Insights into Conformational Dynamics and Allostery in DNMT1-H3Ub/USP7 Interactions

DNA methyltransferases (DNMTs) including DNMT1 are a conserved family of cytosine methylases that play crucial roles in epigenetic regulation. The versatile functions of DNMT1 rely on allosteric networks between its different interacting partners, emerging as novel therapeutic targets. In this work, based on the modeling structures of DNMT1-ubiquitylated H3 (H3Ub)/ubiquitin specific peptidase 7 (USP7) complexes, we have used a combination of elastic network models, molecular dynamics simulations, structural residue perturbation, network modeling, and pocket pathway analysis to examine their molecular mechanisms of allosteric regulation. The comparative intrinsic and conformational dynamics analysis of three DNMT1 systems has highlighted the pivotal role of the RFTS domain as the dynamics hub in both intra- and inter-molecular interactions. The site perturbation and network modeling approaches have revealed the different and more complex allosteric interaction landscape in both DNMT1 complexes, involving the events caused by mutational hotspots and post-translation modification sites through protein-protein interactions (PPIs). Furthermore, communication pathway analysis and pocket detection have provided new mechanistic insights into molecular mechanisms underlying quaternary structures of DNMT1 complexes, suggesting potential targeting pockets for PPI-based allosteric drug design.     

加强管理健全制度 提高实验教学质量

通过物理实验教学的实践，证明了实验室是提高学生思维能力、动手能力的重要基地。要提高实验教学的质量，培养出符合时代要求的人才，既要提高师资水平，发挥教师的积极性，也要加强实验室的建设和管理。     

Exploring the Potential of Natural Product-Based Nanomedicine for Maintaining Oral Health

Oral diseases pose a major threat to public health across the globe. Diseases such as dental caries, periodontitis, gingivitis, halitosis, and oral cancer affect people of all age groups. Moreover, unhealthy diet practices and the presence of comorbidities aggravate the problem even further. Traditional practices such as the use of miswak for oral hygiene and cloves for toothache have been used for a long time. The present review exhaustively explains the potential of natural products obtained from different sources for the prevention and treatment of dental diseases. Additionally, natural medicine has shown activity in preventing bacterial biofilm resistance and can be one of the major forerunners in the treatment of oral infections. However, in spite of the enormous potential, it is a less explored area due to many setbacks, such as unfavorable physicochemical and pharmacokinetic properties. Nanotechnology has led to many advances in the dental industry, with various applications ranging from maintenance to restoration. However, can nanotechnology help in enhancing the safety and efficacy of natural products? The present review discusses these issues in detail.     

A New Model of Hemoglobin Oxygenation

The study of hemoglobin oxygenation, starting from the classical works of Hill, has laid the foundation for molecular biophysics. The cooperative nature of oxygen binding to hemoglobin has been variously described in different models. In the Adair model, which better fits the experimental data, the constants of oxygen binding at various stages differ. However, the physical meaning of the parameters in this model remains unclear. In this work, we applied Hill’s approach, extending its interpretation; we obtained a good agreement between the theory and the experiment. The equation in which the Hill coefficient is modulated by the Lorentz distribution for oxygen partial pressure approximates the experimental data better than not only the classical Hill equation, but also the Adair equation.     

Evaluating the state-of-the-practice in soil measurements in relation to environmental regulations

 The results of chemical analyses of soils show large variations due to the heterogeneity of the material, differences in pretreatment and analytical methods, and unavoidable random errors. In this article, the analytical aspects in the determination of heavy metals in soils are highlighted. Both within-laboratory and between-laboratory variation must be minimized by validation and standardization procedures, respectively, in order to keep the variations resulting from the analytical procedure at an acceptably low level. Even then, the best results will show uncertainties of 5–20%, an issue that should be recognized by governmental and legal bodies. Received: 9 November 1995 Accepted: 1 December 1995     

Quality (r)evolution – guidelines and practical implementation of quality management: the U.S. perspective

 All clinical laboratories in the United States were required for the first time in 1992 to comply with universal minimum regulations: the Clinical Laboratory Improvement Amendments of 1988 (CLIA'88). The CLIA'88 regulations precipitated revolutionary and evolutionary changes based in both total quality management and continuous quality improvement principles. The regulations specify minimum requirements for personnel, quality control, and proficiency testing. Under quality assurance, the requirements are more individualized and allow laboratories to meet the needs of their customers while being in compliance with the regulations. Biannual inspection is integral to CLIA'88. However, laboratories can choose other federally approved, "deemed" professional organizations, with regulations equivalent to CLIA'88. Selection of one of these organizations allows for some flexibility in the application of the requirements, and eliminates having federal CLIA'88 inspectors perform the inspection. Since CLIA's inception in 1992, inspectors have noted a decline in the number of deficiencies cited. An improved level of proficiency testing performance also indicates that better quality test results are being provided to clinicians. The quality evolution and revolution will continue in the United States, and a major impetus will be health care reform's mandate to reduce cost. Received: 13 December 1995 Accepted: January 1996     

高校实验教学中心贵重仪器的数据经济

The paper discusses how to reduce the cost of scientific research and the operation cost of valuable instruments in the laboratory teaching center of universities, while assuring accurate data acquisition during teaching. The paper expounds the relationship and importance of main factors in the data economy, such as Instrument manager, student, valuable instruments, and rules and regulations. Furthermore, some improvement suggestions are proposed.     

A model of the human M2 muscarinic acetylcholine receptor

The M₂ muscarinic acetylcholine receptor belongs to the family of rhodopsin like G-Protein Coupled Receptors. This subtype of muscarinic receptors is of special interest because it bears, aside from an orthosteric binding site, also an allosteric binding site. Based on the X-ray structure of bovine rhodopsin a complete homology model of the human M₂ receptor was developed. For the orthosteric binding site point mutations and binding studies with different agonists and antagonists are available. This knowledge was utilized for an initial verification of the M₂ model. Allosteric modulation of activity is mediated by structurally different ligands such as gallamine, caracurine V salts or W84 (a hexamethonium-derivative). Caracurine V derivatives with different affinities to M₂ were docked using GRID-fields. Subsequent molecular dynamics simulations yielded different binding energies based on diverse electrostatic and lipophilic interactions. The calculated affinities are in good agreement to experimentally determined affinities.     

Metabolomics comparison of chemical components and metabolic regulations in different parts of Eucommia ulmoides Oliv

Eucommia ulmoides Oliv. (EU) is an herb with variety of pharmacological activities. As the demand for EU as a medical source increases, its limited availability is becoming an urgent problem. The bark of EU—Eucommia cortex (EC)—was the main medicinal part of EU, whose yield has been too low to meet market requirements. The EU leaves—Eucommiae folium (EF)—obtained easily from the trees, traditionally considered less valuable than the EU bark. This study compared chemical components and metabolic regulations in different parts of EU using metabolomics to explore the potential for alternative medical sources of EU. The results demonstrated that the composition of EC differs slightly from the composition of EF, and there are some differences in the content of individual ingredients between EC and EF. Combined pharmacodynamic/metabolomics analysis showed that both EC and EF could improve the bone metabolism markers and trabecular microarchitecture of ovariectomized rats mainly by intervening in amino acid metabolism. Our data suggest that EF is a potential alternative medicinal option when EU resources are scarce, and this study provides a mechanistic framework for the benefits of EF in osteoporosis disease.