Evidence for Inbreeding and Genetic Differentiation among Geographic Populations of the Saprophytic Mushroom Trogia venenata from Southwestern China

During the past 40 years, more than 400 Sudden Unexplained Deaths (SUDs) have occurred in Yunnan, southwestern China. Epidemiological and toxicological analyses suggested that a newly discovered mushroom called Trogia venenata was the leading culprit for SUDs. At present, relatively little is known about the genetics and natural history of this mushroom. In this study, we analyzed the sequence variation at four DNA fragments among 232 fruiting bodies of T. venenata collected from seven locations. Our ITS sequence analyses confirmed that all the isolates belonged to the same species. The widespread presence of sequence heterozygosity within many strains at each of three protein-coding genes suggested that the fruiting bodies were diploid, dikaryotic or heterokaryotic. Within individual geographic populations, we found significant deviations of genotype frequencies from Hardy-Weinberg expectations, with the overall observed heterozygosity lower than that expected under random mating, consistent with prevalent inbreeding within local populations. The geographic populations were overall genetically differentiated. Interestingly, while a positive correlation was found between population genetic distance and geographic distance, there was little correlation between genetic distance and barium concentration difference for the geographic populations. Our results suggest frequent inbreeding, geographic structuring, and limited gene flow among geographic populations of T. venenata from southwestern China.     

酪氨酸羟化酶基因载体－pCMVTH 质粒的构建及在大鼠骨骼肌内的表达

为用转基因方法治疗巴金森氏病大鼠模型,本研究采用分子克隆技术,将合成多巴胺的关键酶－酪氨酸羟化酶（ＴＨ）的基因,克隆进入以巨细胞病毒ＣＭＶ为启动子的载体质粒内,经限制性内切酶定位分析证实该重组的ＤＮＡ质粒的可靠性。携带ＴＨ基因的ＰＣＭＶＴＨ质粒以ＬＩＰＯ－ＦＥＣＴＩＮ介导,在培养的原代骨骼肌细胞中高效表达。本研究为进一步用转基因的细胞植入脑内以治疗巴金森氏病打下一定基础。     

中国省域生态文明建设进程区域差异化

中国生态文明理论体系和示范实践为我国各地全面推进生态文明建设奠定了基础,区域差异化研究希望通过探究不同区域生态文明建设特征、潜力以及与经济发展的联系,为我国各地区全面推进生态文明实践提供的支持。构建“社会、经济、政治、文化和生态”生态文明指数五维度评价指标体系,运用2005、2010、2015和2019年我国面板数据,刻画31个省份(统计数据尚未包含我国港澳台)生态文明建设的前期、初期、快速发展期和当前各时段时空变化,提出区域的发展速度和发展加速度概念描述各省份建设能力差异,基于各省份生态文明五维度预期目标和历史发展速度探究各省份的发展潜势差异,并初步探究各省份生态文明差异与经济发展的关系。研究结果表明：(1)总体上,各省份的生态文明指数反映出生态文明建设效果显著;时间序列变化上,各省份生态文明建设整体水平和过程存在较大差异性,尽管增长速度都呈现出先快后慢的特点,各省份生态文明水平差距仍然持续拉大;在空间上,明显呈现出东部地区好于西部地区、南部地区好于北部地区的特征,通过分析31个省份所属的六个地区的生态文明等级,发现华东地区和中南地区生态文明等级领先于其他地区,且在各阶段进步最大,而...     

Identification of a novel germline BRCA2 variant in a Chinese breast cancer family

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer‐related deaths in women worldwide. In this study, a large Chinese pedigree with breast cancer including a proband and two female patients was recruited and a familial history of breast cancer was collected by questionnaire. Clinicopathological assessments and neoadjuvant therapy‐related information were obtained for the proband. Blood samples were taken, and gDNA was extracted. The BRCA1/2 and PALB2 genes were screened using next‐generation sequencing by a targeted gene panel. We have successfully identified a novel, germline heterozygous, missense mutation of the gene BRCA2: c.7007G>T, p.R2336L, which is likely to be pathogenic in the proband and her elder sister who both had breast cancer. Furthermore, the risk factors for developing breast cancer in this family are discussed. Thus, genetic counselling and long‐term follow‐up should be provided for this family of breast cancer patients as well as carriers carrying a germline variant of BRCA2: c.7007G>T (p.R2336L).     

Immunomodulatory effects of four polysaccharides purified from Erythronium sibiricum bulb on macrophages

Four neutral polysaccharides (ESBP1-1, ESBP1-2, ESBP2-1 and ESBP3-1) were successfully purified from the water extracted crude polysaccharides of Erythronium sibiricum bulbs through the combination of DEAE Sepharose CL-6B and Sephadex G-100 chromatography; their average molecular weights were 1.3?×?10⁴, 1.7?×?10⁴, 9.4?×?10⁵ and 4.1?×?10⁵ Da, respectively. Monosaccharide component analysis indicated that ESBP1-1 and ESBP1-2 were mainly composed of glucose (Glc). ESBP2-1 was composed of Glc, galactose (Gal) and arabinose, with a molar ratio of 24.3:1.1:1, whereas ESBP3-1 comprised Glc and Gal at a molar ratio of 14.8:1. In-vitro study showed that all of the four polysaccharides were able to considerably promote the proliferation and neutral red phagocytosis of RAW 264.7 macrophage cell. They could also stimulate the production of the cell lines’ secretory molecules [nitric oxide, tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)] in a dose-dependent manner. However, ESBP1-2 was not included in IL-1β. Overall, these results suggested that polysaccharides from E. sibiricum bulbs can be developed as immunomodulatory ingredients for complementary medicines or functional foods. However, further animal or clinical studies are required.

     

Evaluation of the efficacy and safety of hydroxychloroquine in comparison with chloroquine in moderate and severe patients with COVID-19

Science China Life Sciences -     

Porous Allograft Bone Scaffolds: Doping with Strontium

Strontium (Sr) can promote the process of bone formation. To improve bioactivity, porous allograft bone scaffolds (ABS) were doped with Sr and the mechanical strength and bioactivity of the scaffolds were evaluated. Sr-doped ABS were prepared using the ion exchange method. The density and distribution of Sr in bone scaffolds were investigated by inductively coupled plasma optical emission spectrometry (ICP-OES), X-ray photoelectron spectroscopy (XPS), and energy-dispersive X-ray spectroscopy (EDS). Controlled release of strontium ions was measured and mechanical strength was evaluated by a compressive strength test. The bioactivity of Sr-doped ABS was investigated by a simulated body fluid (SBF) assay, cytotoxicity testing, and an in vivo implantation experiment. The Sr molar concentration [Sr/(Sr+Ca)] in ABS surpassed 5% and Sr was distributed nearly evenly. XPS analyses suggest that Sr combined with oxygen and carbonate radicals. Released Sr ions were detected in the immersion solution at higher concentration than calcium ions until day 30. The compressive strength of the Sr-doped ABS did not change significantly. The bioactivity of Sr-doped material, as measured by the in vitro SBF immersion method, was superior to that of the Sr-free freeze-dried bone and the Sr-doped material did not show cytotoxicity compared with Sr-free culture medium. The rate of bone mineral deposition for Sr-doped ABS was faster than that of the control at 4 weeks (3.28±0.23 µm/day vs. 2.60±0.20 µm/day; p<0.05). Sr can be evenly doped into porous ABS at relevant concentrations to create highly active bone substitutes.     

Circular RNAs expression profiles in plasma exosomes from early-stage lung adenocarcinoma and the potential biomarkers

This study aimed to identify differential circular RNA (circRNA) in the plasma exosomes of patients with lung adenocarcinoma (LUAD) using high-throughput sequencing. First, exosomes were isolated using an exosome isolation kit and confirmed by Western blotting, transmission electron microscopy, and NanoSight Assay. Subsequently, plasma circRNA expression profiles were screened by high-throughput sequencing and confirmed by fluorescence quantitative real-time polymerase chain reaction (qRT-PCR) and Sanger sequencing. Finally, the circRNA-miRNA-mRNA network was performed to forecast the potential function of circRNAs. The result of high-throughput sequencing data documented that 182 differentially expressed exosomal circRNAs in all were screened, which included 105 that were upregulated and 78 that were downregulated in LUAD patients plasma compared with controls. The four upregulated circRNAs including circ_0001492, circ_0001346, circ_0000690, and circ_0001439 were identical to the sequencing data by qRT-PCR, and their latent circRNA-miRNA-mRNA interactions were exhibited. Taken together, our study firstly revealed the altered exosomal circRNA expression from plasma samples in patients with LUAD and supports the need for exploring their potential as biomarkers and the pathological effects of lung cancer.     

Proteomic-based identification of Apg-2 as a therapeutic target for chronic myeloid leukemia

The oncogenic BCR/ABL tyrosine kinase induces constitutive enhanced “spontaneous” DNA damage and unfaithful repair in Philadelphia chromosome positive leukemia cells. Here, we investigated the changes of protein profile in H₂O₂-induced DNA damage/repair in BaF3-MIGR1 and BaF3-BCR/ABL cells through a proteomic strategy consisting of two-dimensional gel electrophoresis (2-DE) coupled with MALDI-TOF mass spectrometry. In total, 41 spots were differentially expressed and 13 proteins were identified with further MS analysis. Two essential proteins, Proto-oncogene tyrosine–protein kinase ABL1 (c-ABL) and Heat shock 70 kDa protein 4 (Apg-2), were confirmed by Western blot and showed consistent changes with proteomic results. Moreover, functional analysis demonstrated that inhibition of Apg-2 not only decreased cell proliferation, but also induced cell apoptosis in BCR/ABL positive cells (BaF3-BCR/ABL, BaF3-BCR/ABL^T315I). We also proved that Apg-2 inhibition aggravated H₂O₂ induced damage in BCR/ABL positive cells, and enhanced the sensitivity of BaF3-BCR/ABL^T315I to STI571. Taken together, the findings in this work provide us with some clues to a better understanding of the molecular mechanisms underlying BCR/ABL in the DNA damage/repair processes and demonstrated that Apg-2 would be a valid target for anti-leukemia drug development.