Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity.

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I (1, 4-11), and two known ones (2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

Selenium nanomaterials alleviate Brassica chinensis L cadmium stress: Reducing accumulation, regulating microorganisms and activating glutathione metabolism.

Agricultural heavy metal contamination can cause significant crop damage, highlighting the urgent need to mitigate its negative effects. Under Cd2+ stress, selenium nanomaterials (Se NMs, 2 mg kg-1) can significantly improve Brassica chinensis L. root growth and vigor, enhance photosynthesis (31.4%), and increase biomass. Se NMs treatment also reduces Brassica chinensis L root and shoot Cd concentration by 67.2 and 72.9%, respectively. This reduction is mainly due to the gene expression of Cd2+ absorption (BcITR1 and BcHMA2) which was down-regulated 51.9 and 67.0% by Se NMs, respectively. Meanwhile, Se NMs can increase the abundance of Cd-resistant microorganisms (Gemmatimonas, RB41, Haliangium, Gaiella, and Steroidobacter) in rhizosphere soil while also reducing Cd migration from soil to plants. Additionally, Se NMs also contribute to reducing ROS accumulation by improving the oxidation-reduction process between GSH and GSSG through enhancing γ-ECS (15.6%), GPx (50.2%) and GR (97.3%) activity. Remarkably, crop Se content can reach 50.8 µg/100 g, which fully meets the standards of Se-rich vegetables. These findings demonstrate the potential of Se NMs in relieving heavy metal stress, while simultaneously increasing crop Se content, making it a promising technology for sustainable agricultural production.

Cordythiazole A, the first member of thiazole alkaloids from Chinese cordyceps, with α-glucosidase inhibitory activity.

Chinese cordyceps, also known as Dong-Chong-Xia-Cao, is widely recognized as a famous precious tonic herb, and used as traditional Chinese medicine for centuries. It is mainly used for regulating the immune system and improving functions of the lung and kidney, with anti-tumor, anti-inflammatory, and anti-diabetic activities. Due to its rarity and preciousness, a few chemical components are isolated and identified. Moreover, most of them are common chemical components and widely distributed in other natural resources, such as nucleosides, sterols, fatty acids, sugar alcohols, and peptides. Therefore, a large number of active substances of Chinese cordyceps is still unclear. During our search for chemical constituents of Chinese cordyceps, a new thiazole alkaloid, cordythiazole A (1), was isolated and identified. Its structure was elucidated by comprehensive spectroscopic analysis and single-crystal X-ray diffraction analysis. This is the first report of the presence of thiazole alkaloid in Chinese cordyceps, which adds a new class of metabolite of Chinese cordyceps. Furthermore, a putative biosynthesis pathway of cordythiazole A was proposed based on possible biogenic precursor, genes, and literatures. In addition, it showed α-glucosidase inhibitory activity with potency close to that of acarbose. The discovery of cordythiazole A with α-glucosidase inhibitory activity adds a new class of potential anti-diabetes ingredient in Chinese cordyceps.

Crosstalk between in situ root exudates and rhizobacteria to promote rice growth by selenium nanomaterials.

Maximizing the potential of plant-microbe systems offers great opportunities to confront sustainability issues in agroecosystems. However, the dialog between root exudates and rhizobacteria remains largely unknown. As a novel nanofertilizer, nanomaterials (NMs) have significant potential to improve agricultural productivity due to their unique properties. Here, soil amendment with 0.1 mg·kg-1 selenium (Se) NMs (30-50 nm) significantly promoted rice seedling growth. Differences in root exudates and rhizobacteria were evident. At an earlier time point (3rd week), Se NMs increased the relative content of malic and citric acid by 15.4- and 8.1-fold, respectively. Meanwhile, the relative abundances of Streptomyces and Sphingomonas were increased by 164.6 % and 38.3 %, respectively. As the exposure time increased, succinic acid (40.5-fold) at the 4th week and salicylic acid (4.7-fold) and indole-3-acetic (7.0-fold) at the 5th week were enhanced, while Pseudomonas and Bacillus increased at the 4th (112.3 % and 50.2 %) and 5th weeks (190.8 % and 53.1 %), respectively. Further analysis indicated that (1) Se NMs directly enhanced the synthesis and secretion of malic and citric acids by upregulating their biosynthesis and transporter genes and then recruited Bacillus and Pseudomonas; (2) Se NMs upregulated the chemotaxis and flagellar genes of Sphingomonas for more interaction with rice plants, thereby promoting rice growth and stimulating root exudate secretion. This crosstalk of root exudates and rhizobacteria enhanced nutrient uptake, resulting in promoted rice growth. Our study offers insights into the crosstalk between root exudates and rhizobacteria by NMs and provides new insights into rhizosphere regulation in nano-enabled agriculture.

Selenium nanomaterials improve the quality of lettuce (Lactuca sativa L.) by modulating root growth, nutrient availability, and photosynthesis.

Macro- or micro-nutrients are essential for crop yield and nutritional quality. In this work, selenium engineering nanomaterials (Se ENMs, 0.5 mg‧kg-1) significantly increased the yield and nutritional quality of lettuce, which was better than that of selenite (Na2SeO3). Under the treatment of Se ENMs, macro-nutrients including nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), and magnesium (Mg) were increased by 15.8%, 98.5%, 42.8%, 146.9%, and 62.5%, respectively, and micro-nutrients including manganese (Mn), iron (Fe), copper (Cu), and zinc (Zn) were also increased by 87.4%, 78.0%, 61.1%, and 56.1%, respectively. As a result, the improved nutritional status of lettuce leaves increased photosynthesis (59.2%) and yield (37.6%). Root diameters and root tips of lettuce were increased by 23.9% and 18.6%, respectively, upon exposure to Se ENMs, which may be responsible for facilitating the absorption of macro and micro nutrients from the soil. These effects were significantly better than SeO32- treated group. Metabolome results indicated that Se ENMs could improve the shikimic acid, phenylalanine, and tyrosine pathway, resulting in an enhancement of the beneficial compounds, including quercetin, rutin, and coumarin, by 2.9, 2.7, and 2.4-fold, respectively. Besides, pyruvic acid and TCA cycle were also improved by Se ENMs. These results provide new insight into the positive effect of Se ENMs on crop yield and nutritional quality, which demonstrate that the Se ENMs-enabled agriculture practices have a promising prospect as a sustainable crop strategy.

Selenium content and nutritional quality of Brassica chinensis L enhanced by selenium engineered nanomaterials: The role of surface charge.

Selenium engineered nanomaterials (Se ENMs)-enabled agriculture has developed rapidly, however, the roles of surface charge in the bioavailability and enrichment efficiency of Se ENMs are still unknown. Herein, various Se ENMs of homogenous size (40-60 nm) and different surface charges (3.2 ± 0.7, -29.0 ± 0.4, and 45.5 ± 1.3 mV) were prepared to explore the Se content and nutritional quality in Brassica chinensis L. The results demonstrated that soil application of various Se ENMs (0.05 mg kg-1) displayed different bio-availabilities via modulating the secretion of root exudates (e.g., tartaric, malic, and citric acids), microbial community composition (e.g., Flavobacterium, Pseudomonas, Paracoccus, Bacillus and Rhizobium) and root cell wall. Negatively charged Se ENMs (Se (-)) showed the highest Se content in the shoot of B. chinensis (3.7-folds). Se (-) also significantly increased yield (156.9%) and improved nutritional quality (e.g., ascorbic acid, amino acids, flavonoids, fatty acids, and tricarboxylic acid) of B. chinensis. Moreover, after harvest, the Se (-) did not lead to significant change in Se residue in soil, but the amount of Se residue in soil was increased by 5.5% after applying the traditional Se fertilizer (selenite). Therefore, this study provides useful information for producing Se-fortified agricultural products, while minimizing environmental risk.

Bioactive pterocarpans from the root of Astragalus membranaceus var. mongholicus.

Eleven undescribed and three known pterocarpans were isolated and identified from the traditional Chinese medicine "Huang-qi", Astragali Radix (the root of Astragalus membranaceus var. mongholicus (Bunge) P.K.Hsiao). The structures of these pterocarpans were determined using spectroscopic, X-ray crystallographic, quantum chemical calculation, and chemical methods. Pterocarpans, almost exclusively distributed in the family of Leguminosae, are the second largest subgroup of isoflavanoids. However, pterocarpan glycoside number is limited, most of which are glucosides, and only one pterocarpan apioside was isolated from nature. Notably, nine rare apiosyl-containing pterocarpan glycosides were isolated and identified. The hypoglycemic activities of all these compounds were evaluated using α-glucosidase and DPP-IV inhibitory assays respectively, and some isolates displayed the α-glucosidase inhibitory function. The antioxidant activities of all compounds were evaluated using the ORAC and DPPH radical scavenging assays, respectively. All compounds exhibited varying degrees of oxygen radical absorbance capacity, and some compounds displayed DPPH radical scavenging ability.

Multiomics understanding of improved quality in cherry radish (Raphanus sativus L. var. radculus pers) after foliar application of selenium nanomaterials.

A selenium (Se)-nanoenabled agriculture strategy was established in this work to improve crop yield and quality. The results demonstrated that Se engineering nanomaterials (Se ENMs, 10 mg·L-1) were absorbed and translocated in cherry radish (Raphanus sativus L. var. radculus pers) from shoots to taproots after foliar application. RNA-Seq and metabolomic results indicated that the glucolysis, pyruvate and tricarboxylic acid (TCA) cycle metabolism pathways were accelerated by exposure to Se ENMs, resulting in increased production of flavonoids (3.2-fold), amino acids (1.4-fold), and TCA (2.5-fold) compared with the control. Moreover, Se content was enhanced by 5.4 and 2.6 times in pericarp and pulp upon Se ENMs exposure, respectively, which was more efficient (2.2 and 1.1 times) than SeO32- treatment. Additionally, the yield of cherry radish was increased by 67.6% under Se ENMs, whereas SeO32- exposure only led to an increase of 7.4%. Therefore, the application of Se ENMs could reduce the amount of fertilizer used to minimize the environmental impact in agriculture while improve crop production and quality. These findings highlighted the significant potential of Se ENMs-enabled agriculture practices as an eco-friendly and sustainable crop strategy.

Development of an eco-friendly and fast HPLC method for quantitative analysis of four nucleosides in Cordyceps and related products.

An eco-friendly and fast HPLC method was developed for the determination of adenosine, inosine, guanosine and uridine in Cordyceps and related products (fermented mycelia of Hirsutella sinensis andPaecilomyces hepiali). The sample was ultrasonically extracted using 0.5% phosphoric acid solutions for 2.5 min. Sample separation was performed on a Poroshell SB-Aq column (50 mm × 4.6 mm, 2.7 µm) using eco-friendly mobile phase consisting of formic acid and ammonium formate aqueous solution at a flow rate of 1.0 mL·min-1. The detection wavelength was 260 nm. The developed HPLC method showed good linearity with correlation coefficients of 1.0000 in the test range. Good precision, repeatability and stability of this method were also observed (RSD ≤ 2.81%). The recovery ranged from 91.84%-105.19% (RSD ≤ 2.59%). Compared with reported methods, the current method did not use harmful organic solvent and took only 10.5 min. It obtained a high eco-score of 91 by the "Analytical Eco-Scale" tool. The developed method is eco-friendly and fast, which is suitable for the quality evaluation of Cordyceps and related products.

Cell Walls Are Remodeled to Alleviate nY2O3 Cytotoxicity by Elaborate Regulation of de Novo Synthesis and Vesicular Transport.

Yttrium oxide nanoparticles (nY2O3), one of the broadly used rare earth nanoparticles, can interact with plants and possibly cause plant health and environmental impacts, but the plant defense response particularly at the nanoparticle-cell interface is largely unknown. To elucidate this, Bright Yellow 2 (BY-2) tobacco (Nicotiana tabacum L.) suspension-cultured cells were exposed to 50 mg L-1 nY2O3 (30 nm) for 12 h. Although 42.2% of the nY2O3 remained outside of protoplasts, nY2O3 could still traverse the cell wall and was partially deposited inside the vacuole. In addition to growth inhibition, morphological and compositional changes in cell walls occurred. Together with a locally thickened (7-13-fold) cell wall, increased content (up to 58%) of pectin and reduction in (up to 29%) hemicellulose were observed. Transcriptome analysis revealed that genes involved in cell wall metabolism and remodeling were highly regulated in response to nY2O3 stress. Expression of genes for pectin synthesis and degradation was up- and down-regulated by 31-78% and 13-42%, respectively, and genes for xyloglucan and pectin modifications were up- and down-regulated by 82% and 81-92%, respectively. Interestingly, vesicle trafficking seemed to be activated, enabling the repair and defense against nY2O3 disturbance. Our findings indicate that, although nY2O3 generated toxicity on BY-2 cells, it is very likely that during the recovery process cell wall remodeling was initiated to gain resistance to nY2O3 stress, demonstrating the plant's cellular regulatory machinery regarding repair and adaptation to nanoparticles like nY2O3.

[Clinical Application of Preoperative Autologous Blood Donation in Selective General Surgery].

OBJECTIVE: To study the clinical effects of preoperative autologous blood donation (PABD) in selective general surgery. METHODS: Paired study was performed in PABD group with 70 PABD cases screened from selective general surgery during the period from November 2017 to August 2018 in our hospital, and the control group included 70 cases without preoperative autologous blood donation, the baseline data before surgery were not significantly different. The transfusion quantities of allogeneic RBC and plasma, the levels of perioperative hemoglobin and platelets, the time and expense of hospitalization were compared between two groups. RESULTS: The levels of Hb and Plt in PABD group before and after blood collection were determined as follows: 138.26±14.73 g/L vs 127.52±13.36 g/L (P＜0.05) and (221.67±52.86)×109/L vs (198.35±52.65)×109/L (P＞0.05) respectively. The analysis of allo-RBC and allo-plasma transfusion in PABD group and control group showed that: the quantity of allogeneic RBC transfusion was 0.20±0.71 U and 0.89±0.97 U, and the quantity of allogeneic plasma transfusion was 30.43±100.81 ml and 106.52±152.61 ml (P＜0.05) respectirdy during perioperation. The comparison results of preoperative Hb and plt in PABD group and control group were 135.65±14.16 g/L vs 134.15±11.98 g/L and (270.36±58.28)×109/L vs (271.67±65.02) ×109/L respectively. The levels of postoperative Hb and plt in PABD group and control group were 120.24±14.40 g/L vs 121.20±14.30 g/L at 1 d after operation, and (241.80±63.58)×109/L vs (241.30±69.11)×109/L at 1 d after operation respectively; 123.15±13.80 g/L vs 121.65±14.33 g/L at 3 d after operation and (251.26±72.94)×109/L vs (255.54±73.85)×109/L at 3 d after operation; 122.78±13.92 g/L and 122.00±13.82 g/L (before discharge) and (262.50±80.96)×109/L and (264.56±71.08)×109/L (before discharge, platelet). These data were not statistically different (P＞0.05). The hospitalization time was 14.84±3.37 days and 14.84±2.24 days, respectively, without statistical difference (P＞0.05) in two groups. The expenses of hospitalization and the blood transfusion in two groups were 50627.27±9889.45 RMB and 50979.43±8195.00 RMB; 354.39±362.57 RMB and 684.02±425.53 RMB (P＜0.05). CONCLUSION: The application of PABD reduces the use of allogeneic blood and costs for patients undergoing selective surgery with blood losts of 1000 ml.

A pair of new tirucallane triterpenoid epimers from the stems of Picrasma quassioides.

A pair of new tirucallane triterpenoid epimers, picraquassins M and N (1> and 2), were isolated from the stems of Picrasma quassioides (D. Don) Benn. Their structures were determined based on comprehensive spectroscopic and X-ray crystallographic analyses. In addition, their AChE inhibitory activity, cytotoxicity against five human tumour cell lines (SW480, MCF-7, HepG2, Hela, and PANC-1), and antimicrobial activity against two bacteria (Staphylococcus. aureus 209P and Escherichia coli ATCC0111) and two fungi (Candida albicans FIM709 and Aspergillus niger R330) were evaluated.

A new cinnamamide derivative and two new ß-carboline alkaloids from the stems of Picrasma quassioides.

Picrasamide A (1), a new cinnamamide derivative, together with two new ß-carboline alkaloids (2 and 3) and five known ß-carboline alkaloids (4-8) were isolated from the stems of Picrasma quassioides (D. Don) Benn. Their structures were elucidated by detailed analyses of UV, IR, HRESIMS, and NMR data. Compound 1 was the first case of cinnamamide derivative from genus Picrasma. The AChE inhibitory activity and the antimicrobial activity of 1-8 were assessed. In addition, preliminary structure-activity relationships of these ß-carboline alkaloids on the AChE inhibitory activity and antimicrobial activity were proposed.

Phenylisotertronic acids from the TCM endophytic fungus Phyllosticta sp.

Four new phenylisotertronic acids (1a/1b, 2a, and 3a) were isolated from a TCM endophytic fungal strain Phyllosticta sp. J13-2-12Y obtained from the leaves of Acorus tatarinowii, along with two known ones (2b and 3b). Compounds 1-3 all existed as mixtures of enantiomers, and their corresponding optically pure enantiomers were successfully isolated by chiral HPLC. The structures of isolated compounds were determined by comprehensive spectroscopic analyses and X-ray diffraction. Their absolute configurations were determined by ECD experiments and quantum chemical calculations. In addition, the antimicrobial activities and the cytotoxicities of these three pairs of optically pure enantiomers (1a/1b, 2a/2b, and 3a/3b) had been evaluated.

[Simultaneous determination of cordycepin and 2'-deoxyadenosine in Cordyceps genus by online SPE-HPLC].

An online SPE-HPLC method for simultaneous determination of cordycepin (3'-deoxyadenosine) and 2'-deoxyadenosine in Cordyceps genus (C. sinensis,C. militaris,Hirsutella sinensis and C. sobolifera) was developed. The samples were enriched on a ZORBAX SB-AQ (4.6 mm×12.5 mm,5 µm) column with isocratic elution by 9% methanol solution. The separation of analytes was performed on a ZORBAX SB-AQ (4.6 mm×150 mm,5 µm) column with gradient elution by 0.1% formic acid solution and methanol (91∶9). The flow rate was 1.0 mL•min⁻¹. Column temperature was 40 ℃ and detection wavelength was 260 nm. This method has been applied for analysis of different Cordyceps genus. The 2'-deoxyadenosine was detected in C. sinensis,Hirsutella sinensis and C. sobolifera. The cordycepin was detected in C. militaris. In summary,the cordycepin chromatographic peak from C. sinensis in some past reports may be the 2'-deoxyadenosine chromatographic peak or the mixture peak of 2'-deoxyadenosine and cordycepin in which 2'-deoxyadenosine content was higher than cordycepin. The developed method is suitable for analysis of cordycepin and 2'-deoxyadenosine in Cordyceps genus.

Phyllomeroterpenoids A-C, Multi-biosynthetic Pathway Derived Meroterpenoids from the TCM Endophytic Fungus Phyllosticta sp. and their Antimicrobial Activities.

Phyllomeroterpenoids A-C (1-3), multi-biosynthetic pathway derived meroterpenoids from amino acid/pentose phosphate/terpenoid pathways, were isolated from the TCM endophytic fungus Phyllosticta sp. J13-2-12Y, together with six biosynthetically related compounds (4-9). All structures were determined by extensive spectroscopic analysis, chemical derivatization, and ECD experiments. A plausible biosynthetic pathway of 1-3 was proposed. In addition, the antimicrobial activities of all isolated compounds were evaluated against Staphylococcus aureus 209P (bacterium) and Candida albicans FIM709 (fungus).

New Isocoumarins and Related Metabolites from Talaromyces flavus.

Two new isocoumarin derivatives, talaisocoumarins A (1) and B (2), and three new related metabolites, talaflavuols A-C (3-5) were isolated from the wetland soil-derived fungus Talaromyces flavus BYD07-13. Their structures were elucidated by spectroscopic (NMR) and MS analyses. The absolute configurations of 1 and 2 were determined by CD and an Rh2(OCOCF3)4-induced CD method. All compounds were evaluated for cytotoxic and antimicrobial activities. However, none of them showed any activity. The plausible biosynthetic pathways for 1-5 were also proposed.

A Pair of New Polyketide Enantiomers from Three Endolichenic Fungal Strains Nigrospora sphaerica, Alternaria alternata, and Phialophora sp.

A pair of new enantiomeric polyketides, (-)- and (+)-nigrosporaol A (1a and 1b), along with one related known compound, (+)-alternarienoic acid (2), were isolated from three endolichenic fungal strains, Nigrospora sphaerica (No.83-1-1-2), Alternaria alternata (No.58-8-4-1), and Phialophora sp.(No.96-1-8-1). Their structures, including the absolute configurations, were elucidated on the basis of spectroscopic methods, X-ray diffraction analysis, and the modified Mosher's method.

Adeninealkylresorcinol, the first alkylresorcinol tethered with nucleobase from Lasiodiplodia sp.

Adeninealkylresorcinol (1), an unusual alkylresorcinol with adenine-alkylresorcinol conjoined skeleton, was isolated from an endophytic fungus Lasiodiplodia sp. obtained from a traditional Chinese medicine Houttuynia cordata Thunb., together with three new biogenetically related compounds (2-4). Their structures were elucidated by comprehensive spectroscopic analysis, and the absolute configuration of 4 was determined by the modified Mosher's method and quantum chemical calculation. Among them, adeninealkylresorcinol (1) is the first alkylresorcinol tethered with nucleobase. In addition, the antioxidant, cytotoxic, and antimicrobial activities of 1-3 were evaluated.

[Quantitative analysis of nucleosides in four Cordyceps genus by HPLC].

To compare the main nucleosides in Cordyceps genus herbs (C. sinensis, C. millitaris, Hirsutella sinensis and C. sobolifera), an HPLC method for simultaneous determination of uridine, inosine, guanosine, adenosine and cordycepine in Cordyceps genus herbs was developed. The sample was extracted with 0.5% phosphoric acid solution to prepare test solution. The separation was performed on a Zorbax SB-Aq (4.6 mm×150 mm, 5 µm) column with gradient elution by 0.04 mol•L⁻¹ potassium dihydrogen phosphate solution and acetonitrile, column temperature 30 ℃,flow rate 0.8 mL•min⁻¹,and detection wavelength 260 nm. The content of nucleosides in four Cordyceps genus herbs was evaluated by fingerprint analysis and hierarchical cluster analysis (HCA). The calibration curves of five nucleosides showed good linear regression (r>0.99) and the average recoveries were between 95.0% and 105.0%. The contents of the five nucleosides in the four Cordyceps genus herbs were different and could be obviously distinguished by HCA. The fingerprint analysis result showed that the similarity between C. sinensis and the others was less than 0.9. The method was accurate and reliable, which can be used for quality control of Cordyceps genus herbs.