Determination of 44 major components and chemical profiling of saccharide in Chinese medicinal formula Lanqin Oral Liquid.

INTRODUCTION: Lanqin Oral Liquid (LQL) is a traditional Chinese medicine preparation (TCMP) containing five herbal medicines and has been commonly used for the treatment of pharyngitis and hand-foot-and-mouth disease in clinic. The material basis of LQL has been reported in our previous study, but the contents of the major components and the features of saccharide in LQL are still unclear. OBJECTIVES: This study aimed to establish accurate and rapid methods for the quantification of the major components and profiling of saccharide in LQL. The quantitative results combined with similarity evaluation were applied to improve the quality control of LQL. METHODOLOGY: An ultra-high performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UPLC-QQQ-MS) method was utilised to determine 44 major components. Cosine similarity was used to evaluate the similarities among 20 batches of LQL based on the quantitative results of 44 major components. The physicochemical properties, structure, composition, and contents of saccharide in LQL were detected by a combination of chemical and instrumental analysis. RESULTS: A total of 44 compounds, including flavonoids, iridoid glycosides, alkaloids, and nucleosides, were accurately determined. The 20 batches of LQL were remarkably similar (> 0.95). In addition, d-glucose, galactose, d-glucuronic acid, arabinose, and d-mannose were detected in saccharide of LQL. The contents of saccharide in LQL were 13.52-21.09 mg/ml. CONCLUSIONS: The established methods can be applied for the comprehensive quality control of LQL, including characterisation of saccharide and quantification of representative components. Our study will provide a robust chemical foundation for disclosing the quality markers of its therapeutic effect.

High-quality Fagopyrum esculentum genome provides insights into the flavonoid accumulation among different tissues and self-incompatibility.

Common buckwheat (Fagopyrum esculentum) and Tartary buckwheat (Fagopyrum tataricum), the two most widely cultivated buckwheat species, differ greatly in flavonoid content and reproductive mode. Here, we report the first high-quality and chromosome-level genome assembly of common buckwheat with 1.2 Gb. Comparative genomic analysis revealed that common buckwheat underwent a burst of long terminal repeat retrotransposons insertion accompanied by numerous large chromosome rearrangements after divergence from Tartary buckwheat. Moreover, multiple gene families involved in stress tolerance and flavonoid biosynthesis such as multidrug and toxic compound extrusion (MATE) and chalcone synthase (CHS) underwent significant expansion in buckwheat, especially in common buckwheat. Integrated multi-omics analysis identified high expression of catechin biosynthesis-related genes in flower and seed in common buckwheat and high expression of rutin biosynthesis-related genes in seed in Tartary buckwheat as being important for the differences in flavonoid type and content between these buckwheat species. We also identified a candidate key rutin-degrading enzyme gene (Ft8.2377) that was highly expressed in Tartary buckwheat seed. In addition, we identified a haplotype-resolved candidate locus containing many genes reportedly associated with the development of flower and pollen, which was potentially related to self-incompatibility in common buckwheat. Our study provides important resources facilitating future functional genomics-related research of flavonoid biosynthesis and self-incompatibility in buckwheat.

Sparstolonin B suppresses free fatty acid palmitate-induced chondrocyte inflammation and mitigates post-traumatic arthritis in obese mice.

Abnormal lipid metabolism, such as systemic increased free fatty acid, results in overproduction of pro-inflammatory enzymes and cytokines, which is crucial in the development of obesity-related osteoarthritis (OA). However, there are only a few drugs that target the lipotoxicity of OA. Recent researches have documented that the traditional Chinese medicine, Sparstolonin B (Ssn B), exerted anti-inflammatory effects in various diseases, but not yet in OA. On the basis of this evidence, our works purposed to evaluate the effect of Ssn B on free fatty acid (FFA) palmitate (PA)-stimulated human osteoarthritic chondrocytes and obesity-associated mouse OA model. We found that Ssn B suppressed PA-triggered inflammatory response and extracellular matrix catabolism in a concentration-dependent approach. In vivo, Ssn B treatment inhibited cartilage degeneration and subchondral bone calcification caused by joint mechanical imbalance and alleviated metabolic inflammation in obesity. Mechanistically, co-immunoprecipitine and molecular docking analysis showed that the formation of toll-like receptor 4 (TLR4)/myeloid differentiation protein-2 (MD-2) complex caused by PA was blocked by Ssn B. Subsequently, it leads to inactivation of PA-caused myeloid differentiation factor 88 (MyD88)-dependent nuclear factor-kappaB (NF-κB) cascade. Together, these findings demonstrated that Ssn B is a potential treatment agent for joint degenerative diseases in obese individuals.

Maltol prevents the progression of osteoarthritis by targeting PI3K/Akt/NF-κB pathway: In vitro and in vivo studies.

Osteoarthritis (OA), a prevalent degenerative arthritis disease, principle characterized by the destruction of cartilage and associated with the inflammatory response. Maltol, a product formed during the processing of red ginseng (Panax ginseng, CA Meyer), has been reported to have the potential effect of anti-inflammatory. However, its specific mechanisms are not demonstrated. We investigated the protective effect of maltol in the progression of OA both in vitro and in vivo experiments. Human chondrocytes were pre-treated with maltol (0, 20, 40, 60 µM, 24 hours) and incubated with IL-1ß (10 ng/mL, 24 hours) in vitro. Expression of PGE2, TNF-α and NO was measured by the ELISA and Griess reaction. The expression of iNOs, COX-2, aggrecan, ADAMTS-5, MMP-13, IκB-α, p65, P-AKT, AKT, PI3K and P-PI3K was analysed by Western blotting. The expression of collagen II and p65-active protein was detected by immunofluorescence. Moreover, the serious level of OA was evaluated by histological analysis in vivo. We identified that maltol could suppress the IL-1ß-stimulated generation of PGE2 and NO. Besides, maltol not only suppressed the production of COX-2, iNOs, TNF-α, IL-6, ADAMTS-5, MMP-13, but also attenuated the degradation of collagen II and aggrecan. Furthermore, maltol remarkably suppressed the phosphorylation of PI3K/AKT and NF-κB induced by IL-1ß in human OA chondrocytes. Moreover, maltol could block the cartilage destroy in OA mice in vivo. To date, all data indicate maltol is a potential therapeutic agent by inhibiting inflammatory response via the regulation of NF-κB signalling for OA.

The Tartary Buckwheat Genome Provides Insights into Rutin Biosynthesis and Abiotic Stress Tolerance.

Tartary buckwheat (Fagopyrum tataricum) is an important pseudocereal crop that is strongly adapted to growth in adverse environments. Its gluten-free grain contains complete proteins with a well-balanced composition of essential amino acids and is a rich source of beneficial phytochemicals that provide significant health benefits. Here, we report a high-quality, chromosome-scale Tartary buckwheat genome sequence of 489.3 Mb that is assembled by combining whole-genome shotgun sequencing of both Illumina short reads and single-molecule real-time long reads, sequence tags of a large DNA insert fosmid library, Hi-C sequencing data, and BioNano genome maps. We annotated 33 366 high-confidence protein-coding genes based on expression evidence. Comparisons of the intra-genome with the sugar beet genome revealed an independent whole-genome duplication that occurred in the buckwheat lineage after they diverged from the common ancestor, which was not shared with rosids or asterids. The reference genome facilitated the identification of many new genes predicted to be involved in rutin biosynthesis and regulation, aluminum stress resistance, and in drought and cold stress responses. Our data suggest that Tartary buckwheat's ability to tolerate high levels of abiotic stress is attributed to the expansion of several gene families involved in signal transduction, gene regulation, and membrane transport. The availability of these genomic resources will facilitate the discovery of agronomically and nutritionally important genes and genetic improvement of Tartary buckwheat.

Optimization-based multicriteria decision analysis for identification of desired petroleum-contaminated groundwater remediation strategies.

The conventional multicriteria decision analysis (MCDA) methods used for pollution control generally depend on the data currently available. This could limit their real-world applications, especially where the input data (e.g., the most cost-effective remediation cost and eventual contaminant concentration) might vary by scenario. This study proposes an optimization-based MCDA (OMCDA) framework to address such a challenge. It is capable of (1) capturing various preferences of decision-makers, (2) screening and analyzing the performance of various optimized remediation strategies under changeable scenarios, and (3) compromising incongruous decision analysis results. A real-world case study is employed for demonstration, where four scenarios are considered with each one corresponding to a set of weights representative of the preference of the decision-makers. Four criteria are selected, i.e., optimal total pumping rate, remediation cost, contaminant concentration, and fitting error. Their values are determined through running optimization and optimization-based simulation procedures. Four sets of the most desired groundwater remediation strategies are identified, implying specific pumping rates under varied scenarios. Results indicate that the best action lies in groups 32 and 16 for the 5-year, groups 49 and 36 for the 10-year, groups 26 and 13 for the 15-year, and groups 47 and 13 for the 20-year remediation.

Design of optimal groundwater remediation systems under flexible environmental-standard constraints.

In developing optimal groundwater remediation strategies, limited effort has been exerted to solve the uncertainty in environmental quality standards. When such uncertainty is not considered, either over optimistic or over pessimistic optimization strategies may be developed, probably leading to the formulation of rigid remediation strategies. This study advances a mathematical programming modeling approach for optimizing groundwater remediation design. This approach not only prevents the formulation of over optimistic and over pessimistic optimization strategies but also provides a satisfaction level that indicates the degree to which the environmental quality standard is satisfied. Therefore the approach may be expected to be significantly more acknowledged by the decision maker than those who do not consider standard uncertainty. The proposed approach is applied to a petroleum-contaminated site in western Canada. Results from the case study show that (1) the peak benzene concentrations can always satisfy the environmental standard under the optimal strategy, (2) the pumping rates of all wells decrease under a relaxed standard or long-term remediation approach, (3) the pumping rates are less affected by environmental quality constraints under short-term remediation, and (4) increased flexible environmental standards have a reduced effect on the optimal remediation strategy.

Quasi-Monte Carlo based global uncertainty and sensitivity analysis in modeling free product migration and recovery from petroleum-contaminated aquifers.

This paper presents a global uncertainty and sensitivity analysis (GUSA) framework based on global sensitivity analysis (GSA) and generalized likelihood uncertainty estimation (GLUE) methods. Quasi-Monte Carlo (QMC) is employed by GUSA to obtain realizations of uncertain parameters, which are then input to the simulation model for analysis. Compared to GLUE, GUSA can not only evaluate global sensitivity and uncertainty of modeling parameter sets, but also quantify the uncertainty in modeling prediction sets. Moreover, GUSA's another advantage lies in alleviation of computational effort, since those globally-insensitive parameters can be identified and removed from the uncertain-parameter set. GUSA is applied to a practical petroleum-contaminated site in Canada to investigate free product migration and recovery processes under aquifer remediation operations. Results from global sensitivity analysis show that (1) initial free product thickness has the most significant impact on total recovery volume but least impact on residual free product thickness and recovery rate; (2) total recovery volume and recovery rate are sensitive to residual LNAPL phase saturations and soil porosity. Results from uncertainty predictions reveal that the residual thickness would remain high and almost unchanged after about half-year of skimmer-well scheme; the rather high residual thickness (0.73-1.56 m 20 years later) indicates that natural attenuation would not be suitable for the remediation. The largest total recovery volume would be from water pumping, followed by vacuum pumping, and then skimmer. The recovery rates of the three schemes would rapidly decrease after 2 years (less than 0.05 m(3)/day), thus short-term remediation is not suggested.

An integrated simulation, inference, and optimization method for identifying groundwater remediation strategies at petroleum-contaminated aquifers in western Canada.

This study advances an integrated simulation, inference, and optimization method (ISIOM) for optimizing groundwater remediation systems. SIOM has the advantages of (i) automotive screening of potential explanatory variables (e.g., the pumping rates at various remediation wells), (ii) providing a flexible manner for investigating the linear, interactive, and quadratic effects of operating conditions on the benzene levels, and (iii) mitigating the computational efforts in optimization processes. The method is applied to a petroleum-contaminated site in western Canada for identifying the optimal remediation strategies under a given set of remediation durations and environmental standard levels. To examine the effect of pumping duration on contaminants removing efficiency, 4 duration options are considered including 5, 10, 15, and 20 years, respectively. The results indicate that the pumping duration would have effect on the optimized scheme. It is suggested that the 10-year duration would be more desirable than the 15-year one. The simulation results demonstrate that the peak benzene concentrations would be reduced to satisfy the environmental standard when the optimal remediation strategy is carried out.

[An improved PID algorithm for temperature control used by tumor combined therapeutic instrument].

The development of a multi-functional tumor combined therapeutic instrument based on improved PID algorithm is introduced. It is based on the theory of 1 + 1 = 3 or 1 + 1 + 1 > 3 curative effect enhancement by tumor combined therapy, and it can be used solely, or with the combination of chemotherapy or actinotheraphy or both for tumor hyperthermia. By adopting improved PID temperature control algorithm, the problem of temperature control precision reduction due to process characteristics changing with different heaters was solved, thus ensuring homogeneous and smooth radio frequency heating by different heaters to intracavity tumor foci. These experiments demonstrated that the new algorithm has strong adaptability and anti-disturbance capability, the equipment works stably and reliably, and it can control therapeutic temperature precisely (+/- 0.1 degree C), which indicates a good value in clinical application.

[Development of RF ablation therapeutic instrument based on improved PID algorithm].

The development of a RF ablation therapeutic instrument based on improved PID algorithm is introduced here. It is based on the theory of radio frequency local destruction. By adopting the improved PID temperature control algorithm, the problem of the temperature control precision reduction due to tumor tissue characteristic changing by heating has been solved, thus ensuring homogeneous and smooth radio frequency heating to tumor foci. Experiments demonstrate that the new algorithm has strong adaptability and anti-disturbance capability, the equipment works stably and reliably, and can control therapeutic temperature precisely (+/- 2 degrees C), which indicates a good clinical application value.