Gambogic acid suppresses nasopharyngeal carcinoma via rewiring molecular network of cancer malignancy and immunosurveillance.

Nasopharyngeal carcinoma (NPC) is a malignant tumor highly prevalent in Southeast Asia. The distant metastasis and disease recurrence are still unsolved clinical problems. In recent years, traditional Chinese medicine (TCM) monomers have become significantly attractive due to their advantages. Using high throughput drug sensitivity screening, we identified gambogic acid (GA) as a common TCM monomer displaying multiple anti-NPC effects. GA could effectively inhibit the proliferation of low differentiated cells and highly metastatic cells in NPC via inducing apoptosis and G2/M cell cycle arrest. In addition, GA obviously repressed the abilities of cell clone, migration, invasion, angiogenesis and represented satisfied synergistic effects combined with chemotherapy. Importantly, we found the elevated immune checkpoint CD47 stimulated after chemotherapy was dramatically impaired by GA treatment. Mechanically, the network pharmacology analyses unraveled that the oncogenic signaling pathways including STATs were rewired by GA treatment. Taken together, our study reveals a molecular basis and provides a rationale for GA application as the treatment regime in NPC therapy in future.

Excessive phosphorus inputs dominate soil legacy phosphorus accumulation and its potential loss under intensive greenhouse vegetable production system.

Phosphorus (P) is an essential element for crop growth and it plays a critical role in agricultural production. Excessive P applications has become a serious concern in Chinese greenhouse vegetable production (GVP) systems. Nevertheless, P accumulation (legacy P) in GVP profile soils and its potential loss remain poorly documented. Hence, this study aimed to response this issue via paired collection of 136 soil samples (0-30, 30-60 and 60-90 cm depth) and 41 vegetable samples from both plastic greenhouses (PG) and solar greenhouses (SG) in Shouguang, Shandong province. Results showed that the annual input of P ranged from 772 to 2458 kg ha-1 for different vegetables through the whole growing season versus little vegetable P uptake (ranging from 47.8 to 155 kg ha-1). Results also revealed significant P accumulation in both SG and PG profile soils. Compared to arable soils (background soils), legacy P to the depth of 90 cm in PG and SG soils were 3.28 and 11.16 Mg P ha-1, respectively. The content of total P in PG and SG soils significantly increased with cultivation duration. The maximum environmental capacity of P in SG soils was 187 Mg ha-1, and the maximum number of years for safe planting was 38 yrs. After four years of cultivation, P loss would occur in these soils and the loss rate of P increased with cultivation duration. Opposite to PG soils, a potentially higher risk of P losses took place in SG soils. Our results also demonstrated that excessive P inputs driven by intensive agricultural practices dominated legacy P accumulation within the profile soils and its losses in GVP systems. Site-specific P managements, including improving P use efficiency, reducing further P surplus and reusing legacy P in soils, are urgently needed to minimize P loss. At the same time, the potential loss of subsoil P could not be neglected.

Research Progress in Genetic Research of Fatigue / 中国实验方剂学杂志

Fatigue refers to the manifestation of disorders in the process of carrying out or maintaining random activities， which can be regarded as an independent disease or as a symptom in a variety of chronic diseases. The high incidence of fatigue has seriously affected people's physical and mental health， and the prevention and treatment of fatigue has become an important problem to be solved urgently. The pathogenesis of fatigue mainly includes energy consumpation， accumulation of metabolites， abnormal secretion of neurotransmitters， decline of mitochondrial function， dysfunction of hypothalamus pituitary adrenal axis， etc. At present， there is no unified understanding about the pathogenesis of fatigue at home and abroad. The gene research of fatigue is the current research frontier. Gene expression profiling provides a new method for the study of the mechanism of fatigue. The combination of gene chip technology and traditional Chinese medicine（TCM） theory is expected to bring a breakthrough in the study of the pathogenesis of fatigue. In the study of fatigue gene chip， messenger RNA（mRNA） and microRNA（miRNA） are the common research objects， but few explorations are focused on the gene expression rule of fatigue by a specific signaling pathway and the effective regulation targets of TCM for treating fatigue. In recent years， the dysfunction of reward and inhibition mechanism in the central nervous system has become a research hotspot. In particular， gamma amino butyric acid （GABA） and dopamine （DA） have attracted much attention as the main substances of inhibition and reward mechanism， respectively. GABA and DA are used as inhibition and reward mechanisms to maintain the balance， and the body will not feel fatigue. Once the balance is broken， the fatigue will be formed. At the same time， DA and GABA receptors can also regulate cyclic adenosine monophosphate signaling pathway（cAMP） to affect fatigue. The research on key genes in GABA/DA balance mechanism and related cAMP signaling pathway by gene chip technology is expected to reveal the pathogenesis of fatigue in depth. The gene chip method is used to detect the changes of key genes in GABA/DA pathway and the related cAMP signaling pathway in the fatigue population and the normal population， so as to further explore the pathogenesis of fatigue. In this paper， the key genes in GABA/DA balance mechanism and cAMP signaling pathway related to fatigue were summarized by using the review method， so as to provide the basis for further study on the pathogenesis of fatigue and effective prevention and treatment from the perspective of genetics.

Phosphate-Based Ultrahigh Molecular Weight Polyethylene Fibers for Efficient Removal of Uranium from Carbonate Solution Containing Fluoride Ions.

This work provides a cost-effective approach for preparing functional polymeric fibers used for removing uranium (U(VI)) from carbonate solution containing NaF. Phosphate-based ultrahigh molecular weight polyethylene (UHMWPE-g-PO4) fibers were developed by grafting of glycidyl methacrylate, and ring-opening reaction using phosphoric acid. Uranium (U(VI)) adsorption capacity of UHMWPE-g-PO4 fibers was dependent on the density of phosphate groups (DPO, mmol∙g−1). UHMWPE-g-PO4 fibers with a DPO of 2.01 mmol∙g−1 removed 99.5% of U(VI) from a Na2CO3 solution without the presence of NaF. In addition, when NaF concentration was 3 g∙L−1, 150 times larger than that of U(VI), the U(VI) removal ratio was still able to reach 92%. The adsorption process was proved to follow pseudo-second-order kinetics and Langmuir isotherm model. The experimental maximum U(VI) adsorption capacity (Qmax) of UHMWPE-g-PO4 fibers reached 110.7 mg∙g−1, which is close to the calculated Qmax (117.1 mg∙g−1) by Langmuir equation. Compared to F−, Cl−, NO3−, and SO4²− did not influence U(VI) removal ratio, but, H2PO4− and CO3²− significantly reduced U(VI) removal ratio in the order of F− > H2PO4− > CO3²−. Cyclic U(VI) sorption-desorption tests suggested that UHMWPE-g-PO4 fibers were reusable. These results support that UHMWPE-g-PO4 fibers can efficiently remove U(VI) from carbonate solutions containing NaF.

Comparative proteomic analysis of hypothalamus tissue from Huoyan geese between pre-laying period and laying period using an iTRAQ-based approach.

The hypothalamus plays a central role in controlling poultry endocrine and reproductive activities. So far there is limited information focused on the proteome profiles of the hypothalamus from geese during different stages of the egg-laying cycle. In order to identify proteins regulating the egg-laying process of Huoyan geese, we investigated the proteome profiles of the hypothalamus from Huoyan geese during the laying period and pre-laying period by applying an isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic technology. A total number of 3,337 were identified and quantified, of which 18 were significantly up-regulated and 16 were significantly down-regulated. These differentially expressed proteins were subjected to bioinformatics analyses based on the Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway. Some of these were revealed to be involved in hormone and neurotransmitter secretion, exocytosis, calcium ion transport and synaptic transmission. Subsequently, excitatory amino acid transporter 2, complexin-1 and inositol 1,4,5-trisphosphate receptor, type 3 were confirmed at the messenger RNA level using quantitative real-time RT-PCR. Then, the abundance change of these proteins was verified further using Western blotting analysis. These data may aid in elucidating the molecular mechanism of higher laying performance in Huoyan geese.

Determination and evaluation of heavy metals in soils under two different greenhouse vegetable production systems in eastern China.

The evaluation of heavy metals (HMs) in greenhouse soils is crucial for both environmental monitoring and human health; thus, it is imperative to determine their concentrations, identify their sources and assess their potential risks. In this study, eight metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in 167 surface soils were investigated in two representative greenhouse vegetable systems of China: perennial solar greenhouse (SG) and seasonal plastic greenhouse (PG). The results indicated accumulations of Cd, Cu, Hg and Zn in the SG soils and Cd, Pb, Hg and Zn in the PG soils, with higher concentrations than the background values. In particular, Cd and Hg exhibited high levels of pollution under both GVP systems due to their positive Igeo values. Principle component analysis (PCA) and correlation analysis suggested that Cd, Cu, Hg and Zn in the SG soils and Cd, Hg and Zn in the PG soils were mainly related to intensive farming practices; Pb in the PG soils was significantly affected by atmospheric deposition. The results showed that soil characteristics, in particular soil organic matter, total nitrogen and total phosphorus, exerted significant influence on Hg, Cu, Cd, and Zn under the SG system. However, the HMs in the PG soils were weakly affected by soil properties. Overall, this study provides comparative research on the accumulation, potential risks and sources of HMs in two typical greenhouse soils in China, and our findings suggest that, Cd and Hg in both greenhouse soils could potentially represent environmental problems.

Molecular cloning and expression analysis of neuregulin 1 (Nrg1) in the hypothalamus of Huoyan goose during different stages of the egg-laying cycle.

Neuregulin 1 (Nrg1) is one of the most active members of the epidermal growth factor (EGF)-like family, which bind to the ErbB tyrosine kinase receptor and play many roles in modulation of synaptic activity, synaptogenesis, GABAergic neurotransmission, neurotransmitter receptor expression and the hormonal control of neuroendocrine reproductive development. In this study, we cloned and characterized the cDNA of goose Nrg1 originating from hypothalamus tissues of Huoyan goose using RACE method, investigated the mRNA expression profiles during different stages of the egg-laying cycle by real-time PCR. Multiple alignments and phylogenetic analyses of the deduced amino acid sequence were conducted using bioinformatics tools. We also determined the profiles of blood serum progesterone, estradiol, FSH and LH content during different egg-laying stages using radioimmunoassay. The cDNA of Nrg1 is consisted of 2061bp open reading frame encoding 686 amino acids. The deduced amino acid sequence of goose Nrg1 contains one EGF domain from amino acid residues 224 to 265 and shows a closer genetic relationship to the avian species than to other mammal species. The expression level of Nrg1 mRNA increased from the pre-laying period to the peak-laying period, reached its peak in the peak-laying period, and then decreased in the ceased period. The concentrations of FSH and estradiol in blood serum have the similar changing trend. These results might suggest a potential correlation between Nrg1/ErbB signaling network with the reproductive neuroendocrine of Huoyan goose.