Licochalcone A Protects the Blood–Milk Barrier Integrity and Relieves the Inflammatory Response in LPS-Induced Mastitis

Background/Aims: Mastitis is an acute clinical inflammatory response. The occurrence and development of mastitis seriously disturb women's physical and mental health. Licochalcone A, a phenolic compound in Glycyrrhiza uralensis, has anti-inflammatory properties. Here, we examined the effect of licochalcone A on blood-milk barrier and inflammatory response in LPS-induced mice mastitis.Methods:In vivo, we firstly established mice models of mastitis by canal injection of LPS to mammary gland, and then detected the effect of licochalcone A on pathological indexes, inflammatory responses and blood-milk barrier in this model. In vivo, Mouse mammary epithelial cells (mMECs) were treated with licochalcone A prior to the incubation of LPS, and then the inflammatory responses, tight junction which is the basic structure of blood-milk barrier were analyzed. Last, we elucidated the anti-inflammatory mechanism by examining the activation of mitogen-activated protein kinase (MAPK) and AKT/NF-κB signaling pathways in vivo and in vitro.Result: The in vivo results showed that licochalcone A significantly decreased the histopathological impairment and the inflammatory responses, and improved integrity of blood-milk barrier. The in vitro results demonstrated that licochalcone A inhibited LPS-induced inflammatory responses and increase the protein levels of ZO-1, occludin, and claudin3 in mMECs. The in vivo and in vitro mechanistic study found that the anti-inflammatory effect of licochalcone A in LPS-induced mice mastitis was mediated by MAPK and AKT/NF-κB signaling pathways.Conclusions and Implications: Our experiments collectively indicate that licochalcone A protected against LPS-induced mice mastitis via improving the blood–milk barrier integrity and inhibits the inflammatory response by MAPK and AKT/NF-κB signaling pathways

Farrerol Relieve Lipopolysaccharide (LPS)-Induced Mastitis by Inhibiting AKT/NF-κB p65, ERK1/2 and P38 Signaling Pathway

Farrerol has been proved to have an anti-inflammatory effect. However, the effects of farrerol on mastitis have not been investigated. This study was aimed to investigate the effect and mechanism of farrerol in lipopolysaccharide (LPS)-induced mouse mastitis and LPS-induced inflammatory response of mouse mammary epithelial cells (mMECs). In vivo, LPS were injected to the tetrad pair of nipples for establishing mouse mastitis, and then tested the effect of farrerol on histopathological changes, inflammatory response and activation degree of protein kinase B (AKT), nuclear factor-kappa B p65 (NF-κB p65), p38, extracellular regulated protein kinase (ERK1/2). In vitro, the mMECs were incubated by farrerol for 1 h following by stimulating with LPS, and then the inflammatory response and the related signaling pathways were detected. The in vivo results found that farrerol could improve pathological injury of mammary gland, attenuate the activity of myeloperoxidase (MPO), inhibit the production of pro-inflammatory mediators and the phosphorylation of AKT, NF-κB p65, p38 and ERK1/2. The in vitro results also found farrerol inhibited inflammatory response and the related signaling pathways. Collectively, this study revealed that farrerol inhibits the further development of LPS-induced mastitis by inhibiting inflammatory response via down regulating phosphorylation of AKT, NF-κB p65, p38, and ERK1/2. These findings suggest that farrerol may be used as an anti-inflammatory drug for mastitis

Peiminine Protects against Lipopolysaccharide-Induced Mastitis by Inhibiting the AKT/NF-κB, ERK1/2 and p38 Signaling Pathways

Peiminine, an alkaloid extracted from Fritillaria plants, has been reported to have potent anti-inflammatory properties. However, the anti-inflammatory effect of peiminine on a mouse lipopolysaccharide (LPS)-induced mastitis model remains to be elucidated. The purpose of this experiment was to investigate the effect of peiminine on LPS-induced mastitis in mice. LPS was injected through the canals of the mammary gland to generate the mouse LPS-induced mastitis model. Peiminine was administered intraperitoneally 1 h before and 12 h after the LPS injection. In vitro, mouse mammary epithelial cells (mMECs) were pretreated with different concentrations of peiminine for 1 h and were then stimulated with LPS. The mechanism of peiminine on mastitis was studied by hematoxylin-eosin staining (H&E) staining, western blotting, and enzyme-linked immunosorbent assay (ELISA). The results showed that peiminine significantly decreased the histopathological impairment of the mammary gland in vivo and reduced the production of pro-inflammatory mediators in vivo and in vitro. Furthermore, peiminine inhibited the phosphorylation of the protein kinase B (AKT)/ nuclear factor-κB (NF-κB), extracellular regulated protein kinase (ERK1/2), and p38 signaling pathways both in vivo and in vitro. All the results suggested that peiminine exerted potent anti-inflammatory effects on LPS-induced mastitis in mice. Therefore, peiminine might be a potential therapeutic agent for mastitis

An Improved Fast Flocking Algorithm with Obstacle Avoidance for Multiagent Dynamic Systems

Flocking behavior is a common phenomenon in nature, such as flocks of birds and groups of fish. In order to make the agents effectively avoid obstacles and fast form flocking towards the direction of destination point, this paper proposes a fast multiagent obstacle avoidance (FMOA) algorithm. FMOA is illustrated based on the status of whether the flocking has formed. If flocking has not formed, agents should avoid the obstacles toward the direction of target. If otherwise, these agents have reached the state of lattice and then these agents only need to avoid the obstacles and ignore the direction of target. The experimental results show that the proposed FMOA algorithm has better performance in terms of flocking path length. Furthermore, the proposed FMOA algorithm is applied to the formation flying of quad-rotor helicopters. Compared with other technologies to perform the localization of quad-rotor helicopter, this paper innovatively constructs a smart environment by deploying some wireless sensor network (WSN) nodes using the proposed localization algorithm. Finally, the proposed FMOA algorithm is used to conduct the formation flying of these quad-rotor helicopters in the smart environment

Structure Manipulation of Carbon Aerogels by Managing Solution Concentration of Precursor and Its Application for CO2 Capture

A series of carbon aerogels were synthesized by polycondensation of resorcinol and formaldehyde, and their structure was adjusted by managing solution concentration of precursors. Carbon aerogels were characterized by X-ray diffraction (XRD), Raman, Fourier transform infrared spectroscopy (FTIR), N2 adsorption/desorption and scanning electron microscope (SEM) technologies. It was found that the pore structure and morphology of carbon aerogels can be efficiently manipulated by managing solution concentration. The relative micropore volume of carbon aerogels, defined by Vmicro/Vtol, first increased and then decreased with the increase of solution concentration, leading to the same trend of CO2 adsorption capacity. Specifically, the CA-45 (the solution concentration of precursors is 45 wt%) sample had the highest CO2 adsorption capacity (83.71 cm3/g) and the highest selectivity of CO2/N2 (53) at 1 bar and 0 °C

Enhanced CO₂ Adsorption Performance on Hierarchical Porous ZSM‑5 Zeolite

Hierarchical porous ZSM-5 (HP-ZSM-5) was constructed using organosilanes as the growth inhibitors for CO₂ capture. The properties of adsorbents were characterized by X-ray diffraction, N₂ adsorption/desorption, scanning electron microscopy, temperature-programmed desorption of carbon dioxide, and ²⁷Al magic angle spinning nuclear magnetic resonance. It was found that HP-ZSM-5 samples synthesized by organosilanes had a significant effect on the microstructure and morphology. CO₂ adsorption capacity of HP-ZSM-5 was up to 58.26 cm³ g^–1 at 0 °C and 1 bar, significantly higher than that of the ZSM-5 sample. The effective improvement of CO₂ adsorption performance mainly originated from the micro-/mesoporous composite structure and complex surface morphology, which can provide low-resistant pathways for CO₂ through the porous network. Besides, <i>in situ</i> Fourier transform infrared spectroscopy was carried out to study the adsorption process on adsorbents, and the results indicated that a faster physical adsorption process was achieved as a result of the introduction of mesopores

Deep learning enhancing guide RNA design for CRISPR/Cas12a‐based diagnostics

Publication status: PublishedAbstractRapid and accurate diagnostic tests are fundamental for improving patient outcomes and combating infectious diseases. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas12a‐based detection system has emerged as a promising solution for on‐site nucleic acid testing. Nonetheless, the effective design of CRISPR RNA (crRNA) for Cas12a‐based detection remains challenging and time‐consuming. In this study, we propose an enhanced crRNA design system with deep learning for Cas12a‐mediated diagnostics, referred to as EasyDesign. This system employs an optimized convolutional neural network (CNN) prediction model, trained on a comprehensive data set comprising 11,496 experimentally validated Cas12a‐based detection cases, encompassing a wide spectrum of prevalent pathogens, achieving Spearman's ρ = 0.812. We further assessed the model performance in crRNA design for four pathogens not included in the training data: Monkeypox Virus, Enterovirus 71, Coxsackievirus A16, and Listeria monocytogenes. The results demonstrated superior prediction performance compared to the traditional experiment screening. Furthermore, we have developed an interactive web server (https://crispr.zhejianglab.com/) that integrates EasyDesign with recombinase polymerase amplification (RPA) primer design, enhancing user accessibility. Through this web‐based platform, we successfully designed optimal Cas12a crRNAs for six human papillomavirus (HPV) subtypes. Remarkably, all the top five predicted crRNAs for each HPV subtype exhibited robust fluorescent signals in CRISPR assays, thereby suggesting that the platform could effectively facilitate clinical sample testing. In conclusion, EasyDesign offers a rapid and reliable solution for crRNA design in Cas12a‐based detection, which could serve as a valuable tool for clinical diagnostics and research applications.</jats:p