Bimin Kang ameliorates the minimal persistent inflammation in allergic rhinitis by reducing BCL11B expression and regulating ILC2 plasticity.

ETHNOPHARMACOLOGICAL RELEVANCE: Minimal persistent inflammation (MPI) is a major contributor to the recurrence of allergic rhinitis (AR). The traditional Chinese herbal medicine known as Bimin Kang Mixture (BMK) have been used in clinics for decades to treat AR, which can relieve AR symptoms, reduce inflammatory response and improve immune function. However, its mechanism in controlling MPI is still unclear. AIM OF THE STUDY: This study aims to assess the therapeutic effect of BMK on MPI, and elaborate the mechanism involved in BMK intervention in BCL11B regulation of type 2 innate lymphoid cell (ILC2) plasticity in the treatment of MPI. MATERIAL AND METHODS: The effect of BMK (9.1 ml/kg) and Loratadine (15.15 mg/kg) on MPI was evaluated based on symptoms, pathological staining, and ELISA assays. RT-qPCR and flow cytometry were also employed to assess the expression of BCL11B, IL-12/IL-12Rß2, and IL-18/IL-18Rα signaling pathways associated with ILC2 plasticity in the airway tissues of MPI mice following BMK intervention. RESULTS: BMK restored the airway epithelial barrier, and markedly reduced inflammatory cells (eosinophils, neutrophils) infiltration (P < 0.01) and goblet cells hyperplasia (P < 0.05). BCL11B expression positively correlated with the ILC2 proportion in the lungs and nasal mucosa of AR and MPI mice (P < 0.01). BMK downregulated BCL11B expression (P < 0.05) and reduced the proportion of ILC2, ILC3 and ILC3-like ILC2 subsets (P < 0.05). Moreover, BMK promoted the conversion of ILC2 into an ILC1-like phenotype through IL-12/IL-12Rß2 and IL-18/IL-18Rα signaling pathways in MPI mice. CONCLUSION: By downregulating BCL11B expression, BMK regulates ILC2 plasticity and decreases the proportion of ILC2, ILC3, and ILC3-like ILC2 subsets, promoting the conversion of ILC2 to ILC1, thus restoring balance of ILC subsets in airway tissues and control MPI.

Two new sesquiterpene glycosides from the stems of Dendrobium henanense and their anti-inflammatory activity.

Two new sesquiterpene glycosides, 8α,12,15ß-trihydroxycopacamphan-15-O-ß-D-glucopyranoside (1) and dendrobiumane C-11-O-ß-D-glucopyranoside (2), along with three known terpenoids (3-5) were isolated from the aerial stems of Dendrobium henanense. Their structures were elucidated based on NMR-spectroscopic and HR-MS analyses. All compounds could reduce the levels of NO, TNF-α and IL-1ß in LPS-induced RAW264.7 cells with IC50 values ranging from 10.37 to 34.55 µΜ.

Three new isocoumarin analogues from an endolichenic fungus Aspergillus flavus CPCC 400810.

Five isocoumarin derivatives including three new compounds, aspermarolides A-C (1-3), and two known analogues, 8-methoxyldiaporthin (4) and diaporthin (5) were obtained from the culture extract of Aspergillus flavus CPCC 400810. The structures of these compounds were elucidated by spectroscopic methods. The double bond geometry of 1 and 2 were assigned by the coupling constants. The absolute configuration of 3 was determined by electronic circular dichroism experiment. All compounds showed no cytotoxic activities against the two human cancer cells HepG2 and Hela.

Molecular Mechanisms Underlying the Effects of Bimin Kang Mixture on Allergic Rhinitis: Network Pharmacology and RNA Sequencing Analysis.

Background: Allergic rhinitis (AR) is a highly prevalent chronic inflammatory disease of the respiratory tract. Previous studies have demonstrated that Bimin Kang Mixture (BMK) is effective in alleviating AR symptoms and reducing the secretion of inflammatory factors and mucin; however, the precise mechanisms underlying these effects remain unclear. Methods: We built target networks for each medication component using a network pharmacology technique and used RNA-seq transcriptome analysis to screen differentially expressed genes (DEGs) for AR patients and control groups. The overlapping targets in the two groups were assessed using PPI networks, GO, and KEGG enrichment analyses. The binding ability of essential components to dock with hub target genes was investigated using molecular docking. Finally, we demonstrate how BMK can treat AR by regulating the NF-κB signaling pathway through animal experiments. Results: Effective targets from network pharmacology were combined with DEGs from RNA-seq, with 20 intersections as key target genes. The construction of the PPI network finally identified 5 hub target genes, and all hub target genes were in the NF-κB signaling pathway. Molecular docking suggests that citric acid, deoxyandrographolide, quercetin, luteolin, and kaempferol are structurally stable and can spontaneously attach to IL-1ß, CXCL2, CXCL8, CCL20, and PTGS2 receptors. Animal experiments have shown that BMK inhibits NF-κB transcription factor activation, reduces the expression of proinflammatory cytokines and chemokines IL-1ß, CXCL2, IL-8, and COX-2, and exerts anti-inflammatory and anti-allergic effects. Conclusion: BMK by regulating the NF-κB signaling pathway improves inflammatory cell infiltration, regulates mucosal immune balance, and reduces airway hypersensitivity. These findings provide theoretical support for the clinical efficacy of BMK for AR treatment.

[Integrated Assessment of Runoff Quality from Green Roofs with Different Configurations].

Green roofs are regarded as one of the important measures for the sponge city construction. However, the comprehensive impacts of configuration factors (e.g., vegetation and substrates) on runoff quality from green roofs are not clear, which limits the promotion of green roofs. In this study, 12 green roofs with three vegetation types (i.e., Sedum lineare, Portulaca grandiflora, and non-vegetated substrates), three substrate types (i.e., local planting soil, engineered soil, and light growing medium), and two substrate depths (i.e., 10 cm and 15 cm) were set up in Beijing. During the rainy season of 2019, the rainfall characteristics, runoff volumes, and concentrations of nutrients and heavy metals of runoff from the green roofs were monitored. Based on the measured data, a runoff quality index (RQI) was developed to evaluate the comprehensive influences of configurations on runoff quality of the green roofs. The results showed that vegetation could improve runoff reduction rate and decrease the concentrations of NO3--N in runoff of green roofs. The RQIs of green roofs planted with S. linear and P. grandiflora were similar, and the evaluation results of runoff quality were better than those with non-vegetated substrates. The materials of substrates had significant influences on the runoff reduction rate and pollutant concentrations in runoff from green roofs. The green roofs with light growing medium, which had the lowest runoff reduction rates and the highest concentrations of NH4+-N, DFe, DMn, and DZn in the runoff, showed poorer runoff quality than the green roofs with local planting soil and engineered soil. The green roofs with a substrate depth of 15 cm had higher runoff reduction rates than those with 10 cm deep substrate, and the runoff quality was better than those with a substrate depth of 10 cm. The results of this study provide scientific reference for the design and integrated assessment of green roofs.

ILC3-like ILC2 subset increases in minimal persistent inflammation after acute type II inflammation of allergic rhinitis and inhibited by Biminkang: Plasticity of ILC2 in minimal persistent inflammation.

Minimal persistent inflammation (MPI), the local inflammation that occurs after an acute type II immune response in patients with allergic rhinitis (AR), is responsible for airway hyperreactivity and the recurrence of AR. Innate lymphoid cells (ILCs) play a crucial role in mucosal immune homeostasis, but the changes of ILC subsets in the MPI stage remain unclear. In this study, the levels of ILC-secreting cytokines in nasal lavages were analyzed from 19 AR patients and 8 healthy volunteers. AR and MPI model mice were established to study the ILC subsets. The results showed that IL-17A was significantly increased in nasal lavage of AR patients in the MPI stage by MSD technology. When compared with the AR model mice, the frequency of IL-13+ ILC2 in the nasal mucosa and lungs decreased, while IL-5+ ILC2 remain high in MPI model mice. A part of the IL-5+ ILC2 subset displayed ILC3-like characteristics with elevated RORγt, IL-17A and IL-23R expression. Especially, these ILC3-like ILC2 exhibited up-regulation of GATA3+ RORγt+ were increased in MPI model mice. After the treatment of Biminkang, the frequencies of IL-5+ ILC2, IL-17A+ ILC3, and GATA3+ RORγt+ ILC3-like ILC2 were significantly reduced, and IL-23R expression was also decreased on ILC3-like-ILC2 subset. These results suggested that the elevated IL-17A in the MPI stage has been related to or at least partly due to the increased of ILC3-like ILC2. Biminkang could effectively decrease IL-17A+ ILC3 and inhibit ILC3-like ILC2 subset in the MPI stage. Biminkang is effective in administrating MPI by regulating airway ILC homeostasis.

[Inter-annual Changes in Runoff Quality from Green Roofs with Different Vegetation].

As an important measure of the sponge city, green roofs have received extensive attention in recent years. To investigate the inter-annual changes in runoff quality of green roofs with different vegetation types, three green roofs with different vegetation cover (Sedum lineare, Portulaca grandiflora, and a non-vegetated control) were set up in Beijing. The influences of vegetation and monitoring period on runoff quality from the green roofs were evaluated using the plant growth characteristics and the quality of rainwater and runoff from the green roofs during the rainy season of 2017-2019. The results showed that all three green roofs were the sinks of NH4+-N, and the average mass concentration reduction rates were between 50.1% and 79.2%. However, all three green roofs were sources of PO43--P, DCr, DCu, and DNi. The green roofs covered with S. lineare and P. grandiflora were sinks of NO3--N in 2017, and the average mass concentration reduction rates were 71.4% and 99.5%, respectively, but they became sources of NO3--N in both 2018 and 2019. However, the non-vegetated control was the source of NO3--N in all three rainy seasons. Both vegetation type and length of monitoring period had significant effects on the mass concentrations of NO3--N, PO43--P, DNi, and DCu in runoff from the green roofs (P<0.05) but had no significant effects on the mass concentrations of NH4+-N and DCr in runoff from the green roofs (P>0.05). In 2017-2019, the mass concentrations of NO3--N in runoff from the non-vegetated control and the green roofs covered by S. lineare and the mass concentration of PO43--P in runoff from the green roof covered by P. grandiflora increased yearly. The mass concentrations of DNi and DCu in runoff from all three green roofs increased in 2018 but dropped in 2019. Among the green roofs with different vegetation types, the green roof covered by P. grandiflora showed better NO3--N retention capacity than that of the other green roofs but may have increased the concentrations of PO43--P, DNi, and DCu in the runoff.

Fusapyrone A, a γ-pyrone derived from a desert Fusarium sp.

In this work, we isolated and characterized fusapyrone A (1), a new γ-pyrone derivative, along with six previously described compounds from the rice fermentation of Fusarium sp. CPCC 401218, a fungus collected from the desert. The structure of 1 was characterized using various spectroscopic analyses, such as MS, IR, 1D, and 2D NMR. The absolute configuration of 1 was determined through the use of 13C NMR chemical shifts, electronic circular dichroism (ECD) and optical rotation (OR) calculations. Compound 1 was found to have weak antiproliferative activity for Hela cells, with an IC50 of 50.6 µM.[Formula: see text].

Ahmpatinin iBu, a new HIV-1 protease inhibitor, from Streptomyces sp. CPCC 202950.

Ahmpatinin iBu (1) and statinin iBu (2), two new linear peptides, a novel pyrrolidine derivative, (-)-(S)-2-[3-(6-methylheptanamido)-2-oxopyrrolidin-1-yl] acetic acid (3), and three known pepstatin derivatives (4-6) along with their corresponding methanolysis artifacts (7-9) were isolated from Streptomyces sp. CPCC 202950. Their structures were elucidated on the basis of extensive spectroscopic data using Marfey's analysis, chiral-phase HPLC, and ECD and OR calculation to determine the absolute configurations. Compound 1 contains an unusual amino acid, 4-amino-3-hydroxy-5-(4-methoxyphenyl)pentanoic acid (Ahmppa), and 3 is the first natural product with a 2-(3-amino-2-oxopyrrolidin-1-yl)acetic acid system. Compounds 1, 2, and 4-9 are HIV-1 protease inhibitors. In particular, ahmpatinin iBu (1) exhibits significant inhibitory activity against HIV-1 protease with an IC50 value of 1.79 nM. A preliminary structure-activity relationship is discussed.

[A new benzamide derivative from rice fermentation of Streptomyces sp. CPCC 202950].

Eight compounds were isolated from the rice fermentation of Streptomyces sp. CPCC 202950 by a combination of various chromatographic techniques including column chromatography over silica, Sephadex LH-20, flash C18, and reversed-phase HPLC. Their structures were identified as 3-[(3'-amino-3'-oxoprop-1'-en-2'-yl)oxy]benzamide (1), m-hydroxybenzamide (2), leptosphaepin (3), 5-methyluracil (4), feruloylamide (5), p-hydroxyphenylacetoamide (6), vanillamide (7), cyclo (L-val-L-ala) (8). Among them, 1 was a new benzamide analogue, and 2 was a new natural product. In the preliminary assays, none of the compounds 1-8 exhibited obvious inhibition of HIV-1 protease activity, and toxic with the Hela, HepG2, and U2OS cells. (IC50 > 10 µmol•L⁻¹).

[Separation, purification and primary reverse cholesterol transport study of Cordyceps militaris polysaccharide].

The authors designed to separate, purify and determine the monosaccharide composition of the polysaccharide from Cordyceps militaris, and study its effect on reverse cholesterol transport in vivo by isotope tracing assay. Polysaccharides were separate and purify by ion exchange column Q-sepharose Fast Flow and size exclusion column Sephacryl S200HR; the molecular weight and monosaccharide composition of the polysaccharides were determined by high performance gel permeation chromatography and high performance liquid chromatography coming with pre-column derivation, respectively. Finally, three purified polysaccharides CMBW1, CMBW2 and CMYW1 were obtained, their total carbohydrate contents were 87%, 89%, 95%, respectively; their protein contents were 6.5%, 1.3%, 2.8%, respectively; their molecular weights were 772.1, 20.9, 13.2 kDa, respectively; CMBW1 was composed of mannose, glucosamine, rhamnose, glucuronic acid, glucose, galactose and arabinose with a molar ratio of 7.25: 0.17: 1.29: 0.23: 6.30: 11.08: 0.79; CMBW2 was composed of mannose, glucosamine, galactose and arabinose with a molar ratio of 2.40: 0.16: 2.92: 0.24; CMYW1 was composed of mannose, glucosamine, glucuronic acid and glucose with a molar ratio of 0.59: 0.57: 0.45: 25.61. Polysaccharide at 50 mg x kg(-1) could significantly improve the transport of 3H- cholesterol to blood and excretion from feces. All of the three purified polysaccharides CMBW1, CMBW2 and CMYW1 were heteropolysaccharide; and they could improve reverse cholesterol transport in vivo, the underlying mechanisms are being studied.

The effects of warming and nitrogen addition on soil nitrogen cycling in a temperate grassland, northeastern China.

BACKGROUND: Both climate warming and atmospheric nitrogen (N) deposition are predicted to affect soil N cycling in terrestrial biomes over the next century. However, the interactive effects of warming and N deposition on soil N mineralization in temperate grasslands are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: A field manipulation experiment was conducted to examine the effects of warming and N addition on soil N cycling in a temperate grassland of northeastern China from 2007 to 2009. Soil samples were incubated at a constant temperature and moisture, from samples collected in the field. The results showed that both warming and N addition significantly stimulated soil net N mineralization rate and net nitrification rate. Combined warming and N addition caused an interactive effect on N mineralization, which could be explained by the relative shift of soil microbial community structure because of fungal biomass increase and strong plant uptake of added N due to warming. Irrespective of strong intra- and inter-annual variations in soil N mineralization, the responses of N mineralization to warming and N addition did not change during the three growing seasons, suggesting independence of warming and N responses of N mineralization from precipitation variations in the temperate grassland. CONCLUSIONS/SIGNIFICANCE: Interactions between climate warming and N deposition on soil N cycling were significant. These findings will improve our understanding on the response of soil N cycling to the simultaneous climate change drivers in temperate grassland ecosystem.

Variations of plant life form diversity along the Northeast China Transect and its direct gradient analysis.

Plant life form diversity and its direct gradient analysis on a larger scale climate change gradient were tested, based on the data from Northeast China Transect platform. The results showed that the species numbers, life form richness and life form diversity were relative higher at the eastern forests and the ecotone between typical vegetation, while those on the meadow grasslands and typical steppes were lower. Although plant life forms can reflect the climate variations, life form diversity is not consistent with the major global gradient along the NECT.

Intra-specific variations of two Leymus chinensis divergence populations in Songnen Plain, northeast China.

Population demography, seed production, biomass allocation, net photosynthesis and transpiration of two Leymus chinensis divergent populations and between two years in Songnen plain, northeast China were compared. Strong differences between the dry 1997 and moist 1998 occurred in vegetative shoot and sexual shoot densities, sexual differentiation and tiller densities, as well as in the lengths of inflorescence, seed numbers per inflorescence, seed weights and biomass allocation in each population respectively (P < 0.01). While strong differences between the two populations occurred in vegetative shoot densities, sexual shoot densities, sexual differentiation and seed weights in each year (P < 0.01). The differences between the two populations in tiller densities and in biomass allocation to sexual shoots were significant (P < 0.05). But there were no significant differences between the two populations in the lengths of inflorescence, seed numbers per inflorescence and biomass allocation to rhizomes and vegetative shoots (P > 0.05). Excepting the transpiration rate in the early June, the differences between the two populations in net photosynthesis and transpiration rate of vegetative shoots and sexual shoots were strongly significant in the early June and July respectively (P < 0.01). Relative stable variations in population demography and physiological traits between the two populations indicated that they are divergently in the Songnen Plain.