Accelerating Factor Xa inhibitor discovery with a de novo drug design pipeline

Small-molecule drugs are essential for maintaining human health. The objective of this study is to identify a molecule that can inhibit the Factor Xa protein and be easily procured. An optimization-based de novo drug design framework, Drug CAMD, that integrates a deep learning model with a mixed-integer nonlinear programming model is used for designing drug candidates. Within this framework, a virtual chemical library is specifically tailored to inhibit Factor Xa. To further filter and narrow down the lead compounds from the designed compounds, comprehensive approaches involving molecular docking,binding pose metadynamics(BPMD), binding free energy calculations, and enzyme activity inhibition analysis are utilized. To maximize efficiency in terms of time and resources, molecules for in vitro activity testing are initially selected from commercially available portions of customized virtual chemical libraries. In vitro studies assessing inhibitor activities have confirmed that the compound EN300-331859shows potential Factor Xa inhibition, with an IC_(50)value of 34.57 μmol·L^(-1). Through in silico molecular docking and BPMD, the most plausible binding pose for the EN300-331859-Factor Xa complex are identified. The estimated binding free energy values correlate well with the results obtained from biological assays. Consequently, EN300-331859 is identified as a novel and effective sub-micromolar inhibitor of Factor Xa.

A Strategy for Multi-objective Optimization under Uncertainty in Chemical Process Design

In many circumstances, chemical process design can be formulated as a multi-objective optimization （MOO） problem. Examples include bi-objective optimization problems, where the economic objective is maximized and environmental impact is minimized simultaneously. Moreover, the random behavior in the process,property, market fluctuation, errors in model prediction and so on would affect the performance of a process. Therefore, it is essential to develop a MOO methodology under uncertainty. In this article, the authors propose a generic and systematic optimization methodology for chemical process design under uncertainty. It aims at identifying the optimal design from a number of candidates. The utility of this methodology is demonstrated by a case study based on the design of a condensate treatment unit in an ammonia plant.

Chemical interaction motivated structure design of layered metal carbonate hydroxide/MXene composites for fast and durable lithium ion storage

Rational architecture design has turned out to be an effective strategy in improving the electrochemical performance of electrode materials for batteries.However,an elaborate structure that could simultaneously endow active materials with promoted reaction reversibility,accelerated kinetic and restricted volume change still remains a huge challenge.Herein,a novel chemical interaction motivated structure design strategy has been proposed,and a chemically bonded Co(CO_(3))_(0.5)OH·0.11 H_(2)O@MXene(CoCH@MXene)layered-composite was fabricated for the first time.In such a composite,the chemical interaction between Co^(2+)and MXene drives the growth of smaller-sized CoCH crystals and the subsequent formation of interwoven CoCH wires sandwiched in-between MXene nanosheets.This unique layered structure not only encourages charge transfer for faster reaction dynamics,but buffers the volume change of CoCH during lithiation-delithiation process,owing to the confined crystal growth between conductive MXene layers with the help of chemical bonding.Besides,the sandwiched interwoven CoCH wires also prevent the stacking of MXene layers,further conducive to the electrochemical performance of the composite.As a result,the as-prepared CoCH@MXene anode demonstrates a high reversible capacity(903.1 mAh g^(-1)at 100 mA g^(-1))and excellent cycling stability(maintains 733.6 mAh g^(-1)at1000 mA g^(-1)after 500 cycles)for lithium ion batteries.This work highlights a novel concept of layerby-layer chemical interaction motivated architecture design for futuristic high performance electrode materials in energy storage systems.

Process-oriented knowledge-sharing platform for chemical engineering design projects

A process-oriented knowledge-sharing platform is studied to improve knowledge sharing and project management of chemical engineering design enterprises. First, problems and characteristics of knowledge sharing in multi-projects of chemical engineering design are analyzed. Then based on theories of project management, process management, and knowledge management, a process-oriented knowledge-sharing platform is proposed. The platform has three characteristics: knowledge is divided into professional knowledge and project management knowledge; knowledge sharing is integrated with the project process, which makes knowledge sharing a necessary part of the project process and ensures the quantity of knowledge shared; the platform provides quantitative measurements of incentive mechanisms for knowledge providers and users which ensures the quality of knowledge shared. This knowledge-sharing platform uses two knowledge management tools, a knowledge map and a knowledge base, to support the platform.

China's Chemical Engineering Design Capability

During the early days of New China, to support the domestic construction of those projects aided by the former Soviet Union, the design institution formed a chemical engineering production installation design team. During the 1950s, this team designed an ammonia synthesis unit with an annual capacity of 75000 tons, set up the Sichuan Chemical Plant and worked out a

Some Construction Methods of Optimum Chemical Balance Weighing Designs III

Methods of constructing the optimum chemical balance weighing designs from symmetric balanced incomplete block designs are proposed with illustration. As a by-product pairwise efficiency and variance balanced designs are also obtained.

Development of Sustainable Solutions for Zebra Mussel Control Through Chemical Product Engineering

The zebra mussel is an important aquatic pest that causes great damage to freshwater-dependent industries, due to biofouling. The main goal of the project discussed here is to develop improved solutions to control this species. Three approaches have been explored in an attempt to design innovative application strategies for existing biocides： （i） encapsulation of toxins; （ii） combination of toxins; （iii） investigation of the seasonal variation of the species＇ tolerance to toxins. In this paper, the principles behind these approaches and the major results on each topic are presented. The benefits of adopting a chemical product engineering approach in conducting this project are also discussed.

A novel coated-particle design and fluidized-bed chemical vapor deposition preparation method for fuel-element identification in a nuclear reactor

Particle coating is an important method that can be used to expand particle-technology applications. Coated-particle design and preparation for nuclear fuel-element trajectory tracing were focused on in this paper. Particles that contain elemental cobalt were selected because of the characteristic gamma ray spectra of 60Co. A novel particle-structure design was proposed by coating particles that contain elemental cobalt with a high-density silicon-carbide （SiC） layer. During the coating process with the high-density SiC layer, cobalt metal was formed and diffused towards the coating, so an inner SiC–CoxSi layer was designed and obtained by fluidized-bed chemical vapor deposition coupled with in-situ chemical reaction. The coating layers were studied by X-ray diffractometry, scanning electron microscopy, and energy dispersive X-ray spectroscopy techniques. The chemical composition was also determined by inductively coupled plasma optical emission spectrometry. The novel particle design can reduce the formation of metallic cobalt and prevent cobalt diffusion in the coating process, which can maintain safety in a nuclear reactor for an extended period. The experimental results also validated that coated particles maintain their structural integrity at extremely high temperatures （～1950 °C）, which meets the requirements of next-generation nuclear reactors.

Simultaneous optimization of transit network and public bicycle station network

The traditional manner to design public transportation system is to sequentially design the transit network and public bicycle network. A new public transportation system design problem that simultaneously considers both bus network design and public bicycle network design is proposed. The chemical reaction optimization(CRO) is designed to solve the problem. A shortcoming of CRO is that, when the two-molecule collisions take place, the molecules are randomly picked from the container.Hence, we improve CRO by employing different mating strategies. The computational results confirm the benefits of the mating strategies. Numerical experiments are conducted on the Sioux-Falls network. A comparison with the traditional sequential modeling framework indicates that the proposed approach has a better performance and is more robust. The practical applicability of the approach is proved by employing a real size network.

Homochirality in Ferroelectrochemistry

What is the most favorite and original chemistry developed in your research group?We originally proposed the design principle for molecular ferroelectrics:ferroelectrochemistry,including quasi-spherical theory,the introduction of homochirality,and H/F substitution.Ferroelectrochemistry changed the blind search for molecular ferroelectrics into targeted chemical design,which will develop into a new discipline.

Efficient nanozyme engineering for antibacterial therapy

Antimicrobial resistance(AMR)poses a huge threat to human health.It is urgent to explore efficient ways to suppress the spread of AMR.Antibacterial nanozymes have become one of the powerful weapons to combat AMR due to their enzyme-like catalytic activity with a broad-spectrum antibacterial performance.However,the inherent low catalytic activity of nanozymes limits their expansion into antibacterial applications.In this regard,a variety of advanced chemical design strategies have been developed to improve the antimicrobial activity of nanozymes.In this review,we have summarized the recent progress of advanced strategies to engineer efficient nanozymes for fighting against AMR,which can be mainly classified as catalytic activity improvement,external stimuli,bacterial affinity enhancement,and multifunctional platform construction according to the basic principles of engineering efficient nanocatalysts and the mechanism of nanozyme catalysis.Moreover,the deep insights into the effects of these enhancing strategies on the nanozyme structures and properties are highlighted.Finally,current challenges and future perspectives of antibacterial nanozymes are discussed for their future clinical potential.