Maternal High-Fat Diet Promotes the Development and Progression of Prostate Cancer in Transgenic Adenocarcinoma Mouse Prostate Offspring

Background/Aims: We aim to investigate the impact of maternal high fat diet (HFD) on the development and progression of prostate cancer (PCa) in transgenic adenocarcinoma mouse prostate (TRAMP) offspring. Methods: The TRAMP model was used, and divided into maternal HFD group and normal diet (ND) group in the present study. Each group contained 36 TRAMP mice. Serum levels of leptin, adiponectin, interleukin (IL) -1α, IL-1β, IL-6, tumor necrosis factor-α and monocyte chemotactic protein-1 were measured by the 20th, 24th and 28th week old through ProcartaPlex Multiplex Immunoassay. Body fat ratio was measured by MiniQMR. Tumor formation rate was measured through hematoxylin and eosin (H&E) staining, and mortality rate was measured meantime. Western blot was applied to determine the levels of Protein Kinase B (Akt) and Phosphatase and tensin homolog (PTEN). Results: The mortality rate of maternal HFD group was significantly higher than that of ND group (P = 0.046). The tumor formation rate was significantly higher in maternal HFD group than in ND group only in 20th week subgroup (P = 0.040). A significant increase of leptin was seen in maternal HFD 20th and 24th week subgroups (P = 0.001 and < 0.001, respectively) and a decrease of adiponectin was seen in maternal HFD 20th and 28th week subgroups (P =0.006 and < 0.001, respectively). Besides, an activated phos-Akt (P-Akt) and deactivated PTEN were observed in maternal HFD group. Conclusions: Maternal HFD could increase the standard serum leptin level, inhibit the expression of PTEN protein, promote P-Akt protein expression, activate the PI3K/Akt pathway, and ultimately promote the development and progression of PCa in TRAMP offspring

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

Combination of rapamycin, CI-1040, and 17-AAG inhibits metastatic capacity of prostate cancer via Slug inhibition.

Though prostate cancer (PCa) has slow progression, the hormone refractory (HRCP) and metastatic entities are substantially lethal and lack effective treatments. Transcription factor Slug is critical in regulating metastases of various tumors including PCa. Here we studied targeted therapy against Slug using combination of 3 drugs targeting 3 pathways respectively converging via Slug and further regulating PCa metastasis. Using in vitro assays we confirmed that Slug up-regulation incurred inhibition of E-cadherin that was anti-metastatic, and inhibited Bim-regulated cell apoptosis in PCa. Upstream PTEN/Akt, mTOR, Erk, and AR/Hsp90 pathways were responsible for Slug up-regulation and each of these could be targeted by rapamycin, CI-1040, and 17-AAG respectively. In 4 PCa cell lines with different traits in terms of PTEN loss and androgen sensitivity we tested the efficacy of mono- and combined therapy with the drugs. We found that metastatic capacity of the cells was maximally inhibited only when all 3 drugs were combined, due to the crosstalk between the pathways. 17-AAG decreases Slug expression via blockade of HSP90-dependent AR stability. Combination of rapamycin and CI-1040 diminishes invasiveness more potently in PCa cells that are androgen insensitive and with PTEN loss. Slug inhibited Bim-mediated apoptosis that could be rescued by mTOR/Erk/HSP90 inhibitors. Using mouse models for circulating PCa DNA quantification, we found that combination of mTOR/Erk/HSP90 inhibitors reduced circulating PCa cells in vivo significantly more potently than combination of 2 or monotherapy. Conclusively, combination of mTOR/Erk/Hsp90 inhibits metastatic capacity of prostate cancer via Slug inhibition

Investigation on the Optical Properties of Micro-LEDs Based on InGaN Quantum Dots Grown by Molecular Beam Epitaxy

InGaN quantum dots (QDs) have attracted significant attention as a promising material for high-efficiency micro-LEDs. In this study, plasma-assisted molecular beam epitaxy (PA-MBE) was used to grow self-assembled InGaN QDs for the fabrication of green micro-LEDs. The InGaN QDs exhibited a high density of over 3.0 × 1010 cm−2, along with good dispersion and uniform size distribution. Micro-LEDs based on QDs with side lengths of the square mesa of 4, 8, 10, and 20 μm were prepared. Attributed to the shielding effect of QDs on the polarized field, luminescence tests indicated that InGaN QDs micro-LEDs exhibited excellent wavelength stability with increasing injection current density. The micro-LEDs with a side length of 8 μm showed a shift of 16.9 nm in the peak of emission wavelength as the injection current increased from 1 A/cm2 to 1000 A/cm2. Furthermore, InGaN QDs micro-LEDs maintained good performance stability with decreasing platform size at low current density. The EQE peak of the 8 μm micro-LEDs is 0.42%, which is 91% of the EQE peak of the 20 µm devices. This phenomenon can be attributed to the confinement effect of QDs on carriers, which is significant for the development of full-color micro-LED displays

Isochron Al-26/Be-10 burial dating of Xihoudu: Evidence for the earliest human settlement in northern China

The mainstream school of human evolution posits that Homo erectus was the earliest species to leave Africa at similar to 1.85 million years (Ma) ago. Recent discoveries from the Shangchen loess-palaeosol sequence near the Lantian hominid site in northern China, however, show lithic artifacts up to 2.12 Ma, pre-dating the fossil record of H. erectus. Here we apply the recently established isochron Al-26/Be-10 burial dating, whose reliability has been verified by intercomparison with Ar-40/Ar-39 dating, to two locations at the Palaeolithic site of Xihoudu similar to 100 km east of Shangchen. The results show that the stone tools found within river gravels there are 2.43 +/- 0.06 Ma (1 sigma) old, making them the earliest radioisotopically dated evidence for human occupation in Eurasia. The new date is supported by relative dating of the associated fauna, by consistent simple burial ages of quartz sand from deep cores, and by agreement between the two isochrons. Although the validity of the Xihoudu artifacts has been previously debated because of marked fluvial abrasion, there is clear evidence of intentional flaking. In particular, in addition to two cores with small amounts of cortex, a number of flakes lack original rock cortex, which indicate multiple and sustained removals that do not occur naturally. The great antiquity of the Xihoudu artifacts renders firm support to an earlier "Out of Africa I" that approaches the emergence of the genus Homo and the Oldowan industry. (C) 2020 Elsevier Masson SAS. All rights reserved

Optical conductivity of an electron gas driven by a pulsed terahertz radiation field

We present a theoretical study to examine the optical conductivity of an electron gas in the presence of a pulsed terahertz (THz) radiation field. Applying a very simple Drude like approach, we calculate the transit current for an electron gas driven by a pulsed light field. By taking three types of the pulsed radiation fields with different analytical forms, we prove analytically or numerically that although the corresponding transit current depends on the shape of the radiation field in time-domain, the optical conductivity in frequency-domain is independent upon the profile of the pulsed light field when optical conductivity in frequency-domain is obtained by Fourier transformation of both the pulsed radiation field and the transit current. Thus, the optical conductivity in frequency-domain can be described by the well known Drude formula even in the presence of the pulsed THz field. This finding can be applied for experimental measurement of the real and imaginary parts of optical conductivity in electronic and optoelectronic materials by using, e.g., the THz time-domain spectroscopy (TDS)