Oroxylin A attenuates psoriasiform skin inflammation by direct targeting p62 (sequestosome 1) via suppressing M1 macrophage polarization.

BACKGROUND AND PURPOSE: Psoriasis results from the interplay of innate and adaptive immunity in the skin. Oroxylin A (OA) has shown anti-inflammatory effects in various disorders. This study explores oroxylin A potential in treating psoriasis, particularly its impact on type I macrophage (Mφ1) polarization. EXPERIMENTAL APPROACH: Oroxylin A-mediated therapeutic effects were evaluated using imiquimod-induced or IL-23-injected psoriatic mice models, followed by proteomics assays to predict potential signalling and targeting proteins. Immunofluorescence and immunoblot assays verified that oroxylin A suppresses NF-kB signalling in M1 macrophages. Co-immunoprecipitation and microscale thermophoresis (MST) assays further demonstrated that p62 (sequestosome 1) is the target protein for oroxylin A in macrophages. Oroxylin A-p62-mediated suppression of psoriasis was validated in an imiquimod-induced p62 conditional knockout (cKO) mice model. KEY RESULTS: Oroxylin A demonstrated therapeutic efficacy in murine models induced by imiquimod or IL-23 by attenuating cutaneous inflammation and mitigating Mφ1 polarization via NF-κB signalling. Proteomics analysis suggested SQSTM1/p62 as a key target, confirmed to interact directly with oroxylin A. Oroxylin A disrupted the p62-PKCζ interaction by binding to PB1 domain of p62. Its anti-inflammatory effects were significantly reduced in macrophages from p62 cKO mice compared to the wild-type (WT) mice in psoriasis model, supporting oroxylin A role in suppressing Mφ1 polarization through its interaction with p62. CONCLUSION AND IMPLICATIONS: Our findings demonstrated oroxylin A suppressed psoriasiform skin inflammation in mouse models by blocking the PKCζ-p62 interaction, subsequently inhibiting the activation of NF-κB p65 phosphorylation in macrophages.

EGFR-targeting oxygen-saturated nanophotosensitizers for orchestrating multifaceted antitumor responses by counteracting immunosuppressive milieu.

High Epidermal growth factor receptor (EGFR) in Cutaneous Squamous Cell Carcinoma (cSCC) is associated with poor prognosis and advanced metastatic stages, severely impeding the efficacy of EGFR-targeting immunotherapy. This is commonly attributed to the combinatory outcomes of hypoxic tumor microenvironment (TME) and immunosuppressive effector cells together. Herein, a novel paradigm of EGFR-targeting oxygen-saturated nanophotosensitizers, designated as CHPFN-O2, has been specifically tailored to mitigate tumor hypoxia in EGFR-positive cSCC and achieve Cetuximab (CTX)-mediated immunotherapy (CIT). The conjugated CTX in CHPFN-O2 serves to initiate immune responses by recruiting Fc receptor (FcR)-expressing immune effector cells towards tumor cells, thereby eliciting antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular trogocytosis (ADCT) and antibody-dependent cellular cytotoxicity (ADCC). Besides, CHPFN-O2 can engender a shift from a tumor-friendly to a tumor-hostile one through improved tumor oxygenation, contributing to oxygen-elevated photodynamic therapy (oxPDT). Notably, the combination of oxPDT and CIT eventually promotes T-cell-mediated antitumor activity and successfully inhibits the growth of EGFR-expressing cSCC with good safety profiles. This comprehensive oxPDT/CIT integration aims not only to enhance therapeutic efficacy against EGFRhigh cSCC but also to extend its applicability to other EGFRhigh malignancies, thus delineating a new avenue for the highly efficient synergistic treatment of EGFR-expressing malignancies.

Schizonepeta tenuifolia Briq-Saposhnikovia divaricata decoction alleviates atopic dermatitis via downregulating macrophage TRPV1.

Objective: Schizonepeta tenuifolia -Saposhnikovia divaricata (Jingjie-Fangfeng, JF) has been used for years to treat allergic inflammatory skin diseases like atopic dermatitis, but the specific effects and mechanisms of JF are still unclear. Purpose: We aim to investigate the therapeutic effect and mechanism of JF in MC903-induced atopic dermatitis-like model. Methods: JF decoction was subjected to rigorous HPLC and GC analysis. The JF decoction was then freshly prepared and administered to MC903-induced atopic dermatitis -like mice models to investigate its therapeutic effects. Our evaluation focused on several markers of inflammation including the TEWL index, ear thickness, swelling, and specific inflammation indicators such as TSLP, IL33, IgE, and immune cell presence at the lesion sites. We measured Transient Receptor Potential Vanilloid 1 (TRPV1) expression levels through immunofluorescent staining in skin tissue from both atopic dermatitis patients and the MC903-treated mice. Furthermore, TRPV1 expression and macrophage activation markers were measured in LPS/IFN-γ-stimulated Raw264.7 and THP-1 cell models in vitro. Additionally, we developed cell lines that overexpress TRPV1 and investigated how JF treatment affects NF-κB p65 phosphorylation in these cells to understand better the role of TRPV1 in atopic dermatitis. Results: The JF decoction met the standards outlined in the Chinese pharmacopeia. The JF decoction significantly alleviated inflammatory skin symptoms and helped restore skin barrier function. Additionally, it reduced the levels of IgE and pro-inflammatory cytokines TSLP, IL-33, and IL-4. There was also a noticeable decrease in mast cell infiltration and degranulation. Notably, JF decoction reduced infiltrated macrophages with limited affection on T cell infiltration. It also decreased F4/80+/TRPV1+ cells in atopic dermatitis mice and TRPV1 expression in LPS/IFNγ-stimulated microphages. Additionally, we observed that CD68+/TRPV1+ cells increased in human atopic dermatitis tissue. Further studies showed that JF water extract (JF-WE) suppressed TRPV1 expression in macrophages, potentially by affecting NF-κB p65 phosphorylation rather than the JAK-STAT6 pathway. Conclusion: This study offers initial evidence of the effectiveness of JF-WE in suppressing inflammation in atopic dermatitis. The therapeutic effect might stems from its ability to downregulate TRPV1 expression and subsequent NF-κB p65 phosphorylation in macrophages.

[Research on a special model of nerve impulse propagation].

Hodgkin-Huxley (HH) nerve model is a famous model which is used to describe nerve impulse propagation in nerve fibre. FitzHugh-Nagumo (FHN) model is a simplification of HH model, and Huxley equation is a special case of FHN equation. It has been shown that Huxley equation possesses the basic characteristics of nerve model. Researching on these models was often carried out in virtue of numerical techniques in the past. And, in so for as is known, an efficient and simple method which can be used to obtain analytic solutions is lacking. Yet, a qualitative analysis on Huxley equation's traveling system has been carried through in this paper. There is a bounded heteroclinic orbit having its one end in connection with a saddle point for the traveling wave system. Then a linear plane autonomous system whose singular point is a saddle point is chosen. By means of the system orbit vector's slope, and according to homogeneous balance principle, the traveling wave solutions of Huxley equation's traveling system are constructed. The method used here is called LS method.

Advanced oxygenation efficiency and purification of wastewater using a constant partially unsaturated scheme in column experiments simulating vertical subsurface flow constructed wetlands.

The presence of sufficient dissolved oxygen (DO) in a constructed wetland (CW) is vital to the process of removing ammonia nitrogen and organics from wastewater. To achieve total nitrogen removal, which is characterised by enhanced ammonia nitrogen removal, this study offers an efficient strategy to increase the oxygen supply by establishing constant unsaturated zones and baffles in simulating constructed wetlands (SCWs). Henceforth, this strategy is addressed as a partially unsaturated SCW. A centrally located high tube was set up inside the wetland to create an unsaturated zone at a higher level. The effectiveness of the unsaturated zone to supplement the oxygen content was evaluated by comparing with controls (an unaerated SCW and an aerated SCW). The results show the chemical oxygen demand removal rate (85 ±â€¯6%) in the partially unsaturated SCW was equivalent to that in the aerated SCW (83 ±â€¯6%), while the ammonia nitrogen removal rate was 11 times higher compared to that of the unaerated SCW. The removal potential of the partially unsaturated SCW under different HRT (hydraulic retention time)s (12, 24, and 36 h) was examined, and the 36 h-SCW performed the best in the removal of organics and nitrogen. The mechanisms behind the unsaturated zone strategy were studied by analysing water and microbe samples along the pathway. The results from the water quality indicators and the quantitative polymerase chain reactions along the pathway showed the unsaturated zone contributed to the removal of primary organics and ammonia nitrogen. The superior performance of unsaturated zone strategy was discussed further using the enrichment of ammonia-oxidising bacteria, mass of oxygen uptake, and baffle design. The results indicate that the amoA gene/16s rRNA gene abundance ratio and the oxygen uptake (336 ±â€¯44 g m-3 d-1) in the partially unsaturated SCW was higher than that observed in the two controls.

The configuration, purification effect and mechanism of intensified constructed wetland for wastewater treatment from the aspect of nitrogen removal: A review.

Constructed wetland (CW) for wastewater treatment has attracted increasing attention. In this review, the system configuration optimization, purification effect and general mechanisms of nitrogen removal in CW are systematically summarized and discussed. Ammonia oxidation is a crucial and primary process for total nitrogen (TN) removal in domestic or livestock wastewater treatment. Aeration, waterdrop influent and tidal operation are three main methods to strengthen the oxygen supplement and nitrification process in CW. Aeration significantly increases the ammonia removal rate (almost 100%), followed by the removal of chemical oxygen demand (COD) and TN. Solid carbon source, iron and anode material can be filled as electron donor for the denitrification process. The co-adjustment of oxygen and carbon/electron donor can form different conditions for different nitrogen removal pathways (e.g. the simultaneous nitrification-denitrification, the partial nitrification-denitrification and the anammox process), and achieve the optimal removal of nitrogen.

Carbon dioxide emissions from the electricity sector in major countries: a decomposition analysis.

The electric power sector is one of the primary sources of CO2 emissions. Analyzing the influential factors that result in CO2 emissions from the power sector would provide valuable information to reduce the world's CO2 emissions. Herein, we applied the Divisia decomposition method to analyze the influential factors for CO2 emissions from the power sector from 11 countries, which account for 67% of the world's emissions from 1990 to 2013. We decompose the influential factors for CO2 emissions into seven areas: the emission coefficient, energy intensity, the share of electricity generation, the share of thermal power generation, electricity intensity, economic activity, and population. The decomposition analysis results show that economic activity, population, and the emission coefficient have positive roles in increasing CO2 emissions, and their contribution rates are 119, 23.9, and 0.5%, respectively. Energy intensity, electricity intensity, the share of electricity generation, and the share of thermal power generation curb CO2 emissions and their contribution rates are 17.2, 15.7, 7.7, and 2.8%, respectively. Through decomposition analysis for each country, economic activity and population are the major factors responsible for increasing CO2 emissions from the power sector. However, the other factors from developed countries can offset the growth in CO2 emissions due to economic activities.