Interleukin 38 (IL-38) is a novel identified cytokine of IL-1 family in which some members are important in inflammation and angiogenesis. However, the role of IL-38 in regulating angiogenesis is unknown. The aim of the present study is to explore the effect of IL-38 on angiogenesis. Oxygen-induced retinopathy (OIR) of C57BL/6 J mice was induced by exposure of hyperoxia (75% oxygen) from postnatal day 7 (P7) to P12 and then returned to room air. The mice were injected with IL-38. At P17, neovascular region (tufts) and avascular area of the retinas were analyzed. The data showed that administration of IL-38 in vivo inhibited retinal angiogenesis significantly. Furthermore, the addition of IL-38 to the cell cultures attenuated the proliferation, scratch wound healing and tube formation of vascular endothelial cells induced by VEGF significantly. Our findings suggest that IL-38 is an antiangiogenic cytokine in pathophysiological settings and may have therapeutic potential for angiogenesis related diseases.

Due to the interest in the potential pharmacological application of dandelion, the chemical constituents and activities of Taraxacum mongolicum Hand.-Mazz were studied. Box-Behnken response surface methodology was employed to optimize the protocol for extraction of flavonoid from dandelion. The molecular structures of different flavonoid compounds were acquired and analyzed by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy. Several major flavonoid compounds were isolated and purified, namely, hesperetin-5'-O-β-rhamnoglucoside, hesperetin-7-glucuronide, kaempferol-3-glucoside, baicalein, hyperseroside, which were extracted for the first time from dandelion. Hesperetin-5'-O-β-rhamnoglucoside was identified as a new type of flavonoid that had never reported in the literature. This new flavonoid has outstanding antioxidant activity, as shown by its IC50 value (8.72 mg/L) for scavenging DPPH free radicals. The determination of the structure-related antioxidant activities could be interpreted based on DFT calculations. As such, we have not only illustrated the rich flavonoid contents in Taraxacum mongolicum Hand.-Mazz, but also revealed new types of flavonoid compounds in dandelion in terms of structure and antioxidant properties.

The mouse lens capsular injury model has been widely used in investigating the mechanisms of anterior subcapsular cataract (ASC) and posterior capsule opacification (PCO), and evaluating the efficacy of antifibrotic compounds. Nevertheless, there is no available protocol to quantitatively assess the treatment outcomes. Our aim is to describe a new method that can successfully quantify the wound and epithelial-mesenchymal transition (EMT) markers expression in vivo. In this model, lens anterior capsule was punctured with a hypodermic needle, which triggered lens epithelial cells (LECs) proliferation and EMT rapidly. Immunofluorescent staining of injured lens anterior capsule whole-mounts revealed the formation of ASC and high expression of EMT markers in the subcapsular plaques. A series of sectional images of lens capsule were acquired from laser scanning confocal microscopy (LSCM) three-dimensional (3D) scanning. Using LSCM Image Browser software, we can not only obtain high resolution stereo images to present the spatial structures of ASC, but also quantify the subcapsular plaques and EMT markers distribution successfully. Moreover, we also demonstrated that histone deacetylases (HDACs) inhibitor TSA significantly prevented injury-induced ASC using this method. Therefore, the present research provides a useful tool to study ASC and PCO biology as well as the efficacy of new therapies.

Heterosis can increase the yield of many crops and has been extensively applied in agriculture. In maize, female inflorescence architecture directly determines grain yield. Thus, exploring the relationship between early maize ear inflorescence development and heterosis regarding yield-related traits may be helpful for characterizing the molecular mechanisms underlying heterotic performance. In this study, we fine mapped the overdominant heterotic locus (hlEW2b), associated with ear width, in an approximately 1.98-Mb region based on analyses of chromosome segment substitution lines and the corresponding testcross population. Maize ear inflorescences at the floral meristem stage were collected from two inbred lines, one chromosome segment substitution line that carried hlEW2b (sub-CSSL16), the receptor parent lx9801, and the Zheng58 × sub-CSSL16 and Zheng58 × lx9801 hybrid lines. A total of 256 metabolites were identified, including 31 and 24 metabolites that were differentially accumulated between the two hybrid lines and between the two inbred lines, respectively. Most of these metabolites are involved in complex regulatory mechanisms important for maize ear development. For example, nucleotides are basic metabolites affecting cell composition and carbohydrate synthesis. Additionally, nicotinate and nicotinamide metabolism is important for photosynthesis, plant stress responses, and cell expansion. Moreover, flavonoid and phenolic metabolites regulate auxin transport and cell apoptosis. Meanwhile, phytohormone biosynthesis and distribution influence the cell cycle and cell proliferation. Our results revealed that changes in metabolite contents may affect the heterotic performance related to ear width and yield in maize hybrid lines. This study provides new clues in heterosis at the metabolomics level and implies that differentially accumulated metabolites made distinct contributions to the heterosis at an early stage of ear inflorescences development.

Sheathless particle focusing which utilises the secondary flow with a high throughput has great potential for use in microfluidic applications. In this work, an innovative particle focusing method was proposed. This method makes use of a mechanism that takes advantage of secondary flow and inertial migration. The device was a straight channel with arrays of arc-shaped grooves on the top surface. First, the mechanism and expected focusing phenomenon are explained using numerical simulation of the flow field and force balance. A simulation of particle trajectories was conducted as a reference, and then a series of experiments was designed and the effects of changes in particle size, flow rate and quantity of the groove structure were discussed. The microscopic images show that this particle focusing method performed well for different size particles, and the results agreed well with the theory and simulated results. Finally, the channel successfully concentrated Jurkat cells, which showed a good compatibility in the biological assay field. In this work, the arc-shaped groove channel was demonstrated to have the ability to achieve high-throughput, sheathless and three-dimensional particle focusing with simple operations.

MicroRNAs (miRNAs) play important roles in multiple biological processes and have attracted much scientific attention recently. Their expression can be altered by environmental factors (EFs), which are associated with many diseases. Identification of the phenotype-genotype relationships among miRNAs, EFs, and diseases at the network level will help us to better understand toxicology mechanisms and disease etiologies. In this study, we developed a computational systems toxicology framework to predict new associations among EFs, miRNAs and diseases by integrating EF structure similarity and disease phenotypic similarity. Specifically, three comprehensive bipartite networks: EF-miRNA, EF-disease and miRNA-disease associations, were constructed to build predictive models. The areas under the receiver operating characteristic curves using 10-fold cross validation ranged from 0.686 to 0.910. Furthermore, we successfully inferred novel EF-miRNA-disease networks in two case studies for breast cancer and cigarette smoke. Collectively, our methods provide a reliable and useful tool for the study of chemical risk assessment and disease etiology involving miRNAs.

Starch is an important nutrient component of maize kernels, and starch granule size largely determines kernel waxiness, viscosity, and other physiochemical and processing properties. To explore the genetic basis of maize starch granule size, 266 tropical, subtropical, and temperate inbred lines were subjected to genome-wide association analyses with an array of 56,110 random single nucleotide polymorphisms (SNPs). In the present panel, the kernel starch granule size ranged from 7-15.8 µm long and 6.8-14.3 µm wide. Fourteen significant SNPs were identified as being associated with the length of starch granules and 9 with their width. One linkage disequilibrium block flanking both sides of a significant SNP was defined as a quantitative trait locus (QTL) interval, and seven QTLs were mapped for both granule length and width. A total of 79 and 88 candidate genes associated with starch length and width, respectively, were identified as being distributed on QTL genomic regions. Among these candidate genes, six with high scores were predicted to be associated with maize starch granule size. A candidate gene association analysis identified significant SNPs within genes GRMZM2G419655 and GRMZM2G511067, which could be used as functional markers in screening starch granule size for different commercial uses.

Host-microbe interactions determine the outcome of host responses to commensal and pathogenic microbes. Previously, two epithelial cell-binding peptides were found to be homologues of two sites (B, aa168-174; F, aa303-309) in the flagellar hook protein FlgE of Pseudomonas aeruginosa. Tertiary modeling predicted these sites at the interface of neighboring FlgE monomers in the fully formed hook. Recombinant FlgE protein stimulated proinflammatory cytokine production in a human cell line and in murine lung organoid culture as detected with real-time RT-PCR and ELISA assays. When administered to mice, FlgE induced lung inflammation and enhanced the Th2-biased humoral response to ovalbumin. A pull-down assay performed with FlgE-saturated resin identified caveolin-1 as an FlgE-binding protein, and caveolin-1 deficiency impaired FlgE-induced inflammation and downstream Erk1/2 pathway activation in lung organoids. Intact flagellar hooks from bacteria were also proinflammatory. Mutations to sites B and F impaired bacteria motility and proinflammatory potency of FlgE without altering adjuvanticity of FlgE. These findings suggest that the flagellar hook and FlgE are novel players in host-bacterial interactions at immunological level. Further studies along this direction would provide new opportunities for understanding and management of diseases related with bacterial infection.

Owing to the rapid development of urbanisation and industrialisation, heavy metal pollution has become a widespread environmental problem. Maize planted on mercury (Hg)-polluted soil can absorb and accumulate Hg in its edible parts, posing a potential threat to human health. To understand the genetic mechanism of Hg accumulation in maize, we performed a genome-wide association study using a mixed linear model on an association population consisting of 230 maize inbred lines with abundant genetic variation. The order of relative Hg concentrations in different maize tissues was as follows: leaves > bracts > stems > axes > kernels. Combined two locations, a total of 37 significant single-nucleotide polymorphisms (SNPs) associated with kernels, 12 with axes, 13 with stems, 27 with bracts and 23 with leaves were detected with p < 0.0001. Each significant SNP was calculated and the SNPs significant associated with kernels, axes, stems, bracts and leaves explained 6.96%-10.56%, 7.19%-15.87%, 7.11%-10.19%, 7.16%-8.71% and 6.91%-9.17% of the phenotypic variation, respectively. Among the significant SNPs, nine co-localised with previously detected quantitative trait loci. This study will aid in the selection of Hg-accumulation inbred lines that satisfy the needs for pollution-safe cultivars and maintaining maize production.

To determine the effect of intravenous injection of recombinant human brain natriuretic peptide (rhBNP) on lowering the incidence of asymptomatic peri-procedural myocardial injury (PMI) in patients who underwent coronary stent implantation. In this retrospective observational study, data pooled from a tertiary hospital electronic medical records were used to quantify the troponin enzyme change after patients with coronary artery disease (CAD) were pretreated with rhBNP infusion one day prior to percutaneous coronary intervention (PCI). The primary end point was to analyze the incidence of the elevated high-sensitivity cardiac troponin I serum levels above the upper normal limit after PCI. A total of 156 CAD patients were enrolled into rhBNP group (n = 76) and control group (n = 80). The incidence of asymptomatic PMI was 33% in the rhBNP group versus 51% in the control group (P = 0.02) after PCI. At eight months, the incidences of composite endpoints were 25.3% in the control group and 13% in the rhBNP group (difference, 12.3 percentage points; 95% confidence interval (CI), 0.197 to 1.048; P = 0.061). There were 7 visits in the rhBNP group and 15 visits in the control group for recurrent angina (difference, 10 percentage points; 95% CI 0.168-1.147; P = 0.087). A time-to-event analysis of the composite clinical endpoints and the recurrent angina between the control group and rhBNP group showed that the hazard ratios were 2.566 (95% CI 1.187-5.551; P = 0.017) and 2.607 (95% CI 1.089-6.244; P = 0.032) respectively. The decreased incidence of asymptomatic PMI after PCI and the reduced episodes of recurrent angina at eight months follow-up were associated with the administration of rhBNP infusion prior to PCI.