Kaixian Chen

Bio: Kaixian Chen is an academic researcher from Chinese Academy of Sciences. The author has contributed to research in topics: Virtual screening & Docking (molecular). The author has an hindex of 47, co-authored 380 publications receiving 9209 citations. Previous affiliations of Kaixian Chen include Shanghai University & East China University of Science and Technology.

17‑AAG synergizes with Belinostat to exhibit a negative effect on the proliferation and invasion of MDA‑MB‑231 breast cancer cells

Abstract: Breast cancer is one of the most common malignancies that threaten the health of women. Although there are a few chemotherapies for the clinical treatment of breast cancer, these therapies are faced with the problems of drug‑resistance and metastasis. Drug combination can help to reduce the adverse side effects of chemotherapies using single drugs, and also help to overcome common drug‑resistance during clinical treatment of breast cancer. The present study reported the synergistic effect of the heat shock protein 90 inhibitor 17‑AAG and the histone deacetylase 6 inhibitor Belinostat in triple‑negative breast cancer (TNBC) MDA‑MB‑231 cells, by detection of proliferation, apoptosis and cell cycle arrest following treatment with this combination. Subsequently, RNA sequencing (RNA‑seq) data was collected and analyzed to investigate the synergistic mechanism of this combination. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways revealed by RNA‑seq data analysis, a wound‑healing assay was used to investigate the effect of this combination on the migration of MDA‑MB‑231 cells. Compared with treatment with 17‑AAG or Belinostat alone, both the viability inhibition and apoptosis rate of MDA‑MB‑231 cells were significantly enhanced in the combination group. The combination index values were <1 in three concentration groups. Revealed by the RNA‑seq data analysis, the most significantly enriched KEGG pathways in the combination group were closely associated with cell migration. Based on these findings, the anti‑migration effect of this combination was investigated. It was revealed that the migration of MDA‑MB‑231 cells was significantly suppressed in the combination group compared with in the groups treated with 17‑AAG or Belinostat alone. In terms of specific genes, the mRNA expression levels of TEA domain family proteins were significantly decreased in the combination group, whereas the phosphorylation of YY1 associated protein 1 and modulator of VRAC current 1 was significantly enhanced in the combination group. These alterations may help to explain the anti‑migration effect of this combination. Belinostat has already been approved as a treatment for T‑cell lymphoma and 17‑AAG is undergoing clinical trials. These findings could provide a beneficial reference for the clinical treatment of patients with TNBC.

Review of melt casting of dense ceramics and glasses by high gravity combustion synthesis

Abstract: High gravity combustion synthesis is a recently reported technique to prepare dense ceramics and glasses by melt casting instead of conventional powder sintering. This technique combines strong exothermic chemical reactions with a high gravity field, and offers an efficient and furnace free way for rapid production of bulk ceramic and glass materials. This article reviews major results on melt casting of dense ceramics and glasses by high gravity combustion synthesis. Several ceramic and glass materials prepared by high gravity combustion synthesis are firstly presented as examples, including single phase ceramics, multiphase eutectic or composite ceramics, glasses and glass–ceramics. Then, the reaction kinetics in high gravity combustion synthesis are discussed in detail, with an emphasis on phase separation, solidification and microstructure evolution. Finally, a conclusion is drawn with a perspective on further development and application of high gravity combustion synthesis.

Quantum Chemistry Investigation on the Dihydrogen Bond between Silicane and Ammonium

Abstract: Quantum chemical calculations are performed on the complex formed by silicane and ammonium in order to investigate the binding characteristics and nature of the dihydrogen bond. The calculation results using B3LYP and MP2 methods with the basis sets from 6-31G* to 6-311++G(2df,2pd) reveal that the dihydrogen-bond angle is ∼180.0° and that the bond length is ∼1.60 A. The calculated enthalpies of formation of this complex using B3LYP/6-311++G(2df,2pd) and MP2/6-311++G(d,p) methods, corrected by basis-set superposition error (BSSE) and thermal energy, are −5.595 and −4.465 kcal/mol, respectively. Taking into account our CCSD(T)/6-311++G(2df,2p) and G2 results, we suggest that the binding strength between SiH4 and NH4+ is ∼5.0 ± 0.5 kcal/mol. The BSSE released from the B3LYP method seems to converge at the basis set 6-311++G(d,p). In addition, charge distribution, electrostatic interaction energy, and the molecular-orbital coefficient analysis on all molecular orbitals of this complex show that s−s orbital in...

Pattern Recognition and Machine Learning

Abstract: Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.

“Bioinformatics” 특집을 내면서

Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors

Abstract: A new coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the aetiological agent responsible for the 2019–2020 viral pneumonia outbreak of coronavirus disease 2019 (COVID-19)1–4. Currently, there are no targeted therapeutic agents for the treatment of this disease, and effective treatment options remain very limited. Here we describe the results of a programme that aimed to rapidly discover lead compounds for clinical use, by combining structure-assisted drug design, virtual drug screening and high-throughput screening. This programme focused on identifying drug leads that target main protease (Mpro) of SARS-CoV-2: Mpro is a key enzyme of coronaviruses and has a pivotal role in mediating viral replication and transcription, making it an attractive drug target for SARS-CoV-25,6. We identified a mechanism-based inhibitor (N3) by computer-aided drug design, and then determined the crystal structure of Mpro of SARS-CoV-2 in complex with this compound. Through a combination of structure-based virtual and high-throughput screening, we assayed more than 10,000 compounds—including approved drugs, drug candidates in clinical trials and other pharmacologically active compounds—as inhibitors of Mpro. Six of these compounds inhibited Mpro, showing half-maximal inhibitory concentration values that ranged from 0.67 to 21.4 μM. One of these compounds (ebselen) also exhibited promising antiviral activity in cell-based assays. Our results demonstrate the efficacy of our screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases for which no specific drugs or vaccines are available. A programme of structure-assisted drug design and high-throughput screening identifies six compounds that inhibit the main protease of SARS-CoV-2, demonstrating the ability of this strategy to isolate drug leads with clinical potential.

New Substructure Filters for Removal of Pan Assay Interference Compounds (PAINS) from Screening Libraries and for Their Exclusion in Bioassays

Abstract: This report describes a number of substructural features which can help to identify compounds that appear as frequent hitters (promiscuous compounds) in many biochemical high throughput screens. The compounds identified by such substructural features are not recognized by filters commonly used to identify reactive compounds. Even though these substructural features were identified using only one assay detection technology, such compounds have been reported to be active from many different assays. In fact, these compounds are increasingly prevalent in the literature as potential starting points for further exploration, whereas they may not be.