4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

<p>Abstract</p> <p>Background</p> <p>The crude extract of the fruit bearing plant, <it>Physalis peruviana </it>(golden berry), demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown.</p> <p>Methods</p> <p>Herein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug.</p> <p>Results</p> <p>It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (<it>p </it>< 0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4βHWE in both dose- and time-dependent manners (<it>p </it>< 0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC₅₀) of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub-G₁accumulation and slight arrest at the G₂/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G₂/M arrest for H1299 cells treated with 5 μg/mL for 24 h.</p> <p>Conclusions</p> <p>In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.</p

Genome-Wide Association Study of Lung Adenocarcinoma in East Asia and Comparison With a European Population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Effect of Co replacement with Cu on structure and magnetic properties of metastable L11 CoPt thin films

垂直磁記錄的方式已然成為未來記錄媒體的趨勢，在提升記錄密度的同時現有的記錄材料面臨其超順磁的物理極限，尋找具備高磁晶異相能的替代材料成為首要的重要工作。L11-CoPt的材料因為具備高磁晶異向能(Ku = 3.7 × 107 erg/cm 3)與極低的序化溫度(200℃)，故為高潛力的磁記錄媒體候選材料，亦為本研究的主題。L11-CoPt，為一菱體晶(rhombohedral)的構造，其Co與Pt的原子層在晶體內以交替的方式沿[111]的方向堆疊，是CoPt合金相圖上不存在之介穩態，也是CoPt合金相中最晚被發現的(1997)。為了提升L11-CoPt的矯頑磁力，本實驗藉由在L11-CoPt中添加Cu取代Co的方式，在L11-CoPt中形成非磁性相的L11- CuPt，來達成此一目標。本研究使用超高真空磁控濺鍍的方式，在真空度5 × 10-8 torr下進行雙靶(Co與Pt)與三靶(Co、Pt與Cu)的共鍍，並以兩種薄膜厚度：20 nm與50 nm，故改變成份與臨場退火溫度的情況下當作實驗組與對照組討論之。 實驗室先前的研究指出，L11-CoPt較佳的晶體結構與磁性質可在製程溫度350℃的情況下得到，所以本研究以兩種不同的薄膜厚度在該溫度下去改變L11- (CoCu)Pt/MgO(111)的薄膜成份，發現在Co：30 at.%、Pt：47 at.%與Cu：23 at.%的成份下薄膜有其最佳的垂直的矯頑磁力與角型比，發現20 nm的薄膜垂直矯頑磁力由1.1 kOe提升到1.5 kOe，垂直角型比維持在0.9，水平矯頑磁力由0.5 kOe降到小於0.1 kOe。50 nm的薄膜垂直矯頑磁力由1.1 kOe提升到2.2 kOe，垂直角型比由0.35提升到0.97，水平矯頑磁力由1.4 kOe降到小於0.1 kOe。磁區研究發現Cu的取代使得平均磁域尺寸變小，穿透式電子顯微鏡結果發現明顯成份偏析現象，証明非磁性相L11-CuPt或CoCu的存在，而此結構造成磁化過程中磁域壁移動的阻礙，故增加垂直方向的矯頑磁力。而降低 L11-CoPt 水平方向的矯頑磁力，則意味著L11-(CoCu)Pt沿[111]方向排列的完美度的提升。 L11-CoPt是目前發現高Ku的材料中具有最低序化溫度者，彰顯了其於新一代垂直磁記錄媒體應用上的高度潛力，本研究証實Cu的添加可增加此一材料的垂直矯頑磁力並減少了水平矯頑磁力，更進一步提升了L11-CoPt的實用性。Due to increasing recording density toward 1 Tbit/inch2, currently-used perpendicular magnetic media encounter a physical limitation arising from superparamagnetism due to the reduction of grain size to several nanometers. Replacing the recording material with high magnetocrystalline anisotropy (Ku) materials becomes an imminent issue. L11-CoPt, a recently discovered metastable phase of CoPt having a rhombohedral lattice and consisting of alternatively stacked Co and Pt closed-packed atomic planes along [111], exhibits great potential owing to its high Ku of about 3.7 × 107 erg/cm3 and low formation temperature of 200℃. In this study, we replace some Co atoms in L11-CoPt with Cu to modify the microstructure and magnetic properties because L11 phase is thermodynamically stable in CuPt. (Co1-xCux)50Pt50 thin films with thickness of 20 nm and 50 nm were prepared using magnetron co-sputtering with background vacuum better than 10-8 torr on MgO(111) substrates with 0 ≦ x ≦ 1. Our results show a significant enhancement in out-of-plane coercivity (Hc⊥) from 0.1 to 1.9 kOe for 20-nm-thick films and 0.2 to 2.2 kOe for 50-nm-thick films with x = 23, respectively. This increase accompanies a reduction of in-plane coercivity (Hc//) from 0.5 to 0.02 kOe and from 1.4 to 0.07 kOe for films with thicknesses of 20 and 50 nm respectively. Reduced magnetic domain size from about 500 nm to 100 nm suggests that the enhanced Hc⊥ results from domain wall pinning mechanism. TEM microstructure analysis confirms a nanometer-scaled compositional segregation, forming Co-Pt rich and Cu-Pt rich regions. The nonmagnetic Cu-Pt precipitates may act as pinning sites to confine the domain size and block the domain wall motion. The results demonstrate that replacing Co by Cu effectively increases the perpendicular magnetic properties of L11-CoPt phase, which further support the possibility to use L11-CoPt in the future high-density recording medium

Synthesis and Applications of Halide Perovskite Nanocrystals in Optoelectronics

The perovskites used for optoelectronic devices have been more attractive during recent years due to their wide variety of advantages, such as their low cost, high photoluminescence quantum yield (PLQY), high carrier mobility, flexible bandgap tunability, and high light absorption ability. However, optoelectronic applications for traditional inorganic and organic materials present dilemmas due to their hardly tunable bandgap and instability. On the other hand, there are some more important benefits for perovskite nanocrystals, such as a size-dependent bandgap and the availability of anion exchange at room temperature. Therefore, perovskite NC-based applications are currently favored, offering a research direction beyond perovskite, and much research has focused on the stability issue and device performance. Thus, the synthesis and applications of perovskite NCs need to be thoroughly discussed for the future development of solar cells, light-emitting diodes, photodetectors, and laser research