Acylation-stimulating protein/C5L2-neutralizing antibodies alter triglyceride metabolism in vitro and in vivo

Acylation-stimulating protein (ASP), a lipogenic hormone, stimulates triglyceride (TG) synthesis and glucose transport upon activation of C5L2, a G protein-coupled receptor. ASP-deficient mice have reduced adipose tissue mass due to increased energy expenditure despite increased food intake. The objective of this study was to evaluate the blocking of ASP-C5L2 interaction via neutralizing antibodies (anti-ASP and anti-C5L2-L1 against C5L2 extracellular loop 1). In vitro, anti-ASP and anti-C5L2-L1 blocked ASP binding to C5L2 and efficiently inhibited ASP stimulation of TG synthesis and glucose transport. In vivo, neither anti-ASP nor anti-C5L2-L1 altered body weight, adipose tissue mass, food intake, or hormone levels (insulin, leptin, and adiponectin), but they did induce a significant delay in TG clearance [P < 0.0001, 2-way repeated-measures (RM) ANOVA] and NEFA clearance (P < 0.0001, 2-way RM ANOVA) after a fat load. After treatment with either anti-ASP or anti-C5L2-L1 antibody there was no change in adipose tissue AMPK activity, but neutralizing antibodies decreased perirenal TG mass (-38.4% anti-ASP, -18.8% anti-C5L2, P < 0.01-0.001) and perirenal LPL activity (-75.6% anti-ASP, -72.5% anti-C5L2, P < 0.05). In liver, anti-C5L2-L1 decreased TG mass (-42.8%, P < 0.05), whereas anti-ASP increased AMPK activity (+34.6%, P < 0.001). In the muscle, anti-C5L2-L1 significantly increased TG mass (+128.0%, P < 0.05), LPL activity (+226.1%, P < 0.001), and AMPK activity (+71.1%, P < 0.01). In addition, anti-ASP increased LPL activity (+164.4, P < 0.05) and AMPK activity (+53.9%, P < 0.05) in muscle. ASP/C5L2-neutralizing antibodies effectively block ASP-C5L2 interaction, altering lipid distribution and energy utilization.     

Iodine Nutrition and Thyroid Function in Pregnant Women Exposed to Different Iodine Sources

Determination of the public health concern about magnesium (Mg) in health and disease has been confounded by the lack of a practical measure of status. This has resulted in a lack of consistency in associating Mg deficiency with specific pathological conditions. Some attempts at associating Mg with a chronic disease have used the Dietary Reference Intakes (DRIs) as a status assessment measure. Use of current DRIs for Mg is problematic because recent evidence suggests that they should be updated and based on body weight. An evidence-based suggested Estimated Average Requirement (EAR) and Recommended Dietary Allowance (RDA) for a 70-kg individual is 175 and 250 mg/day, respectively. However, numerous dietary and physiological factors can affect the need for Mg and thus affect the use of the current or suggested new DRIs to assess Mg status. Calcium intakes above normal requirements can decrease Mg balance and exacerbate signs of Mg deficiency. Mg deficiency apparently occurs often in obesity because of increased need to counteract the inflammatory stress induced by adipose tissue dysfunction. Deficiency in anti-oxidant nutrients such as vitamin E and selenium can exacerbate a response to low dietary Mg indicated by increased oxidative stress which can lead to chronic disease. Dietary modifiers of Mg absorption and excretion affect balance and thus the need for Mg. Factors decreasing Mg balance include low dietary protein and non-fermentable fiber, while factors that can increase balance include fructose and fermentable fiber and fructose-containing oligosaccharides. Use of the DRIs to assess the Mg status of a population or group needs to consider their physiological characteristics and dietary habits and be aware that the DRIs may need updating. The DRIs only can be considered a component of a toolbox that presently includes serum Mg concentration and the daily urinary Mg excretion to assess the Mg status of an individual.

     

EP300 contributes to high-altitude adaptation in Tibetans by regulating nitric oxide production

The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway,as suggested by earlier studies.To test the adaptive role of the previously reported candidate gene EP300 (histone acetyltransferase p300),we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans.The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans,with a group of variants showing allelic divergence between Tibetans and lowland reference populations,including Han Chinese,Europeans,and Africans.Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation.More importantly,genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide (NO) concentration.Collectively,we propose that EP300 harbors adaptive variants in Tibetans,which might contribute to high-altitude adaptation through regulating NO production.     

Single Nanostructure Electrochemical Devices for Studying Electronic Properties and Structural Changes in Lithiated Si Nanowires

Nanostructured Si is a promising anode material for the next generation of Li‐ion batteries, but few studies have focused on the electrical properties of the Li‐Si alloy phase, which are important for determining power capabilities and ensuring sufficient electrical conduction in the electrode structure. Here, we demonstrate an electrochemical device framework suitable for testing the electrical properties of single Si nanowires (NWs) at different lithiation states and correlating these properties with structural changes via transmission electron microscopy (TEM). We find that single Si NWs usually exhibit Ohmic I–V response in the lithiated state, with conductivities two to three orders of magnitude higher than in the delithiated state. After a number of sequential lithiation/delithiation cycles, the single NWs show similar conductivity after each lithiation step but show large variations in conductivity in the delithiated state. Finally, devices with groups of NWs in physical contact were fabricated, and structural changes in the NWs were observed after lithiation to investigate how the electrical resistance of NW junctions and the NWs themselves affect the lithiation behavior. The results suggest that electrical resistance of NW junctions can limit lithiation. Overall, this study shows the importance of investigating the electronic properties of individual components of a battery electrode (single nanostructures in this case) along with studying the nature of interactions within a collection of these component structures.     

Ferrous Iron Induces Nrf2 Expression in Mouse Brain Astrocytes to Prevent Neurotoxicity

Free radical damage caused by ferrous iron is involved in the pathogenesis of secondary brain injury after intracerebral hemorrhage (ICH). NF‐E2‐related factor 2 (Nrf2), a major phase II gene regulator that binds to antioxidant response element, represents an important cellular cytoprotective mechanism against oxidative damage. We hypothesized that Nrf2 might protect astrocytes from damage by Fe²⁺. Therefore, we examined cytotoxicity in primary astrocytes induced by iron overload and evaluated the effects of Fe²⁺ on Nrf2 expression. The results demonstrated that 24‐h Fe²⁺ exposure exerted time‐ and concentration‐dependent cytotoxicity in astrocytes. Furthermore, Fe²⁺ exposure in astrocytes resulted in time‐ and concentration‐dependent increases in Nrf2 expression, which preceded Fe²⁺ toxicity. Nrf2‐specific siRNA further knocked down Nrf2 levels, resulting in greater Fe²⁺‐induced astrocyte cytotoxicity. These data indicate that induction of Nrf2 expression could serve as an adaptive self‐defense mechanism, although it is insufficient to completely protect primary astrocytes from Fe²⁺‐induced neurotoxicity.     

Digestion-Promoting Effects and Mechanisms of Dashanzha Pill Based on Raw and Charred Crataegi Fructus

Emerging evidence suggests that a high-fat diet (HFD) can influence endoplasmic reticulum (ER) stress and gut microbiota. Crataegi Fructus is a traditional Chinese herb widely used in formulas for dyspepsia, with Dashanzha Pill composed of raw Crataegi Fructus (DR) being a representative drug. Processing products of Crataegi Fructus, however, have a stronger pro-digestive effect, and we hypothesized that Dashanzha Pill composed of charred Crataegi Fructus (DC) is more effective. We found that the contents of glucose 1-phosphate and luteolin in DR and DC were substantially different via ultra-high performance liquid chromatography-hybrid quadrupole-Orbitrap high-resolution mass spectrometry. DC outperformed DR in improving histopathological changes, increasing gastrin and motilin, and decreasing vasoactive intestinal peptides in rats with HFD induced dyspepsia. Fecal microbiota analysis revealed that DC could restore the disturbed intestinal microbiota composition, including that of Bacteroides, Akkermansia, and Intestinimonas to normal levels. Furthermore, DC significantly reduced the mRNA and protein levels of glucose-regulated protein 78, protein kinase R-like ER kinase, and eukaryotic initiation factor 2α. Taken together, DC outperformed DR in relieving dyspepsia by regulating gut microbiota and alleviating ER stress.     

中华通草蛉成虫越冬体色变化与滞育的关系

对自然条件下中华通草蛉成虫越冬体色变化与滞育关系的系统研究表明,成虫在越冬过程中都经历了一个较明显的体色变化过程,主要表现在体躯底色从绿色到土黄色及体背面滞育斑由褐色到红褐色的改变,据此将成虫体色分成5个级别,在越冬过程中约80%个体体色经历了在生殖型体色（1级）和滞育型体色（4,5级）之间的明显变化,约有20%个体体色维持在2、3级,在越冬前,成虫滞育斑出现后其卵巢不再发育或者发育受抑而逐渐停止发育,滞育斑的出现是成虫开始滞育的重要标志;越冬后,随着成虫体色由滞育型向生殖型的转变,当大多数个体体色变为3级以下时,卵巢开始发育,这些结果说明,中华通草蛉越冬成虫体色的变化是其滞育越冬的一个重要形态指标,越冬前后体色的改变,标志着成虫滞育的开始和结束。     

SDX on the X chromosome is required for male sex determination

Dear Editor, Sex determination is one of the most fundamental develop-ment processes,as gender is the first and most important identity of human.In most mammals...