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Since the coronavirus pandemic, mRNA vaccines have revolutionized the field of vaccinology. Lipid nanoparticles (LNPs) are proposed to enhance mRNA delivery efficiency; however, their design is suboptimal. Here, a rational method for designing LNPs is explored, focusing on the ionizable lipid composition and structural optimization using machine learning (ML) techniques. A total of 213 LNPs are analyzed using random forest regression models trained with 314 features to predict the mRNA expression efficiency. The models, which predict mRNA expression levels post-administration of intradermal injection in mice, identify phenol as the dominant substructure affecting mRNA encapsulation and expression. The specific phospholipids used as components of the LNPs, as well as the N/P ratio and mass ratio, are found to affect the efficacy of mRNA delivery. Structural analysis highlights the impact of the carbon chain length on the encapsulation efficiency and LNP stability. This integrated approach offers a framework for designing advanced LNPs and has the potential to unlock the full potential of mRNA therapeutics.

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Owing to its low incidence, small trauma, fast recovery, and high efficiency, left atrial appendage occlusion has become a new strategy for preventing stroke caused by atrial fibrillation. Due to a lack of relevant research information on this emerging technology, the effectiveness, stability, or related complications of occluders are mostly observed from a clinical perspective. However, there are fewer studies on the mechanical properties and safety of these occluders. In this study, a new left atrial appendage occluder is proposed, and a complete numerical simulation analysis framework is established through the finite element method to simulate the actual implantation and service process of the left atrial appendage occluder. Besides, the influence of the structural size and release scale of the occluder on its support performance, occluding effect, and safety is also explored. The results demonstrate that the structural size and release scale exert a significant impact on the support performance, occluding effect, and safety of the occluder. The structural optimization of the occluder contributes to enhancing its mechanical performance, thus ensuring its stability and effectiveness after implantation. Overall, these efforts may lay a scientific foundation for the structural optimization, safety evaluation, and effectiveness prediction of the occluder. Furthermore, these findings also provide effective reference for the application of numerical simulation technology in the research on the left atrial appendage occlusion.

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This paper presents a comprehensive study of the structural optimization of polyimide-film (PI-film) capacitive humidity sensors, with a focus on enhancing their performance for application in new energy vehicles (NEVs). Given the critical role of humidity sensors in ensuring the safety and efficiency of vehicle operations─particularly in monitoring lithium-ion battery systems─the study explores the intricate relationship between the interdigitated electrode (IDE) dimensions and the PI-film thickness to optimize sensor responsiveness and reliability. Through a combination of COMSOL Multiphysics simulations (a powerful finite element analysis, solver, and simulation software) and experimental validation, the research identifies the optimal geometrical combination that maximizes the sensitivity and minimizes the response time. The fabrication process is streamlined for batch preparation, leveraging the spin-coating process to achieve consistent and reliable PI films. Extensive characterizations confirm the superior morphology, chemical composition, and humidity-sensing capabilities of the developed sensors. Practical performance tests further validate their exceptional repeatability, long-term stability, low hysteresis, and excellent selectivity, underpinning their suitability for automotive applications. The final explanation of the sensing mechanism provides a solid theoretical foundation for observed performance improvements. This work not only advances the field of humidity sensing for vehicle safety but also offers a robust theoretical and practical framework for the batch preparation of PI-film humidity sensors, promising enhanced safety and reliability for NEVs.

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Cellulose nanofibril (CNF) films with both high strength and high toughness are attractive for applications in energy, packaging, and flexible electronics. However, simultaneously achieving these mechanical properties remains a significant challenge. Herein, a multiscale structural optimization strategy is proposed to prepare high aspect ratio CNFs with reduced crystallinity for strong and tough films. Carboxymethylation coupled with mild mechanical disintegration is employed to modulate the multiscale structure of CNFs. The as-prepared CNFs feature an aspect ratio of >800 and a crystallinity of <60 %. The film prepared using CNFs with a high aspect ratio (~1100) and reduced crystallinity (~54 %) exhibits a tensile strength of 229.9 ± 9.9 MPa and toughness of 22.2 ± 1.4 MJ/m3. The underlying mechanism for balancing these mechanical properties is unveiled. The high aspect ratio of the CNFs facilitates the transfer and distribution of local stress, thus endowing the corresponding film with high strength and toughness. Moreover, the low crystallinity of the CNFs permits the movement of the cellulose chains in the amorphous regions, thereby dissipating energy and finally increasing the film toughness. This work introduces an innovative and straightforward method for producing strong and tough CNF films, paving the way for their broader applications.

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Polyimide (PI) films are well recognized for their outstanding chemical resistance, radiation resistance, thermal properties, and mechanical strength, rendering them highly valuable in advanced fields such as aerospace, sophisticated electronic components, and semiconductors. However, improving their optical transparency while maintaining excellent thermal properties remains a significant challenge. This review systematically checks over recent advancements in enhancing the optical and thermal performance of PI films, focusing on various strategies through molecular design. These strategies include optimizing the main chain, side chain, non-coplanar structures, and endcap groups. Rigid and flexible structural characteristics in the proper combination can contribute to the balance thermal stability and optical transparency. Introducing fluorinated substituents and bulky side groups significantly reduces the formation of charge transfer complexes, enhancing both transparency and thermal properties. Non-coplanar structures, such as spiro and cardo configurations, further improve the optical properties while maintaining thermal stability. Future research trends include nanoparticle doping, intrinsic microporous PI polymers, photosensitive polyimides, machine learning-assisted molecular design, and metal coating techniques, which are expected to further enhance the comprehensive optical and thermal performance of PI films and expand their applications in flexible displays, solar cells, and high-performance electronic devices. Overall, systematic molecular design and optimization have significantly improved the optical and thermal performance of PI films, showing broad application prospects. This review aims to provide researchers with valuable references, stimulate more innovative research and applications, and promote the deep integration of PI films into modern technology and industry.

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The acoustically actuated nanomechanical magnetoelectric (ME) antennas represent a promising new technology that can significantly reduce antenna size by 1-2 orders of magnitude compared to traditional antennas. However, current ME antennas face challenges such as low antenna gain and narrow operating bandwidth, limiting their engineering applications. In this paper, we enhance the bandwidth and radiation performance of ME antennas through structural optimization, leveraging theoretical analysis and numerical simulations. Our findings indicate that optimizing the inner diameter of the ring-shaped ME antenna can elevate the average stress of the magnetic layer, leading to improved radiation performance and bandwidth compared to circular ME antennas. We establish an optimization model for the radiation performance of the ME antenna and conduct shape optimization simulations using COMSOL Multiphysics. The results of the Multiphysics field optimization align with the stress concentration theory, demonstrating a strong correlation between the radiation performance and bandwidth of the ME antenna with the average stress of the magnetic film. The resonant frequency in the thickness vibration mode is determined to be 170 MHz. Furthermore, shape optimization can enhance the bandwidth by up to 104% compared to circular ME antenna structures of the same size.

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To amplify the displacement of the radiation shell, a double-shell type-IV curved hydroacoustic transducer was proposed. Through Ansys finite element simulation, the vibration modes of the transducer in different stages and the harmonic response characteristics in air and water were studied, and the bandwidth emission of the hydroacoustic transducer was achieved. By optimizing the size of each component, the resonant frequency of the transducer is 740 Hz, the maximum conductivity was 0.66 mS, and the maximum transmitting voltage response was 130 dB. According to the optimized parameters, a longitudinal acoustic transducer prototype was manufactured, and a physical test was conducted in an anechoic pool. The obtained resonant frequency was 750 Hz, the maximum conductivity was 0.44 mS, the maximum transmitting voltage response was 129.25 dB, and the maximum linear dimension was 250 mm, which match the simulated value of the virtual prototype and meet the expected requirements.

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Considering the high strength and excellent biocompatibility of low-nickel stainless steel, this paper focused on optimizing the design of a vascular stent made from this material using finite element analysis (FEA) combined with the response surface methodology (RSM). The aim is to achieve the desired compressive resistance for the stent while maintaining a thin stent wall thickness. The parameters of the stent's support unit width (H), strut width (W), and thickness (T) were selected as input parameters, while the output parameters obtained from FEA included the compressive load, the equivalent plastic strain (PEEQ), axial shortening rate, radial recoil rate, and metal coverage rate. The mathematical models of input parameters and output parameters were established by using the Box Behnken design (BBD) of RSM. The model equations were solved under constrained conditions, and the optimal structural parameters, namely H, W, and T, were finally determined as 0.770 mm, 0.100 mm, and 0.075 mm respectively. In this situation, the compression load of the stent reached the target value of 0.38 N/mm; the PEEQ resulting from the stent expansion was small; the axial shortening, radial recoil, and metal coverage index were all minimized within the required range.

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Amorphous carbon materials with sophisticated morphologies, variable carbon layer structures, abundant defects, and tunable porosities are favorable as anodes for potassium-ion batteries (PIBs). Synthesizing amorphous carbon materials typically involves the pyrolysis of carbonaceous precursors. Nonetheless, there is still a lack of studies focused on achieving multifaceted structural optimizations of amorphous carbon through precursor formulation. Herein, nitrogen-doped amorphous carbon nanotubes (NACNTs) are derived from a novel composite precursor of cobalt-based metal-organic framework (CMOF) and graphitic carbon nitride (g-CN). The addition of g-CN in the precursor optimizes the structure of amorphous carbon such as morphology, interlayer spacing, nitrogen doping, and porosity. As a result, NACNTs demonstrate significantly improved electrochemical performance. The specific capacities of NACNTs after cycling at current densities of 100 mA/g and 1000 mA/g increased by 194 % and 230 %, reaching 346.6 mAh/g and 211.8 mAh/g, respectively. Furthermore, the NACNTs anode is matched with an organic cathode for full-cell evaluation. The full-cell attains a high specific capacity of 106 mAh/gcathode at a current density of 100 mA/g, retaining 90.5 % of the specific capacity of the cathode half-cell. This study provides a valuable reference for multifaceted structural optimization of amorphous carbon to improve potassium-ion storage capability.

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Necroptosis is a form of regulated necrotic cell death and has been confirmed to play pivotal roles in the pathogenesis of multiple autoimmune diseases such as rheumatoid arthritis (RA) and psoriasis. The development of necroptosis inhibitors may offer a promising therapeutic strategy for the treatment of these autoimmune diseases. Herein, starting from the in-house hit compound 1, we systematically performed structural optimization to discover potent necroptosis inhibitors with good pharmacokinetic profiles. The resulting compound 33 was a potent necroptosis inhibitor for both human I2.1 cells (IC50 < 0.2 nM) and murine Hepa1-6 cells (IC50 < 5 nM). Further target identification revealed that compound 33 was an inhibitor of receptor interacting protein kinase 1 (RIPK1) with favorable selectivity. In addition, compound 33 also exhibited favorable pharmacokinetic profiles (T1/2 = 1.32 h, AUC = 1157 ng·h/mL) in Sprague-Dawley rats. Molecular docking and molecular dynamics simulations confirmed that compound 33 could bind to RIPK1 with high affinity. In silico ADMET analysis demonstrated that compound 33 possesses good drug-likeness profiles. Collectively, compound 33 is a promising candidate for antinecroptotic drug discovery.

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Purpose: To address the application requirements of soft actuators in rehabilitation training gloves, and in combination with ergonomic requirements, we designed a segmented soft actuator with bending and elongation modules. This actuator can achieve independent or coupled movements of the finger joints. Methods: A finite element model of the joint actuator was established to compare the driving performance of actuators with different structural forms. Numerical calculations were used to analyze the effects of structural size parameters on the bending characteristics and end output force of the actuator. The design was then refined based on these analyses. Results: The joint actuator designed in this study demonstrated a 71% increase in bending angle compared to the standard fast pneumatic network structure. Key factors affecting the driving performance include the thickness of the constraint layer, the inner wall thickness of the chamber, chamber height, chamber width, chamber spacing, chamber length, and the number of chambers. After improvements, the bending angle of the joint actuator increased by 60.6%, and the output force increased by 145.9%, indicating significant improvement. Conclusion: This study designed and improved a soft actuator for hand rehabilitation training, achieving independent and coupled joint movements. The bending angle, bending shape, and joint driving force of the soft actuator meet the requirements for finger rehabilitation training.

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Celangulin V is a novel botanical insecticide with significant bioactivity and a unique molecular target, but its complex polyol ester structure hinders its broader application in agriculture. To discover new analogues of celangulin V with a simpler structure and enhanced biological activities, we initiated a research project aimed at simplifying its structure and assessing insecticidal efficacy. In this study, a series of novel 1-tetralone derivatives were designed via a structure-based rational design approach and synthesized by a facile method. The biological activities of the target compounds were determined against Mythimna separata (M. separata), Plutella xylostella, and Rhopalosiphum padi. The results revealed that most of the synthesized compounds exhibited superior activities compared to celangulin V. Remarkably, the insecticidal activity of compound 6.16 demonstrated 102-fold greater stomach toxicity than celangulin V against M. separata. In addition, certain compounds showed significant contact toxicity against M. separata, a finding not reported previously in the structural optimization studies of celangulin V. Molecular docking analysis illustrated that the binding pocket of compound 6.16 with the H subunit of V-ATPase was the same as celangulin V. This study presents novel insights into the structural optimization of botanical pesticides.

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Land use changes have profoundly influenced global environmental dynamics. The Yellow River (YR), as the world's fifth-longest river, significantly contributes to regional social and economic growth due to its extensive drainage area, making it a key global player. To ensure ecological stability and coordinate land use demand, modeling the future land allocation patterns of the Yellow River Basin (YRB) will assist in striking a balance between land use functions and the optimization of its spatial design, particularly in water and sand management. In this research, we used a multi-objective genetic algorithm (MOGA) with the PLUS model to simulate several different futures for the YRB's land use between 1990 and 2020 and predict its spatial pattern in 2030. An analysis of the spatiotemporal evolution of land use changes in the YRB indicated that construction land expansion is the primary driver of landscape pattern and structure changes and ecological degradation, with climate change also contributing to the expansion of the watershed area. On the other hand, the multi-scenario simulation, constrained by specific targets, revealed that economic development was mainly reflected in land expansion for construction. At the same time, grassland and woodland were essential pillars to support the region's ecological health, and increasing the development of unused land emerged as a potential pathway towards sustainable development in the region. This study could be used as a template for the long-term growth of other large river basins by elucidating the impacts of human activities on land use and rationalizing land resource allocation under various policy constraints.

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This paper discusses the influence of the digital economy (DE) on carbon emissions based on evidence at the global level. Specifically, based on the panel data from 80 countries from 2010 to 2020, this paper creates a DE measurement index and uses the System-GMM model to assess the influence of DE on carbon emissions. The results show that: (1) The development of DE significantly promotes carbon emissions reduction. (2) The development of DE significantly promotes carbon emissions reduction through technological advancement, structural optimization, and educational enhancement; (3) Regulatory quality and financial development play a positively moderating role in DE's promoting effect on carbon emissions reduction; (4) DE of European and North American nations have stronger promoting effect on carbon emissions reduction than DE of other countries. Compared to DE of developing countries, DE of developed countries has a stronger promoting effect on carbon emissions reduction. Additionally, this paper also finds that institutional differences can impact the carbon emission reduction effects of DE. Based on the results, this paper suggests that governments globally should promote the development of DE and foster international cooperation to enhance DE's driving role in promoting carbon emissions reduction.

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The clinical performance of biodegradable polymer stents implanted in blood vessels is affected by uneven degradation. Stress distribution plays an important role in polymer degradation, and local stress concentration leads to the premature fracture of stents. Numerical simulations combined with in vitro experimental validation can accurately describe the degradation process and perform structural optimization. Compared with traditional design techniques, optimization based on surrogate models is more scientifically effective. Three stent structures were designed and optimized, with the effective working time during degradation as the optimization goal. The finite element method was employed to simulate the degradation process of the stent. Surrogate models were employed to establish the functional relationship between the design parameters and the degradation performance. The proposed function models accurately predicted the degradation performance of various stents. The optimized stent structures demonstrated improved degradation performance, with the kriging model showing a better optimization effect. This study provided a novel approach for optimizing the structural design of biodegradable polymer stents to enhance degradation performance.

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Small-molecule glucagon-like peptide-1 receptor (GLP-1R) agonists are recognized as promising therapeutics for type 2 diabetes mellitus (T2DM) and obesity. Danuglipron, an investigational small-molecule agonist, has demonstrated high efficacy in clinical trials. However, further development of danuglipron is challenged by a high rate of gastrointestinal adverse events. While these effects may be target-related, it is plausible that the carboxylic acid group present in danuglipron may also play a role in these outcomes by affecting the pharmacokinetic properties and dosing regimen of danuglipron, as well as by exerting direct gastrointestinal irritation. Therefore, this study aims to replace the problematic carboxylic acid group by exploring the internal binding cavity of danuglipron bound to GLP-1R using a water molecule displacement strategy. A series of novel triazole-containing compounds have been designed and synthesized during the structure-activity relationship (SAR) study. These efforts resulted in the discovery of compound 2j with high potency (EC50 = 0.065 nM). Moreover, docking simulations revealed that compound 2j directly interacts with the residue Glu387 within the internal cavity of GLP-1R, effectively displacing the structural water previously bound to Glu387. Subsequent in vitro and in vivo experiments demonstrated that compound 2j had comparable efficacy to danuglipron in enhancing insulin secretion and improving glycemic control. Collectively, this study offers a practicable approach for the discovery of novel small-molecule GLP-1R agonists based on danuglipron, and compound 2j may serve as a lead compound to further exploit the unoccupied internal cavity of danuglipron's binding pocket.

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BACKGROUND: Transketolase (TKL, EC 2.2.1.1) is a key enzyme in the pentose phosphate pathway and Calvin cycle, and is expected to act as a herbicidal site-of-action. On the basis of TKL, we designed and synthesized a series of 1-oxy-propionamide-pyrazole-3-carboxylate analogues and evaluated their herbicidal activities. RESULTS: Methyl 1-methyl-5-((1-oxo-1-((4-(trifluoromethyl)phenyl)amino)propan-2-yl)oxy)-1H-pyrazole-3-carboxylate (C23) and methyl 1-methyl-5-((1-oxo-1-((perfluorophenyl)amino)propan-2-yl)oxy)-1H-pyrazole-3-carboxylate (C33) were found to provide better growth-inhibition activities against Digitaria sanguinalis root than those of nicosulfuron, mesotrione and pretilachlor at 200 mg L-1 using the small-cup method. These compounds were also identified as promising compounds in pre-emergence and postemergence herbicidal-activity experiments, with relatively good inhibitory effects toward Amaranthus retroflexus and D. sanguinalis at 150 g ai ha-1. In addition, enzyme inhibition assays and molecular docking studies revealed that C23 and C33 interact favourably with SvTKL (Setaria viridis TKL). CONCLUSION: C23 and C33 are promising lead TKL inhibitors for the optimization of new herbicides. © 2024 Society of Chemical Industry.

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Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and high mortality lung disease. Although the antifibrotic drugs pirfenidone and nintedanib could slow the rate of lung function decline, the usual course of the condition is inexorably to respiratory failure and death. Therefore, new approaches and novel therapeutic drugs for the treatment of IPF are urgently needed. And the selective PDE4 inhibitor has in vivo and in vitro anti-fibrotic effects in IPF models. But the clinical application of most PDE4 inhibitors are limited by their unexpected and severe side effects such as nausea, vomiting, and diarrhea. Herein, structure-based optimizations of the natural product Moracin M resulted in a novel a novel series of 2-arylbenzofurans as potent PDE4 inhibitors. The most potent inhibitor L13 has an IC50 of 36 ± 7 nM with remarkable selectivity across the PDE families and administration of L13·citrate (10.0 mg/kg) exhibited comparable anti-pulmonary fibrosis effects to pirfenidone (300 mg/kg) in a bleomycin-induced IPF mice model, indicate that L13 is a potential lead for the treatment of IPF.

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Conventional cooling channels used in die casting molds exhibit significant drawbacks, resulting in extended cooling times for cast parts. Issues such as the formation of dirt, limescale, and corrosion substantially diminish the thermal efficiency of these channels, leading to challenges in achieving uniform cooling and potential quality issues. In response to these challenges, this study proposes Topology Optimization as a novel approach. It involves designing cooling structures through Topology Optimization to replace traditional cooling channels, incorporating both Discrete and Gaussian boundary conditions to optimize thermal efficiency. Additionally, Structural Topology Optimization is employed to ensure structural integrity, preventing deformation or yielding under high loads during the die casting process. Numerical analysis revealed superior thermal performance compared to conventional channels, particularly when subjected to Discrete and Gaussian boundary conditions. Furthermore, the application of the latter establishes conformal cooling and minimizes temperature gradients in the casting, reducing casting defects such as shrinkage porosity. These findings highlight the efficacy of Topology Optimization in addressing the challenges of traditional cooling methods, with wide-ranging implications for manufacturing processes utilizing permanent molds for shaping materials.

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We previously revealed that phosphine-boranes can function as molecular frameworks for biofunctional molecules. In the present study, we exploited the diversity of available phosphines to design and synthesize a series of B-(trifluoromethyl)phenyl phosphine-borane derivatives as novel progesterone receptor (PR) antagonists. We revealed that the synthesized phosphine-borane derivatives exhibited LogP values in a predictable manner and that the P-H group in the phosphine-borane was almost nonpolar. Among the synthesized phosphine-boranes, which exhibited PR antagonistic activity, B-(4-trifluoromethyl)phenyl tricyclopropylphosphine-borane was the most potent with an IC50 value of 0.54 µM. A docking simulation indicated that the tricyclopropylphosphine moiety plays an important role in ligand-receptor interactions. These results support the idea that phosphine-boranes are versatile structural options in drug discovery, and the developed compounds are promising lead compounds for further structural development of next-generation PR antagonists.

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