Glycation End Products (RAGE) and Promotes Proliferation in ECV304 Cells via the c-Jun N-Terminal Kinases (JNK) Pathway Following Stimulation by Advanced Glycation End-Products In Vitro

Abstract: Hyperoside is a major active constituent in many medicinal plants which are traditionally used in Chinese medicines for their neuroprotective, anti-inflammatory and antioxidative effects. The molecular mechanisms underlying these effects are unknown. In this study, quiescent ECV304 cells were treated in vitro with advanced glycation end products (AGEs) in the presence or absence of hyperoside. The results demonstrated that AGEs induced c-Jun N-terminal kinases (JNK) activation and apoptosis in ECV304 cells. Hyperoside inhibited these effects and promoted ECV304 cell proliferation. Furthermore, hyperoside significantly inhibited RAGE expression in AGE-stimulated ECV304 cells, whereas knockdown of RAGE inhibited AGE-induced JNK activation. These results suggested that AGEs may promote JNK activation, leading to viability inhibition of ECV304 cells via the RAGE signaling pathway. These effects could be inhibited by hyperoside. Our findings suggest a novel role for hyperoside in the treatment and prevention of diabetes

3D Face Arbitrary Style Transfer

Style transfer of 3D faces has gained more and more attention. However, previous methods mainly use images of artistic faces for style transfer while ignoring arbitrary style images such as abstract paintings. To solve this problem, we propose a novel method, namely Face-guided Dual Style Transfer (FDST). To begin with, FDST employs a 3D decoupling module to separate facial geometry and texture. Then we propose a style fusion strategy for facial geometry. Subsequently, we design an optimization-based DDSG mechanism for textures that can guide the style transfer by two style images. Besides the normal style image input, DDSG can utilize the original face input as another style input as the face prior. By this means, high-quality face arbitrary style transfer results can be obtained. Furthermore, FDST can be applied in many downstream tasks, including region-controllable style transfer, high-fidelity face texture reconstruction, large-pose face reconstruction, and artistic face reconstruction. Comprehensive quantitative and qualitative results show that our method can achieve comparable performance. All source codes and pre-trained weights will be released to the public

Effect of dietary Ginkgo biloba leaf on the growth performance and nonspecific immunity of red swamp crayfish Procambarus clarkii

This trial investigated the effect of dietary Ginkgo biloba leaf (GBL) on the growth performance and nonspecific immunity of red swamp crayfish Procambarus clarkii. 180 Crayfishes were randomly divided into three groups. One group was fed with basic diet, whereas the other two groups were fed with diets containing 1% and 3% GBL. After 32 days of feeding, GBL addition tended to increase the body weight gain rate compared with control. In 3% GBL group, the bodyweight gain rate of male crayfish was higher than that of female crayfish. While female crayfish were advantageous in terms of meat yield. Liver-related indexes were influenced by GBL addition and 3% GBL could reduce glutamic pyruvic transaminase and glutamic oxaloacetic transaminase as well as total cholesterol in male crayfish, showing its function in liver protection. Moreover, GBL addition effects on liver protection was better in male crayfish than female crayfish

Comprehensive FGFR3 alteration-related transcriptomic characterization is involved in immune infiltration and correlated with prognosis and immunotherapy response of bladder cancer

BackgroundBladder cancer (BC) threatens the health of human beings worldwide because of its high recurrence rate and mortality. As an actionable biomarker, fibroblast growth factor receptor 3 (FGFR3) alterations have been revealed as a vital biomarker and associated with favorable outcomes in BC. However, the comprehensive relationship between the FGFR3 alteration associated gene expression profile and the prognosis of BC remains ambiguous.Materials and MethodsGenomic alteration profile, gene expression data, and related clinical information of BC patients were downloaded from The Cancer Genomics database (TCGA), as a training cohort. Subsequently, the Weighted Gene Co-expression Network Analysis (WGCNA) was conducted to identify the hub modules correlated with FGFR3 alteration. The univariate, multivariate, and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to obtain an FGFR3 alteration-related gene (FARG) prognostic signature and FARG-based nomogram. The receiver operating characteristic (ROC) curve analysis was used for evaluation of the ability of prognosis prediction. The FARG signature was validated in four independent datasets, namely, GSE13507, GSE31684, GSE32548, and GSE48075, from Gene Expression Omnibus (GEO). Then, clinical feature association analysis, functional enrichment, genomic alteration enrichment, and tumor environment analysis were conducted to reveal differential clinical and molecular characterizations in different risk groups. Lastly, the treatment response was evaluated in the immunotherapy-related dataset of the IMvigor210 cohort and the frontline chemotherapy dataset of GSE48276, and the chemo-drug sensitivity was estimated via Genomics of Drug Sensitivity in Cancer (GDSC).ResultsThere were a total of eleven genes (CERCAM, TPST1, OSBPL10, EMP1, CYTH3, NCRNA00201, PCDH10, GAP43, COLQ, DGKB, and SETBP1) identified in the FARG signature, which divided BC patients from the TCGA cohort into high- and low-risk groups. The Kaplan–Meier curve analysis demonstrated that BC patients in the low-risk group have superior overall survival (OS) than those in the high-risk group (median OS: 27.06 months vs. 104.65 months, p < 0.0001). Moreover, the FARG signature not only showed a good performance in prognosis prediction, but also could distinguish patients with different neoplasm disease stages, notably whether patients presented with muscle invasive phenotype. Compared to clinicopathological features, the FARG signature was found to be the only independent prognostic factor, and subsequently, a FARG-based prognostic nomogram was constructed with better ability of prognosis prediction, indicated by area under ROC curve (AUC) values for 1-, 3-, and 5-year OS of 0.69, 0.71, and 0.79, respectively. Underlying the FARG signature, multiple kinds of metabolism- and immune-related signaling pathways were enriched. Genomic alteration enrichment further identified that FGFR3 alterations, especially c.746C>G (p.Ser249Cys), were more prevalent in the low-risk group. Additionally, FARG score was positively correlated with ESTIMATE and TIDE scores, and the low-risk group had abundant enrichment of plasma B cells, CD8+ T cells, CD4+ naive T cells, and helper follicular T cells, implying that patients in the low-risk group were likely to make significant responses to immunotherapy, which was further supported by the analysis in the IMvigor210 cohort as there was a significantly higher response rate among patients with lower FARG scores. The analysis of the GDSC database finally demonstrated that low-risk samples were more sensitive to methotrexate and tipifarnib, whereas those in the high-risk group had higher sensitivities in cisplatin, docetaxel, and paclitaxel, instead.ConclusionThe novel established FARG signature based on a comprehensive FGFR3 alteration-related transcriptomic profile performed well in prognosis prediction and was also correlated with immunotherapy and chemotherapy treatment responses, which had great potential in future clinical applications

Grafted c-kit+/SSEA1− eye-wall progenitor cells delay retinal degeneration in mice by regulating neural plasticity and forming new graft-to-host synapses

Background: Despite diverse pathogenesis, the common pathological change observed in age-related macular degeneration and in most hereditary retinal degeneration (RD) diseases is photoreceptor loss. Photoreceptor replacement by cell transplantation may be a feasible treatment for RD. The major obstacles to clinical translation of stem cell-based cell therapy in RD remain the difficulty of obtaining sufficient quantities of appropriate and safe donor cells and the poor integration of grafted stem cell-derived photoreceptors into the remaining retinal circuitry. Methods: Eye-wall c-kit+/stage-specific embryonic antigen 1 (SSEA1)− cells were isolated via fluorescence-activated cell sorting, and their self-renewal and differentiation potential were detected by immunochemistry and flow cytometry in vitro. After labeling with quantum nanocrystal dots and transplantation into the subretinal space of rd1 RD mice, differentiation and synapse formation by daughter cells of the eye-wall c-kit+/SSEA1− cells were evaluated by immunochemistry and western blotting. Morphological changes of the inner retina of rd1 mice after cell transplantation were demonstrated by immunochemistry. Retinal function of rd1 mice that received cell grafts was tested via flash electroretinograms and the light/dark transition test. Results: Eye-wall c-kit+/SSEA1− cells were self-renewing and clonogenic, and they retained their proliferative potential through more than 20 passages. Additionally, eye-wall c-kit+/SSEA1− cells were capable of differentiating into multiple retinal cell types including photoreceptors, bipolar cells, horizontal cells, amacrine cells, Müller cells, and retinal pigment epithelium cells and of transdifferentiating into smooth muscle cells and endothelial cells in vitro. The levels of synaptophysin and postsynaptic density-95 in the retinas of eye-wall c-kit+/SSEA1− cell-transplanted rd1 mice were significantly increased at 4 weeks post transplantation. The c-kit+/SSEA1− cells were capable of differentiating into functional photoreceptors that formed new synaptic connections with recipient retinas in rd1 mice. Transplantation also partially corrected the abnormalities of inner retina of rd1 mice. At 4 and 8 weeks post transplantation, the rd1 mice that received c-kit+/SSEA1− cells showed significant increases in a-wave and b-wave amplitude and the percentage of time spent in the dark area. Conclusions: Grafted c-kit+/SSEA1− cells restored the retinal function of rd1 mice via regulating neural plasticity and forming new graft-to-host synapses. Electronic supplementary material The online version of this article (doi:10.1186/s13287-016-0451-8) contains supplementary material, which is available to authorized users

Genome-wide association study uncovers new genetic loci and candidate genes underlying seed chilling-germination in maize

As one of the major crops, maize (Zea mays L.) is mainly distributed in tropical and temperate regions. However, with the changes of the environments, chilling stress has become a significantly abiotic stress affecting seed germination and thus the reproductive and biomass accumulation of maize. Herein, we investigated five seed germination-related phenotypes among 300 inbred lines under low-temperature condition (10 °C). By combining 43,943 single nucleotide polymorphisms (SNPs), a total of 15 significant (P < 2.03 ×  10-6) SNPs were identified to correlate with seed germination under cold stress based on the FarmCPU model in GWAS, among which three loci were repeatedly associated with multiple traits. Ten gene models were closely linked to these three variations, among which Zm00001d010454, Zm00001d010458, Zm00001d010459, and Zm00001d050021 were further verified by candidate gene association study and expression pattern analysis. Importantly, these candidate genes were previously reported to involve plant tolerance to chilling stress and other abiotic stress. Our findings contribute to the understanding of the genetic and molecular mechanisms underlying chilling germination in maize

The genome of broomcorn millet

Broomcorn millet (Panicum miliaceum L.) is the most water-efficient cereal and one of the earliest domesticated plants. Here we report its high-quality, chromosome-scale genome assembly using a combination of short-read sequencing, single-molecule real-time sequencing, Hi-C, and a high-density genetic map. Phylogenetic analyses reveal two sets of homologous chromosomes that may have merged ~5.6 million years ago, both of which exhibit strong synteny with other grass species. Broomcorn millet contains 55,930 proteincoding genes and 339 microRNA genes. We find Paniceae-specific expansion in several subfamilies of the BTB (broad complex/tramtrack/bric-a-brac) subunit of ubiquitin E3 ligases, suggesting enhanced regulation of protein dynamics may have contributed to the evolution of broomcorn millet. In addition, we identify the coexistence of all three C4 subtypes of carbon fixation candidate genes. The genome sequence is a valuable resource for breeders and will provide the foundation for studying the exceptional stress tolerance as well as C4 biology

Mid-Infrared Sensor Based on Dirac Semimetal Coupling Structure

A multilayer structure based on Dirac semimetals is investigated, where long-range surface plasmon resonance (LRSPR) of a dielectric layer/Dirac semimetal/dielectric layer are coupled with surface plasmon polaritons (SPPs) on graphene to substantially improve the Goos&ndash;H&auml;nchen (GH) shift of Dirac semimetals in the mid-infrared band. This has important implications for the study of mid-infrared sensors. We studied the reflection coefficient and phase of this multilayer structure using a generalized transport matrix. We established that subtle changes in the refractive index of the sensing medium and the Fermi energy of the Dirac semimetal significantly affected the GH shift. Our numerical simulations show that the sensitivity of the coupling structure is more than 2.7&times;107&nbsp;&lambda;/RIU, which can be used as a potential new sensor application. The novelty of this work is the design of a tunable, highly sensitive, and simple structured mid-infrared sensor that takes advantage of the excellent properties of Dirac semimetals