无机化学课程思政探索——以“配位化学基础”中部分内容的教学设计为例

课程思政是将思想政治教育元素融入课程教学,深化专业课程教书育人的内涵。在教学过程中,以基础理论知识为主线,融入化学发展史、化学家的主要贡献、化学学科和生产生活的紧密联系以及当代科技研究前沿等内容,构建无机化学课程思政教学体系。本文以配位化学基础中部分内容的教学设计为例,对思政案例进行介绍。

Investigating Interaction Between Biochanin A and Human Serum Albumin by Multi-spectroscopic and Molecular Simulation Methods

Biochanin A (BCA), the most abundant isoflavone in chickpeas, presents a wide range of biological activities, such as hypolipidaemic, anti-oxidative, anti-proliferative, and estrogen-like effects. We investigated the interaction between BCA and human serum albumin (HSA) via several techniques. UV–Vis absorption spectroscopy verified the conformational variation of HSA after BCA addition, and fluorescence spectroscopy revealed the relevant binding parameters. Circular dichroism spectroscopy was used to estimate the secondary structural changes of HSA with and without BCA. Molecular docking and dynamics simulations were then applied to study the characteristics of HSA with BCA. Energy decomposition analysis was used to prove that Trp214 in subdomain IIA of HSA is the most likely binding site of BCA. Van der Waals forces and hydrophobic interactions may play important roles during the binding process. All of our results showed that BCA presents significant binding affinity to HSA, thus confirming that the role of HSA has as an efficient transporter of biomolecules. © 2017, Tianjin University and Springer-Verlag Berlin Heidelberg.

Genome-wide Studies Reveal Genetic Risk Factors for Hepatic Fat Content

Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly characterized.Accurate characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk factors.We performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FLI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center Groningen(UMCG)Genetics Lifelines Initiative(UGLI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CREB3L1(rs72910057-T,P=5.40E−09)and GCM1(rs1491489378-T,P=3.16E−09),respectively,as well as three previously reported loci:PNPLA3,TM6SF2,and APOE.GWAS of FLI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGLI,with top signals in ZPR1(P=3.35E−13)and FTO(P=2.11E−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FLI(UGLI)GWAS results was found(rg=0.5276,P=1.45E−03).Novel MRI-PDFF genetic signals(CREB3L1 and GCM1)were replicated in the FLI GWAS.We identified two novel genes for MRI-PDFF and 49 replicable loci for FLI.Despite a difference in hepatic fat content assessment between MRI-PDFF and FLI,a substantial similar genetic architecture was found.FLI is identified as an easy and reliable approach to study hepatic fat content at the population level.

Human germline editing: Insights to future clinical treatment of diseases

Last year, the first attempt to genetically modify human embryos in the United States was reported and sparked a huge debate (Ma et al., 2017). Although the first human germline modification was only performed two years ago, the study showed that rapid adva nces in tech no logy has allowed the rate of off-target effects and mosaicism to be reduced considerably (Liang et al., 2015). Recently, Vertex and CRISPR therapeutics collaborated and developed CTX001, the first CRISPR/Cas9-based therapy, targeting patients with P-thalassemia and have begun phase 1/2 clinical trials. With policies and technologies regarding genome editing both developing rapidly, explorations into the possibility of clinical gene editing for hundreds of hereditary diseases are starting to become achievable. Here, we address the progress of huma n embryo editi ng tech no logies so far and its promise and risks in advancing therapy for hereditary diseases.

CRISPR/Cas9-edited Pax6-GFP reporter system facilitates the generation of mouse neural progenitor cells during differentiation

Embryonic stem cells （ESCs） obtained from blastocysts can self-renew and potentially differentiate into three germ layers, thus acting as a promising platform in cell-replacement therapies and developmental research （Evans and Kaufman, 1981; Thomson et al., 1998）. Neural specification of ESCs has been extensively studied due to their superior value as a cellular resource in studying neurodegenerative diseases （Tao and Zhang, 2016）.

Quorum sensing-based interactions among drugs,microbes,and diseases

Many diseases and health conditions are closely related to various microbes,which participate in complex interactions with diverse drugs;nonetheless,the detailed targets of such drugs remain to be elucidated.Many existing studies have reported causal associations among drugs,gut microbes,or diseases,calling for a workflow to reveal their intricate interactions.In this study,we developed a systematic workflow comprising three modules to construct a Quorum Sensing-based Drug-Microbe-Disease(QSDMD)database(http://www.qsdmd.lbci.net/),which includes diverse interactions for more than 8,000 drugs,163 microbes,and 42 common diseases.Potential interactions between microbes and more than 8,000 drugs have been systematically studied by targeting microbial QS receptors combined with a docking-based virtual screening technique and in vitro experimental validations.Furthermore,we have constructed a QS-based drug-receptor interaction network,proposed a systematic framework including various drug-receptor-microbe-disease connections,and mapped a paradigmatic circular interaction network based on the QS-DMD,which can provide the underlying QS-based mechanisms for the reported causal associations.The QS-DMD will promote an understanding of personalized medicine and the development of potential therapies for diverse diseases.This work contributes to a paradigm for the construction of a molecule-receptor-microbe-disease interaction network for human health that may form one of the key knowledge maps of precision medicine in the future.

Molecular simulation of the interaction mechanism between CodY protein and DNA in Lactococcus lactis

In Lactococcus lactis, the global transcriptional regulatory factor CodY can interact with the promoter DNA to regulate the growth, metabolism, environmental adaptation and other biological activities of the strains. In order to study the mechanism of interaction between CodY and its target DNA, molecular docking and molecular dynamics simulations were used to explore the binding process at molecular level. Through the calculations of the free energy of binding, hydrogen bonding and energy decomposition, nine key residues of CodY were identified, corresponding to SERI84, SERI 86, SER20& THR217, ARG21 & SER219, ASN223, LYS242 and GLY243, among which SERI86, ARG218 and LYS242 play a vital role in DNA binding. Our research results provide important theoretical guidance for using wet-lab methods to study and optimize the metabolic network regulated by CodY.

Molecular dynamic simulation on the conformation of mouse muscle type nAChR

A mouse muscle type nAChR model((α1)_(2)βδg)was built based on the cryoelectron microscopic structure of intact Torpedo marmorata nAChR and the high resolution crystal structure of nAChR-α1 subunit.The conformation of the pentameric nAChR model was investigated by molecular dynamic simulation.The function of water molecule in the hydrophilic interior was clarified.The reason for Tyr127 showing two alternative conformations was discussed in detail.

Reconstructing the state space of chaotic BZ reaction system using power spectrum method

The BZ reaction in continuous-flow stirred tank reactor (CSTR) is selected, and the chaotic time series in low CSTR flow rates have been achieved. The power spectrum method (PSM) from physics and mathematics is introduced to compute the time delay %T%, the embedded dimension %m% so as to reconstruct the state space of the chaotic BZ reaction system by the time delayed coordinates. Further analysis and characterizations on the reconstructed chaotic attractor show that the results are in agreement with the references. It indicates that PSM is faster, simpler and reliable for processing the chaotic chemical system.