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An N-heterocyclic carbene-catalyzed [4 + 2] annulation of β,γ-unsaturated α-keto esters and phenylacetate esters was developed for the direct and efficient construction of 2-pyrones. This approach provides a practical synthesis pathway for various 3,4,6-trisubstituted 2-pyrones in moderate to good yields and features broad substrate scope and good functional group tolerance. Moreover, the products can also be readily transformed to naphthalene and acylamide.

Role-based collaboration (RBC) is a new problem-solving paradigm that uses model environments-classes, agents, roles, groups, and objects (E-CARGO) to facilitate modeling. Task decomposition is widely adopted to reduce the difficulty of execution, resulting in multigroup collaboration problems. Multigroup role assignment (MGRA) has been proposed to solve the assignment of multiple groups. In many actual scenarios, there are dependencies between the decomposed subtasks, which is neglected by existing MGRA methods. Moreover, they disregard the fact that subtasks have diverse significance in the development of a project, which is of paramount importance to ensure the proper allocation of resources. To solve the complicated problem, the structured subtasks are formalized based on the emerging and promising RBC theory and E-CARGO model. Then, the assignment is abstracted into a complicated single-objective multiconstraint problem, named adaptive-equalized MGRA (AE-MGRA). In the formulated AE-MGRA problem, to improve the utilization of limited resources, the performance of each E-CARGO group needs to be equalized according to the corresponding subtask’s weight. As the optimal solution is difficult and time consuming to obtain, a tolerable deviation is utilized to achieve a near-optimal solution. Extensive experiments are conducted to sufficiently demonstrate the efficiency and stability of the proposed practical solution. In addition, the experimental results on static assignment and dynamic assignment further prove the effectiveness of the solution.

To improve the oral absorption and anticancer efficacy of the BCS-IV drug etoposide (ETO), oral nanocrystal-loaded lipid carriers (Lipo@NCs) were developed in this study by modifying the BCS-IV drug nanocrystal with the lipid bilayer. The ETO-Lipo@NCs were prepared by the thin film hydration high-pressure homogenization method, and the core of positively charged ETO nanocrystals was prepared by the sonoprecipitation-high pressure homogenization method. The optimized ETO-Lipo@NCs were spherical particles with an average particle size of 220.3 ± 14.2 nm and a zeta potential of −9.95 ± 0.81 mV, respectively. The successful coating of a lipid bilayer on the surface of nanocrystals in ETO-Lipo@NCs was confirmed by several characterization methods. Compared to nanocrystals, the release rate and degree of Lipo@NCs in SIF were significantly decreased, indicating that the lipid bilayer can effectively prevent the rapid dissolution of core nanocrystals. ETO-Lipo@NCs demonstrated a significant improvement in the intestinal permeability and absorption of ETO in a single intestinal perfusion experiment. In the cells, ETO-Lipo@NCs showed enhanced cellular uptake and transepithelial transport compared with ETO nanocrystals. Pharmacokinetic analysis indicated that ETO-Lipo@NCs had a longer plasma half-life than ETO solution, and the oral bioavailability of ETO-Lipo@NCs was 1.96- and 10.92-fold higher than that of ETO nanocrystals and ETO coarse crystals, respectively. Moreover, the ETO-Lipo@NCs orally dosed at 10 mg/kg exhibited an excellent inhibitory effect against tumors in a subcutaneous Lewis lung carcinoma (LLC) xenograft model compared with other preparations. These results indicate that the Lipo@NCs formulation has an oral absorption-promoting effect of the BCS-IV drug ETO, which could warrant further application in the oral delivery of other poorly bioavailable drugs.

In situations involving teams of diverse robots, assigning appropriate roles to each robot and evaluating their performance is crucial. These roles define the specific characteristics of a robot within a given context. The stream of actions exhibited by a robot based on its assigned role are referred to as the process role. Our research addresses the depiction of process roles using a multivariate probabilistic function. The main aim of this study is to develop a role engine for collaborative multirobot systems and optimize the behavior of the robots. The role engine is designed to assign suitable roles to each robot, generate approximately optimal process roles, update them on time, and identify instances of robot malfunction or trigger replanning when necessary. The environment considered is dynamic, involving obstacles and other agents. The role engine operates hybrid, with central initiation and decentralized action, and assigns unlabeled roles to agents. We employ the Gaussian process (GP) inference method to optimize process roles based on local constraints and constraints related to other agents. Furthermore, we propose an innovative approach that utilizes the environment’s skeleton to address initialization and feasibility evaluation challenges. We successfully demonstrated the proposed approach’s feasibility, and efficiency through simulation studies and real-world experiments involving diverse mobile robots.

The biological activity of plant polysaccharides can be enhanced by sulfated modification. In this study, the immunomodulatory effect of sulfated Cyclocarya paliuruspolysaccharides (SCP3) on macrophages RAW264.7 and its potential molecular mechanism were investigated. Results showed that SCP3 at 25−100 μg/mL increased viability and improved phagocytosis of RAW264.7 cells. Meanwhile, SCP3 could activate mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways, which increased the phosphorylation of Erk1/2, JNK, p38 and NF-κB p65, promoting secretion of cytokines tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and nitric oxide (NO) as well as the production of reactive oxygen species (ROS). In addition, Toll-like receptor 4 (TLR4) receptor inhibitors were able to block the production of NO and TNF-α by SCP3-stimulated macrophages. Based on Western blot analysis and validation using specific inhibitors against MAPK and NF-κB signaling pathways, the results demonstrated that SCP3 induced macrophages activation and enhanced TNF-α and NO production via TLR4-mediated MAPK and NF-κB pathways. In summary, SCP3 has significant immunomodulatory potential. The underlying molecular mechanism was that SCP3 activates macrophages via TLR4 receptors to promote ROS production, which in turn activates the downstream MAPK/NF-κB signaling pathway and then increases the secretion levels of cytokines and NO.

Dry reforming of methane (DRM) is an efficient way for CO2utilization to convert CH4and CO2to syngas (H2and CO), which is an ingredient to produce hydrogen and methanol and hydrocarbons viaFischer–Tropsch process. Considerable attention is drawn to Ni-based catalyst due to its remarkable reactivity for CH4and CO2conversion. However, the weakness of sintering and coking restrains its industrial applications. The successful design of cost-effective, efficient and stable Ni-based catalysts would be a grand breakthrough for the technology. Herein, the thermodynamic analysis and the mechanisms of sintering and coking are presented. Then, the strategies for improving the performance of catalysts are elaborated as follows, with 1) supports improving the particle dispersion of nickels and changing the reaction process for the hindrance of coking; 2) promoters for regulating the nickel's chemical properties to enable catalytic DRM performance; 3) catalysts obtained by varied preparation methods possess different sizes and interactions. Finally, the challenges and future perspectives are highlighted.

For the first time, finite element analysis (FEA) is applied to the thermal-compression flip-chip process in microelectronics. By adding the bump height non-uniformity and the morphology variance, a common basal line is established. Although the experiment confirms the rate-dependence of indium, an approximation is made to derive the material properties in FEA. The relative standard deviation (RSD) of deformation between the FEA model and the reality is around 1% when predicting the misaligned flip-chip specimen. Besides, the modeled bump characteristic with misalignment coincides with the cross-sectional scanning electron microscope (SEM) picture. The model could be served as a powerful tool to guide the manufacturing process.

Magnetoelectric (ME) antennas have offered significant advantages in the design of very-low-frequency (VLF) communication systems operating in challenging environments such as underground, underwater, and inside metallic enclosures. However, state-of-the-art ME-based communication systems either depend on bulky commercial signal processing instruments or have limited reports on digital signal transmissions. In this work, we demonstrate a compact design of an ME VLF communication system based on self-designed modulator and demodulator circuits, working at the electromechanical resonance (EMR) frequency of the ME antenna and having a remarkably reduced size for greater applicability in realistic industrial scenarios. The concept of sending Morse code through amplitude-shift-keying (ASK) modulation was confirmed in the proposed ME VLF communication system. Our findings revealed that the maximum communication distance can be considered as 5.7 m when the bit error rate (BER) is limited to $10^{-2}$ . Furthermore, VLF wireless signal transfer through a harsh environment (metal box) was verified with our communication system. An effective communication distance of 0.85 m could be realized when placing the ME receiver in a 5-mm iron box, demonstrating the ability of the wireless signal to penetrate conductive media. The proposed fully packed ME VLF communication system provides advantageous alternative for underground, underwater, and inside-metal-container communications.

T-cell receptor (TCR)-engineered T cells can precisely recognize a broad repertoire of targets derived from both intracellular and surface proteins of tumor cells. TCR-T adoptive cell therapy has shown safety and promising efficacy in solid tumor immunotherapy. However, antigen-specific functional TCR screening is time-consuming and expensive, which limits its application clinically. Here, we developed a novel integrated antigen–TCR screening platform based on droplet microfluidic technology, enabling high-throughput peptide–major histocompatibility complex (pMHC)-to-TCR paired screening with a high sensitivity and low background signal. We introduced DNA barcoding technology to label peptide antigen candidate-loaded antigen-presenting cells and Jurkat reporter cells to check the specificity of pMHC–TCR candidates. Coupled with the next-generation sequencing pipeline, interpretation of the DNA barcodes and the gene expression level of the Jurkat T-cell activation pathway provided a clear peptide–MHC–TCR recognition relationship. Our proof-of-principle study demonstrates that the platform could achieve pMHC–TCR paired high-throughput screening, which is expected to be used in the cross-reactivity and off-target high-throughput paired testing of candidate pMHC–TCRs in clinical applications.

This article systematically establishes a new category of assignment problems by reviewing and extending the problems related to group role assignment (GRA) from a novel vision. After reviewing seven related GRA with Constraints (GRA+) problems, this article specifies three new major assignment problems to make GRA+ problems complete and coherent. In addition, this article proves a series of new related theorems, proposes new conditions for the specified problems to have feasible solutions, and verifies the hardness of the newly specified problems. This article finally verifies the value of the presented theoretical work and provides a generalized formalization of this category of problems, i.e., the one highly abstract optimization problem, which is specified the first time. This article contributes to the literature of assignment problems with a novel category of well-defined problems, i.e., GRA+. The presented problem category is original, consistent, but far from complete. It will initiate further innovations in assignment research along with the presented directions. This article again demonstrates the power of the methodology role-based collaboration (RBC), and the environments—classes, agents, roles, groups, and objects (E-CARGO) model.