Immunogenicity and protective efficacy of a novel bacterium-like particle-based vaccine displaying canine distemper virus antigens in mice and dogs.

Canine distemper virus (CDV) poses a severe threat to both domesticated and wild animals, including multiple carnivores. With the continued expansion of its host range, there is an urgent need for the development of a safer and more effective vaccine. In this study, we developed subunit vaccines based on a bacterium-like particle (BLP) delivery platform containing BLPs-F and BLPs-H, which display the CDV F and H glycoprotein antigens, respectively, using the antigen-protein anchor fusions produced by a recombinant baculovirus insect cell expression system. The combination of BLPs-F and BLPs-H (CDV-BLPs), formulated with colloidal manganese salt [Mn jelly (MnJ)] adjuvant, triggered robust CDV-specific antibody responses and a substantial increase in the number of interferon gamma (IFN-γ)-secreting CD4+ and CD8+ T cells in mice. Dogs immunized intramuscularly with this vaccine not only produced CDV-specific IgG but also displayed elevated concentrations of IFN-γ and interleukin 6 in their serum, along with an increase of the CD3+CD4+ and CD3+CD8+ T cell subsets. Consequently, this heightened immune response provided effective protection against disease development and reduced viral shedding levels following challenge with a virulent strain. These findings suggest that this BLP-based subunit vaccine has the potential to become a novel canine distemper vaccine. IMPORTANCE: Many sensitive species require a safe and effective distemper vaccine. Non-replicating vaccines are preferred. We constructed subunit particles displaying canine distemper virus (CDV) antigens based on a bacterium-like particle (BLP) delivery platform. The CDV-BLPs formulated with theMn jelly adjuvant induced robust humoral and cell-mediated immune responses to CDV in mice and dogs, thereby providing effective protection against a virulent virus challenge. This work is an important step in developing a CDV subunit vaccine.

Guanxining injection alleviates fibrosis in heart failure mice and regulates SLC7A11/GPX4 axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Lamiaceae, Danshen in Chinese) and Chuanxiong Rhizoma (rhizomes of Ligusticum chuanxiong Hort., Apiaceae, Chuanxiong in Chinese) both are important traditional Chinese medicine (TCM) for activating blood and eliminating stasis. Danshen-chuanxiong herb pair has been used for more than 600 years in China. Guanxinning injection (GXN) is a Chinese clinical prescription refined from aqueous extract of Danshen and Chuanxiong at the ratio of 1:1 (w/w). GXN has been mainly used in the clinical therapy of angina, heart failure (HF) and chronic kidney disease in China for almost twenty years. AIM OF THE STUDY: This study aimed to explore the role of GXN on renal fibrosis in heart failure mice and the regulation of GXN on SLC7A11/GPX4 axis. MATARIALS AND METHODS: The transverse aortic constriction model was used to mimic HF accompanied by kidney fibrosis model. GXN was administrated by tail vein injection in dose of 12.0, 6.0, 3.0 mL/kg, respectively. Telmisartan (6.1 mg/kg, gavage) was used as a positive control drug. Cardiac ultrasound indexes of ejection fraction (EF), cardiac output (CO), left ventricle volume (LV Vol), HF biomarker of pro-B type natriuretic peptide (Pro-BNP), kidney function index of serum creatinine (Scr), kidney fibrosis index of collagen volume fraction (CVF) and connective tissue growth factor (CTGF) were evaluated and contrasted. Metabolomic method was employed to analyze the endogenous metabolites changes in kidneys. Besides, contents of catalase (CAT), xanthine oxidase (XOD), nitricoxidesynthase (NOS), glutathione peroxidase 4 (GPX4), the x(c)(-) cysteine/glutamate antiporter (SLC7A11) and ferritin heavy chain (FTH1) in kidney were quantitatively analyzed. In addition, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the chemical composition of GXN and network pharmacology was used to predict possible mechanisms and the active ingredients of GXN. RESULTS: The cardiac function indexes of EF, CO and LV Vol, kidney functional indicators of Scr, the degree of kidney fibrosis indicators CVF and CTGF were all relieved to different extent for the model mice treated with GXN. 21 differential metabolites involved in redox regulation, energy metabolism, organic acid metabolism, nucleotide metabolism, etc were identified. Aspartic acid, homocysteine, glycine, and serine, methionine, purine, phenylalanine and tyrosine metabolism were found to be the core redox metabolic pathways regulated by GXN. Furthermore, GXN were found to increase CAT content, upregulate GPX4, SLC7A11 and FTH1 expression in kidney significantly. Not only that, GXN also showed good effect in down-regulating XOD and NOS contents in kidney. Besides, 35 chemical constituents were initially identified in GXN. Active ingredients of GXN-targets-related enzymes/transporters-metabolites network was established to find out that GPX4 was a core protein for GXN and the top 10 active ingredients with the most relevant to renal protective effects of GXN were rosmarinic acid, caffeic acid, ferulic acid, senkyunolide E, protocatechualdehyde, protocatechuic acid, danshensu, L-Ile, vanillic acid, salvianolic acid A. CONCLUSION: GXN could significantly maintain cardiac function and alleviate the progression of fibrosis in the kidney for HF mice, and the mechanisms of action were related to regulating redox metabolism of aspartate, glycine, serine, and cystine metabolism and SLC7A11/GPX4 axis in kidney. The cardio-renal protective effect of GXN may be attributed to multi-components like rosmarinic acid, caffeic acid, ferulic acid, senkyunolide E, protocatechualdehyde, protocatechuic acid, danshensu, L-Ile, vanillic acid, salvianolic acid A et al.

Ta-Xi-San Suppresses Atopic Dermatitis Involved in Multitarget Mechanism Using Experimental and Network Pharmacology Analysis.

Atopic dermatitis (AD) is a relapsing and chronic skin inflammation with a common incidence worldwide. Ta-Xi-San (TXS) is a Chinese herbal formula usually used for atopic dermatitis in clinic; however, its active compounds and mechanisms of action are still unclear. Our study was designed to reveal the pharmacological activities, the active compounds, and the pharmacological mechanisms of TXS for atopic dermatitis. Mice were induced by 2,4-dinitrocluorobenzene (DNCB) to build atopic dermatitis model. The pathological evaluation, enzyme-linked immunosorbent assay (ELISA), and hematoxylin and eosin (H&E) assay were performed. The UPLC-Q-Exactive-MSE and network pharmacology analysis were performed to explore active ingredients and therapeutic mechanisms of TXS. TXS treatment decreased levels of immunoglobulin E (IgE), interleukin-4 (IL-4), and tumor necrosis factor-α (TNF-α) in serum induced by DNCB. TXS reduced scratching behavior and alleviated inflammatory pathology of skin and ear. Meanwhile, TXS decreased the spleen index and increased spleen index. The UPLC-Q-Exactive-MSE results showed that 65 compounds of TXS were detected and 337 targets were fished. We collected 1371 AD disease targets, and the compound-target gene network reveled that the top 3 active ingredients were (-)-epigallocatechin gallate, apigenin, and esculetin, and the core target genes were PTGS2, PTGS1, and HSP90AA1. The KEGG pathway and GO analysis showed that TXS remedied atopic dermatitis via PI3K-Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and Toll-like receptor (TLR) signaling pathway with the regulation of inflammatory response and transcription. Further, we found that the targets of PTGS2 and HSP90AA1 were both elevated in ears and skin of AD model mouse; however, TXS decreased the elevated expressions of PTGS2 and HSP90AA1. Our study revealed that TXS ameliorated AD based on (-)-epigallocatechin gallate, apigenin, and esculetin via targeting PTGS2 and HSP90AA1.

The contribution of sediment desiccation and rewetting process to eutrophication in the presence and absence of emergent macrophytes.

The purpose of current study was to investigate the effects of sediment desiccation on nutrient dynamics and eutrophication in wetlands during the presence or absence of wiry and sturdy rooted emergent macrophytes, based on the hypothesis that sediment desiccation negatively correlated with plants nutrient uptake abilities and positively with nutrients fluxes at sediment-water interface. Growth of four emergent macrophytes, including two wiry rooted plants, i.e., Alocasia cucullata and Aglaonema commutatum, and two sturdy rooted plants, i.e., Cannabis indica and Acorus calamus, were grown and investigated in dried-rewetted sediments (DS) and constantly wet sediments (WS), respectively, for 6 months. The findings revealed that sediment drying and rewetting process significantly decreased the diffusion of overlying nutrient into sediment and the particle size density, porosity, and nutrients' repository ability in DS treatments, while the sediment bulk density and mineralization of organic macronutrients increased. Compared to WS treatments, the DS treatments impaired plant growth, root biomass, shoot biomass, and stimulated higher fluxes of ammonium nitrogen ([Formula: see text]-N, 0.042-0.081 mg m - 2 d - 1) and phosphate (P[Formula: see text] 0.009-0.030 mg m-2 d-1) at sediment-water interface upon rewetting. The higher internal release of macronutrients and dissolved organic carbon (DOC) from DS led to the higher chlorophyll-a (Chl-a) concentrations (34.47-21.28 to 41.76-33.36 µg L-1) in their water column than in the water column of WS. The wiry rooted plants with higher root biomass displayed lower internal release of [Formula: see text]-N, PO43-P and DOC and water column Chl-a concentrations than the sturdy rooted plants in two sediment types. Root biomass of plants correlated positively with TN (63-87%) and TP (56-78%) removal percentages from WS and DS. These results demonstrated that sediment desiccation process reduced plant growth and enhanced internal loading of nutrients and consequently accelerated eutrophication in these wetlands.

The feasibility of recycling drinking water treatment residue as suspended substrate for the removal of excess P and N from natural water.

Eutrophication of natural water commonly involves the pollution of both P and N. Here, we developed a new application of drinking water treatment residuals (DWTRs) for suspensions that permits the simultaneous removal of excess P and N from natural water and demonstrates that DWTRs recycling can provide a means for eutrophication control. Based on 364-day continuous flow tests, the suspension application of DWTRs effectively adsorbed P from overlying water under various conditions, decreasing total P concentrations from 0.0739 ± 0.0462 to 0.0111 ± 0.0079-0.0149 ± 0.0106 mg L-1, which achieved a class Ⅱ level of the China surface water quality standards during the tests. The total N concentrations were also reduced from 1.46 ± 0.63-1.52 ± 0.63 to 0.435 ± 0.185-0.495 ± 0.198 mg L-1, which achieved a class Ⅲ level during the stable stage of the tests. N removal was closely related to doses of DWTRs and aeration intensities. Effective N removal was mediated by the enriched microbial communities in the suspended DWTRs with simple, stable, and resilient networks, including many taxa associated with the N cycle (e.g., Rhodoplanes, Brevibacillus, and Pseudomonas). Further analysis indicated that both effective P adsorption and functional microbial community construction were closely related to Fe and Al in DWTRs. Suspension application prevented the burial effect of solids sinking from overlying water, which aided the ability of DWTRs to control pollution, and is potentially applicable to other materials for natural water remediation.

Molecular dynamic investigate the affection of EGFR by Tubemoside.

Tubemoside as a common traditional Chinese medicine is playing an important role in the field of prevention and treatment of lung cancer without any side effects. However, the reason and its mechanism remain unclear. In our study, the molecular dynamic simulation was used to investigate the mechanism at the molecular level. We found that the hydrogen bond network of proteins (three states of EGFR) was affected by Tubemoside. The movement and opening/closing state of protein was changed when combine with Tubemoside. The results of principal component analysis were used to prove the transform of proteins and the change of its movement. Electrostatic interactions of proteins also were studied. The numbers of active interaction sites will decrease while Tubemoside emerged in the protein, which will cause the activity change of EGFR for forming asymmetric dimers required for activation.

Effect of superfine pulverization on physicochemical and medicinal properties of Qili Powder

Qili Powder, a preparation from Traditional Chinese Medicine, commonly used to treat injuries from falling or stumbling, pain caused by bruising, and traumatic hemorrhage. The aim of the present work was to investigate the application of the superfine pulverization on Qili Powder properties. The physicochemical and medicinal properties of fine Qili Powder with D90 particle size of 164.5 μm, and superfine Qili Powder with D90 particle size of 32.2 μm were investigated. The results showed that with decreasing particle size, the specific surface area and pore volume increased, the fluidity decreased, and the percentage of moisture absorption and the balanced moisture content decreased. Analysis HPLC, XRD and FTIR results indicated that superfine pulverization didn’t influence dracorhodin content, nor the molecular structure and crystal form of Qili Powder. The percentage of dissolution of dracorhodin was significantly improved after superfine pulverization. Pharmacokinetics results confirmed that superfine pulverization increases the absorption rate in rats and dracorhodin content of Qili Powder.