Unraveling the Nanoscale Segregation Mechanism in N-Doped Niobium for Enhanced SRF Performance.

The nitrogen doping (N-doping) treatment for niobium superconducting radio-frequency (SRF) cavities is one of the key enabling technologies that support the development of more efficient future large accelerators. However, the N-doping results have diverged due to a complex chemical profile under the nitrogen-doped surface. Particularly, under industrial-scale production conditions, it is difficult to understand the underlying mechanism thus hindering performance improvement. Herein, a combination of spatially resolved and surface-sensitive approaches is employed to establish the detailed near-surface phase composition of thermally processed niobium. The results show that intermediate phase segregations, particularly the nanometric carbon-rich phase, can impede the nitridation process and limit the interactions between nitrogen and the niobium sub-surface. In comparison, the removal of the carbon-rich layer at the Nb surface leads to enhanced nitrogen binding at the Nb surface. Combining the RF test results, it is shown that the complex uniformity and grain boundary penetrations of impurity elements have a direct correlation with the mid-field quench behavior in the N-doped Nb cavities. Therefore, proper control of the nanometric intermediate phase formation in discrete thermal steps is critical in improving the ultimate performance and production yield of the Nb cavities.

Discovery of Benzothiazolylpyrazole-4-Carboxamides as Potent Succinate Dehydrogenase Inhibitors through Active Fragment Exchange and Link Approach.

Succinate dehydrogenase (SDH) is an attractive target for developing green fungicides to manage agricultural pathogens in modern agriculture research. Herein, in this work, we report the discovery of benzothiazolylpyrazole-4-carboxamides I-III as potent SDH inhibitors using active fragment exchange and link approach. The results of the fungicidal activity assays showed that some of the synthesized compounds exhibited excellent inhibition against the tested fungi. Systematic structure-activity relationship studies led to the discovery of compound Ip, N-(1-((4,6-difluorobenzo[d]thiazol-2-yl)thio)propan-2-yl)-3-(difluoromethyl)-N-methoxy-1-methyl-1H-pyrazole-4-carboxamide, which showed higher fungicidal activity against Fusarium graminearum Schw (EC50 = 0.93 µg/mL) than the commercial fungicides thifluzamide (EC50 > 50 µg/mL) and boscalid (EC50 > 50 µg/mL). The molecular simulation studies suggested that hydrophobic interactions were the primary driving forces between ligands and SDH. Promisingly, we found that Ip could stimulate the growth of wheat seedlings and Arabidopsis thaliana and increase the biomass of the treated plants. Preliminary studies on the plant growth promoter mechanism of Ip indicated that it could increase nitrate reductase activity in planta, that, in turn, stimulates the growth of plants.

ReIPS: A Secure Cloud-Based Reputation Evaluation System for IoT-Enabled Pumped Storage Power Stations.

Reputation evaluation is an effective measure for maintaining secure Internet of Things (IoT) ecosystems, but there are still several challenges when applied in IoT-enabled pumped storage power stations (PSPSs), such as the limited resources of intelligent inspection devices and the threat of single-point and collusion attacks. To address these challenges, in this paper we present ReIPS, a secure cloud-based reputation evaluation system designed to manage intelligent inspection devices' reputations in IoT-enabled PSPSs. Our ReIPS incorporates a resource-rich cloud platform to collect various reputation evaluation indexes and perform complex evaluation operations. To resist single-point attacks, we present a novel reputation evaluation model that combines backpropagation neural networks (BPNNs) with a point reputation-weighted directed network model (PR-WDNM). The BPNNs objectively evaluate device point reputations, which are further integrated into PR-WDNM to detect malicious devices and obtain corrective global reputations. To resist collusion attacks, we introduce a knowledge graph-based collusion device identification method that calculates behavioral and semantic similarities to accurately identify collusion devices. Simulation results show that our ReIPS outperforms existing systems regarding reputation evaluation performance, particularly in single-point and collusion attack scenarios.

Multifunctional Nano-Realgar Hydrogel for Enhanced Glioblastoma Synergistic Chemotherapy and Radiotherapy: A New Paradigm of an Old Drug.

Purpose: Realgar, as a kind of traditional mineral Chinese medicine, can inhibit multiple solid tumor growth and serve as an adjuvant drug in cancer therapy. However, the extremely low solubility and poor body absorptive capacity limit its application in clinical medicine. To overcome this therapeutic hurdle, realgar can here be fabricated into a nano-realgar hydrogel with enhanced chemotherapy and radiotherapy (RT) ability. Our objective is to evaluate the superior biocompatibility and anti-tumor activity of nano-realgar hydrogel. Methods: We have successfully synthesized nano-realgar quantum dots (QDs) coupling with 6-AN molecules (NRA QDs) and further encapsulated with a pH-sensitive dextran hydrogel carrier with hyaluronic acid coating (DEX-HA gel) to promote bioavailability, eventually forming a multifunctional nano-realgar hydrogel (NRA@DH Gel). To better investigate the tumor therapy efficiency of the NRA@DH Gel, we have established the mice in situ bearing GL261 brain glioblastoma as animal models assigned to receive intratumor injection of NRA@DH Gel. Results: The designed NRA@DH Gel as an antitumor drug can not only exert the prominent chemotherapy effect but also as a "sustainable reactive oxygen species (ROS) generator" can inhibit in the pentose phosphate pathway (PPP) metabolism and reduce the production of nicotinamide adenine dinucleotide phosphate (NADPH), thereby inhibiting the conversion of glutathione disulfide (GSSG) to glutathione (GSH), reducing GSH concentrations in tumor cells, triggering the accumulation of ROS, and finally enhancing the effectiveness of RT. Conclusion: Through the synergistic effect of chemotherapy and RT, NRA@DH Gel effectively inhibited the proliferation and migration of tumor cells, suppressed tumor growth, improved motor coordination, and prolonged survival in tumor-bearing mice. Our work aims to improve the NRA@DH Gel-mediated synergistic chemotherapy and RT will endow a "promising future" for the old drug in clinically comprehensive applications.

The aldolase inhibitor aldometanib mimics glucose starvation to activate lysosomal AMPK.

The activity of 5'-adenosine monophosphate-activated protein kinase (AMPK) is inversely correlated with the cellular availability of glucose. When glucose levels are low, the glycolytic enzyme aldolase is not bound to fructose-1,6-bisphosphate (FBP) and, instead, signals to activate lysosomal AMPK. Here, we show that blocking FBP binding to aldolase with the small molecule aldometanib selectively activates the lysosomal pool of AMPK and has beneficial metabolic effects in rodents. We identify aldometanib in a screen for aldolase inhibitors and show that it prevents FBP from binding to v-ATPase-associated aldolase and activates lysosomal AMPK, thereby mimicking a cellular state of glucose starvation. In male mice, aldometanib elicits an insulin-independent glucose-lowering effect, without causing hypoglycaemia. Aldometanib also alleviates fatty liver and nonalcoholic steatohepatitis in obese male rodents. Moreover, aldometanib extends lifespan and healthspan in both Caenorhabditis elegans and mice. Taken together, aldometanib mimics and adopts the lysosomal AMPK activation pathway associated with glucose starvation to exert physiological roles, and might have potential as a therapeutic for metabolic disorders in humans.

Calorie Restriction Enhanced Glycogen Metabolism to Compensate for Lipid Insufficiency.

SCOPE: This study aims to investigate the metabolic phenotype and mechanism of 40% calorie restriction (CR) in mice. METHODS AND RESULTS: CR mice exhibit super-stable blood glucose, as evidenced by increased fasting blood glucose (FBG), decreased postprandial blood glucose, and reduced glucose fluctuations. Additionally, both fasting plasma insulin and the homeostasis model assessment of insulin resistance increase significantly in CR mice. Compared with control, the phosphorylation of insulin receptor substrates-1 and serine/threonine kinase decreases in liver and fat but increases in muscle of CR mice after insulin administration, indicating hepatic and adipose insulin resistance, and muscle insulin sensitization. CR reduces visceral fat much more than subcutaneous fat. The elevated FBG is negatively correlated with low-level fasting ß-hydroxybutyrate, which may result from insufficient free fatty acids and diminishes ketogenic ability in CR mice. Furthermore, liver glycogen increases dramatically in CR mice. Analysis of glycogen metabolism related proteins indicates active glycogen synthesis and decomposition. Additionally, CR elevates plasma corticosterone and hypothalamic orexigenic gene expression. CONCLUSION: CR induces lipid insufficiency and stress, resulting in global physiological insulin resistance except muscle and enhances glycogen metabolism, culminating in the stability of blood glucose manifests in increased FBG, which compensates for insufficient blood ketones.

[Effects of the removal of invasive Moso bamboo on soil microbial biomass and enzyme activities in subtropical forests]. / å ¥ä¾µæ¯›ç«¹çš†ä¼å¯¹äºšçƒ­å¸¦æ£®æž—åœŸå£¤å¾®ç”Ÿç‰©ç”Ÿç‰©é‡å’Œé ¶æ´»æ€§çš„å½±å“.

Removal of invasive plant species is the first step to restoring the invaded ecosystems. The soil microbial biomass and extracellular enzyme activities were measured in Moso bamboo (Phyllostachys edulis) pure forest (completely invasion), invasive P. edulis removal forest (secondary succession 5 years after clear cutting), and the evergreen broadleaved forest (no invasion) in Tianmu Mountain. The results showed that compared with P. edulis pure forest, invasive P. edulis removal significantly increased the contents of soil organic carbon (SOC), nitrate nitrogen, available phosphorus and potassium, as well as microbial biomass carbon (MBC) and microbial biomass phosphorus (MBP), while significantly decreased microbial biomass nitrogen (MBN). The activities of α-glucosidase (AG), ß-glucosidase (BG), leucine aminopeptidase (LAP) and phenol oxidase (POX) in the forest with removal of invasive P. edulis were significantly higher than those in P. edulis pure forest, while invasive P. edulis removal did not change the activities of cellodisaccharide hydrolase (CBH), ß-N-acetyl-glucosaminopeptidase (NAG), acid phosphatase (ACP) and peroxidase (PER). Furthermore, the activities of AG, BG and LAP were positively correlated with SOC and MBC, while the increase in POX activity was positively correlated with soil nitrate content. In addition, MBC, MBN and MBP, and activities of AG, BG, NAG, LAP and ACP in P. edulis removal forest forest were significantly higher than those in evergreen broadleaved forests. Taken together, the removal of invasive P. edulis could increase soil nutrient contents, microbial biomass and extracellular enzyme activities, thus could be considered as an effective way to restore the invaded forests. Our results provide important theoretical basis for controlling P. edulis invasion in subtropical forests.

A quantitative enzyme-linked immunoassay (ELISA) to approximate complement-fixing antibody titers in serum from patients with coccidioidomycosis.

Coccidioidomycosis is most frequently diagnosed serologically, and the quantitative test for complement-fixing antibodies is considered prognostically useful. Because complement-fixing antibody testing is complex, labor-intensive, and poorly standardized, an enzyme-linked immunoassay (ELISA) alternative would be attractive. In this report, we restrict the complement-fixing, antibody-binding domain to a 200-amino-acid recombinant peptide of the known antigen. Over-lapping truncations of this peptide do not bind complement-fixing antibodies, suggesting that the responsible epitope(s) are conformational. Further, anchoring the antigenic peptide to the ELISA plate by means of a C-terminal biotin-mimic peptide tag instead of allowing the peptide to randomly adhere to the plastic plate improves sensitivity of antibody detection by 1-2 logs in different sera. The newly developed ELISA shows a significant quantitative correlation with complement-fixing antibody titers. This ELISA shows potential as the basis for a new quantitative assay for coccidioidal antibodies.

Clinical Observation on Jiechang Qingre Pills Combined with Conventional Western Medicine Therapy in Improving Dampness-heat Syndrome of Large Intestine at Active Stage of Ulcerative Colitis / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Jiechang Qingre pills for dampness-heat syndrome of large intestine at active stage of ulcerative colitis （UC） and investigate its effect on inflammatory factors. Method:One hundred and eight patients with active UC were divided into observation group and control group. Both groups were treated with Mesalazine enteric-coated tablets， 2 g/times， 2 times/day， for 2 weeks. If symptoms were poorly controlled， prednisone acetate tablets would be used instead， 0.75 mg·kg^-1·d^-1in 3 times by oral administration. Patients in the observation group took Jiechang Qingre pills， 10 g/time， 3 times/day before meals. Patients in the control group took Jiechang Qingre pills simulated drug， 10 g/time， 3 times/day before meals. The course of treatment was 12 weeks in both groups and the patients were followed up for 3 months. The modified Mayo score was used to evaluate disease activity. Before and after treatment， large intestine dampness-heat syndrome score， inflammatory bowel disease questionnaire （IBDQ）， mucosal histology assessment and scores of major symptoms and intestinal mucosal lesion severity were graded. The incidence of non-reactivity， hormone failure， hormone dependence， and early recurrence were recorded 2 weeks after treatment. Tumor necrosis factor-<italic>α </italic>（TNF-<italic>α</italic>）， interleukin-6（IL-6） and IL-17 levels were measured before and after treatment. Result:The clinical effective rate in the observation group was 94.00% （47/50）， higher than 77.55% （38/49） in the control group （<italic>χ</italic>²=5.514，<italic>P</italic><0.05）. The clinical remission rate was 82.00%（41/50） in the observation group， higher than 61.22% （30/49） in the control group （<italic>χ</italic>²=5.266，<italic>P</italic><0.05）. The endoscopic response rate was 96.00% （48/50） in the observation group， higher than 79.59% （39/49） in the control group （<italic>χ</italic>²=6.251，<italic>P</italic><0.05）. The rate of mucosal healing in the observation group was 90.00% （45/50）， higher than 79.59% （35/49） in the control group （<italic>χ</italic>²=5.503，<italic>P</italic><0.05）. The scores of diarrhea， purulent stool， abdominal pain， tenesmus， hyperemia， edema， erosion and ulcer in the observation group were lower than those in the control group （<italic>P</italic><0.01）. The rate of non-reactivity in the observation group was 16.00% （8/50）， lower than 34.69% （17/49） in the control group（<italic>χ</italic>²=4.581，<italic>P</italic><0.05）. The hormone failure rate in the observation group was 37.50%（3/8）， lower than 64.71%（11/17）in the control group，but the difference was not statistically significant（tested by the exact probaility method）. The hormone dependence rate in the observation group was 12.50%（1/8）， lower than 23.53% （4/17） in the control group，but the difference was not statistically significant（tested by the exact probaility method）. The early recurrence rate in the observation group was 14.00% （7/50）， lower than 32.65%（16/49） in the control group（<italic>χ</italic>²=4.827，<italic>P</italic><0.05）. The scores of Mayo， dampness and heat syndrome and Geboes index in the observation group were lower than those in the control group （<italic>P</italic><0.01）， and the IBDQ scores were significantly higher than those in the control group （<italic>P</italic><0.01）. The TNF-<italic>α， </italic>IL-6 and IL-17 levels of the patients in the observation group were lower than those in the control group （<italic>P</italic><0.01）. Conclusion:Based on the routine treatment of western medicine， Jiechang Qingre pills treatment for the patients with active UC can effectively induce clinical remission， alleviate inflammatory reaction， promote intestinal mucosal healing， improve clinical symptoms， quality of life and the response of treatment. Its clinical efficacy and enteroscopy efficacy are better than western medicine treatment alone， so it is worthy of clinical use.

[Application of traditional Chinese medicine(TCM) traceability system based on TCM quality characteristics and HACCP system].

It is crucial to establish a complete set of traditional Chinese medicine(TCM) quality traceability management process system, in order to stabilize the pricing order of TCM market and reconstruct the transmission path of TCM quality signals. In this study, we reviewed the mature experience of food and drug supervision at home and abroad, analyzed the quality characteristics of TCM, and put forward that the quality control of TCM products can learn from the hazard analysis and critical control point(HACCP) system in food safety quality control. This study points out that the HACCP system provides not only technical guidance for the traceability management of TCM, but also ideas for improving the quality of TCM products and the safety risk control of TCM. The application of the HACCP system in TCM quality control can help establish an international dialogue platform for TCM and help realize the modernization and internationalization of TCM industry.

Lightweight and Resource-Constrained Learning Network for Face Recognition with Performance Optimization.

Despite considerable progress in face recognition technology in recent years, deep learning (DL) and convolutional neural networks (CNN) have revealed commendable recognition effects with the advent of artificial intelligence and big data. FaceNet was presented in 2015 and is able to significantly improve the accuracy of face recognition, while also being powerfully built to counteract several common issues, such as occlusion, blur, illumination change, and different angles of head pose. However, not all hardware can sustain the heavy computing load in the execution of the FaceNet model. In applications in the security industry, lightweight and efficient face recognition are two key points for facilitating the deployment of DL and CNN models directly in field devices, due to their limited edge computing capability and low equipment cost. To this end, this paper provides a lightweight learning network improved from FaceNet, which is called FN13, to break through the hardware limitation of constrained computational resources. The proposed FN13 takes the advantage of center loss to reduce the variations of the between-class features and enlarge the difference of the within-class features, instead of the triplet loss by using FaceNet. The resulting model reduces the number of parameters and maintains a high degree of accuracy, only requiring few grayscale reference images per subject. The validity of FN13 is demonstrated by conducting experiments on the Labeled Faces in the Wild (LFW) dataset, as well as an analytical discussion regarding specific disguise problems.

[Start-up of CANON Process and Short-cut Nitrification in a Pilot-scale MBBR Reactor].

Using a 150 L moving bed biofilm reactor (MBBR), with the temperature controlled at 28℃ and high NH4+-N concentration (average concentration 350 mg·L-1), inorganic wastewater was used as an influent to start the completely autotrophic nitrogen removal over nitrite (CANON) process. Meanwhile, the flocculent sludge was taken into a 5 L sequencing batch reactor, and the influent NH4+-N concentration was maintained at 90-200 mg·L-1 for the recovery of short-cut nitrification. The results showed that in the MBBR reactor, when the average hydraulic retention time (HRT) was 12 h, short-cut nitrification and total nitrogen (TN) removal rate were mutually constrained, the average TN removal rate was 38.2%, and the average δNO3--N/TN value was 0.274; when the HRT dropped to 6 h, the δNO3--N/TN value decreased from 0.347 to 0.146. The sequencing batch reactor (SBR) maintained aeration and anoxic time for 30 min and 20 min, respectively, by intermittent aeration, while the dissolved oxygen concentration during the aerobic process was 0.5 mg·L-1 to 0.6 mg·L-1, the free nitrous acid concentration was higher than 0.18 mg·L-1 at the end of each cycle, NAR increased from 0 to 99.2% after 12 days, NUR decreased to 0 from an initial 24.8 mg·(g·h)-1, and the TN removal rate decreased from 13% to 3%; the system successfully converted to short-range nitrification. High-throughput sequencing results showed that the abundance of Candidatus Kuenenia in the flocculent sludge and biofilm in the MBBR reactor were 7.91% and 17.38% respectively, Nitrosomonas accounted for 27.43% and 2.55%, respectively, while Nitrospira accounted for 0.30% and 0.28%, respectively. After the recovery of short-cut nitrification in the SBR, the abundance of ammonia-oxidizing bacteria and anaerobic ammonia oxidation decreased to 1.18% and 0.01%, respectively, and the abundance of Nitrospira increased to 1.39%.

[Research on Denitrification Performance of Enhanced Secondary Effluent by Embedded Denitrification Filler and Pilot Application].

The use of an embedded broad-spectrum high-efficiency denitrification filler to treat secondary effluent from municipal wastewater treatment plants can effectively reduce total nitrogen (TN) concentration of the effluent. This study consists of two parts. The D1 stage studies the adaptability of the secondary effluent based on the embedded denitrification, removal effect of total nitrogen, stable working conditions, and backwashing conditions; In the D2 stage, the change in the nitrogen removal performance of the filler under the condition of a year-long stable operation was studied. The variation in the microbial population before and after the operation of the embedded packing was studied by high-throughput sequencing and real-time quantitative PCR detecting system real-time (qPCR). In this research, the embedded denitrification filler had a water temperature of (24±1)℃, pH:7.1, hydraulic retention time (HRT):1 h, and filling rate:10%. Sodium acetate was added to ensure stable operation for seven days. Under adequate carbon source conditions, the filler can adapt to the quality of secondary effluent water and achieve effluent TN<5mg·L-1. By comparing and studying the effect of different HRT on the removal of filler TN, it is concluded that HRT is 30 min and the filling rate is 10%. After a year of stable operation under 7.2 m3·d-1influent conditions, the TN removal rate can reach 90.42%, and the total nitrogen in the effluent can be stabilized below 5 mg·L-1. In comparison with the backwashing effect, the backwashing strength was 5.2 L·(m2·s)-1, and the cycle is three days long. High-throughput sequencing and real-time quantitative PCR analysis results show that the abundance and copy number of denitrifying functional genus in the filler before and after the operation exhibited significant changes, which indicated that the bacteria could achieve good self-growth under embedding conditions.

Virtual Network Embedding for Multi-Domain Heterogeneous Converged Optical Networks: Issues and Challenges.

The emerging 5G applications and the connectivity of billions of devices have driven the investigation of multi-domain heterogeneous converged optical networks. To support emerging applications with their diverse quality of service requirements, network slicing has been proposed as a promising technology. Network virtualization is an enabler for network slicing, where the physical network can be partitioned into different configurable slices in the multi-domain heterogeneous converged optical networks. An efficient resource allocation mechanism for multiple virtual networks in network virtualization is one of the main challenges referred as virtual network embedding (VNE). This paper is a survey on the state-of-the-art works for the VNE problem towards multi-domain heterogeneous converged optical networks, providing the discussion on future research issues and challenges. In this paper, we describe VNE in multi-domain heterogeneous converged optical networks with enabling network orchestration technologies and analyze the literature about VNE algorithms with various network considerations for each network domain. The basic VNE problem with various motivations and performance metrics for general scenarios is discussed. A VNE algorithm taxonomy is presented and discussed by classifying the major VNE algorithms into three categories according to existing literature. We analyze and compare the attributes of algorithms such as node and link embedding methods, objectives, and network architecture, which can give a selection or baseline for future work of VNE. Finally, we explore some broader perspectives in future research issues and challenges on 5G scenario, field trail deployment, and machine learning-based algorithms.

The interactions and adsorption mechanisms of ternary heavy metals on boron nitride.

In this work, the interactions and adsorption mechanisms of Cu2+, Cd2+, and Ni2+ on boron nitride (BN) were tested by the simultaneous removal of metal ions from synthetic wastewater. BN was characterized using XRD, SEM, and FTIR spectroscopy. The adsorption differences between BN and the metal ions were explored through comparative studies in a single and ternary system. In the ternary system, adsorption occurs rapidly in the first 2 min for the metal ions, and the affinity order follows Cu2+>Cd2+>Ni2+. However, adsorption behavior changes due to the interaction between metal ions in the ternary system. Cu2+ showed an antagonistic effect on the adsorption of Cd2+ and Ni2+, while Cd2+ and Ni2+ produced a synergistic effect on Cu2+. In addition, the effect of metal ion concentration on the interaction between ions was studied based on a surface response experiment. An increase in Ni2+ or Cd2+ concentrations plays a synergistic effect on the adsorption of Cu2+, while an antagonistic adsorption for Ni2+ occurred with increasing Cu2+ or Cd2+ concentrations. We also discussed the various adsorption mechanisms as complexation, ion exchange, and electrostatic adsorption based on XPS analysis.

Effects of integrin av ß3 inhibitor CycIo-RGDfK on epithelial- mesenchymal transition of breast epithelial cells induced by fibronectin / 中国药理学通报

Aim To investigate the effect of integrin av ß3 inhibitor (Cyclo-RGDfK) on fibronectin (F N) - induced epithelial-mesenchymal transition in human mammary epithelial cells MCF-10A. Methods M C F - 10A cells were cultured in vitro, and the model of epithelial-mesenchymal transition (E M T) induced by FN was established. The expressions of otv integrin, ß3 integrin, epithelial marker E-cadherin and mesenchymal markers N-cadherin and Vimentin were measured by Western blot. The migration ability and invasion ability of cells were detected by Scratch repair experiment and Transwell chamber experiment. Results Western blot results showed that the expressions of ay integrin, ß3 integrin, N-cadherin, and Vimentin significantly were up-regulated and the expression of E-cadherin protein down-regulated after FN treatment for 48 h. After administration of Cyclo-RGDfK, the increased expression of N-cadherin and Vimentin and decreased expression of E-cadherin induced by FN were significantly reversed. Similarly, the results of Scratch repair experiments and Transwell experiments showed that FN significantly enhanced the ability of MCF-10A cells to migrate and invade, and Cyclo-RGDfK significantly inhibited the induction of FN. Conclusions Cyclo-RGDfK can inhibit the process of EMT induced by FN and reduce the invasion and migration of MCF-10A, which may be a potential drug for the treatment of breast cancer metastasis.

Application of traditional Chinese medicine(TCM) traceability system based on TCM quality characteristics and HACCP system / 中国中药杂志

It is crucial to establish a complete set of traditional Chinese medicine(TCM) quality traceability management process system, in order to stabilize the pricing order of TCM market and reconstruct the transmission path of TCM quality signals. In this study, we reviewed the mature experience of food and drug supervision at home and abroad, analyzed the quality characteristics of TCM, and put forward that the quality control of TCM products can learn from the hazard analysis and critical control point(HACCP) system in food safety quality control. This study points out that the HACCP system provides not only technical guidance for the traceability management of TCM, but also ideas for improving the quality of TCM products and the safety risk control of TCM. The application of the HACCP system in TCM quality control can help establish an international dialogue platform for TCM and help realize the modernization and internationalization of TCM industry.

[Research of classical prescription based on QbD concept:optimization of extraction process for modified Siwu Decoction].

As an advanced concept in international pharmaceutical research,quality by design( QbD) can fulfill the strategic requirements of drug quality from testing to design. In this paper,the extraction process of Yanggong Prescription which was the modified Siwu Decoction was optimized based on QbD concept. With the extraction amount of solid matter,the content of ferulic acid and the content of paeoniflorin as critical quality attributes( CQAs),the failure mode and effect analysis( FMEA) was used to screen potential critical process parameters( p CPPs). The mathematical model was established by Box-Behnken experimental design to investigate the interaction between critical process parameters( CPPs) and CQAs. Then the design space for the extraction process of Yanggong Prescription was further established and optimized. Analysis of variance showed that the variance of all models was significant( P<0. 01),and the lack-of-fit value was not significant,indicating that the model was statistically significant. The relationship between various factors and the response values could be functionalized by the established models. Finally,through the optimization of the design space,the optimum extraction process of Yanggong Prescription was obtained as follows: 3 extraction times,122 minutes extraction,and 7 times of water adding. The extraction process of Yanggong Prescription based on the QbD concept was robust and reliable,which would provide guidance for the process development and quality control of its formulations.

[Study on famous prescription of prestigious traditional Chinese medicine master Lu Zhizheng based on QbD concept: optimization of extraction process and granule forming process of Meiyan Shuqi Prescription].

Based on the concept of quality by design( QbD),the design space of Meiyan Shuqi Prescription extraction process was established,and its granules forming process was optimized. The content of total flavonoids was the critical quality attribute( CQA).The amount of water,extraction time and frequency were used as the critical process parameters( CPPs). Box-Behnken experimental design was used to optimize the extraction process. The design space of Meiyan Shuqi Prescription extraction process was established and verified. The results of variance analysis showed that the P value of the quadratic regression model was less than 0. 01,which indicated that the model had a statistical significance,and the relationship between each factor and response value could be functionalized by the established model. Through further optimization of design space,the optimal extraction process of Meiyan Shuqi prescription was13-fold volume of water,extraction for 3 times and each extraction time of 1. 4 hours. Furthermore,the forming process optimized by single factor was as follows: the excipient was dextrin; the ratio of extract powder to excipient was 1 ∶1; the wetting agent was 70% ethanol; and the amount of wetting agent was 0. 3 m L·g-1. The Meiyan Shuqi Prescription extraction process and the forming process based on QbD concept provide reference for the study of other traditional Chinese medicine prescriptions.

Oxymatrine reverses epithelial-mesenchymal transition in breast cancer cells by depressing αâ ¤ß3 integrin/FAK/PI3K/Akt signaling activation.

PURPOSE: Oxymatrine, an alkaloid extracted from the Chinese herb Sophora flavescens Aiton, possesses anti-inflammatory, anti-immune, anti-hepatic fibrosis, and anti-cancer properties. However, the effects of oxymatrine on epithelial-mesenchymal transition (EMT) of breast cancer cells are still unclear. AIM: The present study was performed to investigate whether oxymatrine reverses EMT in breast cancer cells and to explore the underlying molecular mechanisms. MATERIALS AND METHODS: MTT assay was performed to evaluate cell viability. Wound-healing assay and transwell chamber assay were used to assess cell migration and invasion, respectively. Immunofluorescence and Western blot were used to study the expression of EMT-related molecules and αⅤß3 integrin/focal adhesion kinase (FAK)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling transduction. Fibronectin, a physiologic ligand of αⅤß3 integrin, was used to stimulate αⅤß3 integrin signaling. RESULTS: Our results demonstrated that oxymatrine effectively suppressed the viability of MDA-MB-231 and 4T1 breast cancer cells, and oxymatrine showed less cytotoxicity on normal breast mammary epithelial MCF-10A cells. In addition, oxymatrine reversed EMT in the MDA-MB-231 and 4T1 cells at nontoxic concentrations. Oxymatrine significantly inhibited cell migration and invasion, downregulated the expression of N-cadherin, vimentin, and Snail in MDA-MB-231 and 4T1 cells, but upregulated the expression of E-cadherin in 4T1 cells. The mechanism revealed that oxymatrine decreased the expression of αⅤ and ß3 integrin and their co-localization. It also inhibited αⅤß3 integrin downstream activation by suppressing the phosphorylation of FAK, PI3K, and Akt. Furthermore, oxymatrine prevented fibronectin-induced EMT and αⅤß3 integrin/FAK/PI3K/Akt signaling activation. CONCLUSION: Our results revealed that oxymatrine effectively reversed EMT in breast cancer cells by depressing αⅤß3 integrin/FAK/PI3K/Akt signaling. Thus, oxymatrine could be a potential therapeutic candidate with anti-metastatic potential for the treatment of breast cancer.