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With its profound historical origin, unique value implication and powerful spiritual power, red culture can lead the cultivation of socialist core values for youth. In the context of the new era, promoting red culture to lead the cultivation of socialist core values meets the domestic requirements of building a strong socialist culture. Red culture is highly compatible with the scientific connotation of socialist core values, therefore, it needs to be explored from the practical paths of using red resources to gather the soul, telling red stories to promote understanding, and carrying forward red traditions to continue the bloodline, so as to help cultivate the new generation of the times.

Extracellular vesicle (EV)/exosome secretion is a dynamic process that tunes the cellular communication for response to internal and external cues. The selective enrichment of a newly synthesized EV/exosome has been hindered by the basic fact that all EVs/exosomes, new and old, share the similar inherent parameters and thus are indistinguishable. Here, we developed a method by cotranslational introduction of azide groups into EV/exosome proteins as a timestamp and label them with biotin tag by click chemistry, to separate the newly synthesized EVs/exosomes from preexisting populations by streptavidin-modified herringbone microfluidic chip. For mouse model of anti-PD-L1 immunotherapy, the level of newly synthesized PD-L1+ EVs detected by the developed approach was superior to the total PD-L1+ EVs from mixed time sources (quantified by classical method) for tumor progression. This method makes it possible to address the temporal characteristics of newly synthesized EVs/exosomes in cell and in vivo, for studying EV/exosome secretion to respond to specific stimuli.

Objective. In this study, we propose the adaptive permissible region based random Kaczmarz method as an improved reconstruction method to recover small carotid atherosclerotic plaque targets in rodents with high resolution in fluorescence molecular tomography (FMT). Approach. We introduce the random Kaczmarz method as an advanced minimization method to solve the FMT inverse problem. To satisfy the special condition of this method, we proposed an adaptive permissible region strategy based on traditional permissible region methods to flexibly compress the dimension of the solution space. Main results. Monte Carlo simulations, phantom experiments, and in vivo experiments demonstrate that the proposed method can recover the small carotid atherosclerotic plaque targets with high resolution and accuracy, and can achieve lower root mean squared error and distance error (DE) than other traditional methods. For targets with 1.5 mm diameter and 0.5 mm separation, the DE indicators can be improved by up to 40%. Moreover, the proposed method can be utilized for in vivo locating atherosclerotic plaques with high accuracy and robustness. Significance. We applied the random Kaczmarz method to solve the inverse problem in FMT and improve the reconstruction result via this advanced minimization method. We verified that the FMT technology has a great potential to locate and quantify atherosclerotic plaques with higher accuracy, and can be expanded to more preclinical research.

In this paper, the damage to the bus conductor and expansion joint caused by the tripping accident of bus B of a 330 kV line in Northwest China was taken as an example, and the reasons for the tripping accident were analyzed and improvement measures were proposed utilizing macro inspection and cross-cut test. The results showed that the main reason for this failure is that the manufacturer did not strictly implement the coating process, resulting in insufficient coating adhesion, and the coating gradually cracked and fell off during operation. The peeling coating caused air gap breakdown and ground flashover.

Stripe artifacts can deteriorate the quality of light sheet fluorescence microscopy (LSFM) images. Owing to the inhomogeneous, high-absorption, or scattering objects located in the excitation light path, stripe artifacts are generated in LSFM images in various directions and types, such as horizontal, anisotropic, or multidirectional anisotropic. These artifacts severely degrade the quality of LSFM images. To address this issue, we proposed a new deep-learning-based approach for the elimination of stripe artifacts. This method utilizes an encoder–decoder structure of UNet integrated with residual blocks and attention modules between successive convolutional layers. Our attention module was implemented in the residual blocks to learn useful features and suppress the residual features. The proposed network was trained and validated by generating three different degradation datasets with different types of stripe artifacts in LSFM images. Our method can effectively remove different stripes in generated and actual LSFM images distorted by stripe artifacts. Besides, quantitative analysis and extensive comparison results demonstrated that our method performs the best compared with classical image-based processing algorithms and other powerful deep-learning-based destriping methods for all three generated datasets. Thus, our method has tremendous application prospects to LSFM, and its use can be easily extended to images reconstructed by other modalities affected by the presence of stripe artifacts.

Background Paratuberculosis, is a widespread chronic infection of Mycobacterium avium subsp. paratuberculosis (Map), causes significant economic losses to the sheep industry. The current study investigated this disease, which causes diarrhea in sheep, particularly, in Bayannaoer, Inner Mongolia. Diagnosis was based on clinical symptoms, pathological autopsy, histopathological inspection, and serological and molecular methods. Results Paratuberculosis was confirmed via a polymerase chain reaction using DNA extracted from tissue and fecal samples. Serum samples from 472 individual sheep were obtained to detect antibodies against MAP by ELISA test and MAP antibodies were separately detected in 17.86% (35/196) and 18.48% (51/276) of sheep herds at 6 months and 1 years of age respectively. The results of tissue lesion and pathological section were consistent with paratuberculosis infection. Conclusions This is the first report of Mycobacterium avium subspecies paratuberculosis seroprevalence in Bayannaoer sheep in Inner Mongolia. Our findings show that MAP was prevalent and potentially threaten in this region and more further investigations on long-term epidemiological

Background Reendothelialisation is the natural pathway that inhibits neointimal hyperplasia and in-stent restenosis. Circulating endothelial progenitor cells (EPCs) derived from bone marrow (BM) might contribute to endothelial repair. However, the temporal and spatial distributions of reendothelialisation and neointimal hyperplasia after EPC transplantation in injured arteries are currently unclear. Methods A carotid balloon injury (BI) model was established in Sprague-Dawley rats, and PKH26-labelled BM-derived EPCs were transplanted after BI. The carotid arteries were harvested on the first, fourth, seventh, and 14th day post-injury and analysed via light-sheet fluorescence microscopy and pathological staining (n = 3). EPC and human umbilical vein endothelial cell culture supernatants were collected, and blood samples were collected before and after transplantation. The paracrine effects of VEGF, IGF-1, and TGF-β1 in cell culture supernatants and serum were analysed by enzyme-linked immunosorbent assay (n = 4). Results Transplanted EPCs labelled with PKH26 were attached to the injured luminal surface the first day after BI. In the sham operation group, the transplanted EPCs did not adhere to the luminal surface. From the fourth day after BI, the mean fluorescence intensity of PKH26 decreased significantly. However, reendothelialisation and inhibition of neointimal hyperplasia were significantly promoted by transplanted EPCs. The degree of reendothelialisation of the EPC7d and EPC14d groups was higher than that of the BI7d and BI14d groups, and the difference in neointimal hyperplasia was observed between the EPC14d and BI14d groups. The number of endothelial cells on the luminal surface of the EPC14d group was higher than that of the BI14d group. The number of infiltrated macrophages in the injured artery decreased in the EPC transplanted groups. Conclusions Transplanted EPCs had chemotactic enrichment and attached to the injured arterial luminal surface. Although decreasing significantly after the fourth day at the site of injury after transplantation, transplanted EPCs could still promote reendothelialisation and inhibit neointimal hyperplasia. The underlying mechanism is through paracrine cytokines and not differentiation into mature endothelial cells.

A decentralized control strategy can effectively solve the control problem of the large-scale time delayed structures. In this paper, combining the overlapping decentralized control method, linear matrix inequality (LMI) method, and H∞ control algorithm, overlapping decentralized H∞ control approach of the time delayed structures has been established. The feedback gain matrixes of all subsystems are obtained by this method based on genetic algorithm optimization tools and the specific goal of optimization control. The whole vibration control system of the time delayed structures is divided into a series of overlapping subsystems by overlapping decentralized control strategy. The feedback gain matrixes of each subsystem can be obtained by using H∞ control algorithm to calculate each subsystem. The vibration control of a twenty layers’ antiseismic steel structure Benchmark model was analyzed with the numerical method. The results show that the proposed method can be applied to control system with time delay. The overlapping decentralized control strategies acquire the similar control effects with that of the centralized control strategy. Moreover, the flexibility of the controller design has been enhanced by using overlapping decentralized control strategies.

Static Var Generator (SVG) is an advanced equipment used to manage grid reactive power and low-order harmonics. Considering the influence of the DC side voltage on its performance and power consumption, the DC side voltage control problem of SVG is discussed, the voltage loop system model is given, and the DC side control method is discussed with the help of the dynamic matrix control (DMC) algorithm. The genetic algorithm of elite strategy puts forward the idea of optimization of time domain parameters of dynamic matrix control. The simulation results show that the time-domain parameter optimization method based on genetic algorithm is feasible. Compared with the traditional Proportional Integral (PI) control algorithm, the optimized dynamic matrix control algorithm has better control effect and can be used for DC side voltage control of SVG.

Background CBCSG006 trial reported the superior efficacy of cisplatin plus gemcitabine (GP) regimen than paclitaxel plus gemcitabine (GT) regimen as first-line treatment of metastatic triple-negative breast cancer (mTNBC). This study focused on the updated survival data and the explorations of potential biomarkers for efficacy. Patients and methods Germ-line mutations of homologous recombination (HR) panel, BRCA1/2 included, were evaluated in 55.9% (132/236) patients. PD-L1 expression was evaluated in 48.3% (114/236) patients. A nonparametric sliding-window subpopulation treatment effect pattern plot (STEPP) methodology was used to analyze the absolute survival benefits. All statistical tests were two-sided. Results Median progression-free survival (PFS) was 7.73 [95% confidence interval (CI) 6.46–9.00] months for GP arm and 6.07 (95% CI 5.32–6.83) months for GT arm (P = 0.005). No significant difference in overall survival (OS) was observed. There was significant interaction between HR status and treatment for PFS and status of HR deficient significantly correlated with higher objective response rate (ORR) and longer PFS in GP arm than in GT arm (71.9% versus 38.7%, P = 0.008; 10.37 versus 4.30 months, P = 0.011). There was no significant interaction between germ-line BRCA1/2 (gBRCA1/2) status and treatment for PFS. Patients with gBRCA1/2 mutation had numerically higher ORR and prolonged PFS in GP arm than in GT arm (83.3% versus 37.5%, P = 0.086; 8.90 versus 3.20 months, P = 0.459). There was no significant interaction between PD-L1 status and treatment for PFS, and no significant differences in ORR, PFS or OS between two arms regardless of PD-L1 status. In STEPP analysis, patients with lower composite risks had more absolute benefits in PFS than those with higher composite risks. Conclusions GP regimen has superior efficacy than GT regimen as first-line chemotherapy for mTNBC patients. Germ-line mutations of BRCA1/2 and HR panel are possible biomarkers for better performance of cisplatin-based regimens. A composite risk model was developed to guide patient selection for GP treatment in TNBC patients. Trial registration ClinicalTrials.gov, NCT01287624.

School of Physical Science and Technology, Lanzhou University, Lanzhou, Gansu, 730000, People’s Republic of China

Background: Triple-negative breast cancer (TNBC) is an aggressive disease with limited treatment options and poor prognosis. Gemcitabine plus carboplatin (GC) is one of the preferred chemotherapeutic regimens for patients with metastatic triple-negative breast cancer(mTNBC), with a median progression-free survival(PFS) of 4.6 months in the first-line patients (O'Shaughnessy J, et al. J Clin Oncol 2014). Gemcitabine plus cisplatin (GP) has also demonstrated promising efficacy and safety in the first-line phase III trial of mTNBC, with a median PFS of 7.7 months (Hu XC, Lancet Oncol 2015). A recent analysis, based on data derived from a cohort of 379 mTNBC patients, indicated that patients receiving cisplatin-based regimen as the first-line chemotherapy showed better PFS compared with other platinum agents (8.0 vs 4.3 months, P = 0.03) (Zhang J, et al. Oncotarget 2015). To further investigate the superiority between carboplatin and cisplatin when combined with gemcitabine, this phase II study was conducted to directly compare the efficacy and safety of GP with GC in the first-line treatment for patients with metastatic triple negative breast cancer. Trial Design: This prospective phase II, single center, open-label, randomized study has been designed to compare the efficacy and safety of GP with GC as the first-line treatment for mTNBC. Patients are randomized 1:1 to receive gemcitabine (1250 mg/m2, D1,8) plus cisplatin (75 mg/m2, D1) or gemcitabine (1000mg/m2, D1,8) plus carboplatin (area under the curve 2 mg × min/mL, D1,8) every 21 days until disease progression or intolerable toxicity. Eligibility Criteria: Patients with histologically confirmed triple negative metastatic breast cancer, with no prior chemotherapy in metastatic setting will be included in this trial. Eligible patients must be between 18 and 70 years of age with a performance status of 0–1, adequate organ function and at least one RECIST 1.1-measurable lesion. Specific Aims: The primary endpoint is PFS. Secondary endpoints include objective response rate, safety and overall survival. Statistical Methods: The sample size of the present study was determined based on the results of two phase III clinical trials: the median PFS for patients receiving GC and GP as the first-line treatment for mTNBC was 4.6 and 7.7 months, respectively. This design was hypothesized that GP would be superior to GC in terms of efficacy. Thus, in order to detect an improvement of median PFS from 4.6 months to 7.7 months, with 80% power and a 1-sided type I error of 0.05, 136 patients would be required. Considering a drop-out rate of 10%, a total of 150 patients planned to be enrolled. Present Accrual and Target Accrual: Target accrual: 150. Present accrual (2017/5/24): 83 Contact information: Contact: Xichun Hu, MD, PHD xchu2009@hotmail.com Biyun Wang, MD pro_wangbiyun@163.com ClinicalTrials.gov Identifier: NCT02341911. Citation Format: Gong C, Cao E, Wang Z, Zhang J, Wang L, Cao J, Zhang S, Tao Z, Li T, Zhao Y, Li Y, Wang B, Hu X. A phase II randomized trial of gemcitabine plus cisplatin(GP) vs. gemcitabine plus carboplatin (GC) as the first-line treatment for patients with metastatic triple negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-05-01.

Nitrogen doping is considered to be a promising way to improve the performance of graphene-based supercapacitors. It is crucial to discuss that the role of nitrogen doping in regulating the electronic properties. Herein, we chose urea, NH3·H2O and N2H4·H2O as the nitrogen sources to modify the graphene based cobalt oxide composites to compare which nitrogen source made a great improvement on the supercapacitive performance of the composites. When the urea is used as the nitrogen source, the electrochemical performance was the best among the nitrogen-doped (N-doped) graphene based cobalt oxide composites (334.8 F g−1 at a current density of 5 A g−1 in 2 M KOH aqueous solution). Nitrogen doping worked as a modification to control the structure of graphene sheet and effectively improved the electrochemical performances.

This study sought to assess whether the objective response (OR, including complete response and partial response) of first-line chemotherapy can predict overall survival (OS) for patients with metastatic triple-negative breast cancer (mTNBC) in both clinical trial and a real-world setting. The survival predictable parameters were assessed in two independent cohorts, the training cohort of 236 patients as part of a phase 3 trial (CBCSG006, Trial registration number NCT0128762) and the validation cohort of 360 patients from the real-world setting. Univariable and multivariable Cox proportional hazard models were applied to explore associations with progression-free survival and OS in the training cohort and then in the validation cohort. OR (OR vs non-OR, HR, 0.438, p

Flurochloridone (FLC) is a widely used herbicide in developing countries. Although the testes are a target organ for FLC in rats, the adverse effects of FLC on testes have not been fully elucidated. To clarify them, we performed RNA-seq analysis using the testes of FLC-treated rats from our previous subchronic toxicity tests. Unilateral testes of three male rats from solvent control groupand three FLC-treated groups (3 mg/kg, 31.25 mg/kg and 125 mg/kg) were used for RNA extraction. A poly A selection protocol coupled with an Illumina TruSeq RNA-Seq library protocol was used to construct RNA-Seq libraries. Principal component analysis (PCA), differentially expressed gene (DEG) analysis, and hierarchical clustering analysis (HCA) were conducted using R. Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to understand the biological characteristics of the DEGs using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The results indicated that many up-regulated DEGs were enriched in pathways associated with testicular injury, such as mitogen-activated protein kinase (MAPK) signaling, lysosome and focal adhesion. Many down-regulated DEGs were enriched in pathways associated with testicular reproduction function, such as sexual reproduction, spermatogenesis and germ cell development. Moreover, we confirmed the oral no-observed-adverse-effect level (NOAEL) of 3 mg/kg in subchronic toxicity test, because the overall testicular gene expression in 3 mg/kg FLC-treated group was similar to that of the solvent control group. In 31.25 mg/kg and 125 mg/kg groups, DEGs revealed that testicular injury was related to oxidative stress.

Efficient syntheses of two novel cryptands 2a and 2b based on bis(m-phenylene)-32-crown-10 are reported. Unimolecular macrocyclization of 9 through copper(II)-mediated Eglinton coupling generated the diacetylene-containing cryptand 2a in 93% yield. Pd/C-catalyzed hydrogenation of 2a yielded the cryptand 2b (74%). The complexation behavior of a series of cryptand hosts (1a–2b) with dicationic guests (3–6) has been comprehensively investigated by NMR spectroscopy, mass spectrometry and X-ray analysis. It is found that all four cryptands binding with guests form 1:1 complexes both in solution and in the solid state, except the case of cryptand 1a/1b with 5 forming 2:1 complex. Moreover, it is demonstrated that cryptand 2a/2b not only binds guests more strongly than the corresponding BMP32C10, but also has greater interacting affinities than the cryptand 1a/1b. Meanwhile, the association constants of the N-methyl-substituted guests 4 and 5 with cryptands are higher than non-methyl-substituted guest 3. The X-ray analysis of crystals of these complexes revealed that the complexation is stabilized by π–π stacking interactions and C H⋯O hydrogen bonds between the cryptands and the guests. Additionally, the paraquat derivative 3 penetrated symmetrically through the cavity of the two same 29-membered rings of cryptand 2 in the solid state, while the threading of paraquat unit into the cavity of cryptand 1 was unsymmetrical both in crystal structures of 1a 3 and 1b 3.

Fluorochloridone (FLC) is a herbicide used worldwide that is thought to be safe. However, due to its potential genotoxicity, cytotoxicity, and even systematic toxicity, there are increasing concerns about human exposure to this compound. Thus, the metabolism and bioactivation of FLC was investigated. After oral administration to mice, 27 metabolites were identified by ultrahigh performance liquid chromatography-electrospray ionization-quadrupole time-of-flight-mass spectrometry and with further structural identification by nuclear magnetic resonance spectroscopy. Hydroxylation and oxidative dechlorination were the major phase I pathways, while glutathione (GSH) and N-acetylcysteine conjugations were two major phase II pathways, indicating the formation of a reactive intermediate. In vitro microsomal and cytosolic studies revealed that a GSH conjugate (M13) was the predominant metabolite of FLC formed through a nucleophilic SN2 substitution of 3-Cl by GSH; this pathway is NADPH independent and accelerated by glutathione S-transferase (GST). Further, a kinetic study showed that M13 formation in both human liver microsomes and cytosols obeyed typical Michaelis-Menten kinetics. The maximum clearance (Vmax/Km) of GSH conjugation in human liver microsomes was approximately 5.5-fold higher than human liver cytosol, thus implying that microsomal GST was mainly responsible for M13 formation. These findings are important for understanding the potential hazard of human exposure to FLC.

It is of great interest to develop strategic methods to enable chemicals' metabolites to be accurately and rapidly screened and identified. To screen and identify a category of metabolites with distinct isotopic distribution, this study proposed a generic strategy using in silico metabolite prediction plus accurate-mass-based isotopic pattern recognition (AMBIPR) and library identification on the data acquired via the data dependent MS/MS scan of LC-Q Exactive Orbitrap mass spectrometry. The proposed method was evaluated by the analysis of flurochloridone (FLC) metabolites in rat urine sample collected from toxicity tests. Different from the traditional isotopic pattern recognition (IPR) approach, AMBIPR here was performed based on the potential metabolites predicted via in silico metabolite prediction tools. Thus, the AMBIPR treated FLC data was only associated with FLC metabolites, consequently not only avoiding great efforts made to remove FLC-unrelated information and reveal FLC metabolites, but also increasing the percent of positive hits. Among the FLC metabolite peaks screened using AMBIPR, 87% of them (corresponding 97 metabolites and 49 biotransformation) were successfully identified via multiple MS identification techniques packaged in an established FLC's metabolites library based on Mass Frontier. Noteworthy, 34 metabolites (89%) were identified without distinct naturally isotopic distribution. The universal strategic approach based on background subtraction (BS) and mass defect filtering (MDF) was used to evaluate the AMBIPR and no more false positive and negative metabolites were detected. Furthermore, our results revealed that AMBIPR is very effective, inherently sensitive and accurate, and is easily automated for the rapidly screening and profiling chemicals related metabolites.

The differences of thermodynamics energies from the pure phase to a solution were used to predict the solubility properties of acidic phosphorus-containing rare-earth extractants. Four solvents, namely, tributylphosphate, n-dodecane, toluene, and n-octanol were used. The thermodynamic cycle of the implicit solvation model and the structure model with short carbon chains were used. The relationship obtained by simulation of the solubility properties and extractant structures agreed qualitatively with reported experimental results. These results provide guidance for the design of new efficient extractants.

The elastic properties of the interface structure of nanodiamond composite films are investigated using first-principles calculations. The nanodiamond grains in the films are surrounded by a monolayer heterogeneous interface. The interface phase comprises B, Si, P, and Ge. The elastic constants, bulk, shear and Young's modulus of the interface structures are all obtained with first principle calculations. Calculated elastic constants of the diamond (0 0 1) interface are larger than those of the (1 1 1) interface. For the B, Si, P, and Ge interface structures, as the average atomic distance increases, the average Young's modulus decrease, which follows the sequence E ¯ B > E ¯ Si > E ¯ P > E ¯ Ge , with corresponding values of 927.05, 843.841, 840.152, and 819.805 GPa. The ductility and plasticity, as well as the anisotropy values (A and AU) of the interface structures were discussed based on the obtained mechanical parameters. The results show that P interface structures demonstrate ductile property when stressed longitudinally, whereas the other interface structures are all brittle. Then the visualization of the directional dependence of the Young's modulus are also presented. These reflected an interesting results. For the B, Si, and Ge interface structures, whether they show isotropy or anisotropy depends on the crystal structure, while it depends on the direction of the applied strain for the P interface structures.

A precise, high-throughput and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed for the determination of fluorochloridone (FLC) in rat plasma. The extraction of analytes from plasma samples was carried out by protein precipitation procedure using acetonitrile prior to UPLC-MS/MS analysis. Verapamil was proved as a proper internal standard (IS) among many candidates. The chromatographic separation based on UPLC was well optimized. Multiple reaction monitoring in positive electrospray ionization was used with the optimized MS transitions at: m/z 312.0 → 292.0 for FLC and m/z 456.4 → 165.2 for IS. This method was well validated with good linear response (r(2) > 0.998) observed over the investigated range of 3-3000 ng/mL and with satisfactory stability. This method was also characterized with adequate intra- and inter-day precision and accuracy (within 12%) in the quality control samples, and with high selectivity and less matrix effect observed. Total running time was only 1.5 min. This method has been successfully applied to a pilot FLC pharmacokinetic study after oral administration. Copyright © 2016 John Wiley & Sons, Ltd.

In this work, the effect of the substituent at the α or β position in dialkylphosphinic acids on the extraction of trivalent lanthanide ions was investigated using experimental and theoretical methods. Five dialkylphosphinic acids were synthesized. Their extractions of seven trivalent lanthanide ions, La/Pr, Nd/Dy, and Ho/Yb/Lu, which represent light, middle, and heavy rare-earth metals, were explored. A simplified coordination model was built to explore the bonding between the extractants and lanthanide ions. The results obtained using this model generally explained the experimental results. The model could therefore be used to study the effects of the α and β substituents of extractants on their extraction properties. The theoretical and experimental results indicate that the significance of a β substituent in the dialkylphosphinic acid on extraction was greater than that of an α substituent.

Dialkylphosphinic acids were synthesised by a microwave-assisted method with high yields and wide substrate applicability. A structure–reactivity study indicates that an increase in steric hindrance in the β position led to a decrease of extraction ratio and heavy rare earth element separation activity. A computational study was also conducted to understand the steric effect.

Background The nuclear factor erythroid 2-related factor 2 (Nrf2) is a potential molecular target for cancer chemoprevention. Si–Wu–Tang (SWT), a popular traditional Chinese medicine for women's health, was reported with a novel activity of cancer prevention. Purpose The present study was aimed to identify the bioactive constituents in SWT responsible for the Nrf2 activating and cancer preventive activity and explore the pharmacological mechanisms. Methods Nine compounds detectable from various batches of SWT were ranked using in silico molecular docking based on their ability to interfere the forming of Nrf2-Keap1 complex. The predicted Nrf2 activating effect was validated using the antioxidant response element (ARE) luciferase reporter assay and quantitative RT-PCR analysis for select Nrf2 regulated genes Hmox1, Nqo1 and Slc7a11. The antimutagenic activity of the compounds were determined by the Ames test. The chemopreventive activity of these compounds were assessed on EGF-induced neoplastic transformation of JB6 P+ cells, an established non-cancerous murine epidermal model for studying tumor promotion and identifying cancer preventive agents. These compounds were further characterized using luciferase reporter assay on EGF-induced activation of AP-1, a known transcription factor mediating carcinogenesis. Results Three of the nine compounds predicted as Nrf2 activators by molecular docking, gallic acid (GA), Z-liguistilide (LIG), and senkyunolide A (SA), were confirmed with highest potency of increasing the Nrf2/ARE promoter activity and upregulating the expression of Hmox1, Nqo1 and Slc7a11. In addition, GA, LIG and SA exhibited an antimutagenic activity against the direct mutagen 2-nitrofluorene while no mutagenic effects were observed at the same time in Ames test. At nontoxic concentrations, GA, LIG, and SA inhibited EGF-induced neoplastic transformation of JB6 P+ cells. Combined treatment of GA, LIG and SA, in the same ratio as detected in SWT, showed enhanced effect against JB6 transformation compared with that of the single compound alone. GA, LIG and SA, alone or in combination, suppressed EGF-induced activation of AP-1. Conclusion We identified three bioactive constituents in SWT responsible for the Nrf2 activating and cancer preventive activity. This study provides evidence supporting novel molecular basis of SWT in cancer prevention.

This study presents novel nanodiamond composite films, in which nanodiamond grains are surrounded by a monolayer heterogeneous interface. Calculations of diamond (0 0 1) and (1 1 1) with and without the interface were conducted using the first-principles method. Results showed that silicon particles cannot become a solid solution in diamond crystallites. Thus, the silicon interface can exist among diamond grains. The interface in diamond (0 0 1) is more stable than that in diamond (1 1 1).