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This parallel‐group, open‐label Phase I study evaluated the effect of mild to moderate hepatic impairment on pharmacokinetics (PK), pharmacodynamics (PD), and safety of a single oral dose of SHR4640. Participants with mild or moderate hepatic impairment were enrolled, with each cohort consisting of eight individuals, alongside eight well‐matched controls with normal hepatic function. The participants were administered 10 mg SHR4640, and blood samples were collected for PK evaluation over 72 h. Additionally, serum uric acid (sUA) levels were measured to assess PD changes. Safety was evaluated through adverse events, laboratory tests, vital signs, and electrocardiograms. The Cmax of SHR4640 decreased by 15.0% in the mild hepatic impairment group (geometric least squares means of the ratios [GMR] = 0.850, 90% CI: 0.701‐1.03) and by 17.5% in the moderate hepatic impairment group (GMR = 0.825, 90% CI: 0.681‐1.00). These reductions were not statistically significant compared to the normal hepatic function group. AUC0‐t and AUC0‐inf were similar across all groups, indicating that overall exposure to the drug was not clinical significantly affected by hepatic impairment. Apparent clearance and volume of distribution of SHR4640 showed no association with the severity of hepatic impairment as measured by the Child–Pugh score. There were no significant differences in the changes in sUA levels from baseline across different levels of hepatic function. SHR4640 is well tolerated in participants with mild or moderate hepatic impairment. Mild and moderate hepatic impairment did not have a clinically relevant impact on PK, PD, and safety of SHR4640. SHR4640 can be used in patients with mild to moderate hepatic impairment without the need for dose adjustment. [ABSTRACT FROM AUTHOR]

Brassinosteroids (BRs) perform crucial functions controlling plant growth and developmental processes, encompassing many agronomic traits in crops. Studies of BR-related genes involved in agronomic traits have suggested that BRs could serve as a potential target for crop breeding. Given the pleiotropic effect of BRs, a systematic understanding of their functions and molecular mechanisms is conducive for application in crop improvement. Here, we summarize the functions and underlying mechanisms by which BRs regulate the several major crop agronomic traits, including plant architecture, grain size, as well as the specific trait of symbiotic nitrogen fixation in legume crops. For plant architecture, we discuss the roles of BRs in plant height, branching number and leaf erectness, and propose how progress in these fields may contribute to designing crops with optimal agronomic traits and improved grain yield by accurately modifying BR levels and signaling pathways. [ABSTRACT FROM AUTHOR]

Using amino acid residues in peptide generation has solved several key problems, including precise control of amino acid sequence order, customized peptides for property modification, and large-scale peptide synthesis. Proteins contain unknown amino acid residues. Extracting them for the synthesis of drug-like peptides can create novel structures with unique properties, driving drug development. Computer-aided design of novel peptide drug molecules can solve the high-cost and low-efficiency problems in the traditional drug discovery process. Previous studies faced limitations in enhancing the bioactivity and drug-likeness of polypeptide drugs due to less emphasis on the connection relationships in amino acid structures. Thus, we proposed a reinforcement learning-driven generation model based on graph attention mechanisms for peptide generation. By harnessing the advantages of graph attention mechanisms, this model effectively captured the connectivity structures between amino acid residues in peptides. Simultaneously, leveraging reinforcement learning's strength in guiding optimal sequence searches provided a novel approach to peptide design and optimization. This model introduces an actor-critic framework with real-time feedback loops to achieve dynamic balance between attributes, which can customize the generation of multiple peptides for specific targets and enhance the affinity between peptides and targets. Experimental results demonstrate that the generated drug-like peptides meet specified absorption, distribution, metabolism, excretion, and toxicity properties and bioactivity with a success rate of over 90 |$\%$|⁠ , thereby significantly accelerating the process of drug-like peptide generation. [ABSTRACT FROM AUTHOR]

A reinforcement learning-driven brain storm optimisation idea (RLBSO) is proposed in this paper to solve multi-objective energy-efficient distributed assembly no-wait flow shop scheduling problem. The objectives of the problem include minimising the maximum assembly completion time ( C max ), minimising the total energy consumption (TEC) and achieving resource allocation balanced. Four operations, which are critical factory insert, critical factory swap, critical factory insert to other factories, critical factory swap with other factories, are designed to optimise the objective of maximum assembly completion time. Q-learning mechanism is utilised to guide the selection of operations to avoid blind search in the iteration process. The learning mechanism based on clustering mechanism in brain storm optimisation algorithm is utilised to assign products to factories in the objective space according to the processing time of products to balance the resources allocation. The speed of operations on non-critical path is slowed down to reduce TEC regarded with the characteristics of no-wait flow shop scheduling problem. The experimental results under 810 large-scale instances by RLBSO show that the RLBSO outperforms the comparison algorithm for addressing the problem. [ABSTRACT FROM AUTHOR]

To address the challenges of indoor mold in southern China, this study designed and constructed an innovative experimental system to investigate mold growth in buildings under the combined influence of multiple factors. Using Fluent simulation (Ansys Fluent 19.0), we designed a suitably sized experimental chamber to realistically replicate the effects of factors such as temperature, humidity, and air velocity on mold growth. After establishing and fine-tuning the experimental system, we conducted two preliminary experiments, successfully validating the feasibility of our setup. Additionally, we observed that in a high-temperature, high-humidity environment of 28 °C and 80% relative humidity, the mold growth rate in the experimental chamber increased with the rise in inlet air velocity. This experimental system will serve as the foundation for future studies on indoor mold growth in building spaces in southern China. [ABSTRACT FROM AUTHOR]