Genetically engineered pre-microRNA-34a prodrug suppresses orthotopic osteosarcoma xenograft tumor growth via the induction of apoptosis and cell cycle arrest.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children, and microRNA-34a (miR-34a) replacement therapy represents a new treatment strategy. This study was to define the effectiveness and safety profiles of a novel bioengineered miR-34a prodrug in orthotopic OS xenograft tumor mouse model. Highly purified pre-miR-34a prodrug significantly inhibited the proliferation of human 143B and MG-63 cells in a dose dependent manner and to much greater degrees than controls, which was attributed to induction of apoptosis and G2 cell cycle arrest. Inhibition of OS cell growth and invasion were associated with release of high levels of mature miR-34a from pre-miR-34a prodrug and consequently reduction of protein levels of many miR-34a target genes including SIRT1, BCL2, c-MET, and CDK6. Furthermore, intravenous administration of in vivo-jetPEI formulated miR-34a prodrug significantly reduced OS tumor growth in orthotopic xenograft mouse models. In addition, mouse blood chemistry profiles indicated that therapeutic doses of bioengineered miR-34a prodrug were well tolerated in these animals. The results demonstrated that bioengineered miR-34a prodrug was effective to control OS tumor growth which involved the induction of apoptosis and cell cycle arrest, supporting the development of bioengineered RNAs as a novel class of large molecule therapeutic agents

Multiple Events of Allopolyploidy in the Evolution of the Racemose Lineages in Prunus (Rosaceae) Based on Integrated Evidence from Nuclear and Plastid Data.

Prunus is an economically important genus well-known for cherries, plums, almonds, and peaches. The genus can be divided into three major groups based on inflorescence structure and ploidy levels: (1) the diploid solitary-flower group (subg. Prunus, Amygdalus and Emplectocladus); (2) the diploid corymbose group (subg. Cerasus); and (3) the polyploid racemose group (subg. Padus, subg. Laurocerasus, and the Maddenia group). The plastid phylogeny suggests three major clades within Prunus: Prunus-Amygdalus-Emplectocladus, Cerasus, and Laurocerasus-Padus-Maddenia, while nuclear ITS trees resolve Laurocerasus-Padus-Maddenia as a paraphyletic group. In this study, we employed sequences of the nuclear loci At103, ITS and s6pdh to explore the origins and evolution of the racemose group. Two copies of the At103 gene were identified in Prunus. One copy is found in Prunus species with solitary and corymbose inflorescences as well as those with racemose inflorescences, while the second copy (II) is present only in taxa with racemose inflorescences. The copy I sequences suggest that all racemose species form a paraphyletic group composed of four clades, each of which is definable by morphology and geography. The tree from the combined At103 and ITS sequences and the tree based on the single gene s6pdh had similar general topologies to the tree based on the copy I sequences of At103, with the combined At103-ITS tree showing stronger support in most clades. The nuclear At103, ITS and s6pdh data in conjunction with the plastid data are consistent with the hypothesis that multiple independent allopolyploidy events contributed to the origins of the racemose group. A widespread species or lineage may have served as the maternal parent for multiple hybridizations involving several paternal lineages. This hypothesis of the complex evolutionary history of the racemose group in Prunus reflects a major step forward in our understanding of diversification of the genus and has important implications for the interpretation of its phylogeny, evolution, and classification

Widespread Presence of Glycolaldehyde and Ethylene Glycol Around Sagittarius B2

We report the detection of widespread CH$_2$OHCHO and HOCH$_2$CH$_2$OH emission in Galactic center giant molecular cloud Sagittarius B2 using the Shanghai Tianma 65m Radio Telescope. Our observations show for the first time that the spatial distribution of these two important prebiotic molecules extends over 15 arc-minutes, corresponding to a linear size of approximately 36 pc. These two molecules are not just distributed in or near the hot cores. The abundance of these two molecules seems to decrease from the cold outer region to the central region associated with star-formation activity. Results present here suggest that these two molecules are likely to form through a low temperature process. Recent theoretical and experimental studies demonstrated that prebiotic molecules can be efficiently formed in icy grain mantles through several pathways. However, these complex ice features cannot be directly observed, and most constraints on the ice compositions come from millimeter observations of desorbed ice chemistry products. These results, combined with laboratory studies, strongly support the existence of abundant prebiotic molecules in ices.Comment: 20 pages, 7 figures, accepted by Ap

Quality Difference Study of Six Varieties of Ganoderma lucidum with Different Origins

The quality difference of six varieties Ganoderma lucidum with different origins was investigated in this study by comparing the contents of ganoderic acid A and B, polysaccharide, and triterpenoids. The contents of ganoderic acid A and B in G. lucidum were analyzed by ultra performance liquid chromatography (UPLC). There was higher content of ganoderic acid A in G. lucidum of Dabie Mountain and Longquan. The G. lucidum from Longquan has the highest content of ganoderic acid B. The content of polysaccharide was determined by Anthrone–sulfuric acid method. The highest of polysaccharide content is G. lucidum from Liaocheng. The content of triterpenoid in G. lucidum was quantified by ultraviolet spectrophotometer at 548.1 nm using Ursolic acid as standard. The G. lucidum from Dabie Mountain has the highest content of triterpenoids. In summary, the content of ganoderic acid A and B, polysaccharide, and triterpenoids in G. lucidum with different origins are remarkably different, which may be caused by the conditions of cultivation and geographic environment

De novo intestine-specific transcriptome of the brown planthopper Nilaparvata lugens revealed potential functions in digestion, detoxification and immune response

AbstractThe brown planthopper (Nilaparvata lugens, BPH) is the most serious rice plant pests in Asia. In this study, we performed transcriptome-wide analysis on BPH intestine. We obtained more than 26 million sequencing reads that were then assembled into 53,553 unigenes with a mean size of 388bp. Based on similarity search with the nucleotide sequences available at NCBI, BPH intestine-specific transcriptome analysis identified 21,405 sequences. Assembled sequences were annotated with gene description, gene ontology and clusters of orthologous group terms. The digestion-, defense- and xenobiotic metabolism-related genes were abundantly detected in the transcripts from BPH intestine. Many novel genes including 33 digestion-related genes, 25 immune responsive genes and 27 detoxification-related genes are first reported here. We investigated the gene expression patterns at the transcript levels in different tissues by quantitative real-time PCR analysis, which revealed that some genes had intestine-specific expression, implicating their potential significance for BPH management

Association of sleep disorders with clinical symptoms and age in Chinese older adult patients with and without cognitive decline

ObjectiveTo investigate correlation between cognitive function, age, and sleep disturbances.MethodsThis retrospective clinical study enrolled 78 patients with sleep disorders who were divided into three groups: a group of 24 patients with sleep disorders accompanied by cognitive decline (SD-CD); 54 patients with sleep disorders and no cognitive decline (SD-nCD) was divided into two groups, one of 30 patients aged between 60 and 70 years and another of 24 patients aged >70 years. Polysomnography was used to record patients’ sleep indicators throughout night; these included total sleep duration, sleep efficiency (SE), sleep latency, sleep structure and percentage of N1, N2, and N3 stages, rapid eye movement (REM) stage, as well as apnea hypopnea index (AHI), and oxygen saturation (OS). Analysis of variance (ANOVA) for continuous variables and chi-square test for categorical variables were used to analyze variables between different groups. Pearson’s correlation was used to analyze correlation between sleep parameters and mini-mental state examination (MMSE). Blood samples were used to determine their Aβ, Aβ40, Aβ42, total tau, phosphorylated tau protein (ptau), ptau181, ptau217, the inflammatory factor IL-1β, vitamin B12 (VB12), and melatonin levels.ResultsIn the SD-CD group, there was a significant decrease in SE and an increase in N1 stage sleep in older patients and a significant increase in AHI, REM stage AHI, and non-REM stage AHI. In patients with SD-nCD, the minimum OS, minimum OS in the REM period, and minimum OS in the non-REM period were significantly reduced. OS was significantly correlated with cognitive level, as evaluated by the MMSE. The addition of sleep parameters can significantly improve the accuracy of dementia diagnosis. Dementia biomarkers of Aβ and tau proteins in blood showed cognition-related differences, while ptau181 was associated with both cognition and age-related differences. Regression models revealed that age was related to higher levels of cognitive decline before (β = −0.43, P < 0.001) and after (β = −0.38, P < 0.001) adjustment of gender, BMI, and education level. There was a significant mediation effect of relationship between aging and cognitive function by sleep efficiency and N1 stage sleep.ConclusionSleep disorders and low OS are associated with a higher incidence of cognitive decline and dementia

Spatial transmission and meteorological determinants of tuberculosis incidence in Qinghai Province, China: a spatial clustering panel analysis

BACKGROUND: Tuberculosis (TB) is the notifiable infectious disease with the second highest incidence in the Qinghai province, a province with poor primary health care infrastructure. Understanding the spatial distribution of TB and related environmental factors is necessary for developing effective strategies to control and further eliminate TB. METHODS: Our TB incidence data and meteorological data were extracted from the China Information System of Disease Control and Prevention and statistical yearbooks, respectively. We calculated the global and local Moran's I by using spatial autocorrelation analysis to detect the spatial clustering of TB incidence each year. A spatial panel data model was applied to examine the associations of meteorological factors with TB incidence after adjustment of spatial individual effects and spatial autocorrelation. RESULTS: The Local Moran's I method detected 11 counties with a significantly high-high spatial clustering (average annual incidence: 294/100 000) and 17 counties with a significantly low-low spatial clustering (average annual incidence: 68/100 000) of TB annual incidence within the examined five-year period; the global Moran's I values ranged from 0.40 to 0.58 (all P-values < 0.05). The TB incidence was positively associated with the temperature, precipitation, and wind speed (all P-values < 0.05), which were confirmed by the spatial panel data model. Each 10 °C, 2 cm, and 1 m/s increase in temperature, precipitation, and wind speed associated with 9 % and 3 % decrements and a 7 % increment in the TB incidence, respectively. CONCLUSIONS: High TB incidence areas were mainly concentrated in south-western Qinghai, while low TB incidence areas clustered in eastern and north-western Qinghai. Areas with low temperature and precipitation and with strong wind speeds tended to have higher TB incidences

Functional identification of PGM1 in the regulating development and depositing of inosine monophosphate specific for myoblasts

BackgroundInosine monophosphate (IMP) is naturally present in poultry muscle and plays a key role in improving meat flavour. However, IMP deposition is regulated by numerous genes and complex molecular networks. In order to excavate key candidate genes that may regulate IMP synthesis, we performed proteome and metabolome analyses on the leg muscle, compared to the breast muscle control of 180-day-old Jingyuan chickens (hens), which had different IMP content. The key candidate genes identified by a differential analysis were verified to be associated with regulation of IMP-specific deposition.ResultsThe results showed that the differentially expressed (DE) proteins and metabolites jointly involve 14 metabolic pathways, among which the purine metabolic pathway closely related to IMP synthesis and metabolism is enriched with four DE proteins downregulated (with higher expression in breast muscles than in leg muscles), including adenylate kinase 1 (AK1), adenosine monophosphate deaminase 1 (AMPD1), pyruvate kinase muscle isoenzyme 2 (PKM2) and phosphoglucomutase 1 (PGM1), six DE metabolites, Hypoxanthine, Guanosine, L-Glutamine, AICAR, AMP and Adenylsuccinic acid. Analysis of PGM1 gene showed that the high expression of PGM1 promoted the proliferation and differentiation of myoblasts and inhibited the apoptosis of myoblasts. ELISA tests have shown that PGM1 reduced adenosine triphosphate (ATP) and IMP and uric acid (UA), while enhancing the biosynthesis of hypoxanthine (HX). In addition, up-regulation of PGM1 inhibited the expression of purine metabolism pathway related genes, and promoted the IMP de novo and salvage synthesis pathways.ConclusionThis study preliminarily explored the mechanism of action of PGM1 in regulating the growth and development of myoblasts and specific IMP deposition in Jingyuan chickens, which provided certain theoretical basis for the development and utilization of excellent traits in Jingyuan chickens