TrkB Promotes Breast Cancer Metastasis via Suppression of Runx3 and Keap1 Expression

In metastatic breast cancer, the acquisition of malignant traits has been associated with the increased rate of cell growth and division, mobility, resistance to chemotherapy, and invasiveness. While screening for the key regulators of cancer metastasis, we observed that neurotrophin receptor TrkB is frequently overexpressed in breast cancer patients and breast cancer cell lines. Additionally, we demonstrate that TrkB expression and clinical breast tumor pathological phenotypes show significant correlation. Moreover, TrkB expression was significantly upregulated in basal-like, claudin-low, and metaplastic breast cancers from a published microarray database and in patients with triple-negative breast cancer, which is associated with a higher risk of invasive recurrence. Interestingly, we identified a new TrkB-regulated functional network that is important for the tumorigenicity and metastasis of breast cancer. We demonstrated that TrkB plays a key role in regulation of the tumor suppressors Runx3 and Keap1. A markedly increased expression of Runx3 and Keap1 was observed upon knockdown of TrkB, treatment with a TrkB inhibitor, and in TrkB kinase dead mutants. Additionally, the inhibition of PI3K/AKT activation significantly induced Runx3 and Keap1 expression. Furthermore, we showed that TrkB enhances metastatic potential and induces proliferation. These observations suggest that TrkB plays a key role in tumorigenicity and metastasis of breast cancer cells through suppression of Runx3 or Keap1 and that it is a promising target for future intervention strategies for preventing tumor metastasis and cancer chemoprevention.     

韧性：三角洲地区规划转型的新理念

三角洲地区经过近几十年的快速发展,在城市建设方面取得举世瞩目的成就,然而长期积累的生态问题也更加突出,暴露出的空间脆弱性问题日益显著。面对自然基底脆弱、自然灾害扰动趋势增强等因素在时空上的高度叠合,迫切需要提升三角洲地区应对未来不确定性扰动的能力。首先从景观角度分析三角洲地区自然环境的特殊性,提出韧性规划是对现有三角洲地区规划转型的论点,认为鲁棒性、适应性、学习—转化能力是三角洲地区韧性规划的核心能力,系统性、协同性、底线性、预判性是三角洲地区韧性规划的主要思维特征。其次,进一步从优化整体格局、构建流动性载体、加强对韧性技术策略的研究和应用、重视跨尺度协作与管理等方面提出了构建“格局—连通—关键点”的韧性规划框架。最后,阐述韧性规划作为三角洲地区规划转型的新理念,应用于具体案例的空间布局时须以人为本,依托自然环境,以自然流动性为规划导向;须基于预判式过程,充分构想能够应对不同情景的预案;须整合生态智慧与现代技术,明晰兼顾鲁棒性与适应性的功能分区管治体系。     

Reduced β2-GPI is associated with increased platelet aggregation and activation in patients with prolonged isolated thrombocytopenia after allo-HSCT

We aimed to measure platelet function and its relationship with β2-GPI in prolonged isolated thrombocytopenia(PT) after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Fifty-six patients with PT and 60 allo-HSCT recipients without PT(non-PT controls) were enrolled. Platelet aggregation and activation, β2-GPI and anti-β2-GPI antibody levels, vWF antigen,and vWF activity were analyzed. The effect of β2-GPI on platelet aggregation was also measured ex vivo. Results showed that ADP-induced platelet aggregation significantly increased(39%±7.5% vs. 23%±8.5%, P=0.032), and the platelet expression of both CD62 p(33.6%±11.6% vs. 8.5%±3.5%, P0.001) and PAC-1(42.4%±7.6% vs. 6.8%±2.2%, P0.001) was significantly higher in patients with PT than in those without PT. Significantly lower β2-GPI levels(164.2±12 μg m L–1 vs. 234.2±16 μg mL–1,P0.001), higher anti-β2-GPI IgG levels(1.78±0.46 U mL–1 vs. 0.94±0.39 U mL–1, P0.001), and increased vWF activity(133.06%±30.50% vs. 102.17%±25.90%, P0.001) were observed in patients with PT than in those without PT. Both ADPinduced platelet aggregation(n=116, r~2=-0.5042, P0.001) and vWF activity(n=116, r~2=-0.2872, P0.001) were negatively correlated with β2-GPI levels. In summary, our data suggested that platelet aggregation and activation were significantly higher in patients with PT than in those without PT, which might be associated with reduced β2-GPI levels. The reduced β2-GPI levels might be due to the existence of anti-β2-GPI IgG.     

The first report on the characterization of a virus isolated from Allomyrina dichotoma in the Republic of Korea

This report reveals the structure of a virus extracted from the Korean horn beetle Allomyrina dichotoma. The purified virus particle was 100% identical to Allomyrina virus lef‐8 sequence registered as KM_233709.1. The structure of this virus was confirmed to be closely related to that of the Nudiviridae family, and it was rod shaped and enveloped, and observed to be of approximately the mean length of a single viral nucleocapsid of 200–210 nm and mean diameter of 100–110 nm. These results provide an insight into the structural characteristics of the Nudiviridae family that can be used for nudiviral identification.     

Identification of a novel COL4A5 mutation in the proband initially diagnosed as IgAN from a Chinese family with X-linked Alport syndrome

Alport syndrome(AS) is a hereditary progressive nephropathy characterized by hematuria, ultrastructural lesions of the glomerular basement membrane, ocular lesions and sensorineural hearing loss. Germline mutations of COL4 A5 are associated with X-linked AS with an extreme phenotypic heterogeneity. Here, we investigated a Chinese family with Alport syndrome. The proband was a 9-year-old boy with hematuria and proteinuria. Based on the test results of renal biopsy and immunofluorescence,the proband was initially diagnosed as Ig A nephropathy and the treatment was recommended accordingly. Meanwhile, we found that the treatment outcome was poor. Therefore, for proper clinical diagnosis and appropriate treatment, targeted exome-based next-generation sequencing has been undertaken. We identified a novel hemizygous single nucleotide deletion c.1902 del A in COL4 A5 gene. Segregation analysis identified that this novel mutation is co-segregated among the affected family members but absent in unaffected family members. The clinical diagnosis of the proband was revised as AS accompanied by Ig A nephropathy,which has been rarely reported. Our findings demonstrated the significance of the application of Genetic screening, expanded the mutation spectrum of COL4 A5 associated AS patients with atypical renal phenotypes and provided a good lesson to be learned from our detour during the diagnosis.     

Fluctuations in fruit fly abundance and infestation in sweet gourd fields in relation to varied meteorological factors

The study was conducted with the aim of furthering our understanding of seasonality in the population dynamics and infestation rates of the fruit fly Bactrocera spp. in sweet gourd (Cucurbita moschata) during winter and summer in 2017. We also investigated the effects of using methyl eugenol traps on fly abundance and infestation. Two fruit fly species, namely, B. cucurbitae and B. dorsalis, were present in the sweet gourd field, and we observed fluctuations in their abundance. Compared to B. dorsalis, B. cucurbitae was significantly more abundant in both winter and summer. Infestation level was found to be the highest in fields lacking methyl eugenol traps in both seasons. Fruit fly larval population per infested fruit was higher in summer than in winter. Fly abundance was significantly and positively correlated with mean temperature and rainfall but significantly and negatively correlated with light intensity. Relative humidity was insignificantly but positively correlated with fly abundance. The temperature, light intensity, relative humidity, and rainfall individually explained 48.9, 24.1, 0.8, and 1.6% of variation in fruit fly abundance, respectively. The combined effect of the weather parameters on fruit fly abundance was 75.4% and was significant predictor of fruit fly abundance.