Tripartite motif protein 25 is associated with epirubicin resistance in hepatocellular carcinoma cells via regulating PTEN/AKT pathway

Tripartite motif protein 25 (TRIM25) expression was altered in various human cancers. Herein, we found that the expression of TRIM25 was elevated in hepatocellular carcinoma (HCC) tissues and cell lines. Knockdown of TRIM25 increased the sensitivity of HCC HepG2 cells to epirubicin (EPI), as indicated by reduced cell viability, enhanced cell apoptosis, and downregulated P‐glycoprotein (P‐gp) and multiple drug‐resistance protein 1 (MRP1). Moreover, TRIM25 knockdown strengthened the effects of EPI on phosphatase and tensin homolog (PTEN) and phosphorylated (p)‐AKT. However, overexpression of TRIM25 exerted an opposite effect, weakening the sensitivity of Huh7 to EPI, and obviously increasing PTEN and reducing p‐AKT. Most important, all the changes induced by TRIM25 overexpression in Huh7 were reversed with additional treatment of LY294002 (an AKT pathway inhibitor). Notably, coimmunoprecipitation experiments confirmed the interaction between TRIM25 and PTEN. Knockdown of TRIM25 resulted in reduced ubiquitination of PTEN protein. Collectively, our data suggested that TRIM25 enhanced EPI resistance via modulating PTEN/AKT pathway, and targeting TRIM25 may enhance the sensitivity of HCC cells toward chemotherapy drugs.     

Source identification and risk assessment of heavy metals in road dust of steel industrial city (Anshan), Liaoning,Northeast China

Abstract

The purpose of the study was to acquire the source and evaluate the risk posed by heavy metals in road dust of steel industrial city (Anshan), Liaoning, Northeast China. Potential ecological risk index (RI), pollution index (PI) and geo-accumulation index (Igeo) were applied to evaluate the heavy metal pollution level, and the carcinogenic risk (RI) and hazard index (HI) were calculated to estimate the human health risk. The geographic information system maps clearly reveal the hot spots of heavy metal spatial distribution. Principle component analysis (PCA) and cluster analysis (CA) classified heavy metals into three groups. The metal Zn and Pb originate from the traffic emission, while Cd, Cr, Fe, Mn, Ni and Sb primarily come from industrial activities. These two pathways were the major source of heavy metals pollution by positive matrix factorization (PMF). The Igeo and PI values of heavy metals were decreased in the following order: Cd?>?Sb?>?Zn?>?Fe?>?Pb?>?Cu?>?Cr?>?Sn?>?Mn?>?Ni. The RI index showed the heavy metals were moderate to very high potential ecological risk. The HI values for children and adults presented a decreasing order of Cr?>?Pb?>?Ni?>?Cu?>?Cd?>?Zn. The HI also predicted a possibility of non-carcinogenic risk for children living in urban areas in comparison with adults.     

Distinct genomic traits of acral and mucosal melanomas revealed by targeted mutational profiling

The incidence of melanoma is rising globally including China. Comparing to Caucasians, the incidence of non‐cutaneous melanomas is significantly higher in Chinese. Herein, we performed genomic profiling of 89 Chinese surgically resected primary melanomas, including acral (n = 54), cutaneous (n = 22), and mucosal (n = 13), by hybrid capture‐based next‐generation sequencing. We show that mucosal melanomas tended to harbor more pathogenic mutations than other types of melanoma, though the biological significance of this finding remains uncertain. Chromosomal arm‐level alterations including 6q, 9p, and 10p/q loss were highly recurrent in all subtypes, but mucosal melanoma was significantly associated with increased genomic instability. Importantly, 7p gain significantly correlated with unfavorable clinical outcomes in non‐cutaneous melanomas, representing an intriguing prognostic biomarker of those subtypes. Furthermore, focal amplification of 4q12 (KIT, KDR, and PDGFRα) and RAD51 deletion were more abundant in mucosal melanoma, while NOTCH2 amplification was enriched in acral melanoma. Additionally, cutaneous melanomas had higher mutation load than acral melanomas, while mucosal melanomas did not differ from other subtypes in mutation burden. Together, our data revealed important features of acral and mucosal melanomas in Chinese including distinctive driver mutation pattern and increased genomic instability. These findings highlight the possibilities of combination therapies in the clinical management of melanoma.     

Mild manifestations of COVID-19 in healthcare workers

Medical staff treating Coronavirus Disease 2019 (COVID-19) patients are at high risk for exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and many have been infected, which may cause panic among medical workers, their relatives, health professionals, and government leaders. We report the epidemiologic and clinical characteristics of healthcare workers and that the majority of infected medical staff had milder symptoms/conditions with a better prognosis than admitted patients. Timely improvement to medical staff’s working conditions such as allowing adequate rest and providing sufficient medical protection is extremely important.     

ATP binding cassette transporters ABCG1 and ABCG16 affect reproductive development via auxin signalling in Arabidopsis

Angiosperm reproductive development is a complex event that includes floral organ development, male and female gametophyte formation and interaction between the male and female reproductive organs for successful fertilization. Previous studies have revealed the redundant function of ATP binding cassette subfamily G (ABCG) transporters ABCG1 and ABCG16 in pollen development, but whether they are involved in other reproductive processes is unknown. Here we show that ABCG1 and ABCG16 were not only expressed in anthers and stamen filaments but also enriched in pistil tissues, including the stigma, style, transmitting tract and ovule. We further demonstrated that pistil‐expressed ABCG1 and ABCG16 promoted rapid pollen tube growth through their effects on auxin distribution and auxin flow in the pistil. Moreover, disrupted auxin homeostasis in stamen filaments was associated with defective filament elongation. Our work reveals the key functions of ABCG1 and ABCG16 in reproductive development and provides clues for identifying ABCG1 and ABCG16 substrates in Arabidopsis.     

中国兽类一新纪录白尾高山䶄及西藏、湖北和四川兽类各一省级新纪录

在最近几年开展的小型兽类调查和研究中,通过形态学和分子鉴定的方法,证实在新疆发现的白尾高山䶄（Alticola albicauda True, 1894）是中国新纪录。该种尾全白色,末端有白色毛束;身体背部淡红褐色,腹部纯白。在基于Cyt b构建的系统树中和GenBank中的白尾高山䶄聚在一起,并与银色高山䶄（Alticola argentatus Severtzov,1879）形成姊妹群,两者间遗传距离为5%;在西藏发现小毛足鼠（Phodopus roborovskii Satunin,1902）,其特征和我国其他区域分布的小毛足鼠一致,两者之间Cyt b基因遗传距离（K2P）为0.6%,是西藏新纪录;在四川发现丽江绒鼠（Eothenomys fidelis Hinton, 1923）,牙齿特征,尾长和体长之比和地模标本基本一致,但个体较小,在基于Cyt b构建的系统发育树显示,四川标本为独立分支,表明形态和分子上均存在一定的分化,但和地模标本的遗传 距离只有1.1%,应为同一种,为四川省新纪录;在湖北发现循化鼠兔（Ochotona xunhuaensis Sou and Feng, 1984）,有异耳屏,头骨较扁平,符合循化鼠兔的鉴定特征,与模式产地的循化鼠兔Cyt b基因的遗传距离为1.9%,为湖北新纪录。     

剑叶龙血树内生放线菌活性菌株的筛选和鉴定

为筛选具有抗菌抗肿瘤活性的药用植物内生菌资源,该文对300余株分离自中国云南西双版纳及越南地区剑叶龙血树的内生放线菌采用琼脂块扩散法进行抗病原细菌活性筛选、平板对峙法进行抗真菌活性筛选、SRB法测定菌株的细胞毒活性及PCR扩增方法筛选非核糖体肽合成酶NRPS基因及聚酮合酶PKS-I、PKS-Ⅱ基因;对得到的优势菌株经8种培养基进行发酵,采用10种病原细菌、3种病原真菌及2种人肿瘤细胞株测试其发酵粗提物的抗菌及抗肿瘤活性以确定最佳发酵培养基;用16S rRNA基因测序方法初步鉴定5株优势菌株的分类地位。结果表明:初筛得到5株抗菌活性、体外细胞毒活性及NRPS、PKS相关基因表达阳性的菌株S01-S05,其中4株(S01-S04)属于链霉菌属、1株(S05)属于类诺卡氏菌属;菌株经不同培养基发酵后产物的抗菌和抗肿瘤活性不同,其中Streptomyces sp. S04在7种培养基中的发酵提取物对8种测试病原菌均有较强抑制作用,且该菌株用Medium C的发酵提取物对人肝癌Hep G2细胞株抑制率达到100%,为剑叶龙血树内生菌活性成分挖掘及新型抗菌药物筛选奠定了基础。     

小脑症蛋白ASPM和钙调蛋白的复合物的纯化和表征

常染色体隐性小脑症(Autosomal recessive primary microcephaly, MCPH)是一种与大脑缩小和智力缺陷有关的神经发育障碍。 ASPM(abnormal spindle-like microcephaly-associated)是最常见的MCPH的致病基因,但其潜在机制尚不清楚。我们发现钙调蛋白(calmodulin, CaM)通过与ASPM的IQ区域相互作用而对ASPM的功能有重要的调控作用。我们纯化了ASPM IQ区域和CaM的复合物,并通过分子排阻色谱结合多角度静态光散射（SEC-MALS）和圆二光谱（CD）实验发现了ASPM和apo_CaM的结合比例为1：8。有趣的是,在Ca2+存在时,ASPM的IQ区域与Ca2+_CaM的结合比例变为了1：7。此外,通过比较不同条件下（Ca2+存在与否）的CD光谱,ASPM-CaM复合物显示出Ca2+依赖性的热稳定性变化。综上所述,我们的研究揭示了Ca2+诱导的ASPM-CaM相互作用的调节机制。