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.     

Nanoparticle formulation of mycophenolate mofetil achieves enhanced efficacy against hepatocellular carcinoma by targeting tumour-associated fibroblast

Hepatocellular carcinoma (HCC) is one of the most aggressive tumours with marked fibrosis. Mycophenolate mofetil (MMF) was well-established to have antitumour and anti-fibrotic properties. To overcome the poor bioavailability of MMF, this study constructed two MMF nanosystems, MMF-LA@DSPE-PEG and MMF-LA@PEG-PLA, by covalently conjugating linoleic acid (LA) to MMF and then loading the conjugate into polymer materials, PEG_5k-PLA_8k and DSPE- PEG_2k, respectively. Hepatocellular carcinoma cell lines and C57BL/6 xenograft model were used to examine the anti-HCC efficacy of nanoparticles (NPs), whereas NIH-3T3 fibroblasts and highly-fibrotic HCC models were used to explore the anti-fibrotic efficacy. Administration of NPs dramatically inhibited the proliferation of HCC cells and fibroblasts in vitro. Animal experiments revealed that MMF-LA@DSPE-PEG achieved significantly higher anti-HCC efficacy than free MMF and MMF-LA@PEG-PLA both in C57BL/6 HCC model and highly-fibrotic HCC models. Immunohistochemistry further confirmed that MMF-LA@DSPE-PEG dramatically reduced cancer-associated fibroblast (CAF) density in tumours, as the expression levels of alpha-smooth muscle actin (α-SMA), fibroblast activation protein (FAP) and collagen IV were significantly downregulated. In addition, we found the presence of CAF strongly correlated with increased HCC recurrence risk after liver transplantation. MMF-LA@DSPE-PEG might act as a rational therapeutic strategy in treating HCC and preventing post-transplant HCC recurrence.     

Superior japonica rice variety YJ144 with improved rice blast resistance,yield, and quality achieved using molecular design and multiple breeding strategies

Molecular Breeding - The stem color of young mung bean is a very useful tool in germplasm identification. Flowering time and plant height (PH) are known to be strongly correlated with crop adaption...     

格氏栲天然林林窗植物物种多样性与系统发育多样性

林窗环境异质性导致群落物种多样性与系统发育多样性(phylogenetic diversity, PD)存在差异, 研究不同大小的林窗中群落的物种多样性与系统发育多样性有助于揭示林下生物多样性的形成及维持机制。本文以格氏栲(Castanopsis kawakamii)天然林为研究对象, 通过Pearson相关性分析与广义线性模型探讨了林窗内物种多样性与系统发育多样性间的相互关系及其环境影响因素。结果表明: (1)大林窗(面积 > 200 m²)植物种类及多度均高于中林窗(50 m² ≤ 面积 < 100 m²)、小林窗(30 m² ≤ 面积 < 50 m²)和非林窗(面积 = 100 m²)。大林窗群落系统发育结构趋于发散, 中、小林窗和非林窗群落系统发育结构受到生境过滤和竞争排斥综合作用。(2)群落系统发育多样性指数与物种丰富度(species richness, SR)、Margalef丰富度指数和Shannon-Wiener指数均呈显著正相关, 这与林窗内稀有种种类组成多于优势种有关。(3)林窗面积对物种多样性存在显著正效应; 土壤全氮含量对系统发育多样性和系统发育结构存在显著正效应。林窗形成提高了格氏栲天然林群落物种多样性和系统发育多样性, 林窗面积与土壤全氮共同驱动了格氏栲天然林林窗物种多样性和系统发育多样性的变化。     

传粉昆虫下降背景下的授粉生态弹性: 内涵、机制和展望

全球传粉昆虫多样性正在下降, 如何保障农林生态系统传粉功能是当前研究的热点。理论上说, 传粉功能不仅与生态系统的传粉昆虫多样性相关, 还与生态系统的调节能力有关。近年来, 学者们逐渐认识到授粉生态弹性对传粉功能的影响。本文在回顾已有研究的基础之上, 总结传粉昆虫授粉生态弹性的内涵, 厘清授粉生态弹性与工程弹性、稳定性和抗性的异同。目前, 学者对授粉生态弹性形成机制开展广泛探讨, 提出功能冗余假说、密度补偿假说、响应多样性假说、连接周转假说和跨尺度弹性假说, 但这5个假说间的关系仍不清楚, 存在一词多义、词意混淆等现象。我们依次阐述功能冗余假说、密度补偿假说、响应多样性假说、连接周转假说和跨尺度弹性假说, 介绍不同假说中授粉生态弹性形成过程、研究热点和发展动态。通过解析授粉生态弹性的形成机制可知, 5个假说在内涵上存在紧密联系, 它们从不同空间尺度和研究对象下解释传粉昆虫授粉生态弹性的形成机制。未来授粉生态弹性研究将整合传粉昆虫群落动态和传粉功能动态的量化方法, 通过实验验证5个假说的合理性, 并揭示不同假说间的联系, 由此阐明授粉生态弹性的发生条件、形成阈值和动态规律。随着研究的深入, 授粉生态弹性理论有望用于指导农林生态系统传粉功能的经营管理。     

中国公众的国际野生动物保护意愿调查: 以非洲象为例

我国高度重视野生动物保护事业, 认真履行野生动物保护国际义务, 积极鼓励公众参与, 以扩大野生动物保护事业的公众基础。已有文献多关注了公众的国内野生动物保护意愿, 鲜有文献关注公众对国际野生动物的保护意愿, 难以为促进公众参与国际野生动物保护事业提供决策参考。本研究以全球旗舰物种非洲象(Loxodonta africana)为例, 结合非洲象保护的相关研究与实践, 构建拓展的计划行为理论框架, 通过线下和线上调研获取数据, 运用结构方程模型, 从态度、规范、知觉行为控制、过去经验及个体特征五个方面, 分析了我国公众的非洲象保护意愿及影响因素。结果表明: (1) 68.5%的公众具有非洲象保护愿意; (2)公众规范(系数为0.422)、过去经验(系数为0.253)、知觉行为控制(系数为0.160)、保护态度(系数为0.156)对保护意愿存在显著的正向影响; 男性公众(系数为-0.054)的保护意愿低于女性公众; 居住在西部地区的公众(系数为0.066)保护意愿更高; (3)模型整体通过了拟合检验, 表明研究结果具有稳健性。本研究的政策建议如下: (1)明确政策导向作用, 提升公众的道德义务感和社会责任感; (2)加强宣传教育, 丰富公众知识经验, 培育公众积极的保护态度; (3)拓宽保护参与渠道, 提高公众知觉行为控制; (4)制定合理方案, 提升保护宣教等实践活动成效。     

MicroRNA-520c-3p suppresses vascular endothelium dysfunction by targeting RELA and regulating the AKT and NF-κB signaling pathways

Journal of Physiology and Biochemistry - Endothelial injury, which can cause endothelial inflammation and dysfunction, is an important mechanism for the development of atherosclerotic plaque. This...     

NEK2 plays an active role in Tumorigenesis and Tumor Microenvironment in Non-Small Cell Lung Cancer

Abnormal expression and dysfunction of Never-in-mitosis-A-related kinase 2 (NEK2) result in tumorigenesis. High levels of NEK2 are related to malignant progression, drug resistance, and poor prognosis. However, the relationship between NEK2 levels and the occurrence of non-small cell lung cancer (NSCLC) remains unknown. This study aimed to explore the impacts of NEK2 on the oncogenesis of NSCLC and the tumor microenvironment. Downregulation of NEK2 inhibited A549 and H1299 cell proliferation, migration, and invasion, blocking cell cycle at the G0/G1 phase. Loss of NEK2 inhibited the release of IL-10 from tumor cells, M2-like polarization of macrophages, angiogenesis, and vascular endothelial cell migration. Furthermore, NEK2 deficiency inhibited tumor growth in vivo. Taken together, NEK2 knockdown inhibited the occurrence and development of NSCLC, M2 polarization of macrophages, and angiogenesis. The abnormal expression of NEK2 might not only indicate tumor progression and patient prognosis but also serve as a potential molecular therapeutic target with great development prospects.     

Antigenic and immunogenic properties of truncated VP28 protein of white spot syndrome virus in Procambarus clarkii

Previous studies identify VP28 envelope protein of white spot syndrome virus (WSSV) as its main antigenic protein. Although implicated in viral infectivity, its functional role remains unclear. In the current study, we described the production of polyclonal antibodies to recombinant truncated VP28 proteins including deleted N-terminal (rVP28ΔN), C-terminal (rVP28ΔC) and middle (rVP28ΔM). In antigenicity assays, antibodies developed from VP28 truncations lacking the N-terminal or middle regions showed significantly lowered neutralization of WSSV in crayfish, Procambarus clarkii. Further immunogenicity analysis showed reduced relative percent survival (RPS) in crayfish vaccinating with these truncations before challenge with WSSV. These results indicated that N-terminal (residues 1–27) and middle region (residues 35–95) were essential to maintain the neutralizing linear epitopes of VP28 and responsible in eliciting immune response. Thus, it is most likely that these regions are exposed on VP28, and will be useful for rational design of effective vaccines targeting VP28 of WSSV.