Predicting Relative Binding Affinity Using Nonequilibrium QM/MM Simulations

Calculating binding free energies with quan-tum-mechanical (QM) methods is notoriously time-consum-ing. In this work, we studied whether such calculations can beaccelerated by using nonequilibrium (NE) moleculardynamics simulations employing Jarzynski’s equality. Westudied the binding of nine cyclic carboxylate ligands to theocta-acid deep-cavity host from the SAMPL4 challenge withthe reference potential approach. The binding free energieswere first calculated at the molecular mechanics (MM) levelwith free energy perturbation using the generalized Amberforce field with restrained electrostatic potential charges forthe host and the ligands. Then the free energy corrections for going from the MM Hamiltonian to a hybrid QM/MM Hamiltonian were estimated by averaging over many short NE molecular dynamics simulations. In the QM/MM calculations, the ligand was described at the semiempirical PM6-DH+ level. We show that this approach yields MM → QM/MM free energy corrections that agree with those from other approaches within statistical uncertainties. The desired precision can be obtained by running a proper number of independent NE simulations. For the systems studied in this work, a total simulation length of 20 ps was appropriate for most of the ligands, and 36−324 simulations were necessary in order to reach a precision of 0.3 kJ/ mol

Logarithmic Mean Divisia Index Decomposition of CO2 Emissions from Urban Passenger Transport: An Empirical Study of Global Cities from 1960–2001

The urban transport sector has become one of the major contributors to global CO2 emissions. This paper investigates the driving forces of changes in CO2 emissions from the passenger transport sectors in different cities, which is helpful for formulating effective carbon-reduction policies and strategies. The logarithmic mean Divisia index (LMDI) method is used to decompose the CO2 emissions changes into five driving determinants: Urbanization level, motorization level, mode structure, energy intensity, and energy mix. First, the urban transport CO2 emissions between 1960 and 2001 from 46 global cities are calculated. Then, the multiplicative decomposition results for megacities (London, New York, Paris, and Tokyo) are compared with those of other cities. Moreover, additive decomposition analyses of the 4 megacities are conducted to explore the driving forces of changes in CO2 emissions from the passenger transport sectors in these megacities between 1960 and 2001. Based on the decomposition results, some effective carbon-reduction strategies can be formulated for developing cities experiencing rapid urbanization and motorization. The main suggestions are as follows: (i) Rational land use, such as transit-oriented development, is a feasible way to control the trip distance per capita (ii) fuel economy policies and standards formulated when there are oil crisis are effective ways to suppress the increase of CO2 emissions, and these changes should not be abandoned when oil prices fall and (iii) cities with high population densities should focus on the development of public and non-motorized transport. Document type: Articl

Research progress of drug eluting balloon in arterial circulatory system

The arterial circulatory system diseases are common in clinical practice, and their treatment options have been of great interest due to their high morbidity and mortality. Drug-eluting balloons, as a new type of endovascular interventional treatment option, can avoid the long-term implantation of metal stents and is a new type of angioplasty without stents, so drug-eluting balloons have better therapeutic effects in some arterial circulatory diseases and have been initially used in clinical practice. In this review, we first describe the development, process, and mechanism of drug-eluting balloons. Then we summarize the current studies on the application of drug-eluting balloons in coronary artery lesions, in-stent restenosis, and peripheral vascular disease. As well as the technical difficulties and complications in the application of drug-eluting balloons and possible management options, in order to provide ideas and help for future in-depth studies and provide new strategies for the treatment of more arterial system diseases

Host-Guest Relative Binding Affinities at Density-Functional Theory Level from Semiempirical Molecular Dynamics Simulations

Relative free energies for the binding of nine cyclic carboxylate ligands to the octa-acid deep-cavity host were calculated at the combined density-functional theory and molecular mechanics (DFT/MM) level of theory. The DFT calculations employed the BLYP functional and the 6-31G∗ basis set for the ligand. We employed free-energy perturbations (FEP) with the reference-potential approach and used molecular dynamics (MD) simulations with the semiempirical quantum mechanical (SQM) PM6-DH+ method for the ligand as an intermediate level between MM and DFT/MM to improve the convergence. Thus, the relative binding free energy of two ligands was first calculated at the MM level by an alchemical transformation from one ligand to another in both the bound and unbound states. Then, for each ligand the free-energy correction for going from the MM to the SQM/MM potentials was calculated using explicit SQM/MM MD simulations. Finally, the free-energy correction for going from the SQM/MM to the DFT/MM potentials was estimated with FEP without running any DFT/MM simulations. Instead, the free energy was calculated by single-step exponential averaging (ssEA) or employing the cumulant approximation to the second order (CA). The results show that CA converges much better than ssEA, and with 500-4500 DFT/MM single-point energy calculations, converged free energies with a precision of 0.3 kJ/mol can be obtained. These free energies reproduce the experimental binding free energy differences with a mean absolute deviation of 3.4 kJ/mol, a correlation (R 2 ) of 0.97, and correct signs for all of the eight free-energy differences. This is appreciably better than the results obtained at the SQM/MM level of theory and also slightly better than those obtained with MM. We show that the convergence of the SQM/MM → DFT/MM perturbations can be monitored by the use of Wu and Kofke's bias metric and by the standard deviation of the difference between the SQM/MM and DFT/MM energies. Finally, we show that the use of the intermediate SQM/MM MD simulations improves the convergence of the free energies by a factor of at least two, compared to doing direct MM → DFT/MM perturbations

Efficacy of different oral H1 antihistamine treatments on allergic rhinitis: a systematic review and network meta-analysis of randomized controlled trials

Introduction: Oral H1 antihistamines are the first-line treatment for patients with allergic rhinitis, while it is uncertain which kind and dosage of the antihistamines are more effective in improving symptoms of patients. Objective: To evaluate the efficacy of different oral H1 antihistamine treatments on patients with allergic rhinitis by performing a network meta-analysis. Methods: The search was executed in PubMed, Embase, OVID, the Cochrane Library and ClinicalTrials.gov for relevant studies. The network meta-analysis was performed by using Stata 16.0, and the outcome measures of the analysis were symptom score reductions of patients. Relative risks with 95% Confidence Intervals were used in the network meta-analysis to compare the clinical effect of treatments involved, and Surface Under the Cumulative Ranking Curves (SUCRAs) were also calculated to rank the treatments’ efficacy. Results: 18 eligible randomized controlled studies, involving a total of 9419 participants, were included in this meta-analysis. All the antihistamine treatments outperformed placebo in total symptom score reduction and each individual symptom score reduction. According to the results of SUCRA, rupatadine 20 mg and rupatadine 10 mg were ranked relatively high in reductions of total symptom score (SUCRA: 99.7%, 76.3%), nasal congestion score (SUCRA: 96.4%, 76.4%), rhinorrhea score (SUCRA: 96.6%, 74.6%) and ocular symptom score (SUCRA: 97.2%, 88.8%); rupatadine 20 mg and levocetirizine 5 mg were ranked relatively high in reductions of nasal itching score (SUCRA: 84.8%, 83.4%) and sneezing score (SUCRA: 87.3%, 95.4%); loratadine 10 mg was ranked the lowest in each symptom score reduction besides placebo. Conclusion: This study suggests that rupatadine is the most effective in alleviating symptoms of patients with allergic rhinitis among different oral H1 antihistamine treatments involved, and rupatadine 20 mg performs better than rupatadine 10 mg. While loratadine 10 mg has inferior efficacy for patients to the other antihistamine treatments

Data from: Determination of sulfonamides in milk by capillary electrophoresis with PEG@MoS2 as a dispersive solid-phase extraction sorbent

A synthetic polyethylene glycol-molybdenum disulfide (PEG@MoS2) composite was prepared using a simple method, and the application of this material in dispersive solid-phase extraction (DSPE) was investigated for the enrichment of eight sulfonamides (SAs) in milk samples. The composite was characterized by energy dispersive spectroscopy, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy and Brunner-Emmett-Teller measurements. The results showed that the MoS2 synthesized in the presence of PEG has the advantage of a larger surface area and that the adsorption effect of this MoS2 was enhanced. After extraction, the eight SAs were separated by capillary zone electrophoresis with a good linear relationship (R2 > 0.9902) in the range of 0.3-30 µg/mL and good precision (between 0.32% and 9.83%). Additionally, good recoveries (between 60.52% and 110.91%) were obtained for the SAs in the milk samples. The developed PEG@MoS2-based DSPE method could be applied for the enrichment of SAs in real milk samples

Assessing the Spatiotemporal Development of Ecological Civilization for China’s Sustainable Development

The ecological civilization strategy in China has accelerated its national sustainability. However, few systematic evaluations of Chinese Ecological Civilization Construction (ECC) have provided detailed and timely information regarding estimations of the sustainable development levels. Here, we combined indicators and policies of the United Nations (UN) sustainable development goals (SDGs) with Chinese ecological civilization and built an integrated assessment system with mixed indicators for evaluating the sustainable development levels in five dimensions (i.e., economy, society, ecology, culture, and institutions). Based on the acquired sustainability index from the system, we revealed the spatiotemporal transitions at the national and provincial levels from 2005 to 2019 in China. Specifically, both the national and provincial ECC temporally increased in this period, while spatially, the development performance of ECC was differentiated across provinces and regions. In particular, sustainable trajectories in east China and coastal regions presented better than the west and inland. Moreover, we identified the different dimensional contributions between the top and bottom provinces in ECC development. The results showed that the institutional, social, and cultural dimensions created more effects than the economic and ecological dimensions. By analyzing the provincial development patterns, we recommend the comprehensive development of ECC across the five dimensions and suggest that addressing weak dimensions is a priority. The proposed system will elevate the sustainable development strategies and pave the way for the broadening of the framework’s application to other regions and countries in the future

Identification of key potential infection processes and risk factors in the computed tomography examination process by FMEA method under COVID-19

Abstract Purpose To identify the key infection processes and risk factors in Computed Tomography (CT) examination process within the standard prevention and control measures for the COVID-19 epidemic, aiming to mitigate cross-infection occurrences in the hospital. Method The case hospital has assembled a team of 30 experts specialized in CT examination. Based on the CT examination process, the potential failure modes were assessed from the perspective of severity (S), occurrence probability (O), and detectability (D); they were then combined with corresponding risk prevention measures. Finally, key infection processes and risk factors were identified according to the risk priority number (RPN) and expert analysis. Results Through the application of RPN and further analysis, four key potential infection processes were identified, including “CT request form (A 1),” “during the scan of CT patient (B 2),” “CT room and objects disposal (C 2),” and “medical waste (garbage) disposal (C 3)”. In addition, eight key risk factors were also identified, including “cleaning personnel does not wear masks normatively (C 32),” “nurse does not select the vein well, resulting in extravasation of the peripheral vein for enhanced CT (B 25),” “patient cannot find the CT room (A 13),” “patient has obtained a CT request form but does not know the procedure (A 12),” “patient is too unwell to continue with the CT scan (B 24),” “auxiliary staff (or technician) does not have a good grasp of the sterilization and disinfection standards (C 21),” “auxiliary staff (or technician) does not sterilize the CT machine thoroughly (C 22),” and “cleaning personnel lacks of knowledge of COVID-19 prevention and control (C 33)”. Conclusion Hospitals can publicize the precautions regarding CT examination through various channels, reducing the incidence of CT examination failure. Hospitals’ cleaning services are usually outsourced, and the educational background of the staff employed in these services is generally not high. Therefore, during training and communication, it is more necessary to provide a series of scope and training programs that are aligned with their understanding level. The model developed in this study effectively identifies the key infection prevention process and critical risk factors, enhancing the safety of medical staff and patients. This has significant research implications for the potential epidemic of major infectious diseases

Impact Evaluation of Cyberattacks on Connected and Automated Vehicles in Mixed Traffic Flow and Its Resilient and Robust Control Strategy

Connected and automated vehicles (CAVs) present significant potential for improving road safety and mitigating traffic congestion for the future mobility system. However, cooperative driving vehicles are more vulnerable to cyberattacks when communicating with each other, which will introduce a new threat to the transportation system. In order to guarantee safety aspects, it is also necessary to ensure a high level of information quality for CAV. To the best of our knowledge, this is the first investigation on the impacts of cyberattacks on CAV in mixed traffic (large vehicles, medium vehicles, and small vehicles) from the perspective of vehicle dynamics. The paper aims to explore the influence of cyberattacks on the evolution of CAV mixed traffic flow and propose a resilient and robust control strategy (RRCS) to alleviate the threat of cyberattacks. First, we propose a CAV mixed traffic car-following model considering cyberattacks based on the Intelligent Driver Model (IDM). Furthermore, a RRCS for cyberattacks is developed by setting the acceleration control switch and its impacts on the mixed traffic flow are explored in different cyberattack types. Finally, sensitivity analyses are conducted in different platoon compositions, vehicle distributions, and cyberattack intensities. The results show that the proposed RRCS of cyberattacks is robust and can resist the negative threats of cyberattacks on the CAV platoon, thereby providing a theoretical basis for restoring the stability and improving the safety of the CAV

Sequence-controlled polymers constructed by alkyne-based polymerizations

Synthesizing polymers with precise sequence structures is of great significance but is still a great challenge in polymer science. The exploration of alkyne-based polymerizations recently has attracted considerable attention due to their great potential to construct polymers with diverse structures and versatile functions, especially those with precise sequence structures. In this review, we summarized recent advances in the preparation of sequence-controlled polymers by alkyne-base polymerizations. Representative examples of each method were selected to illustrate the essential construction principles and implementation approaches, which are expected to provide guidance for the development of sequence-controlled polymers. In addition, we also systematically introduce the diverse and appealing properties and applications of the obtained sequence-controlled polymers, hoping to promote the development of polymeric materials with more superior and innovative properties and applications