抑制剂对溴结构域蛋白4的两个溴结构域选择机制的多副本分子动力学模拟和自由能分析

溴结构域蛋白4在细胞周期调节中至关重要,已成为治疗各种癌症的潜在靶标、溴结构域蛋白4包含两个溴结构域,即BD1和BD2.研究表明,选择性地抑制BD1或BD2可能提供更有效的治疗方案.因此,了解抑制剂对BD1和BD2结合的选择性机制对于开发BD1和BD2的高选择性抑制剂至关重要.本文利用多副本分子动力学模拟研究了抑制剂SG3-179、GSK778和GSK620对BD1和BD2的结合选择性.结果显示,BD1比BD2具有更强的结构灵活性,而且BD1和BD2表现出不同的内部动力学.对自由能景观的分析表明,BD1和BD2的构象分布存在明显的差异.结合自由能预测表明,熵变、静电相互作用和范德华相互作用是SG3-179、GSK778和GSK620对BD1和BD2选择性结合的关键因素.单个残基能量贡献的计算表明,(BD1,BD2)中的残基(W81,W374)、(P82,P375)、(Q85,K378)、(V87,V380)、(L92,L385)、(N93,G386)、(L94,L387)、(C136,C429)、(N140,N433)、(K141,P434)、(D144,H437)和(I146,V439)在SG3-179、GSK778和GSK620与BD1和BD2的结合中产生明显的能量差异,它们可以作为开发针对BD1或BD2的高选择性抑制剂的有效靶点.相关信息可为提高抑制剂对BD1和BD2的选择性提供重要的理论指导.

Optimization of Compound Coptis Ointment Extraction through the Integration of Pharmacodynamic Indices and Orthogonal Test

[Objectives]To determine the optimal reflux extraction process conditions for Compound Coptis Ointment.[Methods]The study employed the orthogonal experimental design method and drug-sensitive disc agar diffusion method to evaluate the extraction rate,berberine hydrochloride content,and bacteriostatic ring diameter of the extract as comprehensive indices,and optimized the extraction process conditions of Compound Coptis Ointment using ethanol reflux.[Results]Based on the results of comprehensive indices,the optimal reflux extraction conditions for Compound Coptis Ointment were determined to be soaking in 1.5 times the amount of 70%ethanol for 2 h,followed by two extractions with 6 times the amount of 70%ethanol for 1 h each time.Three verification tests were conducted under the optimal process conditions.The yield of the extract was 28.32%±0.53%,the content of berberine hydrochloride was 4.68%±0.45%,and the diameter of the bacteriostatic ring was(2.5±0.2)cm.[Conclusions]The extract had higher drug content and exhibited better antibacterial effects.The optimized extraction process is simple,stable,and reliable,and can be effectively used to optimize the extraction process of Compound Coptis Ointment.

Progress in heavy ion cancer therapy at IMP and future development

Basic research on heavy ion cancer therapy such as radiobiology, medicalphysics, and therapeutic technique has been conducted at the Institute ofModern Physics (IMP), Chinese Academy of Sciences since 1995. Based on theachievements acquired in the basic research and the requirements for a heavyion accelerator for radiotherapy purposes, a dedicated heavy ion therapy facilitynamed Heavy Ion Medical Machine (HIMM) was designed at IMP andconstructed in Wuwei, China. The HIMM facility consists of two electroncyclotron resonance ion sources, one cyclotron as the injector and onesynchrotron as the main accelerator, and four different treatment roomsequipped with passive or active beam delivery systems, and accelerates carbonions up to 400 MeV/u. After the performance inspection of HIMM organized bythe National Medical Device Inspection Center, preclinical tests like cell andanimal radiobiological experiments and dosimetric verification using anthropomorphicphantoms for elucidating the biophysical properties of the carbon ionbeams provided by HIMM were carried out. According to the Chinese medicaldevice regulations, a clinical trial in which 46 tumor patients were recruited andtwo hospitals participated was conducted in the HIMM facility, aiming atevaluating the treatment safety and short-term efficacy of the medical device.The success of the clinical trial helped the HIMM facility be authorized by theChinese government as a class III medical device. In this paper, all the aspectsmentioned above are introduced and discussed, and implications for futureimprovements are also given.

A new Chinese standard for testing of quality control in medical proton/heavy ion beam radiotherapy equipment

With the development of social economy and radiotherapy technique,proton/heavy ion radiotherapy has been applied widely to clinical practices.At present,there are at least 29 hospitals in China at various stages of planning,construction,commissioning or clinical operation of medical proton/heavy ion beam radiotherapy equipment.Compared with common radiotherapy accelerators used in conventional external beam radiotherapy,the proton/heavy ion therapy system has more stringent requirements for quality control so as to achieve an optimum therapeutic effect.In order to protect the health rights of patients undergoing radiotherapy,to facilitate the relevant administrative supervision departments to carry out standard-based approval and routine supervision and to promote the development of related medical undertakings,the standard for testing of quality control for medical proton/heavy ion beam radiotherapy equipment is drafted to fill the gap in this regard in China and even worldwide.The standard contains five indicators and corresponding testing methods for radiological protection and safety and 16 indicators for quality control of equipment performance.The standard is a mandatory standard and is based on the relevant Chinese legal requirements for the testing of radiotherapy equipment,so all the indicators listed in the standard shall be tested.During the drafting of the standard,the opinions from hospitals that are currently using proton/heavy ion medical accelerators for radiotherapy purpose and from the related equipment manufacturers were taken into account.The draft standard was revised with reference to these opinions and the feasibility of the related quality control requirements.The official version of the standard was released on March 7,2023,and implementation is scheduled to begin on March 1,2024.

3D hypothesis clustering for cross-view matching in multiperson motion capture

We present a multiview method for markerless motion capture of multiple people. The main challenge in this problem is to determine crossview correspondences for the 2 D joints in the presence of noise. We propose a 3 D hypothesis clustering technique to solve this problem. The core idea is to transform joint matching in 2 D space into a clustering problem in a 3 D hypothesis space. In this way, evidence from photometric appearance, multiview geometry, and bone length can be integrated to solve the clustering problem efficiently and robustly. Each cluster encodes a set of matched 2 D joints for the same person across different views, from which the 3 D joints can be effectively inferred. We then assemble the inferred 3 D joints to form full-body skeletons for all persons in a bottom–up way. Our experiments demonstrate the robustness of our approach even in challenging cases with heavy occlusion,closely interacting people, and few cameras. We have evaluated our method on many datasets, and our results show that it has significantly lower estimation errors than many state-of-the-art methods.