Selenium-enriched Bacillus subtilis Improves Growth Performance, Antioxidant Capacity, Immune Status, and Gut Health of Broiler Chickens.

This study aimed to investigate the effects of selenium (Se)-enriched Bacillus subtilis (Se-BS) on growth performance, antioxidant capacity, immune status, and gut health in broilers. A total of 240 one-day-old Arbor Acres broilers were randomly allotted to four groups and fed with basal diet (control group), 0.30 mg/kg Se (SS group), 3 × 109 CFU/g B. subtilis (BS group), and 0.30 mg/kg Se + 3 × 109 CFU/g B. subtilis (Se-BS group) for 42 days. The results showed that Se-BS supplementation increased body weight (BW), average daily gain, the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and peroxidase (POD), total antioxidant capacity (T-AOC), and the contents of interleukin (IL)-2, IL-4, and immunoglobulin (Ig) G in plasma, the index and wall thickness of the duodenum, the villus height and crypt depth of the jejunum, and GPx-1 and thioredoxin reductase 1 mRNA levels in liver and intestine and decreased feed conversion ratio (FCR) and plasma malondialdehyde (MDA) content compared with the control group on day 42 (P < 0.05). Compared with groups SS and BS, Se-BS supplementation increased BW, the activities of GPx, CAT, and POD, and the contents of IL-2, IL-4, and IgG in plasma, the index and wall thickness of the duodenum, the crypt depth and secretory IgA content of the jejunum, and GPx-1 mRNA levels in liver and intestine and decreased FCR and plasma MDA content on day 42 (P < 0.05). In conclusion, Se-BS supplementation effectively improved the growth performance antioxidant capacity, immune status, and gut health of broilers.

Novel Integrated Tiered Cumulative Risk Assessment of Heavy Metals in Food Homologous Traditional Chinese Medicine Based on a Real-Life-Exposure Scenario.

In order to serve population health better, the first integrated tiered decision tree for cumulative risk assessment of co-exposure of Pb-, Cd-, and As-associated health risks in food homologous traditional Chinese medicine (TCM) was designed, after measuring their concentrations by inductively coupled plasma-mass spectroscopy (ICP-MS). Basically, our three-step decision tree involving hazard quotient (HQ), hazard index (HI), and target-organ toxicity dose (TTD) modification of the HI method was developed to evaluate the potential risks of 949 batches of 15 types of food homologous TCM. To acquire a real-life exposure scenario, the cumulative risk assessment model was established by optimizing key parameters, such as ingestion rates, frequency, and duration of exposure to food homologous TCM based on questionnaire data. As a result, the mean concentrations of Pb, Cd, and As in 949 batches of food homologous TCM were 0.896, 0.133, and 0.192 mg/kg, respectively. The HQ values of As for Angelica sinensis (Oliv.) Diels and Houttuynia cordata Thunb. were 1.04 and 1.01, respectively, for females. Other HQs of Pb, Cd, or As in food homologous TCM were lower than 1 for both males and females. However, after rapid screening of the co-exposure health risks of heavy metals by the HI method, cumulative risk assessment results acquired by TTD modification of the HI method implied that the potential health risks associated with the co-exposure of Pb, Cd, and As in Lonicera japonica Thunb. and Houttuynia cordata Thunb. ingested as both TCM and food were of concern in the clinic. Additionally, the cumulative risks of Pb, Cd, and As in Mentha canadensis L., Chrysanthemum indicum L., and Zaocys dhumnades (Cantor) only used as food exceeded the human tolerance dose. Collectively, our innovation on the tiered strategy of decision tree based on a real-life exposure scenario provides a novel approach engaging in the cumulative risk assessment of heavy metals in food homologous TCM. All in all, such effort attempts to scientifically guide the rational use of TCM in the treatment of the complex diseases and the improvement of population health.

Effect of Adulteration on Quality and Preliminary Risk Assessment of the Decoction Pieces of Farfarae Flos Based on the Determination of Hepatotoxic Pyrrolizidine Alkaloids by UHPLC-MS/MS.

BACKGROUND: Farfarae Flos (FF) is a frequently used traditional herbal medicine with outstanding antitussive actions. The adulteration of FF decoction pieces is common. OBJECTIVE: This study aimed to study the effect of adulteration on the safety and quality of FF decoction pieces. METHODS: The proportion of impurities was conducted by cone quartering method. A simple and accurate ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was established to simultaneous determinate three pyrrolizidine alkaloids (PAs) as endogenous toxic compounds in FF. The traditional medicinal parts (flower bud), impurities (pedicel and rhizome) and unselected samples were determined respectively. The values of estimated daily intake (EDI) and margin of exposure (MOE) were used for risk assessment. RESULTS: Twenty batches of samples were collected from different habitats, and the proportion of impurities ranged from 17.51% to 41.27%. Pedicel and rhizome were the main impurities, accounting for more than 87.40% of the total impurities. The content of PAs in impurities was significantly higher. The EDI value range was 5.34 to 16.59 µg/kg bw/day, which was much higher than the standard safety value of 7.00 × 10-3 µg/kg bw/day. The MOE values ranges for life long time and shorter exposure were 14.29 to 44.37 and 371.53 to 1153.63, respectively, indicating that at least 80% of the samples had safety risks. Correlation analysis showed that the proportion of adulterated impurities had significant correlation with the values of EDI and MOE. CONCLUSIONS: Adulteration of non medicinal parts may significantly increase the risk of medications of FF decoction pieces. HIGHLIGHTS: This study provides an efficient methodology reference for the control of PAs and a basis for adulteration to affect the safety and quality of FF decoction pieces.

Recognition Method of Wushu Human Complex Movement Based on Bone Point Feature.

The existing recognition methods of complex human movements in Wushu have the problem of imperfect kinetic energy model, which leads to low recognition accuracy. A complex human motion recognition method based on bone point features is designed. Identify martial arts movement posture, combine the upward movement of human center of gravity trajectory, establish the kinetic energy model of joints according to the positioning results of extremity points, set the threshold of local spatial differences of human bones with the central node of hip joint as the center point, avoid overcalculation, and optimize the complex motion identification process by combining the characteristics of bone points. Experimental Results. The correct rate of different types of actions identified by this method is 90.1% and 92.7%, and the identification time is 1.2 s and 1.41 s, which shows that this method can identify actions quickly and effectively by combining the feature information of bone points.

Fungicidal Activity and Mechanism of Action of Glabridin from Glycyrrhiza glabra L.

Glycyrrhiza glabra (Licorice) belongs to the Fabaceae family and its extracts have exhibited significant fungicidal activity against phytopathogenic fungi, which has mainly been attributed to the presence of phenolic compounds such as flavonoids, isoflavonoids and chalcones. In this study, a series of licorice flavonoids, isoflavonoids and chalcones were evaluated for their fungicidal activity against phytopathogenic fungi. Among them, glabridin exhibited significant fungicidal activity against ten kinds of phytopathogenic fungi. Notably, glabridin displayed the most active against Sclerotinia sclerotiorum with an EC50 value of 6.78 µg/mL and was 8-fold more potent than azoxystrobin (EC50, 57.39 µg/mL). Moreover, the in vivo bioassay also demonstrated that glabridin could effectively control S. sclerotiorum. The mechanism studies revealed that glabridin could induce reactive oxygen species accumulation, the loss of mitochondrial membrane potential and cell membrane destruction through effecting the expression levels of phosphatidylserine decarboxylase that exerted its fungicidal activity. These findings indicated that glabridin exhibited pronounced fungicidal activities against S. sclerotiorum and could be served as a potential fungicidal candidate.

Manipulating Gut Microbiota Composition to Enhance the Therapeutic Effect of Cancer Immunotherapy.

In the past decade, a growing set of immunotherapies including immune checkpoint blockade, chimeric antigen receptor T cells, and bispecific antibodies propelled the advancement of oncology therapeutics. Accumulating evidence demonstrates that immunotherapy could eliminate tumors better than traditional chemotherapy or radiotherapy with lower risk of adverse events in numerous cancer types. Unfortunately, a substantial proportion of patients eventually acquire resistance to immunotherapy. By analyzing the differences between immunotherapy-sensitive and immunotherapy-resistant populations, it was noticed that the composition of gut microbiota is closely related to treatment effect. Moreover, in xenograft models, interventional regulation of gut microbiota could effectively enhance efficacy and relieve resistance during immunotherapy. Thus, we believe that gut microbiota composition might be helpful to explain the heterogeneity of treatment effect, and manipulating gut microbiota could be a promising adjuvant treatment for cancer immunotherapy. In this mini review, we focus on the latest understanding of the cross-talk between gut microbiota and host immunity. Moreover, we highlight the role of gut microbiota in cancer immunotherapy including immune checkpoint inhibitor and adoptive cell transfer.

[Determination of forbidden and restricted pesticides in Angelicae Sinensis Radix].

The present study is to establish a method for simultaneous determination of 50 kinds of pesticides in Angelicae Sinensis Radix by using liquid chromatography tandem mass spectrometry. The forbidden,restricted and customary pesticides were picked out as detecting indexes according to the principals of risk management. The factors affecting the extraction,purification,and detection were optimized,and the final condition was established as follows: the samples were extracted with acetonitrile. The separation of target compounds were performed by liquid column,and quantitative analysis was carried out by LC-MS/MS with MRM model. The calibration curves were linear in the range of 1-100 µg·L~(-1) with correction coefficients of greater than 0. 990. The recoveries of more than 93. 9%pesticides were ranged from 60% to 140% at three spiked levels. The detecting indexes in the method cover most forbidden and restricted pesticides,which is meaningful for the safety supervision of the Angelicae Sinensis Radix. With the advantage of rapidness and accuracy,this method can be used for routine determination of multi-pesticides in Angelicae Sinensis Radix.

Absorption of Codonopsis pilosula Saponins by Coexisting Polysaccharides Alleviates Gut Microbial Dysbiosis with Dextran Sulfate Sodium-Induced Colitis in Model Mice.

OBJECTIVES: Inflammatory Bowel Disease (IBD) is an autoimmune disease, and the gut microbiota has become a new therapeutic target. Herbal medicine (HM) has shown good efficacy in the clinical treatment of IBD; however, the synergistic actions of the dominant chemicals in HM decoctions are unclear. METHODS: In this study, we explored whether the complicated interconnections between HM and the gut microbiota could allow crosstalk between HM ingredients. Saponins and polysaccharides, i.e., the dominant chemicals in the Codonopsis pilosula Nannf (CPN) decoction, were investigated in a dextran sulfate sodium- (DSS-) induced mouse model. Bacterial 16S rRNA sequencing analyzed the change of gut microbiota structure and diversity. Gas chromatography (GC) determined the content of short-chain fatty acids (SCFAs) in feces. ELISA detected the expression of proinflammatory and anti-inflammatory cytokines associated with TH17/Treg balance. UPLC-QTOF-MS technology combined with PKsolver software analyzed the absorption of the highest exposure for monomeric compounds of CPN saponins in serum. The results indicated that CPN polysaccharides showed prebiotic-like effects in mice with DSS-induced colitis by simultaneously stimulating the growth of three important probiotics, i.e., Bifidobacterium spp., Lactobacillus spp., and Akkermansia spp., and inhibiting the growth of pathogenic bacteria, including Desulfovibrio spp., Alistipes spp., and Helicobacter spp. Moreover, CPN polysaccharides improved intestinal metabolism, enhanced the production of short-chain fatty acids, upregulated the expression of anti-inflammatory cytokines and downregulated the secretion of proinflammatory cytokines correlated with Th17/Treg balance, promoted the absorption of certain CPN saponins in the serum, and stimulated recovery of the holistic gut microbiota. CONCLUSION: CPN polysaccharides have the good prebiotic properties and shown good application prospects in the prevention and treatment of acute colitis. These findings provide insights into the specific bacteria responsible for active, inactive biotransformation of HM ingredients and those that are altered by HM administration.

A new strategy for choosing "Q-markers" via network pharmacology, application to the quality control of a Chinese medical preparation.

Due to its chemical complexity, proper quality control for a Chinese medical preparation (CMP) has been a great challenge. Choosing the appropriate quality markers (Q-markers) for quality control of CMP is an important work. Best of all, the chosen Q-markers are the main chemical compounds from the herbals as well as the active constituents of this CMP. Only in this way the established quality control system can really achieve the purpose of controlling the quality of CMP and ensuring the safely and effectively use of CMP. To achieve the purpose, network pharmacology combined with the contents of chemical compounds in the CMP has been used in this research. We took an anti-arrhythmic CMP, Shenxian-Shengmai oral liquid (SSOL), as an example. Firstly, UPLC-QTOF-MS/MS method was used to analyze the main components of SSOL. A total of 64 compounds were unambiguously or tentatively identified and 32 of them were further validated by reference compounds. Secondly, the network was constructed based on the identified compounds to predict the effective compounds related to cardiac arrhythmias. Based on the existing database and the operation method of topology, a method of double network analysis (DNAA) was proposed, from which 10 important targets in the pathway of arrhythmia were screened out, and 26 compounds had good antiarrhythmic activity. Based on the prediction results of network pharmacology along with the contents of the compounds in this CMP, ten representative compounds were chosen as the Q-markers for the quality control of SSOL. We find that five of these ten compounds, including danshensu, rosmarinic acid, salvianolic acid A, epimedin A and icariin, have antiarrhythmic activity. Then, the UPLC-DAD method was established as the control method for SSOL.

[Analysis and evaluation of alkaloids and flavonoids in flower of Sophora flavescens from Shanxi province].

This study intends to explore the potential resource-orientedutilization value of the flower of Sophora flavescents by analyzing alkaloids and flavonoids in the flower of S. flavescens from Shanxi province. This study established a rapid UPLC-TQ-MS/MS method that is used for determination of seven alkaloids and seven flavonoids in the flower of S.flavescens. The different florescences all have the seven detected alkaloids such as cytisine, oxy-matrine, oxy-sophocarpine, sophoridine, N-methylcytisine, matrine, sophocarpine.The total contents of detected alkaloids are as follows: flower buds 1.47%, primal flowers 1.34%, full bloomed flowers 1.17%, faded flowers 1.01%. The top three contents of alkaloids are N-methylcytisine , oxy-sophocarpine and oxymatrine, accounting for about 83% of the total amount of detected alkaloids. All the samples in different florescences have the seven detected flavonoids such as rutin, luteolin, quercetin, isoquercitrin, trifolirhizin, kurarinone, and kushenol I. The total contents of detected alkaloids are as follows: flower buds 495.2 µg•g⁻¹, primal flowers 313.7 µg•g⁻¹, faded flowers 224.2 µg•g⁻¹, full bloomed flowers 193.0 µg•g⁻¹. The content of luteolinis relatively higher than other detected flavonoids, accounting for about 89%-94% of the total amount of detected flavonoids. The results indicated that the flower of S.flavescens could be an important material resource to obtain the resourceful alkaloids. This result can provide scientific basis for resource-oriented utilization and industrial development of the flower of S. flavescens.

[Thinking on development of Shanxi Astragali Radix industry].

Shanxi, a traditional production area to produce genuine Astragali Radix of high quality, has experienced major changes in the pattern of resources. This area once accounted for half of Astragali Radix industry, but now only serves as the largest supply area of traditional wild Astragali Radix. Furthermore, the strategic position of Shanxi Astragali Radix industry will become more prominent and more important to economic and social development in face of the diversity of market demands, especially for the strong demands of high-end Astragali Radix. In addition, Astragalus industry involves the simultaneous development of the first, second and tertiary industries in many areas, and it is typical and representative in the traditional Chinese medicine industry development. However, the application and industrial development of Shanxi Astragali Radix have been restricted due to the problems such as blind promotion of transplanting cultivation technology, and lack of science and technology including efficacy investigation, safety evaluation, standardization and controllability studies. Therefore, we would analyze the production history, resource structure, the current situation and progress of industry development, scientific research foundation and existing problem in this paper, and put forward countermeasures for development and technical innovation in order to make Astragali Radix industry bigger and stronger through innovation-driven and make benefits for demos. This thought provides a reference for the exploratory development of other large varieties of Chinese medicinal materials.

[Evaluation analysis of alkaloids in seed of Sophora flavescens from Shanxi province and exploration of its utilization value].

According to the research strategy of resource chemistry of Chinese medicinal materials and Chinese medicinal resources recycling utilization, this study intends to explore the potential resource-oriented utilization value of the seed of Sophora flavescens by contrasting with its kindred plant S. alopecuroides. This study established a rapid UPLC-Q-TOF-MS/MS and UPLC-TQ-MS/MS method to determine the alkaloids in the seed of S. flavescens. Results of UPLC-Q-TOF-MS/MS analysis showed that the alkaloids in the seed of S. flavescens were highly similar with S. alopecuroides.In the determination of 7 kinds of alkaloids, the total content was 11.203 and 15.506 mg•g⁻¹ in the seed of S. flavescens and S. alopecuroides, respectively. The content of oxymatrine, oxysophocarpine and sophoridine is high in the seed of S. flavescens. The results indicated that the seeds of S. flavescens. could be an important material resource to obtain alkaloids.

Anti-tumor activities of active ingredients in Compound Kushen Injection.

Kushen (Radix Sophorae Flavescentis) has a long history of use for the treatment of tumors, inflammation and other diseases in traditional Chinese medicine. Compound Kushen Injection (CKI) is a mixture of natural compounds extracted from Kushen and Baituling (Rhizoma Smilacis Glabrae). The main principles of CKI are matrine (MT) and oxymatrine (OMT) that exhibit a variety of pharmacological activities, including anti-inflammatory, anti-allergic, anti-viral, anti-fibrotic and cardiovascular protective effects. Recent evidence shows that these compounds also produce anti-cancer actions, such as inhibiting cancer cell proliferation, inducing cell cycle arrest, accelerating apoptosis, restraining angiogenesis, inducing cell differentiation, inhibiting cancer metastasis and invasion, reversing multidrug resistance, and preventing or reducing chemotherapy- and/or radiotherapy-induced toxicity when combined with chemotherapeutic drugs. In this review, we summarize recent progress in studying the anti-cancer activities of MT, OMT and CKI and their potential molecular targets, which provide clues and references for further study.

Spatially resolved one-dimensional boundary states in graphene-hexagonal boron nitride planar heterostructures.

Two-dimensional interfaces between crystalline materials have been shown to generate unusual interfacial electronic states in complex oxides. Recently, a one-dimensional interface has been realized in hexagonal boron nitride and graphene planar heterostructures, where a polar-on-nonpolar one-dimensional boundary is expected to possess peculiar electronic states associated with edge states of graphene and the polarity of boron nitride. Here we present a combined scanning tunnelling microscopy and first-principles theory study of the graphene-boron nitride boundary to provide a first glimpse into the spatial and energetic distributions of the one-dimensional boundary states down to atomic resolution. The revealed boundary states are about 0.6 eV below or above the Fermi level depending on the termination of the boron nitride at the boundary, and are extended along but localized at the boundary. These results suggest that unconventional physical effects similar to those observed at two-dimensional interfaces can also exist in lower dimensions.

[Non-alkaloid components from Sophora flavescens].

Five compounds were obtained from the stems and leaves of Sophora flavescens Ait. and ten compounds were obtained from the roots of S. flavescens by various chromatography methods including silica gel column chromatography and preparative HPLC. Their structures were identified on the basis of spectroscopic methods including 1H-NMR, 13C-NMR and ESI-MS, as corchionoside C (1), syringing (2), 2'-deoxythymidin (3), coniferin (4), benzyl O-beta-D-glucopyranoside (5), piscidic acid (6), trifolirhizin (7), kurarinone (8), trifolirhizin-6'-monoacetate (9), sophoraflavanone G (10), isoxanthohumol (11), noranhydroicaritin (12), 4'-methoxyisoflavone-7-O-beta-D-apiofuranosyl-(1 --> 6)-beta-D-glucopyranoside (13), kushenol O (14) and 6"-beta-D-xylopyranosylgenistin (15). Compounds 1-6 were isolated from the Sophora genus for the first time.

[Status and analysis of Astragali Radix resource in China].

To explore the status of the resources of Astragali Radix, a survey on its germplasm resources was carried out. Some conclusions can be drawn for Astragali Radix: the major source is the cultivated Astragalus mongolicus. The new major cultivation areas for A. mongolicus and A. membranaceus are Shandong and Gansu province. The semi-wildly planting model in Shanxi province maintains the genuine trait of Astragali Radix, but its yield is limited, and now a combination model has been developed. The major problems for Astragali Radix are the selection of planting sites, the rot root and difficulty in collecting and processing. Several developmental proposals for Astragali Radix were put forward including rational distribution of planting areas, establishment of standard system, development and standardization of producing technologies.