterile seedling grows slowly under low-temperature, and its preservation time extends to 360 days. The sterile seedling surviving rate was above 96%. The data indicate that the 4°C low temperature is advantageous to Chrysanthemum plantlets preservation. After preservation, the recovered plantlets grow well and show no differences in morphology and isoenzyme zymogram of peroxidase, ISSR-PCR compared with the control. In addition, the results show that low temperature in vitro plantlets maintain genetic stability.