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This paper studies the robust bipartite consensus problems for heterogeneous nonlinear nonaffine discrete-time multi-agent systems (MASs) with fixed and switching topologies against data dropout and unknown disturbances. At first, the controlled system's virtual linear data model is developed by employing the pseudo partial derivative technique, and a distributed combined measurement error function is established utilizing a signed graph theory. Then, an input gain compensation scheme is formulated to mitigate the effects of data dropout in both feedback and forward channels. Moreover, a data-driven learning-based robust bipartite consensus control (LRBCC) scheme based on a radial basis function neural network observer is proposed to estimate the unknown disturbance, using the online input/output data without requiring any information on the mathematical dynamics. The stability analysis of the proposed LRBCC approach is given. Simulation and hardware testing also illustrate the correctness and effectiveness of the designed method.

The fiducial marker system for LiDAR is crucial for the robotic application but it is still rare to date. In this paper, an Intensity Image-based LiDAR Fiducial Marker (IILFM) system is developed. This system only requires an unstructured point cloud with intensity as the input and it has no restriction on marker placement and shape. A marker detection method that locates the predefined 3D fiducials in the point cloud through the intensity image is introduced. Then, an approach that utilizes the detected 3D fiducials to estimate the LiDAR 6-DOF pose that describes the transmission from the world coordinate system to the LiDAR coordinate system is developed. Moreover, all these processes run in real-time (approx 40 Hz on Livox Mid-40 and approx 143 Hz on VLP-16). Qualitative and quantitative experiments are conducted to demonstrate that the proposed system has similar convenience and accuracy as the conventional visual fiducial marker system. The codes and results are available at: https://github.com/York-SDCNLab/IILFM., 8 pages

Objective: The study aims to investigate the pharmacokinetic profile of Praeruptorin A and khellactone and in vitro hydrolysis of praeruptorin A to khellactone in different biological samples. Methods: A LC-MS/MS method was established. Analytes and internal standard (IS) were isolated using the protein precipitation method and then separated on a Thermo BDS Hypersil C18 (2.1 mm×50 mm, 2.4μm) column using a mobile phase consisting of 0.05% formic acid solution and acetonitrile. Samples were analyzed in positive electrospray-ionization (ESI) mode using multiple reaction monitoring (MRM). Results: The calibration plots gave desirable linearity (r2>0.99) in the concentration range from 0.99-990.0 and 2.0-2000.0 ng/mL for Praeruptorin A and khellactone, respectively. In addition, the LOQs of these analytes were sufficient for vivo pharmacokinetic study and vitro hydrolysis study of Praeruptorin A. The intra-batch and inter-batch precision were all within 14.05%, and the accuracy was between 89.39% and 109.50%. The extraction efficiency of PA and khellactone ranged from 76.35 ~ 89.58%. The matrix effects of analytes and the IS were between 89.67% ~ 105.26%. Conclusion: The liver CYPs mediated by the metabolism of PA may contribute to the systemic exposure of its active metabolite, khellactone, in rats.

Background The long-term excessive intake of exogenous cholesterol can lead to abnormally elevated blood lipid levels and induce cardiovascular and cerebrovascular diseases. However, the influence and relevance of exogenous cholesterol on plasma cholesterol components were still unclear, and the influence on intestinal lipid metabolism targets needs to be further explored. Methods In vivo, the C57BL/6 + NF group and ApoE−/− + NF group mice were fed a normal specific pathogen-free (SPF) diet; the ApoE−/− + HF group mice were fed a high-cholesterol SPF diet. The plasma and jejunum tissue homogenate were obtained for non-targeted lipid metabolomics. The lipid droplets in tissues were observed by transmission electron microscope and oil red O staining. Jejunum tissue morphology was observed by HE staining. The kits were used to detect lipid content in plasma, tissues, intestinal contents, and cells. Western blot, RT-PCR, immunohistochemistry (IHC), and immunofluorescence (IF) were used to observe the key target of lipid metabolism. In vitro, the final concentration of cholesterol was 100 μmol/L in Caco-cells. Oil red O staining, western blot, RT-PCR and immunofluorescence (IF) were used to observe the changes of lipid metabolism. Finally, the influence of liver X receptor alpha (LXRα) on intestinal cholesterol metabolism was clarified by applying the LXRα inhibitor GSK2033 and siRNA targeting LXRα. Results The aortic arch and intestinal villi of the two groups of ApoE−/− mice showed apparent lesions and lipid accumulation, and there were significant changes in a variety of lipids in the plasma and jejunum. Additionally, jejunum LXRα was markedly activated. High cholesterol can significantly activate LXRα in Caco-2 cells. After LXRα was inhibited, the protein level of ATP-binding cassette transporter A1/G5/G8 (ABCA1/G5/G8) decreased, and the quantity and volume of intracellular lipids soared. Conclusion In a high-cholesterol environment, the intestine promotes the excretion of cholesterol from the cell through the LXRα-ABCA1/G5/G8 pathway, reduces the intestinal intake of a variety of exogenous cholesterol, and reduces the risk of AS. Graphical Abstract

Background Acute lung injury (ALI), an acute inflammatory lung disease, can cause a rapid inflammatory response in clinic, which endangers the patient's life. The components of platycodon grandiflorum, such as platycodins have a wide range of pharmacological activities such as expectorant, anti-apoptotic, anti-inflammatory, anti-tumor and anti-oxidant properties, and can be used for improving human immunity. Previous studies have shown that aqueous extract of platycodon grandiflorum (PAE) has a certain protective effect on ALI, but the main pharmacodynamic components and the mechanism of action are not clear. Methods The anti-inflammatory properties of PAE were studied using the lipopolysaccharide (LPS)-induced ALI animal model. Hematoxylin and eosin stains were used to assess the degree of acute lung damage. Changes in RNA levels of pro-inflammatory cytokines in the lungs were measured using quantitative RT-qPCR. The potential molecular mechanism of PAE preventing ALI was predicted by lipidomics and network pharmacology. To examine the anti-apoptotic effects of PAE, TdT-mediated dUTP nick-end labelling (TUNEL) was employed to determine apoptosis-related variables. The amounts of critical pathway proteins and apoptosis-related proteins were measured using Western blotting. Results Twenty-six chemical components from the PAE were identified, and their related pathways were obtained by the network pharmacology. Combined with the analysis of network pharmacology and literature, it was found that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway is related to ALI. The results of lipidomics show that PAE alleviates ALI via regulating lung lipids especially phosphatidylinositol (PI). Finally, the methods of molecular biology were used to verify the mechanism of PAE. It can be found that PAE attenuates the inflammatory response to ALI by inhibiting apoptosis through PI3K/Akt signaling pathway. Conclusion The study revealed that the PAE attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling. Furthermore, our findings provide a novel strategy for the application of PAE as a potential agent for preventing patients with ALI.

Cyclophosphamide (CP) has been proven to be an embryo-fetal toxic. However, the mechanism responsible for the toxicity of the teratogenic agent has not been fully explored. This study aimed to examine the teratogenicity of CP when administered in the sensitive period of pregnant rats. The effect of CP on the lipid and metabolic profiles of amniotic fluid was evaluated using a UHPLC-Q-Exactive Orbitrap MS-based method. Metabolome analysis was performed using the MS-DIAL software with LipidBlast and NIST. Initially, we identified 636 and 154 lipid compounds in the positive and negative ion modes and 118 metabolites for differential analysis. Mainly 4 types of oxidized lipids in the amniotic fluid were found to accumulate most significantly after CP treatment, including very-long-chain unsaturated fatty acids (VLCUFAs), polyunsaturated fatty acid (PUFA)-containing triglycerides (TGs), oxidized phosphatidylcholine (PC), and sphingomyelin (SM). Tryptophan and some long-chain saturated fatty acids were lowered pronouncedly after CP treatment. These findings suggest that CP may exert teratogenic toxicity on pregnant rats through maternal and fetal oxidative stress. The UHPLC-Q-Exactive Orbitrap MS-based lipidomics approach is worthy of wider application for evaluating the potential toxicity of other agents (toxicants) during embryonic development.

Background Epidemiological evidences reveal that populations with psychological stress have an increased likelihood of respiratory viral infection involving influenza A virus (IAV) and SARS-CoV-2, but the mechanism remains elusive. Results By exploiting a chronic restraint stress (CRS) mouse model, we demonstrated that psychiatric stress substantially increased hosts’ vulnerability to viral pneumonia, concurrent with deregulated alveolar macrophages (AMs) and disturbed gut microbiome. The central importance of gut microbiome in stress-exacerbated viral pneumonia was confirmed by microbiome depletion and gut microbiome transplantation. In particular, stress exposure induced a decline in Lactobacillaceae abundance and hence γ-aminobutyric acid (GABA) level in mice. Microbial-derived GABA proved to be released in the peripheral and sensed by AMs via GABAAR, leading to enhanced mitochondrial metabolism and α-ketoglutarate (αKG) generation. The metabolic intermediator in turn served as the cofactor for the epigenetic regulator Tet2 to catalyze DNA hydroxymethylation, and promoted PPARγ-centered gene program underpinning survival, self-renewing, and immunoregulation of AMs. We thus uncover an unappreciated GABA/Tet2/PPARγ regulatory circuitry that was initiated by gut microbiome to instruct distant immune cells through a metabolic-epigenetic program. Accordingly, reconstitution with GABA-producing probiotics, or adoptive transferring of GABA-conditioned AMs, or resumption of pulmonary αKG level remarkably improved AMs homeostasis and alleviated severe pneumonia in stressed mice. Conclusions Together, our study identifies a microbiome-derived tonic signaling that is tuned by mental health status to imprint resident immune cells and defensive response in lungs. The findings are particularly significant for the subpopulation with psychiatric stress to combat critical respiratory viral infection.

Perfluorooctanoic acid (PFOA) represents an increasing public health concern due to its persistence in the environment and its toxic effects. The gut microbiota is known to produce various metabolites that assist the host to maintain metabolic homeostasis. However, few studies have explored the effects of PFOA on gut-microbiota-related metabolites. In the present study, male C57BL/6J mice were exposed to 1 ppm of PFOA in drinking water for four weeks and integrative analysis of the gut microbiome and metabolome was performed to reveal the health effects of PFOA. Our results showed that PFOA disturbed both the gut microbiota composition and the metabolic profiles of the feces, serum, and liver in mice. A correlation was found between Lachnospiraceae UCG004, Turicibacter, Ruminococcaceae, and different fecal metabolites. Significant alterations of gut-microbiota-related metabolites were induced by PFOA exposure, including bile acids and tryptophan metabolites such as 3-indoleacrylic acid and 3-indoleacetic acid. The findings of this study are helpful to improve the understanding of the health effects of PFOA, which might be mediated through the gut microbiota and its related metabolites.

The feedforward inverse compensation is a typical approach to compensate for the hysteresis nonlinearity in smart materials based actuators, which often requires to develop a hysteresis model first and to compute the parameters of the inverse compensator based on the hysteresis model. Different from the above method, a direct inverse model (DIM) constructed by newly proposed clockwise relay operators is developed in this article. The direct inverse modeling approach is free from constructing the inverse compensator, and can be directly used as the inverse compensator. The parameters of DIM can be obtained via the model identification using the experimental data. In order to facilitate the numerical implementation and reduce the model complexity of DIM, a QR factorization based selection mechanism is employed to select the dominant clockwise relay operators. The reduced DIM is capable of preserving the accuracy of the full DIM. The simulation study and experiments are conducted to validate the effectiveness of the developed compensation approach.

This paper studies the dynamics and control of a flexible space structure using double-gimbal variable-speed control moment gyros (DGVSCMGs). The DGVSCMGs are mounted on the flexible structure as a...

Background: Obesity is an established risk factor for higher SARS-CoV-2 viral loads, severe COVID-pneumonia requiring hospitalization, and worse outcomes. However, the underlying mechanisms for the increased risk are not well understood. SARS-CoV-2 is a respiratory virus with the primary route of entry through lungs, where the Spike protein of SARS-CoV-2 binds to ACE2 receptor on pneumocytes. Lung surfactant produced by type II pneumocytes plays a major role in respiratory defense against infections. Surfactant predominantly contains lipids especially phosphatidylcholines (PC) and obesity is characterized by aberrant lipid metabolism. We hypothesized that altered lipid composition in lung surfactant in obesity may promote SARS-CoV-2 infection, leading to severe COVID-disease. Methods: Lipidomic analysis of lung tissue and bronchoalveolar lavage fluid (BALF) was performed using LC-MS/MS. The effects of PCs on SARS-CoV-2 pseudovirus infection were studied in HEK293T cells with ACE2 overexpression and in Vero-E6 cells with endogenous ACE2 expression. Results: Lipidomic analysis revealed that myristic acid containing dimyristoyl-PC (DMPC) and palmitoylmirystoyl-PC (PMPC) were commonly reduced in lung tissue and BALF from high fat diet-induced obese mice. DMPC and PMPC markedly inhibited wild type and D614G mutant SARS-CoV-2 infection in HEK293T-ACE2 and Vero-E6 cells. Feeding obese mice with trimyristin, the triglycerides of myristic acid, increased DMPC and PMPC in lung surfactant. Lipid extract from BALF of trimyristin-treated obese mice reduced wild type and D614G mutant SARS-CoV-2 infection. The inhibitory effects of DMPC and PMPC on SARS-CoV-2 infection were reversed by cholesterol. Conclusions: The reduced DMPC and PMPC in lung surfactant contributes to the increased SARS-CoV-2 infection. Increasing DMPC and PMPC in lung surfactant may be an innovative strategy for preventing and treating severe COVID-disease in obesity. Disclosure K.Du: None. L.Sun: None. Z.Luo: None. Y.Cao: None. J.Shan: None. Q.Yang: None. Funding National Institutes of Health (R01DK121146) ;Pacific Life Foundation Fellowship to UC Irvine Diabetes Center;Chinese National Natural Science Foundation (No.81774156)

Pulmonary surfactant constitutes an important barrier that pathogens must cross to gain access to the rest of the organism via the respiratory surface. The presence of pulmonary surfactant prevents the dissemination of pathogens, modulates immune responses, and optimizes lung biophysical activity. Thus, the application of pulmonary surfactant for the treatment of respiratory diseases provides an effective strategy. Currently, several clinical trials are investigating the use of surfactant preparations to treat patients with coronavirus disease 2019 (COVID-19). Some factors have been considered in the application of pulmonary surfactant for the treatment COVID-19, such as mechanical ventilation strategy, timing of treatment, dose delivered, method of delivery, and preparation utilized. This review supplements this list with two additional factors: accurate measurement of surfactants in patients and proper selection of pulmonary surfactant components. This review provides a reference for ongoing exogenous surfactant trials involving patients with COVID-19 and provides insight for the development of surfactant preparations for the treatment of viral respiratory infections.

Multiple flexible manipulators can be used to complete some repeatable missions. Each flexible manipulator can be described as an underactuated Lagrangian system based on the assumed modes method. Also, the actuator nonlinearity may deteriorate the system performance. Hence, this article aims to develop a distributed controller to solve the leader–follower consensus of multiple flexible manipulators with uncertain parameters, unknown disturbances, and actuator dead zones. The disturbances are classified as repeatable and nonrepeatable ones. The adaptive, iterative learning, and sliding-mode control techniques are used to handle uncertain parameters, repeatable, and nonrepeatable disturbances, respectively. Based on a dead-zone inverse and a finite-time observer, a distributed controller is developed to drive the flexible manipulators to track a moving leader and keep the flexible vibrations bounded simultaneously. Experimental results are presented to verify the effectiveness of the proposed controller.

This paper presents an attitude control method based on Koopman operator theory. A set of observables is discovered to represent the nonlinear attitude dynamics on SO(3) using an infinite-dimension...

Lithocholic acid (LCA), alpha-naphthyl isothiocyanate (ANIT), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and ethinyl estradiol (EE) are four commonly used chemicals for the construction of acute intrahepatic cholestasis. In order to better understand the mechanisms of acute cholestasis caused by these chemicals, the metabolic characteristics of each model were summarized using lipidomics and metabolomics techniques. The results showed that the bile acid profile was altered in all models. The lipid metabolism phenotype of the LCA group was most similar to that of primary biliary cirrhosis (PBC) patients. The ANIT group and the DDC group had similar metabolic disorder characteristics, which were speculated to be related to hepatocyte necrosis and inflammatory pathway activation. The metabolic profile of the EE group was different from other models, suggesting that estrogen-induced cholestasis had its special mechanism. Ceramide and acylcarnitine accumulation was observed in all model groups, indicating that acute cholestasis was closely related to mitochondrial dysfunction. With a deeper understanding of the mechanism of acute intrahepatic cholestasis, this study also provided a reference for the selection of appropriate chemicals for cholestatic liver disease models.

This paper focuses on the robust output feedback tracking control for n-DOF (degree-of-freedom) robot manipulators with limited state measurements. An improved extended high-gain observer (EHGO) is designed to estimate the unavailable states as well as the system uncertainty and disturbance. A novel control framework combining the improved EHGO and continuous PID-sliding mode controller (PID-SMC) is proposed. The Lyapunov approach is used to prove the effectiveness of the EHGO. Moreover, the stability and convergence of the closed-loop system are confirmed through the singular perturbation theory. Numerical simulation and experimental results are presented to show the performance of the proposed control scheme.

Histopathology and serum biochemical indicators (urea nitrogen and creatinine) were investigated to evaluate the kidney injury caused by the combination use of isoniazid (100 mg/(kg·d, ig)) and rifampicin (100 mg/(kg·d, ig) which were used as antitubercular drugs. The endogenous metabolites extracted from kidney tissue were evaluated based on gas chromatography-mass spectrometry coupled with partial least squares-discriminant analysis and other multidimensional, as well as unidimensional statistical methods. Glutathione, which was reported to protect tissue from damage caused by antitubercular drugs, was used to treat rats (250 mg/(kg·d, iv)) with kidney damage. Biochemical indicators showed that creatinine and urea nitrogen increased (p

This article presents a method for determining optimal parameters of positive position feedback controllers used for suppressing vibration of flexible structures. The method is based on solving the H∞ synthesis problem with additional constraints on the controller structure. The method allows for independent control of damping added to each mode. Moreover, optimal parameters for both simple input simple output and multiple input multiple output control formulations can be obtained. The effectiveness of the method is shown by comparing the results of both multiple input multiple output and simple input simple output positive position feedback controllers designed by the proposed method, with the simple input simple output positive position feedback controller designed by analytically derived optimal parameters. Moreover, results of controllers designed with the fixed-order transfer function control structure are also presented to emphasize the advantages offered by the positive position feedback control structure.

This paper develops a new asteroid capture mechanism via triangular libration points based on their stable structure and chaotic motion nearby. Different from collinear libration points, the triang...

A distributed adaptive controller is proposed in this paper for a class of underactuated Lagrangian systems to control the actuated variables to track a dynamic leader and keep unactuated ones bounded under a directed communication graph. A finite-time observer is introduced to estimate the leader's velocity. Based on two sliding variables defined for the actuated and unactuated channels, adaptive controllers are designed for the underactuated Lagrangian systems subject to uncertain parameters and external disturbances without or with actuator faults. The convergences of the proposed controllers are proven based on the separation principle between the observer and the controller. Finally, simulations and experiments are conducted to verify the effectiveness of the proposed controllers.