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The incidence of allergic rhinitis in children is high across the world, as well as in China. Allergic rhinitis in children has serious impact on physical and mental health of the children. At the same time, the caregivers of allergic rhinitis children have heavy burden of care, and their mental problems are severe. It is necessary to implement timely psychological intervention for the caregivers of allergic rhinitis children. Mindfulness-Based Cognitive Therapy (MBCT) is a safe and effective psychological therapy, and the effect of online intervention can be comparable to the traditional face-to-face intervention program. This study focused on the mental health status in the main caregivers of children with allergic rhinitis, and conducted a modified online MBCT intervention on the caregivers, in order to improve their adverse mental state, meanwhile, improve the quality of care they provide. The results show that online MBCT intervention is applicable to the main caregivers of children with allergic rhinitis, and can effectively reduce caregiver burden, relieve anxiety and depression, and improve the level of mindfulness in the caregivers.

Abstract More recently, soft actuators have evoked great interest in the next generation of soft robots. Despite significant progress, the majority of current soft actuators suffer from the lack of real‐time sensory feedback and self‐control functions, prohibiting their effective sensing and multitasking functions. Therefore, in this work, a near‐infrared‐driven bimorph membrane, with self‐sensing and feedback loop control functions, is produced by layer by layer (LBL) assembling MXene/PDDA (PM) onto liquid crystal elastomer (LCE) film. The versatile integration strategy successfully prevents the separation issues that arise from moduli mismatch between the sensing and the actuating layers, ultimately resulting in a stable and tightly bonded interface adhesion. As a result, the resultant membrane exhibited excellent mechanical toughness (tensile strengths equal to 16.3 MPa (||)), strong actuation properties (actuation stress equal to 1.56 MPa), and stable self‐sensing (gauge factor equal to 4.72) capabilities. When applying the near‐infrared (NIR) laser control, the system can perform grasping, traction, and crawling movements. Furthermore, the wing actuation and the closed‐loop controlled motion are demonstrated in combination with the insect microcontroller unit (MCU) models. The remote precision control and the self‐sensing capabilities of the soft actuator pave a way for complex and precise task modulation in the future.

Euphorbia factor L1 (EFL1) is a kind of lathyrane-type diterpenoid and is isolated from the medical herb Euphorbia lathyris L. (Euphorbiaceae); it has been reported with the toxicity that causes intestinal irritation, but the underlying mechanisms are still obscure. The objective of this study was to assess the EFL1-induced intestinal cytotoxicity in human colon adenocarcinoma Caco-2 cells. The Caco-2 cells were treated with EFL1, and the intracellular calcium ion concentration, mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (mPTP), adenosine 5′-triphosphate (ATP) content, ATPase activities, TGF-β1 concentration, and transepithelial electrical resistance (TEER) were detected. The interaction between EFL1 and the tight junction proteins Occludin, Claudin-4, Tricellulin, ZO-1, JAM-1, and E-cadherin was simulated by molecular docking. The expression of proteins involved in the energy metabolism, the ion transporters and aquaporins, the tight junction, and the F-actin cytoskeleton were detected by Western blotting and cell immunofluorescence. As a result, EFL1 decreased the intracellular Ca2+, MMP, mPTP, ATP content, and ATPase activities in the Caco-2 cells. The AMPK/SIRT1/PGC-1α signaling pathway, which regulates the energy metabolism, was inhibited. The ion transporters NEH and CFTR, as well as the aquaporins in the Caco-2 cells, were decreased. The tight junction proteins were down-regulated, and the integrity of the intestinal barrier was injured; TGF-β1 was compensatively increased; so, the intestinal permeability was increased and was characterized by decreased TEER. The morphology of the F-actin cytoskeleton was destroyed. These findings indicated that EFL1 caused cytotoxicity in the human intestinal Caco-2 cells through mitochondrial damage, inhibition of the energy metabolism, and suppression of the ion and water molecule transporters, as well as the down-regulation tight junction and cytoskeleton protiens.

Abstract Background Zuojin formula, a traditional Chinese medicine, comprises Coptis chinensis and Evodia rutaecarpa. In our previous study, the total alkaloid extract from Zuojin formula (TAZF) showed potent and improved efficacy. However, its safety and toxicokinetics remain unknown. The objective of this study was to evaluate the safety of repeated administrations of TAZF and investigate the internal exposure of the main components and its relationship with toxic symptoms. Methods Sprague–Dawley rats were orally administered TAZF at 0.4, 1.2 and 3.7 g/kg for 28 days, which was followed by a 14-day recovery period. The toxic effects were evaluated weekly by assessing body weight changes, food intake, blood biochemistry and haematological indices, organ weights and histological changes. A total of eight components were detected, including berberine, coptisine, epiberberine, palmatine, jatrorrhizine, columbamine, evodiamine, and rutaecarpine. The toxicokinetic profiles of the eight components were investigated after single and repeated administrations. Linear mixed effect models were applied to analyse the associations between internal exposure and toxic symptoms. Network pharmacology analysis was applied to explore the potential toxic mechanisms. Results Compared with the vehicle group, the rats in the low- and medium-dose groups did not show noticeable abnormal changes, while rats in the high-dose group exhibited inhibition of weight gain, a slight reduction in food consumption, abdominal bloating and atrophy of the splenic white pulp during drug administration. The concentration of berberine in plasma was the highest among all compounds. Epiberberine was found to be associated with the inhibition of weight gain. Network pharmacology analysis suggested that the alkaloids might cause abdominal bloating by affecting the proliferation of smooth muscle cells. The benchmark dose lower confidence limits (based on body weight inhibition) of TAZF were 1.27 g/kg (male) and 1.91 g/kg (female). Conclusions TAZF has no notable liver or kidney toxicity but carries risks of gastrointestinal and immune toxicity at high doses. Alkaloids from Coptis chinensis are the main plasma components related to the toxic effects of TAZF.

Eupalinolide A (EA; Z-configuration) and eupalinolide B (EB; E-configuration) are bioactive cis-trans isomers isolated from Eupatorii Lindleyani Herba that exert anti-inflammatory and antitumor effects. Although one pharmacokinetic study found that the metabolic parameters of the isomers were different in rats, metabolic processes relevant to EA and EB remain largely unknown. Our preliminary findings revealed that EA and EB are rapidly hydrolyzed by carboxylesterase. Here, we investigated the metabolic stability and enzyme kinetics of carboxylesterase-mediated hydrolysis and cytochrome P450 (CYP)-mediated oxidation of EA and EB in human liver microsomes (HLMs). We also explored differences in the hydrolytic stability of EA and EB in human liver microsomes and rat liver microsomes (RLMs). Moreover, cytochrome P450 reaction phenotyping of the isomers was performed via in silico methods (i.e., using a quantitative structure-activity relationship model and molecular docking) and confirmed using human recombinant enzymes. The total normalized rate approach was considered to assess the relative contributions of five major cytochrome P450s to EA and EB metabolism. We found that EA and EB were eliminated rapidly, mainly by carboxylesterase-mediated hydrolysis, as compared with cytochrome P450-mediated oxidation. An inter-species difference was observed as well, with faster rates of EA and EB hydrolysis in rat liver microsomes. Furthermore, our findings confirmed EA and EB were metabolized by multiple cytochrome P450s, among which CYP3A4 played a particularly important role.

Abstract. Type 2 inflammation is a complex immune response and primary mechanism for several common allergic diseases including allergic rhinitis, allergic asthma, atopic dermatitis, and chronic rhinosinusitis with nasal polyps. It is the predominant type of immune response against helminths to prevent their tissue infiltration and induce their expulsion. Recent studies suggest that epithelial barrier dysfunction contributes to the development of type 2 inflammation in asthma, which may partly explain the increasing prevalence of asthma in China and around the globe. The epithelial barrier hypothesis has recently been proposed and has received great interest from the scientific community. The development of leaky epithelial barriers leads to microbial dysbiosis and the translocation of bacteria to inter- and sub-epithelial areas and the development of epithelial tissue inflammation. Accordingly, preventing the impairment and promoting the restoration of a deteriorated airway epithelial barrier represents a promising strategy for the treatment of asthma. This review introduces the interaction between type 2 inflammation and the airway epithelial barrier in asthma, the structure and molecular composition of the airway epithelial barrier, and the assessment of epithelial barrier integrity. The role of airway epithelial barrier disruption in the pathogenesis of asthma will be discussed. In addition, the possible mechanisms underlying the airway epithelial barrier dysfunction induced by allergens and environmental pollutants, and current treatments to restore the airway epithelial barrier are reviewed.

In order to further reduce the vibration level of helicopters, the active vibration control technology of helicopters has been extensively studied. Among them, individual blade control (IBC) independently applies high-order harmonics to each blade with an actuator, which can improve the aerodynamic environment of the blade and effectively reduce the vibration load of the hub. The rotor structural dynamics model based on the Hamilton energy variation principle and the medium deformation beam theory were established firstly, and the aerodynamic model based on the dynamic inflow model and the Leishman–Beddoes unsteady aerodynamic model were also established. The structural finite element method and the direct numerical integration method were used to calculate the vibration response of the rotor to determine the vibration load of the hub. After these, the steepest descent-golden section combinatorial optimization algorithm was used to find the optimization parameters of IBC. Based on this, the input parameters of fuzzy neural network PID control were determined, and the rotor hub vibration load control simulation was conducted. Under the effect of IBC, the vibration loads of the hub could be reduced by about 60%. The article gives the best control laws of individual harmonic pitch control and their combinations. These results can theoretically be applied to the design of control law to reduce helicopter vibration loads.

c-Myc (Myc) is a well-known transcription factor that regulates many essential cellular processes. Myc has been implicated in regulating anti-mycobacterial responses. However, its precise mechanism in modulating mycobacterial immunity remains elusive. Here, we found that a secreted Rv1579c (early secreted target with molecular weight 12 kDa, named EST12) protein, encoded by virulent Mycobacterium tuberculosis (M.tb) H37Rv region of deletion (RD)3, induces early expression and late degradation of Myc protein. Interestingly, EST12-induced Myc was further processed by K48 ubiquitin proteasome degradation in E3 ubiquitin ligase FBW7 dependent manner. EST12 protein activates JNK-AP1-Myc signaling pathway, promotes Myc binding to the promoters of IL-6, TNF-α and iNOS, then induces the expression of pro-inflammatory cytokines (IL-6 and TNF-α)/inducible nitric oxide synthase (iNOS)/nitric oxide (NO) to increase mycobacterial clearance in a RACK1 dependent manner, and these effects are impaired by both Myc and JNK inhibitors. Macrophages infected with EST12-deficiency strain (H37RvΔEST12) displayed less production of iNOS, IL-6 and TNF-α. In conclusion, EST12 regulates Myc expression and enhances anti-mycobacterial inflammatory response via RACK1-JNK-AP1-Myc immune pathway. Our finding provides new insights into M.tb-induced immunity through Myc.

AbstractConditional degron technologies, which allow a protein of interest to be degraded in an inducible manner, are important tools for biological research, and are especially useful for creating conditional loss-of-function mutants of essential genes. The auxin-inducible degron (AID) technology, which utilizes plant auxin signaling components to control protein degradation in nonplant species, is a widely used small-molecular-controlled degradation method in yeasts and animals. However, the currently available AID systems still have room for further optimization. Here, we have improved the AID system for the fission yeast Schizosaccharomyces pombeArabidopsis

Euphorbia factors, lathyrane-type diterpenoids isolated from the medical herb Euphorbia lathyris L. (Euphorbiaceae), have been associated with intestinal irritation toxicity, but the mechanisms underlying this phenomenon are still unknown. The objective of this study was to evaluate the transcriptome and miRNA profiles of human colon adenocarcinoma Caco-2 cells in response to Euphorbia factors L1 (EFL1) and EFL2. Whole transcriptomes of mRNA and microRNA (miRNA) were obtained using second generation high-throughput sequencing technology in response to 200 μM EFL treatment for 72 h, and the differentially expressed genes and metabolism pathway were enriched. Gene structure changes were analyzed by comparing them with reference genome sequences. After 72 h of treatment, 16 miRNAs and 154 mRNAs were differently expressed between the EFL1 group and the control group, and 47 miRNAs and 1101 mRNAs were differentially expressed between the EFL2 group and the control. Using clusters of orthologous protein enrichment, the sequenced mRNAs were shown to be mainly involved in transcription, post-translational modification, protein turnover, chaperones, signal transduction mechanisms, intracellular trafficking, secretion, vesicular transport, and the cytoskeleton. The differentially expressed mRNA functions and pathways were enriched in transmembrane transport, T cell extravasation, the IL-17 signaling pathway, apoptosis, and the cell cycle. The differentially expressed miRNA EFLs caused changes in the structure of the gene, including alternative splicing, insertion and deletion, and single nucleotide polymorphisms. This study reveals the underlying mechanism responsible for the toxicity of EFLs in intestinal cells based on transcriptome and miRNA profiles of gene expression and structure.

Accurately identifying the peak value of impact load acting on the helicopter structure during weapon launch is of great significance to the design and finalization of weapon pylons. Firstly, a method of standardized preprocessing load signal is proposed by analyzing the vibration response and the characteristics of the impact load. Then, the test model of the weapon pylon is designed, and the position of the strain gauge is determined; the static load calibration test and the ground impact test are carried out on the test model. Next, the time-domain response measured by the strain gauge is filtered and de-noised. Impact load is processed by a standardized method. The response and load are used to train BP neural network and the mapping relationship between response and load is established. The impact load generated by a specific weapon is statistically processed to obtain the normalized average load time history, and the identified standard load is converted back to the original load pattern. Finally, the network that meets the error requirements is tested. Both the standardized pattern and the original pattern have high identification accuracy, which shows that an effective load identification model can be established based on the time-domain response signal and the standardized processed load signal.

Variable diameter rotor can improve the flight performance of the aircraft both in hovering and forward flying and a duct can improve the rotor performance further both in force and efficiency. In previous studies, those two parts are always studied in the one-factor-at-a-time method, and the duct is lack diameter change so that it cannot cooperate with the variable diameter rotor. In this paper, the Chinese utility helicopter Z9 is taken as the prototype, and the structural parameters of the variable diameter ducted fan (VDDF) are selected by an orthogonal experiment method. Based on the momentum-element theory, the aerodynamic theoretical model of the disk is established, and the structural parameters that can achieve the best efficiency in hover/propulsion and the best lift/thrust force ratio under different modes are obtained in the orthogonal range by computational fluid dynamics method. The structural parameters of the VDDF under the set working conditions are obtained by a technique for order of preference by similarity to ideal solution (TOPSIS) evaluation and the flight performance of the aircraft equipped with the VDDF is superior to the prototype: The max takeoff weight raises 25%; the hover ceiling raises 90%; the cruise altitude raises 11%; the cruise speed raises 23% and the max speed raises further. However, a better engine may be needed to provide greater power.

Impact load is a kind of aperiodic excitation with a short action time and large amplitude, it had more significant effect on the structure than static load. The reconstruction (or identification namely) of impact load is of great importance for validating the structural strength. The aim of this article was to reconstruct the impact load accurately. An impact load identification method based on impulse response theory (IRT) and BP (Back Propagation) neural network is proposed. The excitation and response signals were transformed to the same length by extracting the peak value (amplitude of sine wave) in the rising oscillation period of the response. First, we deduced that there was an approximate linear relationship between the discrete-time integral of impact load and the amplitude of the oscillation period of the response. Secondly, a BP neural network was used to establish a linear relationship between the discrete-time integral of the impact load and the peak value in the rising oscillation period of the response. Thirdly, the network was trained and verified. The error between the actual maximum amplitude of impact load and the identification value was 2.22%. The error between the actual equivalent impulse and the identification value was 0.67%. The results showed that this method had high accuracy and application potential.

A rotor that can realize individual blade pitch control was designed. This paper focuses on finding the trend of helicopter vibration loads after applying multiple high-order harmonic control. The Glauert inflow model was introduced to calculate the induced velocity of rotor blades in a rotor disk plane, and the Leishman Beddoes (L-B) unsteady dynamic model was employed to calculate the aerodynamic forces of each section of a rotor blade. It was found that the influence of each high-order harmonic control on individual blade vibration load reduction is similar in different advanced ratios. After these calculations, the genetic algorithm was used to calculate the best combination of amplitude and phase of the higher order harmonic under a specific flight state. Under the effect of high harmonic input, the vibration loads of the hub could be reduced by about 65%. These results can be theoretically applied to design control law to reduce helicopter vibration loads.

Bionic algorithms are established by imitating human neural structures and animal social behaviors. As an important part of bionic technology, bionic algorithms are often used to solve the control problems of complex nonlinear systems, such as the rotor aeroelasticity dynamics model used in the helicopter individual blade control (IBC) optimization process. Two control methods based on bionic intelligent algorithms are introduced, respectively. The first method is to combine the fuzzy neural network and the classical PID control together. Compared with traditional PID control, the combined one was able to adjust the PID control parameters automatically by using the learning ability of the fuzzy neural network. The second method is to directly search the optimal control parameters by using the particle swarm algorithm. Both two methods demonstrate higher efficiency and accuracy; according to the results obtained by the algorithms, the vibration level was 80% less than without the applied high order harmonics. This indicates great application prospects for bionic intelligent algorithms in solving complex nonlinear system problems.

The PGNAA system for the cement measurement was simulated based on Monte Carlo method. The sizes of the moderator and reflector for the 14 MeV DT neutron generator were optimized for fast and thermal neutron outputs. The DT neutron generator was simulated at the pulse mode, and the gamma-ray detector was set as LaBr3(Ce) scintillator. The characteristic peaks of the major elements (Ca, Si, Al, Fe) can be identified from the gamma-ray spectra which induced at the different time intervals of the neutron radiation. For the different thicknesses of the cement sample the ratios of the gamma-ray peaks were observed, and the result showed that when the thickness was between 20 to 30 cm, the ratios became stable. With the ratios, we can calculate the iron modulus, silica modulus and lime saturation factor.

ObjectiveThe aim of the study was to find the key genes, microRNAs (miRNAs) and transcription factors (TFs) and construct miRNA-target gene-TF regulatory networks to investigate the underlying molecular mechanism in colorectal adenoma (CRA).MethodsFour mRNA expression datasets and one miRNA expression dataset were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) were identified between CRA and normal samples. Moreover, functional enrichment analysis for DEGs was carried out utilizing the Cytoscape-plugin, known as ClueGO. These DEGs were mapped to STRING database to construct a protein-protein interaction (PPI) network. Then, a miRNA-target gene regulatory network was established to screen key DEMs. In addition, similar workflow of the analyses were also performed comparing the CRC samples with CRA ones to screen key DEMs. Finally, miRNA-target gene-TF regulatory networks were constructed for these key DEMs using iRegulon plug-in in Cytoscape.ResultsWe identified 514 DEGs and 167 DEMs in CRA samples compared to healthy samples. Functional enrichment analysis revealed that these DEGs were significantly enriched in several terms and pathways, such as regulation of cell migration and bile secretion pathway. A PPI network was constructed including 325 nodes as well as 890 edges. A total of 59 DEGs and 65 DEMs were identified in CRC samples compared to CRA ones. In addition, Two key DEMs in CRA samples compared to healthy samples were identified, such as hsa-miR-34a and hsa-miR-96. One key DEM, hsa-miR-29c, which was identified when we compared the differentially expressed molecules found in the comparison CRA versus normal samples to the ones obtained in the comparison CRC versus CRA, was also identified in CRC samples compared to CRA ones. The miRNA-target gene-TF regulatory networks for these key miRNAs included two TFs, one TF and five TFs, respectively.ConclusionThese identified key genes, miRNA, TFs and miRNA-target gene-TF regulatory networks associated with CRA, to a certain degree, may provide some hints to enable us to better understand the underlying pathogenesis of CRA.