Prediction of novel biochemical class disease related proteins and microRNAs by machine learning approach

Ph.DDOCTOR OF PHILOSOPH

NAD tagSeq reveals that NAD+-capped RNAs are mostly produced from a large number of protein-coding genes in Arabidopsis.

The 5' end of a eukaryotic mRNA transcript generally has a 7-methylguanosine (m7G) cap that protects mRNA from degradation and mediates almost all other aspects of gene expression. Some RNAs in Escherichia coli, yeast, and mammals were recently found to contain an NAD+ cap. Here, we report the development of the method NAD tagSeq for transcriptome-wide identification and quantification of NAD+-capped RNAs (NAD-RNAs). The method uses an enzymatic reaction and then a click chemistry reaction to label NAD-RNAs with a synthetic RNA tag. The tagged RNA molecules can be enriched and directly sequenced using the Oxford Nanopore sequencing technology. NAD tagSeq can allow more accurate identification and quantification of NAD-RNAs, as well as reveal the sequences of whole NAD-RNA transcripts using single-molecule RNA sequencing. Using NAD tagSeq, we found that NAD-RNAs in Arabidopsis were produced by at least several thousand genes, most of which are protein-coding genes, with the majority of these transcripts coming from <200 genes. For some Arabidopsis genes, over 5% of their transcripts were NAD capped. Gene ontology terms overrepresented in the 2,000 genes that produced the highest numbers of NAD-RNAs are related to photosynthesis, protein synthesis, and responses to cytokinin and stresses. The NAD-RNAs in Arabidopsis generally have the same overall sequence structures as the canonical m7G-capped mRNAs, although most of them appear to have a shorter 5' untranslated region (5' UTR). The identification and quantification of NAD-RNAs and revelation of their sequence features can provide essential steps toward understanding the functions of NAD-RNAs

Waste Oil and Fat Feedstocks for Biodiesel Production

Biodiesel is an alternative for fossil diesel that is produced by transesterification of oils and fats with alcohol. For the sustainable development of this environmental-friendly fuel, feedstock availability is one of the most important issues. Various oils and fats commonly available in China are investigated to clarify their potential as feedstock of biodiesel, in terms of oil yield, characteristics and fatty acid composition. It was found that high potential in feedstock availability can be expected for oils from palm oil. Calculation is made for the amount of waste oils and fats discarded in China. 10 waste oil/fat samples were collected and subjected to the analyses such as acid value, water content, peroxide value, iodine value and fatty acid composition for evaluating as a feedstock of biodiesel. In general, used cooking oil from food service industry and/or households may consist of rapeseed oil and soybean oil according to Chinese dietary habit. China produced 13.74 Mt of waste oil in 2010, including 6.58 Mt of gutter oil, 1.55 Mt of acid oil, and 5.61 Mt of rice bran oil. If all these waste oils and fats were utilized in biodiesel production, nearly 10.84 Mt of biodiesel can be prepared. On the other hand, approximately 146.34 Mt of fossil diesel fuel was on sale annually in China. It was therefore suggested that approximately 7.4% of annual fossil diesel fuel consumption can be replaced by biodiesel derived from wastes. Key words: Waste oil and fat; Biodiesel; Acid value; Fatty acid composition; Characteristic

Propofol affects the biological behavior of ovarian cancer SKOV3 cells via ERK1/2-MMP-2/9 signaling pathway

Purpose: To investigate the effect of propofol on the biological behavior of ovarian cancer SKOV3 cells, and the mechanism of action involved. Methods: SKOV3 cells cultured in vitro were randomly divided into control group, fat emulsion group, low-dose propofol group (LDPG, 25 μmol/L), medium-dose propofol group (MDPG) (50 μmol/L) and high-dose propofol group (HDPG) (100 μmol/L). Apoptosis was determined by flow cytometry, while Transwell assay was used to measure the migration and invasion abilities of the cells. The protein levels of ERK1/2, MMP-2, MMP-9 were assayed with Western blotting. Moreover, the cells were transfected with siERK, and the regulatory effect of propofol on ERK1/2-MMP-2/9 signaling pathway was determined. Results: Apoptosis in HDPG was significantly reduced, relative to MDPG, while migration and invasion were enhanced, relative to MDPG (p < 0.05). Moreover, MMP-2, ERK1/2, and MMP-9 proteins were significantly higher in MDPG and HDPG than in control, fat emulsion and LDPGs (p < 0.05), and were upregulated in HDPGs, relative to MDPG (p < 0.05). In contrast, propofol did not up-regulate these proteins in siRNA-treated cells. Conclusion: Propofol enhances the migration, proliferation, and invasive ability SKOV3 cells, and upregulates the expressions of MMP-2, ERK1/2, and MMP-9 in these cells, via a mechanism related to the activation of ERK1/2-MMP-2/9 signaling route. These properties provide novel leads for the development of new drugs for ovarian cancer Keywords: Propofol, ERK1/2-MMP-2/9 signal route, Ovarian cancer, Biological behavio

Comprehensive MR imaging QA of 0.35 T MR-Linac using a multi-purpose large FOV phantom: A single-institution experience

PURPOSE: Magnetic resonance-guided radiotherapy (MRgRT) is desired for the treatment of diseases in the abdominothoracic region, which has a broad imaging area and continuous motion. To ensure accurate treatment delivery, an effective image quality assurance (QA) program, with a phantom that covers the field of view (FOV) similar to a human torso, is required. However, routine image QA for a large FOV is not readily available at many MRgRT centers. In this work, we present the clinical experience of the large FOV MRgRT Insight phantom for periodic daily and monthly comprehensive magnetic resonance imaging (MRI)-QA and its feasibility compared to the existing institutional routine MRI-QA procedures in 0.35 T MRgRT. METHODS: Three phantoms; ViewRay cylindrical water phantom, Fluke 76-907 uniformity and linearity phantom, and Modus QA large FOV MRgRT Insight phantom, were imaged on the 0.35 T MR-Linac. The measurements were made in MRI mode with the true fast imaging with steady-state free precession (TRUFI) sequence. The ViewRay cylindrical water phantom was imaged in a single-position setup whereas the Fluke phantom and Insight phantom were imaged in three different orientations: axial, sagittal, and coronal. Additionally, the phased array coil QA was performed using the horizontal base plate of the Insight phantom by placing the desired coil around the base section which was compared to an in-house built Polyurethane foam phantom for reference. RESULT: The Insight phantom captured image artifacts across the entire planar field of view, up to 400 mm, in a single image acquisition, which is beyond the FOV of the conventional phantoms. The geometric distortion test showed a similar distortion of 0.45 ± 0.01 and 0.41 ± 0.01 mm near the isocenter, that is, within 300 mm lengths for Fluke and Insight phantoms, respectively, but showed higher geometric distortion of 0.8 ± 0.4 mm in the peripheral region between 300 and 400 mm of the imaging slice for the Insight phantom. The Insight phantom with multiple image quality features and its accompanying software utilized the modulation transform function (MTF) to evaluate the image spatial resolution. The average MTF values were 0.35 ± 0.01, 0.35 ± 0.01, and 0.34 ± 0.03 for axial, coronal, and sagittal images, respectively. The plane alignment and spatial accuracy of the ViewRay water phantom were measured manually. The phased array coil test for both the Insight phantom and the Polyurethane foam phantoms ensured the proper functionality of each coil element. CONCLUSION: The multifunctional large FOV Insight phantom helps in tracking MR imaging quality of the system to a larger extent compared to the routine daily and monthly QA phantoms currently used in our institute. Also, the Insight phantom is found to be more feasible for routine QA with easy setup

PDTD: a web-accessible protein database for drug target identification

<p>Abstract</p> <p>Background</p> <p>Target identification is important for modern drug discovery. With the advances in the development of molecular docking, potential binding proteins may be discovered by docking a small molecule to a repository of proteins with three-dimensional (3D) structures. To complete this task, a reverse docking program and a drug target database with 3D structures are necessary. To this end, we have developed a web server tool, TarFisDock (<it>Tar</it>get <it>Fis</it>hing <it>Dock</it>ing) <url>http://www.dddc.ac.cn/tarfisdock</url>, which has been used widely by others. Recently, we have constructed a protein target database, <it>P</it>otential <it>D</it>rug <it>T</it>arget <it>D</it>atabase (PDTD), and have integrated PDTD with TarFisDock. This combination aims to assist target identification and validation.</p> <p>Description</p> <p>PDTD is a web-accessible protein database for <it>in silico </it>target identification. It currently contains >1100 protein entries with 3D structures presented in the Protein Data Bank. The data are extracted from the literatures and several online databases such as TTD, DrugBank and Thomson Pharma. The database covers diverse information of >830 known or potential drug targets, including protein and active sites structures in both PDB and mol2 formats, related diseases, biological functions as well as associated regulating (signaling) pathways. Each target is categorized by both nosology and biochemical function. PDTD supports keyword search function, such as PDB ID, target name, and disease name. Data set generated by PDTD can be viewed with the plug-in of molecular visualization tools and also can be downloaded freely. Remarkably, PDTD is specially designed for target identification. In conjunction with TarFisDock, PDTD can be used to identify binding proteins for small molecules. The results can be downloaded in the form of mol2 file with the binding pose of the probe compound and a list of potential binding targets according to their ranking scores.</p> <p>Conclusion</p> <p>PDTD serves as a comprehensive and unique repository of drug targets. Integrated with TarFisDock, PDTD is a useful resource to identify binding proteins for active compounds or existing drugs. Its potential applications include <it>in silico </it>drug target identification, virtual screening, and the discovery of the secondary effects of an old drug (i.e. new pharmacological usage) or an existing target (i.e. new pharmacological or toxic relevance), thus it may be a valuable platform for the pharmaceutical researchers. PDTD is available online at <url>http://www.dddc.ac.cn/pdtd/</url>.</p

TarFisDock: a web server for identifying drug targets with docking approach

TarFisDock is a web-based tool for automating the procedure of searching for small molecule–protein interactions over a large repertoire of protein structures. It offers PDTD (potential drug target database), a target database containing 698 protein structures covering 15 therapeutic areas and a reverse ligand–protein docking program. In contrast to conventional ligand–protein docking, reverse ligand–protein docking aims to seek potential protein targets by screening an appropriate protein database. The input file of this web server is the small molecule to be tested, in standard mol2 format; TarFisDock then searches for possible binding proteins for the given small molecule by use of a docking approach. The ligand–protein interaction energy terms of the program DOCK are adopted for ranking the proteins. To test the reliability of the TarFisDock server, we searched the PDTD for putative binding proteins for vitamin E and 4H-tamoxifen. The top 2 and 10% candidates of vitamin E binding proteins identified by TarFisDock respectively cover 30 and 50% of reported targets verified or implicated by experiments; and 30 and 50% of experimentally confirmed targets for 4H-tamoxifen appear amongst the top 2 and 5% of the TarFisDock predicted candidates, respectively. Therefore, TarFisDock may be a useful tool for target identification, mechanism study of old drugs and probes discovered from natural products. TarFisDock and PDTD are available at

Effects of heat waves on heat stroke in Shanghai, 2013—2023

BackgroundThe substantial health damage attributed to heat waves, along with their increasing intensity and frequency in the context of global warming, highlights the importance of exploring the health effects of heat waves. ObjectiveTo calculate the excess heat stroke cases during heat waves in the summer of 2013—2023 in Shanghai, analyze the association between heat waves and heat stroke, and to further explore the modifying effects of heat wave characteristics on heat stroke. MethodsUsing a retrospective ecological study design, data on heat stroke cases were collected from the heat stroke case reporting system of the Chinese Center for Disease Control and Prevention, and concurrent meteorological data from Xujiahui Meteorological Station. A heat wave was defined as at least 3 consecutive days with daily maximum temperature meeting or exceeding 35 ℃ in this study, excess heat stroke cases related to heat waves were assessed as the difference between the numbers of heat stroke cases observed on a given day and the corresponding 31 d (15 d before and after that day) moving average, and statistical analyses using generalized linear model based on time series study were performed to assess the impact of heat waves on heat stroke. ResultsOverall 25 heat waves during the study period were observed, leading to a total of estimated 792.6 extra heat stroke cases. The risk of heat stroke significantly increased during heat waves (RR=2.60, 95%CI: 2.08, 3.26), but no statistically significant differences in heat wave effects were observed among different genders, ages, or regions. In terms of the timing of heat waves, the risk of heat stroke was highest during the first heat wave (RR=3.58, 95%CI: 2.82, 4.55), which was significantly higher than that during the second heat wave (RR=2.19, 95%CI: 1.66, 2.90), and no significant effect was observed during the third or subsequent heat waves. The impact of heat waves on heat stroke persisted for more than 4 d, with the risk higher on the fourth day and beyond (RR=2.95, 95%CI: 2.28, 3.83), significantly higher than on the first day of heat wave (RR=1.74, 95%CI: 1.18, 2.56). ConclusionHeat waves had a substantial effect on heat stroke in Shanghai from 2013 to 2023, and special attention need to be paid to heat waves with early onset and long duration