[Analysis of chemical compositions in different parts of Isodon japonicus using UPLC-Q-TOF-MS technique combined with chemometrics].

In order to analyze the similarities and differences of chemical compositions between the roots and stems and leaves of Isodon japonicus(IJ), this study utilized UPLC-Q-TOF-MS technology to systematically characterize its chemical compositions, analyzed and identified the structure of its main compounds, and established a method for simultaneous determination of its content by refe-rence substance. A total of 34 major compounds in IJ, including 14 reference compounds, were identified or predicted online. Moreover, an UPLC-UV content determination method was developed for 11 compounds [danshensu, caffeic acid, vicenin-2,(1S,2S)-globoidnan B, rutin,(+)-rabdosiin,(-)-rabdosiin,(1S,2S)-rabdosiin, shimobashiric acid C, rosmarinic acid, and pedalitin]. The method exhibited excellent separation, stability, and repeatability, with a wide linear range(0.10-520.00 µg·mL~(-1)) and high linearity(R~2>0.999). The average recovery rates ranged from 94.72% to 104.2%. The principal component analysis(PCA) demonstrated a clear difference between the roots and stems and leaves of IJ, indicating good separation by cluster. Furthermore, the orthogonal partial least squares discriminant analysis(OPLS-DA) model was employed, and six main differentially identified compounds were identified: rosmarinic acid, shimobashiric acid C, epinodosin, pedalitin, rutin, and(1S,2S)-rabdosiin. In summary, this study established a strategy and method for distinguishing different parts of IJ, providing a valuable tool for quality control of IJ and a basis for the ratio-nal utilization and sustainable development of IJ.

[Effects of organic fertilizer from traditional Chinese medicine residues on growth and soil microbial community of Salvia miltiorrhiza by metagenomic technique].

Soil microbiome is a key evaluation index of soil health. Previous studies have shown that organic fertilizer from traditional Chinese medicine(TCM)residues can improve the yield and quality of cultivated traditional Chinese medicinal materials. However, there are few reports on the effects of organic fertilizer from TCM residues on soil microbiome. Therefore, on the basis of evaluating the effects of organic fertilizer from TCM residues on the yield and quality of cultivated Salvia miltiorrhiza, the metagenomic sequencing technique was used to study the effects of organic fertilizer from TCM residues on rhizosphere microbiome community and function of cultivated S. miltiorrhiza. The results showed that:(1) the application of organic fertilizer from TCM residues promoted the growth of S. miltiorrhiza and the accumulation of active components, and the above-ground and underground dry weight and fresh weight of S. miltiorrhiza increased by 371.4%, 288.3%, 313.4%, and 151.9%. The increases of rosmarinic acid and salvianolic acid B were 887.0% and 183.0%.(2)The application of organic fertilizer from TCM residues significantly changed the rhizosphere bacterial and fungal community structures, and the microbial community composition was significantly different.(3)The relative abundance of soil-beneficial bacteria, such as Nitrosospira multiformis, Bacillus subtilis, Lysobacter enzymogenes, and Trichoderma was significantly increased by the application of organic fertilizer from TCM residues.(4)KEGG function prediction analysis showed that metabolism-related microorganisms were more easily enriched in the soil environment after organic fertilizer application. The abundance of functional genes related to nitrification and denitrification could also be increased after the application of organic fertilizer from TCM residues. The results of this study provide guidance for the future application of organic fertilizer from TCM residues in the cultivation of traditio-nal Chinese medicinal materials and enrich the content of green cultivation technology of traditional Chinese medicinal materials.

[Dead heart of pith-decayed Scutellariae Radix: a study based on multi-omics].

Dead heart is an important trait of pith-decayed Scutellariae Radix. The purpose of this study was to clarify the scientific connotation of the dead heart using multi-omics. Metabolomics and transcriptomics combined with multivariate statistical analysis such as principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were used to systematically compare the differences in chemical composition and gene expression among phloem, outer xylem and near-dead xylem of pith-decayed Scutella-riae Radix. The results revealed significant differences in the contents of flavonoid glycosides and aglycones among the three parts. Compared with phloem and outer xylem, near-dead xylem had markedly lowered content of flavonoid glycosides(including baicalin, norwogonin-7-O-ß-D-glucuronide, oroxylin A-7-O-ß-D-glucuronide, and wogonoside) while markedly increased content of aglycones(including 3,5,7,2',6'-pentahydroxy dihydroflavone, baicalin, wogonin, and oroxylin A). The differentially expressed genes were mainly concentrated in KEGG pathways such as phenylpropanoid metabolism, flavonoid biosynthesis, ABC transporter, and plant MAPK signal transduction pathway. This study systematically elucidated the material basis of the dead heart of pith-decayed Scutellariae Radix with multiple growing years. Specifically, the content of flavonoid aglycones was significantly increased in the near-dead xylem, and the gene expression of metabolic pathways such as flavonoid glycoside hydrolysis, interxylary cork development and programmed apoptosis was significantly up-regulated. This study provided a theoretical basis for guiding the high-quality production of pith-decayed Scutellariae Radix.

[Quality of moxa with different leaf-to-moxa ratios based on correlation analysis of thermogravimetric properties, cellulose content, and microscopic characteristics of non-secretory trichomes].

The quality of moxa is a key factor affecting the efficacy of moxibustion. Traditional moxa grades are evaluated by the leaf-to-moxa ratio, but there is a lack of support from scientific data. Scanning electron microscopy(SEM), Image Pro Plus, Van Soest method, and stimultaneous thermal analysis(TGA/DSC) were used to characterize the scientific implication of the combustion differences between moxa with different leaf-to-moxa ratios(processed by crusher). The results showed that the median lengths from non-secretory trichomes(NSTs) of natural NSTs and moxa with leaf-to-moxa ratios of 3∶1, 5∶1, 10∶1, and 15∶1 were 542.46, 303.24, 291.18, 220.69, and 170.61 µm, respectively. The cellulose content of moxa increased significantly(P<0.05) with the increase in leaf-to-moxa ratio and the combustion parameters(T_i, t_i, D_i, C,-R_p,-R_v, S, D_b, and J_(total)) all showed an increasing trend. The correlation results showed that the burning properties of moxa(T_i,-R_v, t_i, and J_2) were significantly and positively correlated with cellulose content. NSTs with a length of 1-200 µm were significantly and positively correlated with J_2. NSTs with a length of 200-600 µm were significantly and positively correlated with J_1, T_(peak2), T_(peak1), and-R_v, and negatively correlated with J_(total), T_b, and t_b. As the leaf-to-moxa ratio increases, the NSTs in the moxa become shorter and the cellulose content increases, which is more conducive to ignition performance, heat release, and a milder, longer-lasting burn. The "NSTs-cellulose-TGA/DSC" quantitative evaluation method scientifically reveals the scientific connotation of the combustion of moxa with different leaf-to-moxa ratios and provides a scientific basis for the establishment of quality evaluation methods for moxa with different leaf-to-moxa ratios.

[Quality of moxa from Artemisia argyi and A. stolonifera in different storage years based on simultaneous thermal analysis].

The quality of moxa is an important factor affecting moxibustion therapy, and traditionally, 3-year moxa is considered optimal, although scientific data are lacking. This study focused on 1-year and 3-year moxa from Artemisia stolonifera and A. argyi(leaf-to-moxa ratio of 10∶1) as research objects. Scanning electron microscopy(SEM), Van Soest method, and simultaneous thermal analysis were used to investigate the differences in the combustion heat quality of 1-year and 3-year moxa and their influencing factors. The results showed that the combustion of A. stolonifera moxa exhibited a balanced heat release pattern. The 3-year moxa released a concentrated heat of 9 998.84 mJ·mg~(-1)(accounting for 54% of the total heat release) in the temperature range of 140-302 ℃, with a heat production efficiency of 122 mW·mg~(-1). It further released 7 512.51 mJ·mg~(-1)(accounting for 41% of the total heat release) in the temperature range of 302-519 ℃. The combustion of A. argyi moxa showed a rapid heat release pattern. The 3-year moxa released a heat of 16 695.28 mJ·mg~(-1)(accounting for 70% of the total heat release) in the temperature range of 140-311 ℃, with an instantaneous power output of 218 mW·mg~(-1). It further released 5 996.95 mJ·mg~(-1)(accounting for 25% of the total heat release) in the temperature range of 311-483 ℃. Combustion parameters such as-R_p,-R_v, D_i, C, and D_b indicated that the combustion heat quality of 3-year moxa was superior to that of 1-year moxa. It exhibited greater combustion heat, heat production efficiency, flammability, mild and sustained burning, and higher instantaneous combustion efficiency. This study utilized scientific data to demonstrate that A. stolonifera could be used as excellent moxa, and the quality of 3-year moxa surpassed that of 1-year moxa. The research results provide a scientific basis for the in-depth development of A. stolonifera moxa and the improvement of moxa quality standards.

[Anti-inflammatory material basis and mechanism of Artemisia stolonifera based on UPLC-Q-TOF-MS combined with network pharmacology and molecular docking].

This study aimed to explore the anti-inflammatory material basis and molecular mechanism of Artemisia stolonifera based on the analysis of the chemical components in different extracted fractions of A. stolonifera and their antioxidant and anti-inflammatory effects in combination with network pharmacology and molecular docking. Thirty-two chemical components were identified from A. stolonifera by ultra-performance liquid chromatography coupled to tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Among them, there were 7, 21 and 22 compounds in water, n-butanol and ethyl acetate fractions, respectively. The antio-xidant capacity of different extracted fractions was evaluated by measuring their scavenging ability against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid)(ABTS) free radicals and total antioxidant capacity [ferric reducing antioxidant power(FRAP) assay]. The inflammatory model of RAW264.7 cells was induced by lipopolysaccharide(LPS), and the levels of nitrite oxide(NO), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) in the supernatant and the mRNA expression of related inflammatory factors in cells were used to evaluate the anti-inflammatory effects. The results revealed that ethyl acetate fraction of A. stolonifera was the optimal antioxidant and anti-inflammatory fraction. By network pharmacology, it was found that flavonoids such as rhamnazin, eupatilin, jaceosidin, luteolin and nepetin could act on key targets such as TNF, serine/threonine protein kinase 1(AKT1), tumor protein p53(TP53), caspase-3(CASP3) and epidermal growth factor receptor(EGFR), and regulate the phosphatidylinositol-3-kinase-protein kinase B(PI3K-AKT) and mitogen-activated protein kinase(MAPK) signaling pathways to exert the anti-inflammatory effects. Molecular docking further indicated excellent binding properties between the above core components and core targets. This study preliminarily clarified the anti-inflammatory material basis and mechanism of ethyl acetate fraction of A. stolonifera, providing a basis for the follow-up clinical application of A. stolonifera and drug development.

[Rapid characterization and identification of non-volatile constituents in Pogostemonis Herba by UPLC-Q-TOF-MS combined with UNIFI and an in-house library].

This study aimed to characterize and identify the non-volatile components in Pogostemonis Herba by using ultra-perfor-mance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS) combined with UNIFI and an in-house library. The chemical components in 50% methanol extract of Pogostemonis Herba were detected by UPLC-Q-TOF-MS in both positive and negative MS~E continuum modes. Then, the MS data were processed in UNIFI combined with an in-house library to automatically characterize the metabolites. Based on the multiple adduct ions, exact mass, diagnostic fragment ions, and peak intensity of compounds and the fragmentation pathways and retention behaviors of reference substances, the structures identified by UNIFI were further verified and those of the unidentified compounds were tentatively elucidated. A total of 120 compound structures were identified or tentatively identified, including flavonoids, phenylpropanoids, phenolic acids, terpenes, fatty acids, alkaloids, and phenylethanoid glycosides. Sixteen of them were accurately identified by comparison with reference substances, and 53 compounds were reported the first time for Pogostemonis Herba. This study systematically characterized and identified the non-volatile compounds in Pogostemonis Herba for the first time. The findings provide a scientific basis for revealing the pharmacodynamic material basis, establishing a quality control system, and developing products of Pogostemonis Herba.

[Rapid detection of zearalenone in Coicis Semen based on ELISA].

Zearalenone(ZEN) is a toxic metabolite produced by Fusarium culmorum, F. graminearum, F. tricinctum, and other fungi, with estrogenic characteristics. Exposure to or ingestion of ZEN during pregnancy can cause reproductive dysfunction, miscarriage, stillbirth, and malformation, and seriously endanger human life and health. The detection methods for ZEN in the Chinese Pharmacopoeia(2020 edition) are liquid chromatography(LC) and liquid chromatography-mass spectrometry(LC-MS), and it is stipulated that ZEN should not exceed 500 µg in 1 000 g of Coicis Semen. Although these detection methods by instruments can achieve the qualitative and quantitative analysis of ZEN in Coicis Semen, their high detection cost and long periods hinder the rapid screening of a large number of samples in the field. In this study, the synthesized ZEN hapten was conjugated with bovine serum albumin(BSA) and ovalbumin(OVA) to obtain the complete ZEN antigen. By virtue of antibody preparation techniques, ZEN monoclonal antibody 4F6 was prepared, which showed 177.5%, 137.1%, and 109.7% cross-reactivity with ZEN structural analogs zearalanol, zearalenone, and α-zearalenol, respectively, and no cross-reactivity with other fungal toxins such as aflatoxin. Direct competitive enzyme-linked immunosorbent assay(dcELISA) based on ZEN monoclonal antibody 4F6 was developed for the determination of ZEN in Coicis Semen with an IC_(50) of 1.3 µg·L~(-1) and a detection range of 0.22-21.92 µg·L~(-1). The recoveries were 83.91%-105.3% and the RSD was 4.4%-8.0%. The established dcELISA method was used to determine the ZEN residuals in nine batches of Coicis Semen samples, and the results were validated by LC-MS. The correlation between the two detection methods was found to be 0.993 9, indicating that the established dcELISA could be used for the rapid qualitative and quantitative detection of ZEN residuals in Coicis Semen.

[Research progress of Codonopsis Radix and prediction of its Q-markers].

Codonopsis Radix is a traditional tonic medicine commonly used in China, which has the effects of strengthening the spleen and tonifying the lung, as well as nourishing blood and engendering liquid. The chemical constituents of Codonopsis species are mainly polyacetylenes, alkaloids, phenylpropanoids, lignans, terpenoids and saponins, flavonoids, steroids, organic acids, saccharides, and so on. Modern pharmacological studies showed that Codonopsis Radix also has a variety of pharmacological effects such as enhancing body immunity, protecting gastrointestinal mucosa and resisting ulcers, promoting hematopoietic function, regulating blood sugar, and delaying aging. In this paper, the chemical constituents of Codonopsis species and the pharmacological effects of Codonopsis Radix were summarized, and on this basis, the quality markers of Codonopsis Radix were analyzed. It was predicted that lobetyolin, tangshenoside I, codonopyrrolidium A, and the oligosaccharides were the possible Q-markers of Codonopsis Radix. This paper will provide scientific references for the quality evaluation and profound research and the development of Codonopsis Radix.

[Nature-effect transformation mechanism of mulberry leaves and silkworm droppings based on chemical composition analysis].

Starting with the relationship between mulberry leaves and silkworm droppings as food and metabolites, this study systematically compared the chemical components, screened out differential components, and quantitatively analyzed the main differential components based on ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and UPLC-Q-TRAP-MS combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). Moreover, the in vitro enzymatic transformation of the representative differential components was studied. The results showed that(1) 95 components were identified from mulberry leaves and silkworm droppings, among which 27 components only exist in mulberry leaves and 8 components in silkworm droppings. The main differential components were flavonoid glycosides and chlorogenic acids.(2) Nineteen components with significant difference were quantitatively analyzed, and the components with significant differences and high content were neochlorogenic acid, chlorogenic acid, and rutin.(3) The crude protease in the mid-gut of silkworm significantly metabolized neochlorogenic acid and chlorogenic acid, which may be an important reason for the efficacy change in mulberry leaves and silkworm droppings. This study lays a scientific foundation for the development, utilization, and quality control of mulberry leaves and silkworm droppings. It provides references for clarifying the possible material basis and mechanism of the pungent-cool and dispersing nature of mulberry leaves transforming into the pungent-warm and dampness-resolving nature of silkworm droppings, and offers a new idea for the study of nature-effect transformation mechanism of traditional Chinese medicine.

[Effect of sulfur fumigation on quality and safety of Lilii Bulbus].

Lilii Bulbus is a commonly used Chinese herbal medicine with both medicinal and edible values, while the market products usually has the problem of sulfur fumigation. Therefore, the quality and safety of Lilii Bulbus products deserve attention. In this study, ultra-high performance liquid chromatography-time of flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was combined with principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) to analyze the differential components of Lilii Bulbus before and after sulfur fumigation. We identified ten markers generated after sulfur fumigation, summarized their mass fragmentation and transformation patterns, and verified the structures of phenylacrylic acid markers of sulfur fumigation. At the same time, the cytotoxicity of the aqueous extracts of Lilii Bulbus before and after sulfur fumigation was evaluated. The results showed that in the concentration range of 0-800 mg·L~(-1), the aqueous extract of Lilii Bulbus after sulfur fumigation had no significant effect on the viability of human liver LO2 cells, human renal proximal tubular HK-2 cells, and rat adrenal pheochromocytoma PC-12 cells. Moreover, the viability of the cells exposed to the aqueous extract of Lilii Bulbus before and after sulfur fumigation showed no significant difference. This study identified phenylacrylic acid and furostanol saponins as markers of sulfur-fumigated Lilii Bulbus for the first time, and made clear that proper sulfur fumigation of Lilii Bulbus would not produce cytotoxicity, providing a theoretical basis for the rapid identification and quality and safety control of sulfur-fumigated Lilii Bulbus.

[Effect of Rhizophagus intraradices on growth of Salvia miltiorrhiza].

The study aimed to explore the effects of inoculation of Rhizophagus intraradices on the biomass, effective component content, and endogenous hormone content of Salvia miltiorrhiza through pot experiments. The number of leaves, plant height, dry weight of aboveground and underground parts, branch number, root number, root length, root diameter, and other biomass were mea-sured by weighing and counting methods. The content of salvianolic acid B, caffeic acid, rosmarinic acid, tanshinone Ⅰ, tanshinone Ⅱ_A, cryptotanshinone, and other effective components was determined by ultra-high performance liquid chromatography. The content of ABA and GA_3 was determined by triple quadrupole mass spectrometry. The correlations between biomass and effective components and between effective components and plant hormones ABA and GA_3 were analyzed. The results showed that R. intraradices significan-tly increased the aboveground dry weight, leaf number, and root number of S. miltiorrhiza by 0.24-0.65 times, respectively. The content of salvianolic acid B and rosmarinic acid in the aboveground part and the content of salvianolic acid B, caffeic acid, rosmarinic acid, tanshinone Ⅰ, and tanshinone Ⅱ_A in the underground part were significantly increased by 0.44-1.78 times, respectively. R. intraradices infection significantly increased the GA_3/ABA values of aboveground and underground parts by 3.82 and 76.47 times, respectively. The correlation analysis showed that caffeic acid, the effective component of the aboveground part, was significantly positively correlated with plant height, tanshinone Ⅱ_A, the effective component of the underground part, was significantly positively correlated with biomass root number, cryptotanshinone, and dry weight, while rosmarinic acid was significantly negatively correlated with dry weight. There were significant positive correlations between cryptotanshinone and ABA, tanshinone Ⅱ_A and ABA and GA_3, and caffeic acid and GA_3. In conclusion, R. intraradices can promote the accumulation of biomass and secondary metabolites of S. miltiorrhiza and regulate the balance between plant hormones ABA and GA_3, thereby promoting the growth of S. miltiorrhiza.

Efficacy and safety of gemcitabine and capecitabine combination for patients with previously treated advanced primary pulmonary lymphoepithelioma-like carcinoma: a retrospective single-arm cohort study.

Background: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and unique subtype of non-small cell lung cancer (NSCLC). Studies reporting on salvage treatment for pretreated PLELC are limited. Positive interactions between gemcitabine (GEM) and capecitabine (CAP) have been demonstrated in preclinical studies. In addition, the clinical benefit of the combination has been reported for other malignancies. However, the efficacy and safety of the combination for pretreated PLELC remain unclear. Therefore, we conducted this retrospective study to examine the activity and safety of gemcitabine plus capecitabine (GEM/CAP) combination for previously treated PLELC. Methods: Patients with PLELC at Sun Yat-sen University Cancer Center who received GEM combined with CAP between May 2013 and January 2021 as the second-line therapy or beyond were retrospectively enrolled. Treatment consisted of intravenous GEM (1,000 mg/m2 on days 1 and 8) and oral CAP (1,000 mg/m2 twice daily on days 1-14) every 3 weeks. Evaluation of response was performed every 2 cycles in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. Safety was assessed in accordance with Common Terminology Criteria for Adverse Events version 5.0. Clinical characteristics were collected from medical records. The survival data were obtained by medical records or telephone. Follow-ups were performed until February 3rd, 2021. Results: A total of 16 patients were enrolled in this study. There were 5, 4, 4, and 3 patients treated with GEM/CAP combination as the second-, third-, fourth-, and fifth-line settings, respectively. There were 8 patients with partial response (PR) (50.00%), 6 with stable disease (SD) (37.50%), 2 with progressive disease (PD) (12.50%), and none with complete response (CR). The objective response rate and disease control rate (DCR) were 50.00% and 87.50%, respectively. The most common hematological and nonhematological adverse events (AEs) at any grade were neutropenia (31.25%) and hand-foot syndrome (43.75%). At a median follow-up of 29.3 months with 95% confidence interval (CI) of 20.3 to 38.3 months, the median progression-free survival (PFS) was 9.3 months (95% CI: 6.5-12.1 months). The median overall survival (OS) was 41.5 months (95% CI: 3.1-79.8 months). Conclusions: This retrospective study demonstrated the potential clinical benefit of GEM in combination with CAP for pretreated PLELC. Future multicenter large-scale, prospective studies are warranted.

Systematic identification of chemical components in Fufang Shuanghua oral liquid and screening of potential active components against SARS-CoV-2 protease.

Coronavirus disease (COVID-19) caused by SARS-COV-2 infection has been widely prevalent in many countries and has become a common challenge facing mankind. Traditional Chinese medicine (TCM) has played a prominent role in this pandemic, and especially TCM with the function of "heat-clearing and detoxifying" has shown an excellent role in anti-virus. Fufang Shuanghua oral liquid (FFSH) has been used to treat the corresponding symptoms of influenza such as fever, nasal congestion, runny nose, sore throat, and upper respiratory tract infections in clinic, which are typical symptoms of COVID-19. The content of chlorogenic acid, andrographolide and dehydrated andrographolide as the quality control components of FFSH is not less than 1.0 mg/mL, 60 µg/mL and 60 µg/mL respectively. In this study, UPLC-Q-TOF-MS/MS was employed to describe the chemical profile of FFSH. Virtual screening and fluorescence resonance energy transfer (FRET) were used to screen the effective components of FFSH acting on SARS-CoV-2 main protease (Mpro). As a result, 214 compounds in FFSH were identified or preliminarily characterized by UPLC-Q-TOF-MS/MS, and 61 active ingredients with potential inhibitory effects on Mpro were selected through receptor-based and ligand-based virtual screening. In particular, quercetin, forsythoside A, and linoleic acid showed a good inhibitory effect on Mpro in FRET evaluation with IC50 values of 26.15 µM, 22.26 µM and 47.09 µM respectively, and had a strong binding affinity with the receptor Mpro (6LU7) in molecular docking. CYS145 and HIS41 were the main amino acid residues affected by small molecules in the protein binding domain. In brief, we characterized, for the first time, 214 chemical components in FFSH, and three of them, including quercetin, forsythoside A and linoleic acid, were screened out to exert beneficial anti-COVID-19 effects through CYS145 and HIS41 sites, which may provide a new research strategy for TCM to develop new therapeutic drugs against COVID-19.

[Chemical and nutrient differences between medicinal material, residues, and residue compost of Moutan Cortex].

Moutan Cortex(MC) residues produced after the extraction of MC can be re-extracted for active components and used to produce organic fertilizer and animal feed. However, they are currently disposed as domestic waste, which pollutes the environment. This study analyzed the chemical composition of the medicinal material, residues, and residue compost of MC by UPLC-UV-Q-TOF-MS. Furthermore, the nutrient composition of MC residues and the residue compost was analyzed. The results showed that:(1)MC residues had lower content of chemicals than the medicinal material, and content of paeonol, gallic acid, and galloylglucose in MC residues were about 1/3 of that in the medicinal material. The content of chemicals were further reduced after residue composting, and the quantitative compounds were all below the limits of detection.(2)Compared with MC residues, the residue compost showed the total nitrogen, total phosphorus, total potassium, and organic matter content increasing by 122.67%, 31.32%, 120.39%, and 32.06%, respectively. Therefore, we concluded that the MC residues can be used to re-extract active compounds such as paeonol, gallic acid, and galloylglucose. The MC residue compost is a high-quality organic fertilizer containing minimal content of chemicals and can be widely used in the cultivation of Chinese medicinal herbs.

Multitype drug interaction prediction based on the deep fusion of drug features and topological relationships.

Drug-drug interaction (DDI) prediction has received considerable attention from industry and academia. Most existing methods predict DDIs from drug attributes or relationships with neighbors, which does not guarantee that informative drug embeddings for prediction will be obtained. To address this limitation, we propose a multitype drug interaction prediction method based on the deep fusion of drug features and topological relationships, abbreviated DM-DDI. The proposed method adopts a deep fusion strategy to combine drug features and topologies to learn representative drug embeddings for DDI prediction. Specifically, a deep neural network model is first used on the drug feature matrix to extract feature information, while a graph convolutional network model is employed to capture structural information from the adjacency matrix. Then, we adopt delivery operations that allow the two models to exchange information between layers, as well as an attention mechanism for a weighted fusion of the two learned embeddings before the output layer. Finally, the unified drug embeddings for the downstream task are obtained. We conducted extensive experiments on real-world datasets, the experimental results demonstrated that DM-DDI achieved more accurate prediction results than state-of-the-art baselines. Furthermore, in two tasks that are more similar to real-world scenarios, DM-DDI outperformed other prediction methods for unknown drugs.

[Development of a monoclonal antibody-based enzyme-linked immunosorbent assay for determination of vomitoxin (DON) in Coicis Semen].

Coicis Semen is a common bulk medicinal material used for both medicine and food, which has the effect of promoting diuresis, draining dampness, invigorating the spleen and checking diarrhea. It is derived from Coix lacryma-jobi var. ma-yuen of the family Poaceae, and is easily contaminated by fungi such as Fusarium graminearum and F. flavum due to climate reasons to produce vomitoxin. The guiding principles for determination of vomitoxin in Chinese medicinal materials in Chinese Pharmacopoeia are mainly HPLC and LC-MS, which have long detection period and are time-consuming and laborious, and thus cannot meet the requirements of on-site quality inspection of drugs. The complete antigen of vomitoxin-protein was obtained by chemical derivatization of vomitoxin. The monoclonal antibody against vomitoxin was prepared by classic monoclonal antibody preparation technology, and enzyme-linked immunosorbent assay(ELISA) method for detection of vomitoxin in Coicis Semen was established through methodological investigation. The IC_(50) based on the ELISA for vomitoxin in Coicis Semen was 3.88 µg·L~(-1), and the average recoveries and the RSD were 77.32%-93.73% and 4.6%-9.7%, respectively. With the established ELISA method, the vomitoxin residue in 14 batches of Coicis Semen samples were determined and validated by LC-MS, and the correlation between the two assays was found to be 0.997 8, indicating that the established ELISA method could be used for quantitative determination of vomitoxin residue in Coicis Semen and could achieve the rapid quantitative determination of the vomitoxin residue.

[Advances in research on chemical composition of Picrorhiza scrophulariiflora and P. kurroa and their biological activities].

At present, 141 compounds have been isolated from Picrorhiza scrophulariiflora and P. kurroa of the Scrophulariaceae plants, including 46 iridoid glycosides, 29 tetracyclic triterpenoids, 25 phenylpropanoids, and 11 phenylethanoid glycosides. Pharmacological studies have demonstrated that they have liver-, heart-, brain-, kidney-, and nerve cells-protecting effects as well as anti-tumor, anti-inflammatory, anti-bacterial, anti-asthma, anti-diabetic, immunomodulatory, and blood lipid-lowering activities. This article reviews the chemical components and pharmacological activities of P. scrophulariiflora and P. kurroa, aiming to provide a basis for the in-depth research, development, and utilization of the two plants.

[Analysis and evaluation of volatile oil content in leaves of different Artemisia argyi germplasm resources].

Volatile oil is the main effective component and an important quality indicator of Artemisia argyi leaves. In this study, 100 germplasm resources of A. argyi were collected from all the related habitats in China. The total volatile oils in A. argyi leaves were extracted by steam distillation and the content was determined by GC-MS. The result demonstrated that the content of total volatile oils was in the range of 0.53%-2.55%, with the average of 1.43%. A total of 39 chemical constituents were identified from the volatile oils, including 13 shared by the 100 germplasm resources. Clustering analysis of the 39 constituents showed that the 100 A. argyi samples were categorized into groups Ⅰ(9), Ⅱ(2), Ⅲ(66) and Ⅳ(23), and group Ⅲ had the most volatile medicinal components, with the highest content. Five principal components(PCs) were extracted from 13 shared constituents, which explained 73.454% of the total variance. PC1, PC2, and PC3 mainly reflected the pharmacological activity of volatile oils and the rest two the aroma information. The volatile oils identified in this study lay a foundation for variety breeding of and rational utilization of volatile oils in A. argyi leaves.

[Morphological comparison of glandular and non-glandular trichomes between Artemisia stolonifera and A. argyi].

The basic features of glandular and non-glandular trichomes on leaves of Artemisia argyi( germplasms from Qichun,Ningbo,Tangyin,and Anguo,respectively) and related species A. stolonifera were observed by scanning electron microscopy( SEM)and compared. There were significant differences in trichome characteristics of leaves at all parts of A. argyi and A. stolonifera,which were closely related to the difference in chemical components. The length of non-glandular trichomes and size of glandular trichomes on middle leaves were the stablest. A. argyi and A. stolonifera can be distinguished by the density of glandular trichome. Additionally,the four germplasms of A. argyi can be discriminated via the density and curvature of non-glandular trichome. The density of non-glandular trichomes was the highest in A. stolonifera. For A. argyi,the germplasm from Qichun had the highest density of non-glandular trichomes on the abaxial surfaces of upper leaves and that from Ningbo had the largest non-glandular trichome curvature. With regard to the germplasm from Anguo,the T-shaped non-glandular trichomes of long stalks on the adaxial surfaces of the middle leaves were lodging-susceptible,and those with slender heads were wave-like. Statistics results of A. argyi and A. stolonifera are as follows: largest glandular trichomes on the adaxial and abaxial surfaces and highest glandular trichome density on the abaxial surfaces of the lower leaves in A. argyi germplasm from Ningbo,highest density of non-glandular trichomes on the abaxial surfaces of upper leaves in A. stolonifera,and highest density of glandular trichomes and non-glandular trichomes on the adaxial surfaces of the upper leaves in A. argyi germplasm from Qichun. According to the observation result under fluorescence microscope( FM),flavonoids were closely related to the size and density of non-glandular trichomes and size of glandular trichomes. The fluorescence intensity was the strongest and fluorescence area was the largest for flavonoids in A. argyi germplasms from Qichun and Tangyin,while the fluorescence for flavonoids was the weakest in A. stolonifera. It was the first time to observe and analyze the trichome ultrastructure of A. argyi leaves at different positions by SEM and FM. This study clarifies the differences between A. stolonifera and four famous A. argyi germplasms,which provides new evidence for the microscopic identification of A. argyi and its related species and serves as a reference for the study of the relationship of A. argyi structure with its components and functions.