Construction of a robust prognostic model for adult adrenocortical carcinoma: Results from bioinformatics and real-world data

This study aims to construct a robust prognostic model for adult adrenocortical carcinoma (ACC) by large-scale multiomics analysis and real-world data. The RPPA data, gene expression profiles and clinical information of adult ACC patients were obtained from The Cancer Proteome Atlas (TCPA), Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Integrated prognosis-related proteins (IPRPs) model was constructed. Immunohistochemistry was used to validate the prognostic value of the IPRPs model in Fudan University Shanghai Cancer Center (FUSCC) cohort. 76 ACC cases from TCGA and 22 ACC cases from GSE10927 in NCBI’s GEO database with full data for clinical information and gene expression were utilized to validate the effectiveness of the IPRPs model. Higher FASN (P = .039), FIBRONECTIN (P < .001), TFRC (P < .001), TSC1 (P < .001) expression indicated significantly worse overall survival for adult ACC patients. Risk assessment suggested significantly a strong predictive capacity of IPRPs model for poor overall survival (P < .05). IPRPs model showed a little stronger ability for predicting prognosis than Ki-67 protein in FUSCC cohort (P = .003, HR = 3.947; P = .005, HR = 3.787). In external validation of IPRPs model using gene expression data, IPRPs model showed strong ability for predicting prognosis in TCGA cohort (P = .005, HR = 3.061) and it exhibited best ability for predicting prognosis in GSE10927 cohort (P = .0898, HR = 2.318). This research constructed IPRPs model for predicting adult ACC patients’ prognosis using proteomic data, gene expression data and real-world data and this prognostic model showed stronger predictive value than other biomarkers (Ki-67, Beta-catenin, etc) in multi-cohorts.     

ARL4C might serve as a prognostic factor and a novel therapeutic target for gastric cancer: bioinformatics analyses and biological experiments

The ADP-ribosylation factor-like proteins (ARLs) have been proved to regulate the malignant phenotypes of several cancers. However, the exact role of ARLs in gastric cancer (GC) remains elusive. In this study, we systematically investigate the expression status, interactive relations, potential pathways, genetic variations and clinical values of ARLs in GC. We find that ARLs are significantly dysregulated in GC and involved in various cancer-related pathways. Subsequently, machine learning models identify ARL4C as one of the two most significant clinical indicators among ARLs for GC. Furthermore, ARL4C silencing remarkably inhibits the growth and metastasis of GC cells both in vitro and in vivo. Moreover, enrichment analysis indicates that ARL4C is highly correlated with TGF-β1 signalling. Correspondingly, TGF-β1 treatment dramatically increases ARL4C expression and ARL4C knockdown inhibits the phosphorylation level of Smads, downstream factors of TGF-β1. Meanwhile, the coexpression of ARL4C and TGF-β1 worsens the prognosis of GC patients. Our work comprehensively demonstrates the crucial role of ARLs in the carcinogenesis of GC and the specific mechanisms underlying the GC-promoting effects of TGF-β1. More importantly, we uncover the great promise of ARL4C-targeted therapy in improving the efficacy of TGF-β1 inhibitors for GC patients.     

KDM5A silencing transcriptionally suppresses the FXYD3-PI3K/AKT axis to inhibit angiogenesis in hepatocellular cancer via miR-433 up-regulation

Hepatocellular cancer (HCC) has been reported to belong to one of the highly vascularized solid tumours accompanied with angiogenesis of human umbilical vein endothelial cells (HUVECs). KDM5A, an attractive drug target, plays a critical role in diverse physiological processes. Thus, this study aims to investigate its role in angiogenesis and underlying mechanisms in HCC. ChIP-qPCR was utilized to validate enrichment of H3K4me3 and KDM5A on the promotor region of miR-433, while dual luciferase assay was carried out to confirm the targeting relationship between miR-433 and FXYD3. Scratch assay, transwell assay, Edu assay, pseudo-tube formation assay and mice with xenografted tumours were conducted to investigate the physiological function of KDM5A-miR-433-FXYD3-PI3K-AKT axis in the progression of HCC after loss- and gain-function assays. KDM5A p-p85 and p-AKT were highly expressed but miR-433 was down-regulated in HCC tissues and cell lines. Depletion of KDM5A led to reduced migrative, invasive and proliferative capacities in HCC cells, including growth and a lowered HUVEC angiogenic capacity in vitro. Furthermore, KDM5A suppressed the expression of miR-433 by demethylating H3K4me3 on its promoterregion. miR-433 negatively targeted FXYD3. Depleting miR-433 or re-expressing FXYD3 restores the reduced migrative, invasive and proliferative capacities, and lowers the HUVEC angiogenic capacity caused by silencing KDM5A. Therefore, KDM5A silencing significantly suppresses HCC tumorigenesis in vivo, accompanied with down-regulated miR-433 and up-regulated FXYD3-PI3K-AKT axis in tumour tissues. Lastly, KDM5A activates the FXYD3-PI3K-AKT axis to enhance angiogenesis in HCC by suppressing miR-433.     

Poly(ADP-ribose) polymerase inhibitor PJ34 protects against UVA-induced oxidative damage in corneal endothelium

Apoptosis - Fuchs endothelial corneal dystrophy (FECD) is one of the main causes for corneal endothelial blindness, which is characterized by the progressive decline of corneal endothelial cells....     

Synergistic inhibitory effect of berberine and icotinib on non-small cell lung cancer cells via inducing autophagic cell death and apoptosis

Apoptosis - Resistance to epidermal growth factor receptor-tyrosin kinase inhibitors (TKIs, e.g. icotinib) remains a major clinical challenge. Non-small cell lung cancer patients with wild-type...     

Plant–soil feedback effects on the performance and functional traits of Dodonaea viscosa in a dry-hot valley,China

Plant–soil feedback has been widely studied and may be particularly important in resource-poor areas. However, the roles of direct and indirect biotic effect in affecting plant growth and functional traits in this process still remained unclear. The aim of this study was to explore the roles of soil biota in affecting plant performance and traits by conducting a two-phase feedback experiment in a dry-hot valley, with a conditioning phase during which there were Dodonaea viscosa or no D. viscosa growing in the soil and a feedback phase in which the effect of the conditioned soil biota on D. viscosa performance was measured. Soil N was reduced by the presence of D. viscosa during the conditioning phase. However, D. viscosa showed a positive plant–soil feedback. In the feedback phase, the D. viscosa-conditioned soil increased the stem diameter, total biomass, and leaf dry mass content of D. viscosa, while the specific leaf area was significantly lower in D. viscosa-conditioned soil than that in bare soil. In contrast, soil sterilization had a negative effect on the growth of D. viscosa, with a significant reduction in biomass, especially in D. viscosa-conditioned soil, and soil sterilization significantly increased the root:shoot biomass ratio and litter mass. Furthermore, we showed that although the biota-driven changes in enzyme activities correlated with leaf N and especially P amount, the enzyme activity was not the main reason to promote D. viscosa growth in conditioned soil. These results suggest that the positive biotic feedback effect was superior to the negative nutrient-depleted effect on D. viscosa growth, and the direct biotic feedback effect would drive the positive effect of soil biota to a greater extent than the indirect effect. The positive biotic plant–soil feedback in dry-hot valley plays an important role in ecosystem restoration and helps in understanding plant adaptation to the local environment in this area.

     

莫古礼(Floyd Alonzo McClure)在华采集和引种竹类植物的历史及其影响

竹类植物是美国采集者在我国采集和引种的一类主要植物。在众多的竹类植物采集者中, 莫古礼(Floyd Alonzo McClure)是最具代表性的一位, 他于1919-1940年在岭南大学开展竹类植物研究, 在此期间多次采集竹类植物标本并引种竹类植物到美国。本研究通过大量文献研究、档案查阅以及实地调研, 整理了莫古礼采集竹类植物的路线和采集地, 并对竹类植物学名进行校对, 分析了莫古礼在华研究、采集和引种竹类植物的历史及其影响。经统计, 莫古礼在华期间竹类植物标本采集地涉及12个省级行政区39个地级市, 主要集中在广东、海南、香港等地; 引种地涉及9个省级行政区的25个地级市; 共采集竹类植物标本727号1,840份, 隶属20属93种(含种下单位, 下同), 分别占我国竹类植物属和种的58.8%和17.4%; 共引种竹类植物255份, 隶属于17属77种, 分别占我国竹类植物属和种的50.0%和14.4%。莫古礼在华采集和引种竹类植物极大地发展了竹类植物分类学, 所采集的竹类植物标本为后人竹类植物研究提供了极大的帮助, 所引种的竹类植物极大丰富了美国竹类植物种类, 也促进了竹类植物在美国的应用。     

中西部幼儿肠道菌群与膳食关系的比较

目的探究中部和西部地区幼儿肠道菌群的结构差异与膳食的关系,为幼儿营养健康状况监测和营养改善工作提供有效的营养干预。方法选择“贫困地区儿童营养改善项目”河南汝阳和贵州福泉,随机抽取107名汉族健康幼儿为调查对象,食物摄入采用24 h消费调查方法。应用高通量测序技术对肠道菌群进行测序和生物信息分析,研究两县幼儿肠道菌群差异。结果两县幼儿肠道菌群组成结构较为一致,但Alpha多样性分析表明,贵州福泉县幼儿肠道物种丰富度和多样性高于河南汝阳县。细菌属水平分析中,两县幼儿肠道内均以拟杆菌属、普雷沃菌、柔嫩梭菌和双歧杆菌属为主导的菌群结构,但河南汝阳县幼儿肠道双歧杆菌属和乳杆菌属丰度显著高于贵州福泉县(12.36% vs. 7.44%;0.19% vs. 0.03%)。结论中西部地区幼儿肠道菌群结构差异不大,但有益菌含量存在显著差异,这为研究肠道菌群与膳食及营养健康状况之间的关系提供了依据。     

Establishment of an efficient shoot regeneration system in vitro in Brassica rapa

In Vitro Cellular & Developmental Biology - Plant - To improve the genetic transformation system for Brassica rapa L., we established a high-efficiency shoot regeneration protocol. A double...