A TOPIC SENSITIVE SIMRANK (TSSR) MODEL FOR EXPERTS FINDING ON ONLINE RESEARCH SOCIAL PLATFORMS

As an efficient online academic information repository and information channel with crowds’ contribution, online research social platforms have become an efficient tool for various kinds of research & management applications. Social network platforms have also become a major source to seek for field experts. They have advantages of crowd contributions, easy to access without geographic restrictions and avoiding conflict of interests over traditional database and search engine based approaches. However, current research attempts to find experts based on features such as published research work, social relationships, and online behaviours (e.g. reads and downloads of publications) on social platforms, they ignore to verify the reliability of identified experts. To bridge this gap, this research proposes an innovative Topic Sensitive SimRank (TSSR) model to identify “real” experts on social network platforms. TSSR model includes three components: LDA for Expertise Extension, Topic Sensitive Network for Reputation Measurement, and Topic Sensitive SimRank for unsuitable experts detection. We also design a parallel computing strategy to improve the efficiency of the proposed methods. Last, to verify the effectiveness of the proposed model, we design an experiment on one of the research social platforms-ScholarMate to seek for experts for companies that need academic-industry collaboration

Design, synthesis, and biological evaluation of truncated deguelin derivatives as Hsp90 inhibitors

A series of novel B and C-rings truncated deguelin derivatives have been designed and synthesized in the present study as heat shock protein 90 (Hsp90) inhibitors. The synthesized compounds exhibited micromolar antiproliferative potency toward a panel of human cancer cell lines. Their structure-activity relationships (SARs) were investigated in a systematic manner. Compound 21c was identified to have high Hsp90 binding potency (60 nM) and caused degradation of client proteins through ubiquitin proteasome system. Further biological studies showed that compound 21c induced a dose-dependent S and G2-phase cell cycle arrest on human breast cancer MCF-7 cells. Flow cytometry and Western blot analyses confirmed that compound 21c caused apoptosis of MCF-7 cells. In addition, compound 21c showed much potent inhibition on the migration and invasion of MCF-7 cells. Taken together, these results suggest that 21c might be a promising lead compound for further development of Hsp90 inhibitors

Design, synthesis and biological evaluation of quinoline-indole derivatives as anti-tubulin agents targeting the colchicine binding site

A series of novel isocombretastatin A-4 (isoCA-4) analogs were designed and synthesized by replacing 3,4,5-trimethoylphenyl and isovanillin of isoCA-4 with quinoline and indole moieties, respectively. The structure activity relationships (SARs) of these synthesized quinoline-indole derivatives have been intensively investigated. Two compounds 27c and 34b exhibited the most potent activities against five cancer cell lines with IC50 values ranging from 2 to 11 nM, which were comparable to those of Combretastatin A-4 (CA-4, 1). Further mechanism investigations revealed that 34b effectively inhibited the microtubule polymerization by binding to the colchicine site of tubulin. Further cellular mechanism studies elucidated that 34b disrupted cell microtubule networks, arrested the cell cycle at G2/M phase, induced apoptosis and depolarized mitochondria of K562 cells. Moreover, 34b displayed potent anti-vascular activity in both wound healing and tube formation assays. Importantly, 27c and 34b significantly inhibited tumor growth in H22 xenograft models without apparent toxicity, suggesting that 27c and 34b deserve further research as potent antitumor agents for cancer therapy

Design, synthesis and biological evaluation of pyridine-chalcone derivatives as novel microtubule-destabilizing agents

Further optimization of the trimethoxyphenyl scaffold of parent chalcone compound (2a) by introducing a pyridine ring afforded a series of novel pyridine-chalcone derivatives as potential anti-tubulin agents. All the target compounds were evaluated for their antiproliferative activities. Among them, representative compound 16f exhibited the most potent activity with the IC50 values ranging from 0.023 to 0.045 μM against a panel of cancer cell lines. Further mechanism study results demonstrated that compound 16f effectively inhibited the microtubule polymerization by binding to the colchicine site of tubulin. Moreover, cellular mechanism studies disclosed that 16f caused G2/M phase arrest, induced cell apoptosis and disrupted the intracellular microtubule network. Also, 16f reduced the cell migration and disrupted the capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). Importantly, 16f significantly inhibited tumor growth in H22 xenograft models without apparent toxicity, which was stronger than the reference compound CA-4, indicating that it is worthy to investigate 16f as a potent microtubule-destabilizing agent for cancer therapy

Serum peptidome profiling for the diagnosis of colorectal cancer: Discovery and validation in two independent cohorts

Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide. Except for the existing fecal occult blood test, colonoscopy and sigmoidoscopy, no widely accepted in vitro diagnostic methods have been available. To identify potential peptide biomarkers for CRC, serum samples from a discovery cohort (100 CRC patients and 100 healthy controls) and an independent validation cohort (91 CRC patients and 91 healthy controls) were collected. Peptides were fractionated by weak cation exchange magnetic beads (MB-WCX) and analysed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDITOF MS). Five peptides (peaks at m/z 1895.3, 2020.9, 2080.7, 2656.8 and 3238.5) were identified as candidate biomarkers for CRC. A diagnostic panel based on the five peptides can discriminate CRC patients from healthy controls, with an accuracy of 91.8%, sensitivity of 95.6%, and specificity of 87.9% in the validation cohort. Peptide peaks at m/z 1895.3, 2020.9 and 3238.5 were identified as the partial sequences of complement component 4 (C4), complement component 3 (C3) and fibrinogen a chain (FGA), respectively. This study potentiated peptidomic analysis as a promising in vitro diagnostic tool for diagnosis of CRC. The identified peptides suggest the involvement of the C3, C4 and FGA in CRC pathogenesis

Surface chromium on Terracotta Army bronze weapons is neither an ancient anti-rust treatment nor the reason for their good preservation.

For forty years, there has been a widely held belief that over 2,000 years ago the Chinese Qin developed an advanced chromate conversion coating technology (CCC) to prevent metal corrosion. This belief was based on the detection of chromium traces on the surface of bronze weapons buried with the Chinese Terracotta Army, and the same weapons' very good preservation. We analysed weapons, lacquer and soils from the site, and conducted experimental replications of CCC and accelerated ageing. Our results show that surface chromium presence is correlated with artefact typology and uncorrelated with bronze preservation. Furthermore we show that the lacquer used to cover warriors and certain parts of weapons is rich in chromium, and we demonstrate that chromium on the metals is contamination from nearby lacquer after burial. The chromium anti-rust treatment theory should therefore be abandoned. The good metal preservation probably results from the moderately alkaline pH and very small particle size of the burial soil, in addition to bronze composition

Comparing pollution patterns and human exposure to atmospheric PBDEs and PCBs emitted from different e-waste dismantling processes

Waste electrical and electronic equipment (E-waste) recycling provides post-consumption economic opportunities, can also exert stress on environment and human health. This study investigated emissions, compositional profiles, and health risks associated with polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) at five workshops (electric blowers to treat mobile phones (EBMP), electric heating furnaces to treat televisions (EHFTV) and routers (EHFR), and rotatory incinerators to treat televisions (RITV) and hard disks (RIHD)) within an e-waste dismantling industrial park. Total suspended particulate (TSP), PBDE, and PCB concentrations were 490-1530 mu g m(-3), 26.6 - 11,800 ng m(-3) and 6.4-19.8 ng m(-3) in different workshops, respectively. Tetra-BDEs were dominant in TV recycling workshops, whereas deca-BDEs were in other workshops. BDE-47, -99, and -209 were the most abundant PBDEs during e-waste recycling activities (expect in RIHD workshop). Penta-CBs were present at high levels in TV workshops, as were tetra-CBs in RIHD workshop. Low brominated BDEs contributed a large portion during working and non-working time. The percentages of octaBDEs and nona-BDEs were higher during non-working than working time. PBDEs posed a higher non-cancer risk; PCBs posed cancer risk to workers through inhalation in TV workshops. This study provides insights into environmental characterization of PBDEs and PCBs during e-waste recycling processes

Identification of a Hydrogen-Sulfide-Releasing Isochroman-4-One Hybrid as a Cardioprotective Candidate for the Treatment of Cardiac Hypertrophy

Cardiac pathological hypertrophy is associated with undesirable epigenetic changes and causes maladaptive cardiac remodeling and heart failure, leading to high mortality rates. Specific drugs for the treatment of cardiac hypertrophy are still in urgent need. In the present study, a hydrogen-sulfide-releasing hybrid 13-E was designed and synthesized by appending p-hydroxythiobenzamide (TBZ), an H2S-releasing donor, to an analog of our previously discovered cardioprotective natural product XJP, 7,8-dihydroxy-3-methyl-isochromanone-4. This hybrid 13-E exhibited excellent H2S-generating ability and low cellular toxicity. The 13-E protected against cardiomyocyte hypertrophy In Vitro and reduced the induction of Anp and Bnp. More importantly, 13-E could reduce TAC-induced cardiac hypertrophy In Vivo, alleviate cardiac interstitial fibrosis and restore cardiac function. Unbiased transcriptomic analysis showed that 13-E regulated the AMPK signaling pathway and influenced fatty acid metabolic processes, which may be attributed to its cardioprotective activities