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In this paper, a hierarchical design framework is proposed for distributed control of multi-agent systems. Different from the traditional distributed design philosophy that directly couples the agents' cooperation and individual regulations, the proposed framework decouples these regulations and separates the distributed control design into two layers, i.e., the layer of reference signal generator design and the layer of tracking controllers design. Specifically, the nodes of the generator play the roles of some virtual agents that achieve the distributed control goal and the agents' tracking controllers are used to track the reference signals produced by the generator. The novel design framework makes the agents reach the distributed control goal well and it has better design flexibility/practicality and stronger versatility/scalability. To demonstrate these advantages, two types of representative examples on hierarchical design are exhibited for multi-agent systems with mismatched disturbances and those with communication/input delays, respectively. All examples confirm that the proposed design framework is a natural choice in the presence of some complex factors, which provides not only simpler design but also more autonomy to the agents. [ABSTRACT FROM AUTHOR]

As an immune-regulator, Astragalus polysaccharides (APS) could effectively modulate the activity of toll-like receptor 4 (TLR4) signaling pathway, and induce anti-inflammatory response in intestinal. Our research before indicated that toll/interleukin 1 receptor-domain-containing adapter-inducing interferon-b (TRIF) might be a critical regulator for APS. So, in this experiment, we analyzed the effects of APS on lipopolysaccharide (LPS)-infected Caco2 cells in the circumstances of TRIF knockout. By using qRT-PCR and flow cytometry method, we analyzed the genes expression at transcriptional and translational level, respectively. The results of genes expression at both transcription and translation level showed that LPS could activate the myeloid differentiation factor 88 (MyD88)-TNF receptor associated factor (TRAF) pathway downstream from TLR4, and induce the high expression of pro-inflammatory cytokines. However, APS could effectively suppress the LPS induced inflammatory response. While, in the context of TRIF knockout, APS couldn't effectively attenuate the LPS activated MyD88-TRAF6 pathway, as well as the expression of pro-inflammatory cytokines. Above all, we concluded that APS could antagonize the LPS induced inflammatory response by a TRIF-dependent manner. Unlabelled Image [ABSTRACT FROM AUTHOR]

Triazole antifungal pesticides work by inhibiting the activity of lanosterol-14-α-demethylase, a member of cytochrome P450 enzymes (CYPs), but this effect is non-specific. Bile acids (BAs) are important physical surfactants for lipids absorption in intestine, and synthesized by CYPs 7A1/27A1. Thus, we presume that triazole exposure might influence the therapeutic effect or safety of oral medication through disturbing the BAs pool, even though the exposure is under an acceptable daily intake (ADI) dose. Short- and long-term of ADI dose tebuconazole (TEB) exposure animal models were established through various routes, and statins with different hydrophilic and lipophilic properties were gavaged. It exhibited that the activity of CYP7A1/27A1 was indeed inhibited but the expression was up-regulated, the BAs pool was changed either the content and the composition, and the absorption behavior of statins with strong and medium degree of lipid-solubility were significantly changed. A series of experiments performed on models of intestinal mucus, Caco-2 cell monolayer and Caco-2/HT29 co-culture system revealed that the TEB-exposure induced BAs disturbance made impacts on drug absorption in many aspects, including drug solubility and the structure of intestinal barriers. This study suggests us to be more alert about the hazard of pesticides residues for elderly and chronically ill groups. [Display omitted] • Acceptable daily intake dose triazoles exposure can lead bile acids (BAs) disturbance. • BAs disturbance remarkably changes the oral absorption behavior of lipophilic drugs. • It may increase additional risk for elderly and chronically ill groups. • We should be more alert about the hazard of pesticide residues. [ABSTRACT FROM AUTHOR]

The motion of charged seawater in a submarine wake, which is affected by the variance in the ion mass and the presence of a background geomagnetic field, results in a consequential wake magnetic field. The magnetic field is critical for the detection and monitoring of underwater targets. Despite its importance, the intricate relationship among hydrodynamics, ion transport, and electromagnetic fields, which collectively affect the generation of magnetic fields in submarine wakes, has yet to be sufficiently and systematically investigated. Hence, we formulate a theoretical model of the submarine wake magnetic field. This innovative interdisciplinary model seamlessly integrates the effects of ion inertia and ion induction in the marine environment. By performing multiphysics coupling simulations, we meticulously replicate the evolution of the wake magnetic field induced by the movement of a submarine propeller system. We comprehensively examine the velocity and magnetic-field components to elucidate the intricate mechanism of wake magnetic field generation. Furthermore, we comprehensively analyze the effects of ion inertia and ion induction on the wake magnetic field. Our findings highlight the predominant role of the ion-induction effect in determining the wake magnetic field when a submarine maintains a constant speed. Additionally, we investigate the effect of the submarine heading on the wake magnetic field and discuss the magnetic-field characteristics and attenuation rules at various axial and radial positions in the wake for different headings. Our scientific insights contribute considerably to the understanding of wake magnetic fields and offer valuable perspectives that can potentially advance future underwater target-detection methodologies based on wake magnetic fields. • The wake magnetic field is critical for the detection and monitoring of underwater targets. • Based on ion-force analysis, a complete theoretical model of the submarine wake magnetic field in an oceanic environment is established. • The effect of the mass difference of ions on the wake magnetic field is investigated. • The effect of the submarine heading on the wake magnetic field is investigated. [ABSTRACT FROM AUTHOR]

Under the influence of the geomagnetic environment, charged seawater motion in the submarine wake generates a wake electromagnetic field, which is of great significance for underwater target detection and tracking. The generation of the wake electromagnetic field involves the coupling of multiple physical fields, such as fluid mechanics, ion transport, and electromagnetic fields, which have not yet been systematically studied. In this context, a coupling model involving the flow and electromagnetic fields is constructed to analyze the evolution of the far-field wake magnetic field of a full-size submarine propeller system. The flow field, current density, and far-field distribution of the wake magnetic field of the submarine propeller system at typical and rotational speeds are obtained. The three-component and total distributions of the far-field wake magnetic field are analyzed, and the longitudinal variation is discussed. The mechanism of the wake magnetic field is revealed based on this. In addition, the attenuation rule of the far-field wake electromagnetic field is studied, and the frequency characteristics of the far-field wake electromagnetic field are analyzed by a power spectrum. The results show that the wake electromagnetic field generated by the submarine propeller system in the far-field region has a wide distribution range (0.1 nT), and the corresponding frequency characteristics can be detected by a precision magnetometer. This study provides useful insight for the further evaluation of the far-field law of wake electromagnetic fields, which is conducive for future underwater target detection based on wake electromagnetic fields. [ABSTRACT FROM AUTHOR]

Generally, autophagy/mitophagy, as a highly conserved lysosomal-based catabolic pathway, compromises the photodynamic therapy (PDT) efficiency by increasing the adaptation of tumor cells toward reactive oxygen species (ROS)-triggered protein damages and mitochondrial destruction. On the other hand, excessively activated autophagy/mitophagy cascades can provoke autophagic cell death and promote the endogenous antigens release of dying cells, thus playing a vital role in initiating the antitumor immune responses. To harness the exquisite immunomodulating effect of pro-death autophagy/mitophagy, we rationally constructed a MnO 2 shell-coated multifunctional porphyrinic metal–organic framework (MOF) to load carbonyl cyanide 3-chlorophenylhydrazone (CCCP). The wrapped MnO 2 shell could not only prevent premature release of CCCP during blood circulation but also conquer tumor hypoxia by catalyzing the decomposition of intratumoral H 2 O 2. After entering tumor cells, the MnO 2 shell could scavenge over-expressed glutathione (GSH), resulting in burst CCCP release and GSH-depletion/O 2 -generation enhanced PDT. More importantly, the released CCCP acts as a mitochondrial uncoupler can elicit mitochondrial depolarization and mitophagy, which could significantly boost the autophagy/mitophagy levels generated during PDT and consequently convert the pro-survival autophagy/mitophagy to pro-death, leading tumor cells to autophagic and immunogenic cell death. In vivo results reveal that the CCCP synergistic PDT could induce excessive immunostimulatory autophagy/mitophagy associated with T-cell responses and immunological memory, leading to complete ablation of primary tumors and prevention of tumor recurrence and lung metastasis. The effectiveness of this strategy may highlight the pro-death role and immunomodulating effect of autophagy/mitophagy in cancer therapy, providing a novel yet versatile avenue to enhance the efficacy of cancer treatments. [ABSTRACT FROM AUTHOR]