Systemic Therapy for Low-grade Pulmonary Neuroendocrine Tumor

The lung is the second most common site of neuroendocrine tumors (NETs). Typical and atypical carcinoids are low-grade NETs of the lung. These rare tumors have received little attention and education is needed for treating physicians. The article describes the classifcation of lung NETs, the epidemiology and pathological characteristics. When lung NETs are diagnosed at an early stage, surgical intervention is often curative. For advanced lung NETs patients, different treatment methods including chemotherapy, somatostatin analogs, m-TOR inhibition, peptide receptor radioligand therapy, and biologic systemic therapy are discussed. The conclusions are generally extrapolated from the outcome of extra-pulmonary carcinoids. Prospective randomized well-designed trials are urgently needed to inform current recommendations on systemic treatment

Profiles of gonadotropins and steroid hormone-like substances in the hemolymph of mud crab Scylla paramamosain during the reproduction cycle

To elucidate the role of gonadotropins-like substances in mud crab Scylla paramamosain, hemolymph samples were measured for concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH) and steroid hormones by enzyme-linked immunosorbent assay (ELISA). Hormonal concentration data were analyzed in association with the stages of gonadal development. ELISA has shown that in the female crab, the level of FSH reaches its peak in the early stage of ovary development, while estradiol and LH peaked during the late maturing stage of the ovary. In the male crab, testosterone and FSH culminated during the spermatid stage, and the level of LH peaked during the sperm stage. These results indicated that substances resembling the vertebrate FSH and LH are present in the hemolymph of S. paramamosain, and they may be involved in the development of the gonad.National Natural Science Foundation of China [40406030, 40776084]; National High Technology Research and Development Program of China [2006AA10A406]; Program for New Century Excellent Talents in Fujian Provinc

Flame Retardant and Stable Li_1.5Al_0.5Ge_1.5(PO₄)₃‑Supported Ionic Liquid Gel Polymer Electrolytes for High Safety Rechargeable Solid-State Lithium Metal Batteries

Recently, poor security in conventional liquid electrolytes and high interfacial resistance at the electrode/electrolyte interface are the most challenging barriers for the expanded application of lithium batteries. In this regard, easy processing and flexible composite ionic liquid gel polymer electrolytes (ILGPEs) supported by Li_1.5Al_0.5­Ge_1.5­(PO₄)₃ (LAGP) are fabricated and investigated. The electrolyte is effectively combined with good electrochemical performances and thermal safety. Among these, the effects of different types of fillers such as the inert filler-SiO₂ and the active filler-LAGP on the ionic conductivity were studied in detail. LAGP particles can not only effectively reduce the crystallinity of the polymer matrix but also provide lithium ions and act as the lithium-ion conductor leading to higher ionic conductivity and Li⁺ ion transference number. Especially, the electrolyte shows good compatibility and no dendrite with the Li metal anode, significantly improving cyclic stability of LiFe­PO₄/Li batteries. The results indicate that the ILGPE-10%LAGP is a potential alternative electrolyte for high safety rechargeable solid-state lithium metal batteries

DNA Methylation Variation Trends during the Embryonic Development of Chicken

<div><p>The embryogenesis period is critical for epigenetic reprogramming and is thus of great significance in the research field of poultry epigenetics for elucidation of the trends in DNA methylation variations during the embryonic development of birds, particularly due to differences in embryogenesis between birds and mammals. Here, we first examined the variations in genomic DNA methylation during chicken embryogenesis through high-performance liquid chromatography using broilers as the model organism. We then identified the degree of DNA methylation of the promoters and gene bodies involved in two specific genes (<i>IGF2</i> and <i>TNF-α</i>) using the bisulfite sequencing polymerase chain reaction method. In addition, we measured the expression levels of <i>IGF2</i>, <i>TNF-α</i> and DNA methyltransferase (<i>DNMT</i>) 1, 3a and 3b. Our results showed that the genomic DNA methylation levels in the liver, heart and muscle increased during embryonic development and that the methylation level of the liver was significantly higher in mid-anaphase. In both the muscle and liver, the promoter methylation levels of <i>TNF-α</i> first increased and then decreased, whereas the gene body methylation levels remained lower at embryonic ages E8, 11 and 14 before increasing notably at E17. The promoter methylation level of <i>IGF2</i> decreased persistently, whereas the methylation levels in the gene body showed a continuous increase. No differences in the expression of <i>TNF-α</i> were found among E8, 11 and 14, whereas a significant increase was observed at E17. <i>IGF2</i> showed increasing expression level during the examined embryonic stages. In addition, the mRNA and protein levels of <i>DNMTs</i> increased with increasing embryonic ages. These results suggest that chicken shows increasing genomic DNA methylation patterns during the embryonic period. Furthermore, the genomic DNA methylation levels in tissues are closely related to the genes expression levels, and gene expression may be simultaneously regulated by promoter hypomethylation and gene body hypermethylation.</p></div

Schematic representation of the proximal promoter region and part of the first intron of tumer necrosis factor-alpha (<i>TNF-α</i>) and insulin-like growth factor 2 (<i>IGF2</i>) for predicting regions with a high GC content.

<p>The proximal promoter regions of <i>TNF-α</i> (a, -2000 to +1 base pairs [bp]) and <i>IGF2</i> (c, -2000 to +1 bp) and part of the first introns of <i>TNF-α</i> (b, +500 to +2500 bp) and <i>IGF2</i> (d, +5000 to +7000 bp) (modified output of MethPrimer program [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0159230#pone.0159230.ref020" target="_blank">20</a>]) were used to predict regions of high GC content. A dashed black line indicates the GC percentage as represented on the y-axis, and the x-axis denotes the bp position on the <i>TNF-α</i> and <i>IGF2</i> 5'-untranslated and gene body regions. The arrows indicate the transcriptional start sites (TSS). The coordinates are given in relation to the translation initiation site (shown as +1); vertical red lines indicate the relative positions of CpG dinucleotides; solid lines depict the locations of the PCR primers. Input sequences are shown as the bold region of the intermediate solid blue line; the untranslated and translated exons of <i>TNF-α</i> and <i>IGF2</i> are indicated by light blue and dark blue bars, respectively. The start sites, end sites and numbers of CG loci of the PCR products are all shown under each bisulfite PCR primer.</p

Variations in the genomic DNA methylation levels in broilers during the embryogenesis.

<p>The samples examined from embryonic ages (E) 2 to 7 were a mixture of the whole embryo; from E 9 to 20, the examined samples were separated into the heart, liver and muscle tissues. 5-mdC: 5-methyldeoxycytosine.</p

Primer sequences for bisulfite sequencing polymerase chain reaction analysis.

<p>Primer sequences for bisulfite sequencing polymerase chain reaction analysis.</p

Relative mRNA levels of DNA methyltransferases (<i>DNMT</i>) 1, <i>DNMT3a</i> and <i>DNMT 3b</i> in the muscles and livers of broilers.

<p>(a): <i>DNMT1</i>, (b): <i>DNMT3a</i>, (c): <i>DNMT 3b</i>. The data represent the means with standard errors (n = 6). Bars with different letters differed significantly (<i>P</i> < 0.05).</p

DNA methylation patterns of the tumer necrosis factor-alpha (<i>TNF-α</i>) and insulin-like growth factor 2 (<i>IGF2</i>) gene bodies in the muscles of broilers.

<p>The analytic method was the bisulfite sequencing polymerase chain reaction. Each line represents an individual bacterial clone, and each circle represents a single CpG dinucleotide. Open circles indicate unmethylated CpGs, and black circles indicate methylated CpGs. (a) <i>TNF-α</i> detected in the muscle. (b) <i>IGF2</i> detected in the muscle. (c) The methylation levels of the <i>TNF-α</i> and <i>IGF2</i> gene bodies in the histogram.</p