Mesenchymal stem cell attenuates spinal cord injury by inhibiting mitochondrial quality control-associated neuronal ferroptosis.

Ferroptosis is a newly discovered form of iron-dependent oxidative cell death and drives the loss of neurons in spinal cord injury (SCI). Mitochondrial damage is a critical contributor to neuronal death, while mitochondrial quality control (MQC) is an essential process for maintaining mitochondrial homeostasis to promote neuronal survival. However, the role of MQC in neuronal ferroptosis has not been clearly elucidated. Here, we further demonstrate that neurons primarily suffer from ferroptosis in SCI at the single-cell RNA sequencing level. Mechanistically, disordered MQC aggravates ferroptosis through excessive mitochondrial fission and mitophagy. Furthermore, mesenchymal stem cells (MSCs)-mediated mitochondrial transfer restores neuronal mitochondria pool and inhibits ferroptosis through mitochondrial fusion by intercellular tunneling nanotubes. Collectively, these results not only suggest that neuronal ferroptosis is regulated in an MQC-dependent manner, but also fulfill the molecular mechanism by which MSCs attenuate neuronal ferroptosis at the subcellular organelle level. More importantly, it provides a promising clinical translation strategy based on stem cell-mediated mitochondrial therapy for mitochondria-related central nervous system disorders.

High-efficiency foam fractionation of anthocyanin from perilla leaves using surfactant-free active Al2O3 nanoparticle as collector and frother: Performance and mechanism.

Anthocyanin (ACN) is a natural pigment with significant industrial applications. However, foam fractionation of ACN from perilla leaves extract presents theoretical challenges due to its limited surface activity and foaming capacity. This work developed a surfactant-free active Al2O3 nanoparticle (ANP) as a collector and frother, which was modified with adipic acid (AA). The ANP-AA efficiently collected ACN through the electrostatic interaction, condensation reaction, and hydrogen bonding, with a Langmuir maximum capacity of 129.62 mg/g. Moreover, ANP-AA could form a stable foam layer by irreversibly adsorbing on the gas-liquid interface, reducing surface tension, and alleviating liquid drainage. Under the appropriate conditions of ANP-AA 400 mg/L and pH 5.0, we achieved a high ACN recovery of 95.68% with an enrichment ratio of 29.87 after ultrasound-assisted extraction of ACN from perilla leaves. Additionally, the recovered ACN displayed promising antioxidant properties. These findings hold significant importance in the food, colorant, and pharmaceutical industries.

Network pharmacological analysis to reveal the mechanism governing the effect of Qin Xi Tong on osteoarthritis and rheumatoid arthritis.

INTRODUCTION: Qin Xi Tong (QXT), produced by water extracts of Caulis Sinomenii, is clinically effective in the therapy of rheumatoid arthritis (RA). It is also a complementary agent for osteoarthritis (OA). This study aimed to screen the candidate targets and identify the potential mechanisms of QXT against RA and OA. METHOD: The active ingredients contained in QXT were queried from the TCMSP database. Their predicted targets were obtained through web-based databases, including TCMSP, BATMAN-TCM, CTD, and PharmMapper. The OA and RA targets were collected from the Genecards database and the GSE55235 dataset. Based on the DAVID database, GO and KEGG enrichment analyses of disease-drug common targets predicted potential signaling pathways for QXT. In addition, core targets were identified by mapping component-target-disease interaction networks with Cytoscape 3.9.1 and STRING. The Swissdock and Pymol tools further validate the predicted results. RESULTS: A total of 161 genes were put forward as potential targets for treating RA and OA. These genes might be involved in joint inflammation, including the IL-17 signaling pathway, MAPK signaling pathway, and TNF signaling pathway. They also regulated the progression of joint injuries, such as apoptosis, Th17 cell differentiation, and osteoclast differentiation. In addition, we identified 12 core targets of QXT. Molecular docking results showed that QXT has a high affinity with these core targets. CONCLUSIONS: This study reveals the mechanism governing the effect of QXT on RA and OA, predicts the direct target, and provides new ideas for clinical treatment. Key Points • Our study reveals the underlying mechanism of QXT in the treatment of RA and OA. • Further research into the effects of compounds in QXT alone would be of interest.

Mechanism of miR-424-5p promoter methylation in promoting epithelial-mesenchymal transition of hepatocellular carcinoma cells.

The current study set out to clarify the role of miR-424-5p promoter methylation in epithelial mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) cells. The findings of quantitative real-time-polymerase chain reaction and methylation-sensitive high-resolution melting assays elicited that miR-424-5p was poorly expressed in HCC tissues and cells while highly methylated. Meanwhile, upon demethylation, miR-424-5p expression levels were partly recovered in HCC cells. In addition, miR-424-5p upregulation reduced cell viability and elevated apoptosis of HCC cells, in parallel with increased N-cadherin and decreased E-cadherin levels. Dual-luciferase reporter assay further validated that miR-424-5p bound to the kinesin family member 2A (KIF2A), and miR-424-5p overexpression downregulated KIF2A. In addition, KIF2A overexpression reversed the miR-424-5p-driven changes in terms of cell viability, apoptosis and EMT-related protein levels. Furthermore, xenograft tumors were established via injection of Huh7 cells, followed by miR-424-5p overexpression in vivo, which inhabited KIF2A downregulation and attenuated tumor growth along with decreased Ki67 positive expression, diminished N-cadherin and elevated E-cadherin levels. Overall, our findings supported the conclusion that miR-424-5p promoter methylation reduced miR-424-5p expression and upregulated KIF2A, thereby promoting HCC EMT.

The Similarity between Species Composition of Vegetation and Soil Seed Bank of Grasslands in Inner Mongolia, China: Implications for the Asymmetric Response to Precipitation.

The asymmetric response of productivity to precipitation was recently proposed as an early warning signal for the shifts in temperate grassland function in China. It was hypothesized that the asymmetry was influenced by the increased growth of the newly emerged seedlings from the soil seed bank. Therefore, the seed density in the soil seed bank and the similarity between species composition of the vegetation and the soil seed bank should be maximized where asymmetry was maximized. However, this knowledge was still limited and unconfirmed. In this study, the desert steppe, typical steppe and the transition zone between them (with the highest asymmetry) were selected for studying the similarity index in both 2018 (dry year) and 2019 (wet year). Plant species composition was monitored in situ using an unmanned aerial vehicle. Soil seed bank samples were collected, and the seed bank density and species composition were then examined and identified in the laboratory. Results showed that: (1) The variation in vegetation species richness between the two years was the highest (41%) in the transition zone (p < 0.05), while it was only 7% and 13% for the desert steppe and typical steppe, respectively. The presence of herbaceous species mainly caused the differences in variation among three grassland types. (2) Seed density was the highest in the transition zone (114 seeds/m2 and 68 seeds/m2 in the transient and persistent soil seed bank, respectively) (p < 0.05). Additionally, herbaceous species were the main components of the soil seed bank. (3) The similarity index was the highest in the transition zone (p < 0.05), with 38%/44% and 33%/44% for the transient/persistent soil seed bank in 2018 and 2019, respectively. Our study demonstrated that variation in vegetation species composition was very similar to the composition of the seeds accumulated in the soil seed bank. These results warrant further investigation for the mechanism of asymmetric response of productivity to precipitation.

The genome of Cleistogenes songorica provides a blueprint for functional dissection of dimorphic flower differentiation and drought adaptability.

Cleistogenes songorica (2n = 4x = 40) is a desert grass with a unique dimorphic flowering mechanism and an ability to survive extreme drought. Little is known about the genetics underlying drought tolerance and its reproductive adaptability. Here, we sequenced and assembled a high-quality chromosome-level C. songorica genome (contig N50 = 21.28 Mb). Complete assemblies of all telomeres, and of ten chromosomes were derived. C. songorica underwent a recent tetraploidization (~19 million years ago) and four major chromosomal rearrangements. Expanded genes were significantly enriched in fatty acid elongation, phenylpropanoid biosynthesis, starch and sucrose metabolism, and circadian rhythm pathways. By comparative transcriptomic analysis we found that conserved drought tolerance related genes were expanded. Transcription of CsMYB genes was associated with differential development of chasmogamous and cleistogamous flowers, as well as drought tolerance. Furthermore, we found that regulation modules encompassing miRNA, transcription factors and target genes are involved in dimorphic flower development, validated by overexpression of CsAP2_9 and its targeted miR172 in rice. Our findings enable further understanding of the mechanisms of drought tolerance and flowering in C. songorica, and provide new insights into the adaptability of native grass species in evolution, along with potential resources for trait improvement in agronomically important species.

Root Transcriptome and Metabolome Profiling Reveal Key Phytohormone-Related Genes and Pathways Involved Clubroot Resistance in Brassica rapa L.

Plasmodiophora brassicae, an obligate biotrophic pathogen-causing clubroot disease, can seriously affect Brassica crops worldwide, especially Chinese cabbage. Understanding the transcriptome and metabolome profiling changes during the infection of P. brassicae will provide key insights in understanding the defense mechanism in Brassica crops. In this study, we estimated the phytohormones using targeted metabolome assays and transcriptomic changes using RNA sequencing (RNA-seq) in the roots of resistant (BrT24) and susceptible (Y510-9) plants at 0, 3, 9, and 20 days after inoculation (DAI) with P. brassicae. Differentially expressed genes (DEGs) in resistant vs. susceptible lines across different time points were identified. The weighted gene co-expression network analysis of the DEGs revealed six pathways including "Plant-pathogen interaction" and "Plant hormone signal transduction" and 15 hub genes including pathogenic type III effector avirulence factor gene (RIN4) and auxin-responsive protein (IAA16) to be involved in plants immune response. Inhibition of Indoleacetic acid, cytokinin, jasmonate acid, and salicylic acid contents and changes in related gene expression in R-line may play important roles in regulation of clubroot resistance (CR). Based on the combined metabolome profiling and hormone-related transcriptomic responses, we propose a general model of hormone-mediated defense mechanism. This study definitely enhances our current understanding and paves the way for improving CR in Brassica rapa.

Herbaceous Dominant the Changes of Normalized Difference Vegetation Index in the Transition Zone Between Desert and Typical Steppe in Inner Mongolia, China.

Asymmetric responses of aboveground net primary productivity (ANPP) to precipitation were identified as a signal to predict ecosystem state shifts at temperate grassland zones in Inner Mongolia, China. However, mechanism studies were still lacking. This study hypothesized that the enhanced growth and newly emerged herbaceous after increased precipitation resulted in the highest asymmetry at the transition zone between desert and typical steppe. We monitored the responses of the normalized difference vegetation index (NDVI) of different species to precipitation events using un-manned aerial vehicle technology to test this hypothesis. NDVI and species richness were measured twice at fixed points in July and August with a time interval of 15 days. Results showed that: (1) From July to August, NDVI in the transition zone increased significantly after precipitation (P < 0.05), but NDVI in both the desert and typical steppe showed a non-significant change (P > 0.05). (2) In the transition zone, NDVI increases from the shrub and herbaceous contributed to 37 and 63% increases of the site NDVI, respectively. (3) There was a significant difference in species richness between July and August in the transition zone (P < 0.05), mainly caused by the herbaceous (Chenopodiaceae, Composite, Convolvulaceae, Gramineae, Leguminosae, and Liliaceae), which either emerged from soil or tillers growth from surviving plants. This study demonstrated that herbaceous dominant the changes of NDVI in the transition zone, which provides a scientific basis for the mechanism studies of ANPP asymmetric response to precipitation and warrants long-term measurements.

Comparative transcriptome analysis in Chinese cabbage (Brassica rapa ssp. pekinesis) for DEGs of Ogura-, Polima-CMS and their shared maintainer.

Cytoplasmic male sterility (CMS) is maternally inherited trait, which hinders the ability to produce viable pollen in plants. It serves as a useful tool for hybrid seed production via exploiting heterosis in crops. The molecular mechanism of CMS and fertility restoration has been investigated in different crops. However, limited number of reports is available on comparison of Ogura- and Polima-CMS with their shared maintainer in Chinese cabbage. We performed transcript profiling of sterile Ogura CMS (Tyms), Polima CMS (22m2) and their shared maintainer line (231-330) with an aim to identify genes associated with male sterility. In this work, we identified 912, 7199 and 6381 DEGs (Differentially Expressed Genes) in 22m2 Vs Tyms, 231-330 VS 22m2 and 231-330 Vs Tyms, respectively. The GO (Gene Ontology) annotation and KEGG pathway analysis suggested that most of the DEGs were involved in pollen development, carbon metabolism, lipase activity, lipid binding, penta-tricopeptide repeat (PPR), citrate cycle and oxidative phosphorylation, which were down-regulated in both CMS lines. This result will provide an important resource for further understanding of functional pollen development, the CMS mechanism and to improve molecular breeding in Chinese cabbage.

Analysis of the relationship between MIR155HG variants and gastric Cancer susceptibility.

BACKGROUND: Gastric cancer is one of the most common cancers in the world and a major cause of cancer-related death. This study aims to determine whether genetic variations in MIR155HG could be associated with gastric cancer risk. MATERIALS & METHODS: A total of 506 gastric cancer patients and 500 healthy controls were enrolled in this study. Genotypes were examined with the MassARRAY platform and data management and analysis were conducted with the Typer Software. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated with logistic regression adjusting for age and gender to evaluate the associations between SNPs with gastric cancer in genetic model analysis. RESULTS: The "CC" genotype of rs4143370 decreased the risk of gastric cancer in genotype model (p = 0.020) and recessive model (p = 0.018). Inversely, the "CC" genotype of rs1893650 increased the risk of gastric cancer in genotype model (p = 0.023) and recessive model (p = 0.014). Stratified analysis showed that rs11911469 was associated with an increased risk of gastric cancer only among the male group in the dominant model (p = 0.039) and additive model (p = 0.030). The haplotype analysis showed a strong linkage disequilibrium among these six SNPs (rs4143370, rs77699734, rs11911469, rs1893650, rs34904192 and rs928883). CONCLUSION: This study confirmed the relationship between SNPs of MIR155HG and the gastric cancer risk among the Chinese Han population. Our data may provide a new perspective to understand the aetiology of gastric cancer.

TNF-α-elicited miR-29b potentiates resistance to apoptosis in peripheral blood monocytes from patients with rheumatoid arthritis.

CD14-positive monocytes from patients with rheumatoid arthritis (RA) are more resistant to apoptosis, which promotes their persistence at the inflammatory site and thereby contributes crucially to immunopathology. We sought to elucidate one mechanism underlying this unique pathogenesis: resistance to apoptosis and the potential involvement of miR-29b in this process. CD14-positive peripheral blood monocytes (PBMs) from RA patients were observed to be resistant to spontaneous apoptosis compared to PBMs from healthy volunteers. Intriguingly, expression of miR-29b was significantly upregulated in PBMs from RA patients than those from healthy volunteers, and this upregulation was correlated with RA disease activity. Functionally, forced expression of the exogenous miR-29b in CD14-positive Ctrl PBMs conferred resistance to spontaneous apoptosis and Fas-induced death, thereafter enhancing the production of major proinflammatory cytokines in there cells. Following identification of the potential miR-29b target transcripts using bioinformatic algorithms, we showed that miR-29b could directly bind to the 3'-UTR of the high-mobility group box-containing protein 1 (HBP1) and inhibited its transcription in PBMs. Importantly, stable expression of the exogenous HBP1 in differentiated THP-1 monocytes effectively abolished miR-29b-elicited resistance to Fas-induced apoptosis. Finally, among patients with RA and good clinical responses to immunotherapy, expression levels of miR-29b were significantly compromised in those treated with infliximab (a TNF-α inhibitor) but not in those treated with tocilizumab (a humanized mAb against the IL-6 receptor), pointing to a potential association between miR-29b activation and TNF-α induction. The available data collectively suggest that TNF-α-elicited miR-29b potentiates resistance to apoptosis in PBMs from RA patients via inhibition of HBP1 signaling, and testing patients for miR-29b/HBP1 expression ratios may provide more accurate prognostic information and could influence the recommended course of immunotherapy.

Network Analysis of Se-and Zn-related Proteins in the Serum Proteomics Expression Profile of the Endemic Dilated Cardiomyopathy Keshan Disease.

Keshan disease (KD) is an endemic cardiomyopathy with high mortality. Selenium (Se) and zinc (Zn) deficiencies are closely related to KD. The molecular mechanism of KD pathogenesis is still unclear. There are only few studies on the interaction of trace elements and proteins associated with the pathogenesis of KD. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional liquid chromatography tandem mass spectrometry (2DLC-MS/MS) technique analysis was used to analyze the differential expression of proteins from serum samples. Comparative Toxicogenomics Database (CTD) was used to screen Se- and Zn-associated proteins. Then, pathway and network analyses of Se- and Zn-associated proteins were constituted by Cytoscape ClueGO and GeneMANIA plugins. One hundred and five differentially expressed proteins were obtained by 2DLC-MS/MS, among them 19 Se- and 3 Zn-associated proteins. Fifty-two pathways were identified from ClueGO and 1 network from GeneMANIA analyses. The results showed that Se-associated proteins STAT3 and MAPK1 and Zn-associated proteins HIF1A and PARP1, the proteins involved in HIF-1 signaling pathway and apoptosis pathway, may play significant roles in the pathogenesis of KD. The approach of this study would be also beneficial for further dissecting molecular mechanism of other trace element-associated disease.

CQDs-Doped Magnetic Electrospun Nanofibers: Fluorescence Self-Display and Adsorption Removal of Mercury(II).

This paper reports the carbon quantum dots-doped magnetic electrospinning nanofibers for the self-display and removal of Hg(II) ions from water. The fluorescent carbon quantum dots and magnetic Fe3O4 nanoparticles were pre-prepared successfully, and they appeared to be homogeneously dispersed in nanofibers via electrospinning. During the sorption of Hg(II) ions, the significant fluorescence signals of nanofibers gradually declined and exhibited a good linear relationship with cumulative adsorption capacity, which could be easily recorded by the photoluminescence spectra. The sorption performance of mercury ions onto the nanofibers was investigated in terms of different experimental factors including contact time, solution pH value, and initial ion concentration. Considering the actual parameters, the nanofibers were sensitive self-display adsorption system for Hg(II) ions in the existence of other cation. The sorption data were described by different kinetic models, which indicate that the whole sorption was controlled by chemical adsorption. The intraparticle diffusion mass transfer was not obvious in this system, which further proved the uniform adsorption and even fluorescence quenching in nanofibers. Additionally, the nanocomposite fiber could regenerate in several cycles with no significant loss of adsorption capacity and fluorescence intensity. Thus, the nanofibers are promising alternatives for environmental pollution incidents. It is especially competent due to its high efficiency for self-display and removal of high concentration of mercury ions.

Carboxymethylcellulose ammonium-derived nitrogen-doped carbon fiber/molybdenum disulfide hybrids for high-performance supercapacitor electrodes.

In this paper, a new type of nitrogen-doped carbon fiber/molybdenum disulfide (N-CFs/MoS2) hybrid electrode materials are prepared via a certain concentration in solvothermal synthesis followed by a high-temperature carbonization process and using the carboxymethylcellulose ammonium (CMC-NH4) as a structure-directing agent for MoS2 nanosheet growth during the solvothermal synthesis process. The addition of CMC-NH4 effectively prevents the agglomeration of MoS2 nanosheets to increase the specific surface area. Moreover, it not only serves as a carbon source to provide conductive pathways, but also introduces N atoms to improve the conductivity of the CFs and promote the transfer of electrons and ions. This ultimately increases the conductivity of the electrode materials. Thus, the as-prepared N-CFs/MoS2 hybrids exhibit excellent electrochemical performance. The specific capacitance is up to 572.6 F g-1 under a current density of 0.75 A g-1 and the specific capacitance retained 98% of the initial capacitance after 5000 cycles of charge-discharge tests at a current density of 2.5 A g-1. Moreover, the hybrids show a maximum energy density of 19.5 W h kg-1 at a power density of 94 W kg-1. Therefore, the as-prepared N-CFs/MoS2 hybrids with remarkable electrochemical properties, low cost and environment protection show potential for practical application in the development of high-performance electrochemical energy storage devices.

Cellulosic Biomass-Reinforced Polyvinylidene Fluoride Separators with Enhanced Dielectric Properties and Thermal Tolerance.

Safety issues are critical barriers to large-scale energy storage applications of lithium-ion batteries (LIBs). Using an ameliorated, thermally stable, shutdown separator is an effective method to overcome the safety issues. Herein, we demonstrate a novel, cellulosic biomass-material-blended polyvinylidene fluoride separator that was prepared using a simple nonsolvent-induced phase separation technique. This process formed a microporous composite separator with reduced crystallinity, uniform pore size distribution, superior thermal tolerance, and enhanced electrolyte wettability and dielectric and mechanical properties. In addition, the separator has a superior capacity retention and a better rate capability compared to the commercialized microporous polypropylene membrane. This fascinating membrane was fabricated via a relatively eco-friendly and cost-effective method and is an alternative, promising separator for high-power LIBs.

N-cadherin promotes thyroid tumorigenesis through modulating major signaling pathways.

Epithelial-mesenchymal transition (EMT), a crucial step in disease progression, plays a key role in tumor metastasis. N-cadherin, a well-known EMT marker, acts as a major oncogene in diverse cancers, whereas its functions in thyroid cancer remains largely unclear. This study was designed to explore the biological roles and related molecular mechanism of N-cadherin in thyroid tumorigenesis. Quantitative RT-PCR (qRT-PCR) and immunohistochemistry assays were used to evaluate N-cadherin expression. A series of in vitro studies such as cell proliferation, colony formation, cell cycle, apoptosis, migration and invasion assays were performed to determine the effect of N-cadherin on malignant behavior of thyroid cancer cells. Our results showed that N-cadherin was significantly upregulated in papillary thyroid cancers (PTCs) as compared with non-cancerous thyroid tissues. N-cadherin knockdown markedly inhibited cell proliferation, colony formation, cell migration and invasion, and induced cell cycle arrest and apoptosis. On the other hand, ectopic expression of N-cadherin promoted thyroid cancer cell growth and invasiveness. Mechanically, our data demonstrated that tumor-promoting role of N-cadherin in thyroid cancer was closely related to the activities of the MAPK/Erk, the phosphatidylinositol-3-kinase (PI3K)/Akt and p16/Rb signaling pathways in addition to affecting the EMT process. Altogether, our findings suggest that N-cadherin promotes thyroid tumorigenesis by modulating the activities of major signaling pathways and EMT process, and may represent a potential therapeutic target for this cancer.

Long telomere length predicts poor clinical outcome in esophageal cancer patients.

BACKGROUND: Abnormal telomere length is widely reported in various human cancers, and it is considered to be an important hallmark of cancer. However, there is remarkably little consensus on the value of telomere length in the prognostic evaluation of esophageal cancers. Here, we attempted to determine the association of variable telomere length with clinical outcome of esophageal cancer patients. MATERIALS AND METHODS: Using real-time quantitative PCR, we examined relative telomere lengths (RTL) in a cohort of esophageal cancer and normal esophageal tissues, and statistically investigated the association between RTL and clinical outcomes of esophageal cancer patients. RESULTS: The majority of esophageal cancers in this study had longer RTLs as compared to adjacent non-tumor tissues. Enhanced tumor RTL was associated with smoking habit, poor differentiation, advanced tumor stage, lymph node metastasis and cancer related death. In particular, a close relationship between longer RTL and poor survival was fully demonstrated by using cox regression and Kaplan-Maier survival curves. CONCLUSIONS: We found frequent telomere elongation in esophageal cancer tissues, and demonstrated longer RTL may be an independent poor prognostic factor for esophageal cancer patients.

Increased expression of EHF contributes to thyroid tumorigenesis through transcriptionally regulating HER2 and HER3.

E26 transformation-specific (ETS) transcription factor EHF plays a tumor suppressor role in prostate cancer and esophageal squamous cell carcinoma (ESCC), whereas it is overexpressed and may act as an oncogene in ovarian and mammary cancers. However, its biological role in thyroid cancer remains totally unknown. The aim of this study was to explore the biological functions of EHF and its potential as a therapeutic target in thyroid cancer. Using quantitative RT-PCR (qRT-PCR) assay, we evaluated mRNA expression of EHF in a cohort of primary papillary thyroid cancers (PTCs) and matched non-cancerous thyroid tissues. The functions of knockdown and ectopic expression of EHF in thyroid cancer cells were determine by a series of in vitro and in vivo experiments. Moreover, dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays were performed to identify its downstream targets. Our data showed that EHF expression was significantly increased in PTCs compared with matched non-cancerous thyroid tissues. EHF knockdown significantly inhibited thyroid cancer cell proliferation, colony formation, migration, invasion and tumorigenic potential in nude mice and induced cell cycle arrested and apoptosis by modulating the PI3K/Akt and MAPK/Erk signaling pathways. On the other hand, ectopic expression of EHF in thyroid cancer cells notably promoted cell growth and invasiveness. Importantly, EHF was identified as a new transcription factor for HER2 and HER3, contributing to thyroid tumorigenesis. Altogether, our findings suggest that EHF is a novel functional oncogene in thyroid cancer by transcriptionally regulating HER2 and HER3, and may represent a potential therapeutic target for this cancer.

Analysis of Quasispecies of Avain Leukosis Virus Subgroup J Using Sanger and High-throughput Sequencing.

BACKGROUND: Avian leukosis viruses subgroup J (ALV-J) exists as a complex mixture of different, but closely related genomes named quasispecies subjected to continuous change according to the Principles of Darwinian evolution. METHOD: The present study seeks to compare conventional Sanger sequencing with deep sequencing using MiSeq platform to study quasispecies dynamics of ALV-J. RESULTS: The accuracy and reproducibility of MiSeq sequencing was determined better than Sanger sequencing by running each experiment in duplicate. According to the mutational rate of single position and the ability to distinguish dominant quasispecies with two sequencing methods, conventional Sanger sequencing technique displayed high randomness due to few sequencing samples, while deep sequencing could reflect the composition of the quasispecies more accurately. In the mean time, the research of quasispecies via Sanger sequencing was simulated and analyzed with the aid of re-sampling strategy with replacement for 1000 times repeat from high-throughput sequencing data, which indicated that the higher antibody titer, the higher sequence entropy, the harder analyzing with the conventional Sanger sequencing, resulted in lower ratios of dominant variants. CONCLUSIONS: In sum, deep sequencing is better suited for detecting rare variants comprehensively. The simulation of Sanger sequencing that we propose here will also help to standardize quasispecies researching under different selection pressure based on next-generation sequencing data.

Isoleojaponin, a new Halimane diterpene isolated from Leonurus japonicus.

Leojaponin (2), a labdane diterpene, was isolated from the EtOH extract of the herb of Leonurus japonicus together with a new halimane diterpene named isoleojaponin (1). Isoleojaponin has a new diterpene skeleton with a unique cross-conjugated α,ß-unsaturated ketone system, Their structures were elucidated by physical and spectroscopic analysis, and the relative configuration of the chiral C-9 carbon was determined by a computational method, and analysis of its possible biogenesis pathways.