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Graphical abstract, MicroRNA (miRNA) deregulation plays a critical role in the heterogeneous development of prostate cancer (PCa) by tuning mRNA levels. Herein, we aimed to characterize the molecular features of PCa by clustering the miRNA-regulated transcriptome with non-negative matrix factorization. Using 478 PCa samples from The Cancer Genome Atlas, four molecular subtypes (S-I, S-II, S-III, and S-IV) were identified and validated in two merged microarray and RNAseq datasets with 656 and 252 samples, respectively. Interestingly, the four subtypes showed distinct clinical and biological features after comprehensive analyses of clinical features, multiomic profiles, immune infiltration, and drug sensitivity. S-I is basal/stem/mesenchymal-like and immune-excluded with marked transforming growth factor β, epithelial-mesenchymal transition and hypoxia signals, increased sensitivity to olaparib, and intermediate prognosis. S-II is luminal/metabolism-active and responsive to androgen deprivation therapy with frequent TMPRSS2-ERG fusion and a good prognosis. S-III is characterized by moderate proliferative and metabolic activity, sensitivity to taxane-based chemotherapy, and intermediate prognosis. S-IV is highly proliferative with moderate EMT and stemness, frequent deletions of TP53, PTEN and RB, and the poorest prognosis; it is also immune-inflamed and sensitive to anti-PD-L1 therapy. Overall, based on miRNA-regulated gene profiles, this study identified four distinct PCa subtypes that could improve risk stratification at diagnosis and provide therapeutic guidance.

Molecular mechanisms underlying intratumoral androgenesis and aberrant androgen receptor (AR) activation in prostate cancer remain poorly understood. Here we demonstrate that ectopic expression of the E3 ubiquitin ligase adaptor speckle-type poxvirus and zinc finger domain protein (SPOP) stabilizes 17βHSD4. SPOP bound a functional substrate-binding consensus (SBC) motif 315RATST319 in 17βHSD4 and promoted nondegradable K27- and K29-linked polyubiquitination of 17βHSD4. The effect of SPOP was antagonized by serum- and glucocorticoid kinase-3 (SGK3)-mediated phosphorylation of serine 318 (S318) in the SBC and S318 phosphorylation-dependent binding of SKP2 E3 ligase and subsequent K48-linked polyubiquitination and proteasomal degradation of 17βHSD4. Prostate cancer–associated SPOP mutations impaired the SPOP-17βHSD4 interaction, caused 17βHSD4 protein destruction in prostate cancer cells in culture and patient specimens, and increased testosterone production and prostate cancer cell growth in vitro and in mouse models. Thus, we have identified SPOP and SKP2 as two essential E3 ubiquitin ligases that exert opposite effects on 17βHSD4 protein degradation and intratumoral androgenesis in prostate cancer cells. We further demonstrate that SPOP mutations or SKP2 overexpression contribute to prostate cancer progression by decreasing 17βHSD4 expression and increasing intratumoral androgen synthesis. Significance: This study reveals a novel mechanism of aberrant AR activation in SPOP-mutated prostate cancer and uncovers putative biomarkers for effective treatment by AR-targeted therapies.

Ultrasonography (US) contrast imaging using US contrast agents has been widely applied for the diagnosis and differential diagnosis of tumors. Commercial US contrast agents have limited applications because of their large size and shorter imaging time. At the same time, the desired therapeutic purpose cannot be achieved by applying only conventional US contrast agents. The development of nanoscale US agents with US imaging and therapeutic functions has attracted increasing attention. In this study, we successfully developed DOX-loaded poly-1,6-hexanedithiol-sodium bicarbonate nanoparticles (DOX@HADT-SS-NaHCO3 NPs) with pH-responsive NaHCO3 and GSH-responsive disulfide linkages. DOX@HADT-SS-NaHCO3 NPs underwent acid-triggered decomposition of NaHCO3 to generate CO2 bubbles and a reduction of disulfide linkages to further promote the release of CO2 and DOX. The potential of DOX@HADT-SS-NaHCO3 NPs for contrast-enhanced US imaging and therapy of prostate cancer was thoroughly evaluated using in vitro agarose gel phantoms and a C4-2 tumor-bearing nude mice model. These polymeric NPs displayed significantly enhanced US contrast at acidic pH and antitumor efficacy. Therefore, the NaHCO3 and DOX-encapsulated polymeric NPs hold tremendous potential for effective US imaging and therapy of prostate cancer.

The synergistic effect between MoOx and Fe markedly promoted the activity on deoxygenation of lactic acid to bio-propionic acid.

The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR), as markers of systematic inflammation response, have been reported to be indicators in metastatic castration-resistant prostate cancer (mCRPC), whereas their prognostic values remain conflict. This study was to assess the prognostic value of NLR and PLR in mCRPC patients and to assess the response of abiraterone or enzalutamide through using NLR and PLR. Databases searching was conducted in the PubMed, EMBASE, Google Scholar, and the Cochrane Library for relevant published literature up to October 2019. Data extraction and quality evaluation were performed on the eligible studies. STATA 14.0 software was used to pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS). A total of 3144 mCRPC patients were enrolled from 15 cohort studies in this meta-analysis. The pooled results demonstrated that elevated NLR had a significant association with inferior OS in mCRPC patients treated with abiraterone (HR = 1.63, 95% CI: 1.43–1.85, P

As most of intracellular reactive oxygen species (ROS) is produced in the mitochondria, mitochondrial modulation of cancer cell is a promising strategy for maximizing the in situ-activable combination therapy of oxidative catastrophe and cascaded chemotherapy. Herein, a serum-stable polymer‑calcium phosphate (CaP) hybrid nanocapsule carrying siRNA against ADP-ribosylation factor 6 (Arf6) overexpressed in cancer cells and parent drug camptothecin (CPT), designated as PTkCPT/siRNA, was developed for the RNAi-induced oxidative catastrophe and cascaded chemotherapy. A copolymer of mPEG-P(Asp-co-TkCPT), covalently tethered with chemotherapeutic CPT via a ROS-labile dithioketal (Tk) linker, was synthesized and self-assembled into a PTkCPT micelle as a nanotemplate for the CaP mineralization. The as-prepared PTkCPT/siRNA nanoparticle showed a core-shell-distinct nanocapsule which was consisted of a spherical polymeric core enclosed within a CaP shell capable of releasing siRNA in response to lysosomal acidity. Blocking Arf6 signal pathway of cancer cells led to their mitochondrial aggregation and subsequently induced a burst of ROS for oxidative catastrophe, which further triggered the cascaded CPT chemotherapy via the breakage of ROS-labile dithioketal linker. This strategy of RNAi-induced oxidative catastrophe and cascaded chemotherapy resulted in a significant combination effect on cancer cell killing and tumor growth inhibition in mice with low side effects, and provided a promising paradigm for precise cancer therapy.

Background Recently, sclerostin, a bone-derived protein, has been shown to play a key role in atherosclerosis progression. However, few studies have investigated the influence of sclerostin on cardiovascular disease prognosis. We investigated the relationship between serum sclerostin levels and adverse outcomes in elderly patients with stable coronary artery disease (SCAD) who were undergoing percutaneous coronary intervention (PCI). Methods We enrolled 310 elderly SCAD patients who underwent PCI in this study and followed them 3 years. According to the median serum sclerostin levels, subjects were stratified into a low sclerostin (low scl) group (n = 144) and a high sclerostin (high scl) group (n = 166). Time-to-event analyses were performed with the Kaplan–Meier method. Associations between sclerostin levels and main adverse cardiovascular and cerebrovascular events (MACCEs) and mortality were evaluated by Cox multivariate regression analysis. The prognostic power of predictive models was verified by the concordance index and receiver operating characteristic curve analysis. Results The high scl group had a significantly higher MACCE-free rate and better survival than the low scl group. Serum sclerostin was an independent predictor and could improve the prognostic power for adverse outcomes. In addition, serum sclerostin levels were significantly associated with bone turnover markers, a lower presence of multivessel disease and a lower CCS angina class. Conclusions Serum sclerostin is a prognostic parameter for predicting and intervening in the adverse outcomes of elderly SCAD patients undergoing PCI, which may be explained by its potential role in the bone–vascular axis.

For the treatment of malignant tumors, drug nanocarriers with long blood circulation time and ability to target the tumor microenvironment are promising therapeutic abilities. In this work, to systematically investigate the roles and functions of polysaccharides as drug nanocarriers targeting the tumor microenvironment, different types of polysaccharides (alginic acid (Alg), hyaluronic acid (HA), and dextran (Dex)) were covalently bonded with doxorubicin (DOX) through a Schiff base reaction to form a pH-sensitive polysaccharide-DOX prodrug having an acid-sensitive imine bond. After screening, Dex-DOX exhibited high drug loading content and good stability, while Alg-DOX and HA-DOX may have disadvantages such as low degree of oxidation, limited drug loading capacity, or instability in physiological conditions. Dex-DOX prodrugs were able to self-assemble into stable nanoparticles in phosphate buffered saline (PBS). Then, Dex6k-DOX and Dex150k-DOX were selected for further comparisons since they had similar drug-binding rates and long circulation time. When compared with Dex6k-DOX, the longer main-chain Dex150k-DOX showed a higher drug release rate under simulated acidic conditions in vitro, which significantly inhibited cell proliferation. Further in vivo experiments showed that Dex150k-DOX could more effectively improve the antitumor efficiency and survival rate while reducing side-effects. Overall, the screening and comparisons provided detailed and systematical information about the polysaccharide-DOX prodrug platform as potential antitumor drugs.

Sustainable production of 2,3-pentanedione from bio-lactic acid via a vapor condensation reaction over KLA/TiPO (KLA: potassium lactate) was investigated in this work. A KNO3 precursor supported on the surface of TiPO was in situ converted to basic sites in a KLA/TiPO catalyst. KLA together with Ti4+(Lewis acidic site) make up the acid–base pairs in the KLA/TiPO catalyst, resulting in excellent activity for the condensation of lactic acid to 2,3-pentanedione. The loading amount of KNO3 was shown to have an important influence on the catalytic performance, since the acid–base properties of the catalysts were found to vary with the addition of KNO3. Reaction conditions such as lactic acid feed flow rate and lactic acid concentration were also discussed. Both lactic acid conversion and 2,3-pentanedione selectivity increased with elevated lactic acid feed flow rates, indicating the existence of an external diffusion resistance of the lactic acid reactant during the catalytic reactions. However, the lactic acid feed flow rate increased to 1.0 mL h−1 (corresponding to LA liquid hourly space velocity (LHSV) = 2.6 H−1), and the external diffusion resistance was efficiently eliminated. Enhancing the LA concentration improved the selectivity of 2,3-pentanedione, suggesting that the reaction order of the lactic acid molecule for lactic acid conversion to 2,3-pentanedione is higher than the other side reactions. Encouragingly, in retaining 30–45% of the lactic acid conversion, the condensation reaction with a 2,3-pentanedione selectivity of around 73% proceeded efficiently for at least 116 h on stream. The long-term stability of the present catalyst was found to be related to its hierarchical pores, which ameliorated the mass transfer effect of the reactant and product, except for the appropriate acid–base properties for lactic acid condensation to 2,3-pentanedione.

Echium plantagineum L. (Boraginaceae) is an invasive species in Australia and contains medicinal shikonins in its roots. In this study, the hairy root lines of E. plantagineum were established using Agrobacterium rhizogenes strain ATCC15834 and confirmed by the amplification of the rolB gene. Results showed significant difference in shikonin production between the hairy root lines in the 1/2B5 and M9 media. The biomass of the lines in the 1/2B5 medium was fivefold of that in the M9 medium. However, the components of detected shikonins were similar in these two liquid media. By contrast, different accumulation profiles appeared in the hairy root lines. HPLC analysis revealed the presence of nine possible related compounds, including shikonins, and acetylshikonin was the most abundant shikonin derivative. The content of acetylshikonin in the 1/2B5 medium (36.25 mg/L on average) was twofold of that in the M9 medium. Our results showed that the hairy root cultures of E. plantagineum can be used in enhancing the production of potential pharmaceutical compounds, such as acetylshikonin.

Multifactor and multistep processes were elucidated to participate in the progression of non-small-cell lung cancer (NSCLC). Circular RNA 0031250 (circ-PRMT5) was a vital factor in NSCLC. However, the role of circ-PRMT5 in cisplatin (DDP)-resistance needed to be further highlighted. Expression profiles of circ-PRMT5, microRNA (miR)-4458, and EV3-like DNA-directed polymerase ζ catalytic subunit (REV3L) were detected using quantitative real-time polymerase chain reaction. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and transwell assays were performed to determine the half-maximal inhibitory concentration of DDP, cell viability, apoptosis, and invasion in vitro. Besides, the protein levels of REV3L and indicated proteins were examined by adopting western blot. Dual-luciferase reporter assay was performed to analyze the interaction between miR-4458 and circ-PRMT5 or REV3L. The functional role of circ-PRMT5 was explored using a xenograft tumor model. Levels of circ-PRMT5 and REV3L were markedly increased, while miR-4458 was downregulated in resistant tissues and cells. Knockdown of circ-PRMT5 enhanced cell apoptosis, DDP-sensitivity, and declined metastasis in NSCLC with DDP resistance. Besides, miR-4458 inhibition or REV3L upregulation could revert circ-PRMT5 absence-mediated effect on DDP-sensitivity in vitro. Mechanically, circ-PRMT5 was a sponge of miR-4458 to regulate REV3L. Importantly, circ-PRMT5 silencing could interact with DDP treatment expedite the decrease of tumor growth in vivo. Circ-PRMT5 promoted DDP resistance via REV3L by sponging miR-4458 in NSCLC, thus providing a novel therapeutic strategy for patients with NSCLC.

Propionic acid obtained from fermentation-derived lactic acid has been appreciated since propionic acid is mainly used as a food preservative, satisfying a natural food idea. Vapor-phase deoxygenation of lactic acid to biopropionic acid over dispersant-dispersed molybdenum oxides was investigated in this work. It was found that different dispersants displayed different performances, and the N element in dispersants had a positive effect. MoO3 was soon reduced to MoO2 under the in situ hydrogen atmosphere, and the latter played an important role in catalytic conversion of lactic acid to propionic acid. The discriminating experiments revealed that propionic acid was formed mainly through direct deoxygenation of lactic acid (main path) and not hydrogenation of acrylic acid as an intermediate (minor path). Furthermore, only in situ hydrogen was efficient, and external hydrogen was hardly efficient during catalytic reaction. Under the base-free conditions, catalyst offered excellent activity and durability and...

A real-time, portable, ultrahigh sensitive and selective biosensing chip is desired to satisfy the urgent requirement of the practical application. In this study, a novel three-dimensional (3D) silver nanocubes@Prussian blue (AgNCs@PB) core-shell material has been designed to develop an ultrasensitive biosensing chip by a seed-mediated interfacial assembly approach. A Prussian blue (PB) shell with the 30.12 nm thickness was precisely controlled to in-situ grow on the whole surface of AgNCs through the electrostatic interaction. A flexible and portable biosensing chip was printed and functionalized by using this 3D AgNCs@PB biosensing material to integrate the superior conductivity from AgNCs and electrocatalytic activity from PB for the remarkable performance enhancement. This chip can realize about four times increase of the sensitivity compared with the other PB based screen-printing electrode (SPE), as well as a very wide linear response from 0.01 mM to 1.3 mM and an ultralow limit of detection (LOD) of 0.005 mM for the glucose detection with an excellent anti-interference ability. Especially, it also presented an ultra-accurate detection of the blood sugar in a real serum with a low deviation (3.37%).

BACKGROUND Metastasis is the major cause of cancer-specific death in patients with prostate cancer (PCa). We previously reported that collapsing response mediator protein-4 (CRMP4) is a PCa metastasis-suppressor gene and the hypermethylation in CRMP4 promoter is responsible for the transcription repression in metastatic PCa. However, the underlying mechanisms remain unknown. In this study, we aimed to investigate the role of calpain-2 in CRMP4 promoter hypermethylation and its functional modulation in PCa metastasis. METHODS Calpain-2 expression in PCa tissues (n = 87) and its specific mechanisms of functional modulation in CRMP4 expression via limited enzymatic cleavage was investigated. We then focused on the cooperative crosstalk of calpain-2 and NF-κB RelA/p65 in CRMP4 promoter methylation for the initiation of PCa metastasis. Statistical differences between groups were determined using a two-tailed Student's t-test. P

Glyphosate is a non-selective organophosphate herbicide that is widely used in agriculture, but its effects on soil microbial communities are highly variable and often contradictory, especially for high dose applications. We applied glyphosate at two rates: the recommended rate of 50 mg active ingredient kg−1 soil and 10-fold this rate to simulate multiple glyphosate applications during a growing season. After 6 months, we investigated the effects on the composition of soil microbial community, the catabolic activity and the genetic diversity of the bacterial community using phospholipid fatty acids (PLFAs), community level catabolic profiles (CLCPs), and 16S rRNA denaturing gradient gel electrophoresis (DGGE). Microbial biomass carbon (Cmic) was reduced by 45%, and the numbers of the cultivable bacteria and fungi were decreased by 84 and 63%, respectively, under the higher glyphosate application rate. According to the PLFA analysis, the fungal biomass was reduced by 29% under both application rates. However, the CLCPs showed that the catabolic activity of the gram-negative (G−) bacterial community was significantly increased under the high glyphosate application rate. Furthermore, the DGGE analysis indicated that the bacterial community in the soil that had received the high glyphosate application rate was dominated by G− bacteria. Real-time PCR results suggested that copies of the glyphosate tolerance gene (EPSPS) increased significantly in the treatment with the high glyphosate application rate. Our results indicated that fungi were impaired through glyphosate while G− bacteria played an important role in the tolerance of microbiota to glyphosate applications.

Background Primary malignant lymphoma of the prostate (PMLP) is prone to occur in the elderly, and it has no significant correlation with lactate dehydrogenase (LDH) and prostate specific antigen (PSA). Clinical symptoms and imaging data of PMLP remain unspecific, and its prognosis is poor. A previous result showed that collapsin response mediator protein 4 (CRMP4) promotor methylation can be used as a predictor for lymph node metastases in prostate biopsies. However, the relationship between CRMP4 promotor methylation and PMLP has not been studied. Methods We investigated the clinicopathological features of PMLP and the significance of CRMP4 methylation in PMLP. The clinical data and diagnosis information of 10 patients with PMLP were retrospectively analyzed. The CRMP4 promotor methylation level in paraffin-embedded tissues of the 10 patients with PMLP were determined and then compared to limited prostate cancer (LPCa) and its negative lymph node tissue [LPCa-LN (−) (10 cases)] and also to metastatic prostate adenocarcinoma (mPCa) and its positive lymph node tissue [mPCa-LN (+) (10 cases)]. Methylation of the CRMP4 promotor in each group was analyzed statistically. A receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of CRMP4 methylation in PMLP. Results The average methylation value of CRMP4 in 10 PMLP patients, 20 cases of prostate adenocarcinoma tissue, 10 cases LPCa-LN (−) and 10 cases mPCa-LN (+) were 42.3, 30.6, 6.7 and 20.3%, respectively. A Kruskal–Wallis test showed that the difference of CRMP4 methylation was significant (X2 = 38.0, P 40.9% could diagnose PMLP. This method had 90% sensitivity and 95% specificity under conditions of CRMP4 methylation > 40.9%. The area under the curve (AUC) was 0.957. Conclusions Methylation of the CRMP4 gene was significantly increased in PMLP, and it is expected to become a new predictor for PMLP.

A series of hetero-binuclear superatom motifs, namely MM′(BO2)n− (M = Na, Mg; M′ = Mg, Al; n = 4 - 6) have been characterized by using density functional theory calculations. It is found that the preferential coordination number is four for central Mg and Al atoms. The dissociation energies of all the low-lying MM′(BO2)n− isomers are positive, showing their thermodynamic stability against fragmentation. The hyperhalogen identity of the MM′(BO2)n− anions can be verified by their vertical electron detachment energies (6.629 – 9.267 eV), which are much larger than that of their superhalogen ligand BO2−. Besides, these anions are superior to their mononuclear counterparts in terms of vertical electron detachment energies (VDE). Hence, the transition from mononuclear to binuclear hyperhalogen is a promising way to develop stronger oxidizing agents.

Heavy metal pollution in mine wastelands is quite severe. Iris sibirica L., an emergent wetland plant, is characterized by an ability to survive under high stress of heavy metals. This study aimed to explore the phytoremediation ability of nickel (Ni), cobalt (Co), and lead (Pb) by Iris sibirica L. under hydroponic conditions. A series of tests were conducted at different metal stress conditions to evaluate the phytoextraction and tolerance of Iris sibirica L. The concentrations of Ni, Co, and Pb in plant shoots reached their highest values in 500 mg L−1 treatments, where they were 6.55%, 23.64%, and 79.24% higher than those in 300 mg L−1, respectively. The same concentrations in roots also reached their peak in 500 mg L−1 treatments, where they were 5.52%, 33.02%, and 70.15% higher than those in 300 mg L−1, respectively. Bioconcentration factors (BCF) for Ni, Co, and Pb revealed the phytoextraction ability of Iris sibirica L., and the translocation factors (TCF) showed that Ni may be most easily translocated in the plant, followed by Co and Pb. This study indicates that, compared with Ni and Co, Iris sibirica L. is more suitable for the phytoremediation of Pb-contaminated metal mine wastelands.

A series of podophyllotoxin derivatives (M1–M16) that were selectively acylated by various phenoxy acids at the C-4 position of podophyllotoxin were synthesized, and their biological activities were also evaluated. Among them, compound M4 showed the most potent anti-cancer activity against HeLa cells with an IC50 value of 1.64 ± 0.41 μM. Additionally, flow cytometry analysis results indicated that it could cause a remarkable cell cycle arrest at G2/M phase, but the effect on apoptosis inducing was not significant. Moreover, the expression of cell cycle relative protein CDK1 was up regulated while cyclin B1 and Cdc25C, two proteins required for mitotic initiation were down regulated. Furthermore, the confocal assay and extracellular polymerized tubulin expression analysis also demonstrated that M4 was a potent tubulin polymerization inhibitor and the effect was comparable to that of colchicine. Finally, docking simulation results showed that M4 could nicely bind to the colchicine binding site of tubulin which further comfirmed the tubulin inhibiton activity of M4.

We optimized the geometry structures of Li1± y (Mg1− x Mn x )P for ( x =0.125; y =0, 0.125) by adopting the first-principles calculation of plane wave ultra-soft pseudo-potential technology based upon the density function theory (DFT). Then we calculated the electronic structures, formation energies, electric density difference and optical properties. The results reveal that spin polarization impurity bands were produced in Mn doped system. The properties of system and the orbits of participate in hybridization could be changed by dominating the amount of Li. The Mn doped system still revealed semiconductor properties, and the width of impurity band is 0.461 eV, and the magnetic moment is 4.98 μ в. The Li overdose system revealed metallicity, and the width of impurity bands increased to 0.890 eV, and the magnetic moment decreased to 4.10 μ в. Meanwhile the total energies and the formation energies reduced, the conductive capability increased. The Li deficient system revealed half metallicity, and the half-metallic band gap is 0.478 eV, and the magnetic moment is 4.02 μ в. Most of the charge overlap populations of LiMgP system are positive. It means all the chemical bonds of LiMgP are covalent bonds. Magnetism element Mn doped into the system creates Mn-P covalent bonds that are stronger than Mg-P bonds. In the Mn doped system, the quantity of share electron increased and the deviation of share electron decreased. The charge overlap population of Li-P bond is −0.02 which reveals ionic bonds. In the Li overdose system, the charge overlap population of Mn-P bonds reach the minimum value of 0.52. The density of states of Mn3 d and P3 p at the Fermi level is larger than that of single doped Mn, but at the same time, the interaction of the Mn-P bonds is weakened due to the participation of Li2 s in orbital hybridization. Formation energy and total energy become lower. And in the Li deficient system, the charge overlap population of Mn-P bonds reached the maximum value of 0.69, and the bonds lengths reached the minimum value. The electron cloud of Mn atoms and P atoms is the densest, and the deviation of the share electron is the weakest. The results reveal that p-d hybridization happened in Mn3 d and P3 p , and the hybridization was the strongest. The deficiency of the electron cloud of P atoms of charge density difference was caused by the deficiency of Li atoms. Analyzing images of optical properties can find that the imaginary part of dielectric function and the optical spectroscopy appeared a new peak at low energy region in Mn doped system. And the complex refractive index functions have a significant change at the same time. It means the system has an augment optical absorption range, and energy loss get lower.

In a wide strain rate range from 10−5 to 103 s−1, the deformation behavior of an Al-based nanocrystalline alloy was investigated. After fracture, the debris collected was used for statistical analysis, which is expected to reflect the profile of the fracture behavior of the alloy. The energy absorption of alloy at different strain rates was elucidated on account of mass distribution of debris. Based on the parameters obtained by the compression experiment at different strain rates, the numerical simulation experiment was carried out to evaluate the performance of Al-based nanocrystalline alloy as spacecraft shielding. The results suggest that Al-based nanocrystalline alloys have better shield performance than aluminum alloy under the identical areal density at velocity of 1–7 km/s. The better shield performance is attributed to high fracture strength, high hardness and low toughness of Al-based nanocrystalline alloy as compared with those of aluminum alloy.

Shikonin and its derivatives extracted from Lithospermeae plants’ red roots have current applications in food and pharmaceutical industries. Previous studies have cloned some genes related to shikonin biosynthesis. However, most genes related to shikonin biosynthesis remain unclear, because the lack of the genome/transcriptome of the Lithospermeae plants. Therefore, in order to provide a new understanding of shikonin biosynthesis, we obtained transcriptome data and unigenes expression profiles in three shikonin-producing Lithospermeae plants, i.e., Lithospermum erythrorhizon, Arnebia euchroma and Echium plantagineum. As a result, two unigenes (i.e., G10H and 12OPR) that are involved in “shikonin downstream biosynthesis” and “methyl jasmonate biosynthesis” were deemed to relate to shikonin biosynthesis in this study. Furthermore, we conducted a Lamiids phylogenetic model and identified orthologous unigenes under positive selection in above three Lithospermeae plants. The results indicated Boraginales was more relative to Solanales/Gentianales than to Lamiales.

The advancement of cancer-fighting drugs has never been a simple linear process. Those drug design professionals begin to find inspiration from the nature after failing to find the ideal products by creative drug design and high-throughput screening. To obtain new molecules for inhibiting tubulin, podophyllotoxin was adopted as the leading compound and 1,3,4-oxadiazole was brought in to the C-4 site of podophyllotoxin in this research. A series of seventeen podophyllotoxin-derived esters have been achieved and then evaluated their antitumor activities against four different cancer cell lines: A549, MCF-7, HepG2, and HeLa. Among all the compounds, compound 7c showed the best antiproliferating properties with IC50 = 2.54 ± 0.82 μm against MCF-7 cancer cell line. It was obvious that the content of ROS grew significantly in MCF-7 in a way depending on the dosage. The time- and dose-dependent cell cycle assays revealed that compound 7c could apparently block cell cycle in the phase of G2/M along with the upregulation of cyclin A2 and CDK2 protein. According to further studies, confocal microscopy experiment has certified that compound 7c could restrain cancer from growing by blocking the polymerization of microtubule. Meanwhile, compound 7c could be ideally integrated with the colchicine site of tubulin. In future, it would be feasible to selectively design tubulin inhibitors with the help of 3D-QSAR. This means that it is hopeful to develop compound 7c as a potential agent against cancer due to its biological characteristics.

The biological importance of microtubules in mitosis makes them an interesting target for the development of anticancer agents. In this study, a series of novel chalcone-containing shikonin derivatives was designed, synthesized, and evaluated for biological activities. Among them, derivative PMMB-259 [(R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl (E)-2-(4-(3-oxo-3-(3-(trifluoromethoxy)phenyl)prop-1-en-1-yl)phenoxy)acetate] was identified as a potent inhibitor of tubulin polymerization. Further investigation confirmed that PMMB-259 can induce MCF-7 cell apoptosis, reduce the mitochondrial transmembrane potential, and arrest the cell cycle at the G2 /M phase. Moreover, the morphological variation of treated cells was visualized by confocal microscopy. The results, along with docking simulations, further indicated that PMMB-259 can bind well to tubulin at the colchicine site. Overall, these studies may provide a new molecular scaffold for the further development of antitumor agents that target tubulin.

Background: Morin is a flavanoid which exhibits potent antioxidant activity in various oxidative stress related diseases. The current study was attempted to scrutinize the preclinical bio-efficacy of morin on focal ischemia.Methods: The animal model of focal cerebral ischemic injury was done by midbrain carotid artery occlusion (MCAO) method, followed by Morin (30mg/kg) administration for seven days.Results: The outcome of the study showed that treatment with morin displayed positive effects in reducing the focal cerebral ischemia. This effect was evident with the improvements in neurological deficits, reduction in MDA content and elevation of antioxidant levels (SOD, GSH and Gpx). Furthermore, protein expression of Bax and caspase-3 were effectively down-regulated, whilst the expression of Bcl-2 was significantly elevated. On the other hand, the mRNA expression of proinflammatory cytokines was significantly reduced in focal cerebral ischemic rats upon morin intervention.Conclusion: Thus, the beneficial effects of morin on cerebral ischemia assault may result from the reduction of oxidative stress, inhibition of apoptosis and inflammation. The neuroprotective effects of morin supplement may serve as potent adjuvant in the amelioration of ischemic stroke.Keywords: Focal cerebral ischemia, oxidative stress, apoptosis, inflammation, lipid peroxidation, morin

Docetaxel (DTX)-based chemotherapy of prostate cancer is still confronted with significant challenges due to insufficient drug accumulation at the tumor sites and the systemic side effects on normal cells and organs. Tumor microenvironment-responsive nanosized drug delivery systems have shown enormous potential to improve the anticancer efficacy and minimize the systemic side effects of chemotherapeutics. However, most of the currently redox-responsive nanoparticles respond only to single stimuli, which compromise the treatment effect. Hence, inspired by the abundance of reactive oxygen species (ROS) and intracellular glutathione (GSH) in cancer cells, we proposed a unique ROS and GSH dual responsive nanocarrier (PCL-SS) for DTX delivery. The DTX-loaded PCL-SS nanoparticles (PCL-SS@DTX NPs) were not only stable in a normal physiological environment but also rapidly triggered DTX release in prostate cancer cells. In vitro experiments showed that PCL-SS@DTX NPs had robust prostate cancer cell cytotoxicity, induced cell apoptosis, inhibited cell migration and invasion and exhibited satisfactory biocompatibility. In mice bearing orthotopic prostate cancer, PCL-SS@DTX NPs could accumulate in orthotopic tumor sites and then significantly weaken tumor growth by inhibiting prostate cancer cell proliferation and inducing cell apoptosis, without obvious damages to major organs. Overall, this dual responsive nanosized drug delivery system may act as a promising therapeutic option for prostate cancer chemotherapy.

A novel salen type dinuclear dysprosium complex e.g., [Dy 2 (H 2 L)(acac) 6 ]·4CH 3 OH ( 1 ) [H 2 L = N , N ′-(1.3-propylene)bis(3-methoxysalicylideneimine) has been isolated by reactions of Dy(acac) 3 ·H 2 O (acac = acetylacetonate) with salen type (H 2 L), respectively. X-ray crystallographic analyses reveal that asymmetric Dy(III) ions for 1 was bridged by one ligand displaying bicapped trigonal prism coordination geometry. Magnetic measurement shows that complex 1 exhibit slow relaxations under zero dc field. The presence of two magnetic relaxations in complex 1 is associated with the presence of minute differences in bond lengths around Dy(III) center.

The development of antibiotics is never a simple stepwise linear process. After numerous setbacks in high-throughput screening and de novo drug design, researchers in this area are turning again to natural products. Shikonin, which is isolated from Lithospermum erythrorhizon, has multifarious pharmacological properties including antibacterial activity. In this study, we utilized shikonin as a template to grow a scaffold and acquire new molecules as tyrosyl-tRNA synthetase inhibitors. Docking simulation combined with a primary screen in vitro was performed to filter the modifications for the lead compound, which was then substituted, synthesized and evaluated for its inhibitory activity against TyrRS and several strains of both Gram-positive and Gram-negative bacteria. Out of the obtained compounds, PMM-154 exhibited high potency with an IC50 of 0.8 ± 0.3 μM against TyrRS. In addition, improved potency against S. aureus ATCC 25923 with an MIC of 1.1 μg mL−1 was observed. In subsequent tests, the results showed that PMM-154 could cause the apoptosis of S. aureus ATCC 25923 at a safe concentration. In general, the biological results suggested that this shikonin derivative outperformed shikonin and may be further developed as a promising TyrRS inhibitor.

A simultaneous testing of the trace catechol (CC) and hydroquinone (HQ) was achieved via an ultrasensitive phenolic biosensor constructed by the truncated cube-shaped gold/Prussian blue analogue (Au/PBA) nanocomposites. A facile charge-assembly strategy was developed to drive the successive mutual attractions for the crystallization among [Fe(CN)6]3-, Co2+, and [AuCl4]- reactants, benefiting the in-situ growth of Au nanoparticles on all faces of the PBA truncated nanocubes. On account of this special architecture, numerous 10 nm Au particles can rapidly gather the electrons from the enzyme reaction to a PBA crystal due to their high conductivity, and then the current signals will be significantly magnified through the reversible redox of the PBA. Using this nanomaterial, the as-prepared biosensor has shown an extreme wide linear range (CC: 0.2–550 µM, HQ: 1–550 µM) and an ultralow detection limit (CC: 0.06 ± 0.001 µM, HQ: 0.3 ± 0.007 µM) for the independent detections of CC and HQ. More importantly, when the two targets coexist, this biosensor can simultaneously exhibit the obvious and accurate responses of CC and HQ at the different potentials (0.17 V for CC and 0.07 V for HQ) with the high sensitivities and rare mutually interferences.

In this study, a shikonin ester derivative, compound 3g, was selected to evaluate its anticancer activities and we found that compound 3g exhibited better antitubulin activities against the human HepG2 cell line with an IC50 value of 1.097 μM. Furthermore, the inhibition of tubulin polymerization results indicated that compound 3g demonstrated the most potent antitubulin activity (IC50 = 13.88), which was compared with shikonin and colchicine as positive controls (IC50 = 25.28 μM and 22.56 μM), respectively. Compound 3g was simulated to have good binding site with tubulin and arrested the cell cycle at G2/M phase, which also induces apoptosis in HepG2 cells, in which P53 and members of Bcl-2 protein family were both involved in the progress of apoptosis revealed by western blot. Confocal microscopy observations revealed compound 3g targeted tubulin and altered its polymerization by interfering with microtubule organization. Based on these results, compound 3g functions as a potent anticancer agent targeting tubulin. Chirality 27:274–280, 2015.. © 2015 Wiley Periodicals, Inc.

C1q/tumor necrosis factor-related protein 6 (CTRP6), an adipose-tissue secretory factor, plays an important role in inflammatory reaction and carcinogenesis. However, the biological function of CTRP6 in adipogenesis remains unclear. In this study, we examined the effects of CTRP6 knockdown on lipogenesis of 3T3-L1 adipocytes. The results showed that after 3T3-L1 adipocytes transfected with anti-CTRP6 small interfering RNA (siRNA), not only levels of secreted CTRP6 protein in the culture medium but also the expression level of the CTRP6 protein in the 3T3-L1 adipocytes was significantly reduced (P

In this study, a series of novel shikonin derivatives (30–49) were designed and synthesized and their anti-proliferative activities were evaluated against five different cancer cell lines, including HeLa, HepG2, MCF-7, BGC and A549. Some of the compounds show strong anti-proliferative effects against HeLa, HepG2 and MCF-7 with IC50 values ranging from 1.26 to 18.50 μM and show lower side effects towards normal cell lines as compared to shikonin. Compared to other compounds and shikonin itself, compound 40 displayed much stronger anti-proliferative effects against various cancer cell lines. Furthermore, the flow cytometry results demonstrated that compound 40 could obviously induce apoptosis in a dose- and time-dependent manner and also cause cell cycle arrest at the G2/M phase. For further investigation of the aforementioned mechanisms, we performed Western blot experiments and found that the cleavage of PARP and upstream caspase-3 increased; moreover, caspase-9 was activated by cleavage but not caspase-8. These aforementioned results also indicate that compound 40 could induce caspase-9 involved apoptosis and G2/M phase cell cycle arrest via the P21, p-CDC2 (Tyr15) pathway independent of P53.

Background The worldwide use of glyphosate has dramatically increased, but also has been raising concern over its impact on mineral nutrition, plant pathogen, and soil microbiota. To date, the bulk of previous studies still have shown different results on the effect of glyphosate application on soil rhizosphere microbial communities. Objective This study aimed to clarify whether glyphosate has impact on nitrogen-fixation, pathogen or disease suppression, and rhizosphere microbial community of a soybean EPSPS-transgenic line ZUTS31 in one growth season. Method Comparative analysis of the soil rhizosphere microbial communities was performed by 16S rRNA gene amplicons sequencing and shotgun metagenome sequencing analysis between the soybean line ZUTS31 foliar sprayed with diluted glyphosate solution and those sprayed with water only in seed-filling stage. Results There were no significant differences of alpha diversity but with small and insignificant difference of beta diversity of soybean rhizosphere bacteria after glyphosate treatment. The significantly enriched Gene Ontology (GO) terms were cellular, metabolic, and single-organism of biological process together with binding, catalytic activity of molecular function. The hits and gene abundances of some functional genes being involved in Plant Growth-Promoting Traits (PGPT), especially most of nitrogen fixation genes, significantly decreased in the rhizosphere after glyphosate treatment. Conclusion Our present study indicated that the formulation of glyphosate-isopropylamine salt did not significantly affect the alpha and beta diversity of the rhizobacterial community of the soybean line ZUTS31, whereas it significantly influenced some functional genes involved in PGPT in the rhizosphere during the single growth season.

Background Shikonin is a naphthoquinone secondary metabolite with important medicinal value and is found in Lithospermum erythrorhizon. Considering the limited knowledge on the membrane transport mechanism of shikonin, this study investigated such molecular mechanism. Results We successfully isolated an ATP-binding cassette protein gene, LeMDR, from L. erythrorhizon. LeMDR is predominantly expressed in L. erythrorhizon roots, where shikonin accumulated. Functional analysis of LeMDR by using the yeast cell expression system revealed that LeMDR is possibly involved in the shikonin efflux transport. The accumulation of shikonin is lower in yeast cells transformed with LeMDR-overexpressing vector than that with empty vector. The transgenic hairy roots of L. erythrorhizon overexpressing LeMDR (MDRO) significantly enhanced shikonin production, whereas the RNA interference of LeMDR (MDRi) displayed a reverse trend. Moreover, the mRNA expression level of LeMDR was up-regulated by treatment with shikonin and shikonin-positive regulators, methyl jasmonate and indole-3-acetic acid. There might be a relationship of mutual regulation between the expression level of LeMDR and shikonin biosynthesis. Conclusions Our findings demonstrated the important role of LeMDR in transmembrane transport and biosynthesis of shikonin. Electronic supplementary material The online version of this article (10.1186/s12870-017-1148-6) contains supplementary material, which is available to authorized users.

Human enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD), particularly in infants and children below 4 years of age. Shikonin is a bioactive compound with anti-inflammatory, antiviral, and antibacterial activities derived from the roots of the Chinese medicinal herb Lithospermum erythrorhizon. This study aimed to examine the antiviral activity of PMM-034, a shikonin ester derivative, against EV71 in rhabdomyosarcoma (RD) cells. Cytotoxicity of PMM-034 on RD cells was determined using WST-1 assay. Dose- and time-dependent effects of PMM-034 on EV71 replication in RD cells were determined using plaque reduction assay. mRNA expression levels of EV71/VP1 and pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were determined by real-time RT-PCR, and EV71/VP1 and phospho-p65 protein expressions were determined by western blot analysis. PMM-034 exhibited only weak cytotoxicity against RD cells. However, PMM-034 exhibited significant antiviral activity against EV71 in RD cells with 50% inhibitory concentration of 2.31 μg/mL. The VP1 mRNA and protein levels were significantly reduced in cells treated with PMM-034. Furthermore, relative mRNA expression levels of IL-1β, IL-6, IL-8, and TNF-α significantly decreased in the cells treated with PMM-034, while the phospho-p65 protein expression was also significantly lower in the treated cells. These results indicated that PMM-034 suppressed the expressions of pro-inflammatory cytokines in RD cells, exhibiting antiviral activity against EV71, as evidenced by the reduced VP1 mRNA and protein levels in PMM-034-treated cells. Thus, PMM-034 is a promising candidate for further development as an EV71 inhibitor.

This study aimed to examine the antiviral effects of shikonin ester ((R)-1-(5, 8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl3-(1H- indol-3-yl) propanoate (PMM-034) against influenza A (H1N1) virus. We investigated PMM-034 anti-H1N1 activity and its effect on caspase 3 gene expression during cellular apoptosis after influenza virus infection in vitro. Neuraminidase (NA) inhibition was assessed in comparison with oseltamivir in the influenza virus standard strains A/PR/8/34 to understand the viral mechanism. MDCK and A549 cells were used to investigate influenza viral infection and the structure-activity relationship between PMM-034 and NA was evaluated by pharmacophore-based docking modeling. The production of viral protein was tested by western blot. A/PR/8/34 induced cell inhibition but this was reduced by PMM-034 to 16μg/mL and this showed a selective index of 10mM. PMM-034 inhibited NA in a dose dependent manner, similar to oseltamivir inhibition. A sharp decrease in viral nucleocapsid protein mRNA was observed in infected cells after treatment with PMM-034. Apoptosis of infected A459 cells was inhibited by PMM-034 with decreased caspase 3 levels. ARG 118, ARG 152, ARG 371 and GLU 227 in the binding pocket of NA bound to PMM-034 in the docking model. Taken together, these results suggest PMM-034 shikonin ester blocked H1N1 infection and might be a potential anti-H1N1 drug.

A novel SOI-MEMS process with galvanic protection technique is presented in this paper. After front-end-of-line processes and metallization with Au on SOI wafers, the moving structures and release trenches are patterned by using a single mask. A combination of RIE and DRIE was employed to define the moving structures and release trenches. In the releasing process, the silicon substrate was etched normally while the exposed silicon on SOI layer was passivated by the galvanic cell that consisted of top silicon layer and Au electrode in TMAH solution. Compared with other methods, this is a simplified process. As no protection layer on the sidewalls was required for TMAH etching, all of the lithography was performed on the plain surface instead of the high topography surface. Aside from this, the released cavity has a large space that provides less air damping. The undercut of the anchor is controlled by anisotropic etching which results in desirable anchors. A double-ended tuning fork resonator was fabricated to verify the processes. The resonant frequency of the resonator was measured as 3.098 MHz with a quality factor of 730 in an atmospheric environment.

The indole network has been identified as an important pharmacophore of several natural products and synthetically prepared molecules. Asymmetric organocatalytic Friedel-Crafts alkylations of electron rich indoles are of enormous significance for the synthesis of many bioactive compounds, natural products and anti-cancer drugs. Chiral BrOnsted acid-catalyzed Friedel-Crafts-type reactions of indole and its derivatives with various carbon-centered electrophiles e.g. electron deficient olefins, carbonyls, imines and some substi- tuted methanamines and carbinols have been employed to prepare optically active indole derivatives. These reactions, their stereochemi- cal outcome and probable modes of activation of the substrates by suitably substituted axially dissymmetric BINOL-derived chiral BrOn- sted acid catalysts are discussed in this review. enhance the catalytic performance of these chiral BrOnsted acids. Given the extensive occurrence of the indole core in biologically active substances and products of natural origin together with the possibility of activating unsaturated groups such as imine, carbonyl or olefinic functionalities by chiral BrOnsted acids (11, 12), the development of enantioselective metal free organocatalytic Friedel- Crafts alkylations of indoles has assumed enormous significance. These reactions, their stereochemical outcome and mechanism of action using chiral bifunctional BrOnsted acid organocatalysts are described in the present review. In continuation to our earlier re- views (13-19) the current article further demonstrates the power of asymmetric organocatalysis to bring about the desired stereoselec- tive transformation through non-covalent hydrogen-bond activation of the components of Friedel-Crafts reaction.

One-dimensional metal oxides have been attracting interest as advanced materials for trace target recognition in chemical sensors due to their ultra-high surface area and electrochemical activity. However, the development of a large-scale and controllable fabrication strategy remains a great challenge and has hindered their practical application. In this work, we design a novel thermal oxidation route for obtaining a large area of CuO nanowires by the use of a film precursor of the nanocubic Cu-Fe Prussian blue analogue (PBA). The nanostructure and distribution of the PBA film was precisely controlled using an electrostatic self-assembly approach. The CuO nanowire shape was formed in-situ via the growth confinement effect through the air-heating collapse and oxidation of PBA crystals. At a very low working potential of 0.1 V, the as-prepared CuO nanowire sensor exhibited excellent sensing performance on ascorbic acid over a wide linear range (20–400 μM) and a low detection limit (0.5 μM), as well as high selectivity despite various interferences.

BACKGROUND/OBJECTIVES The association between tea consumption and risk of coronary heart disease (CHD) remains controversial. This study aimed to determine whether tea consumption has an effect on CHD risk in Chinese adults. SUBJECTS/METHODS In this hospital-based case-control study, 267 cases of CHD and 235 non-CHD controls were enrolled. Blood samples from all cases were examined. Cardiac function indices (left ventricular ejection fraction, left ventricular end-diastolic dimension, lactate dehydrogenase, and creatine kinase of the muscle or brain type), blood lipid index (high-density lipoprotein cholesterol), and blood coagulation function indices (fibrinogen and activated partial thromboplastin time) were recorded. Tea consumption of study participants was assessed by a specifically designed questionnaire. The baseline characteristics of the study populations were recorded, and CHD-related biomarkers were detected. Differences in baseline characteristics of the study participants were examined using t-tests for continuous variables and chi-squared tests for categorical variables. Unconditional logistic regression was used to measure the association between tea and CHD. RESULTS There were significant differences in cardiac function indices, blood lipid index, and blood coagulation indices between CHD cases and controls (P < 0.05). We found tea consumption reduced CHD risk in female participants (adjusted odds ratio (OR) = 0.484, 95% CI: 0.242–0.968, P = 0.0403). Regarding the type of tea consumed, the risk of CHD was reduced in women who drank partially fermented tea (adjusted OR = 0.210, 95% CI: 0.084–0.522, P = 0.0008). Analytic results for the amount of tea consumed per unit time showed CHD risk was reduced in women who consumed 1–2 cups of tea per day (adjusted OR = 0.291, 95% CI: 0.131–0.643, P = 0.0023). A tea-drinking frequency of > 6 days/week was beneficial for CHD prevention (adjusted OR = 0.183, 95% CI: 0.049–0.679, P = 0.0112). When analyzed according to the duration of tea consumption, the risk of CHD was reduced in participants who had been drinking tea for 10–20 years (adjusted OR = 0.360, 95% CI: 0.137–0.946, P = 0.0382). CONCLUSIONS Tea consumption is associated with a reduced risk of CHD in female but not male populations in Guangzhou.

The design structure of the high voltage winding of the box transformer lead to high voltage between the high voltage winding layers, and electric field of each layer winding end is over-concentration, and the additional loss of load loss is too high, and thus lead to further the enameled wire of high voltage terminal happens partial discharge seriously and cryogenic overheating are discussed through the defects analysis of box transformer and a series of related experiments, hanging core inspection and analysis. If the hydrogen content is overweight seriously, total hydrocarbons is overweight, and methane gas content of total hydrocarbons is very high, ethylene and acetylene is very low, it can initially determine that low-energy partial discharge fault is inside the device are demonstrated. Finally, the corrective measures for the common problem of this group box transformer are presented.

Background The phytohormone ethylene (ET) is a key signaling molecule for inducing the biosynthesis of shikonin and its derivatives, which are secondary metabolites in Lithospermum erythrorhizon. Although ETHYLENE INSENSITIVE3 (EIN3)/EIN3-like proteins (EILs) are crucial transcription factors in ET signal transduction pathway, the possible function of EIN3/EIL1 in shikonin biosynthesis remains unknown. In this study, by targeting LeEIL-1 (L. erythrorhizon EIN3-like protein gene 1) at the expression level, we revealed the positive regulatory effect of LeEIL-1 on shikonin formation. Results The mRNA level of LeEIL-1 was significantly up-regulated and down-regulated in the LeEIL-1-overexpressing hairy root lines and LeEIL-1-RNAi hairy root lines, respectively. Specifically, LeEIL-1 overexpression resulted in increased transcript levels of the downstream gene of ET signal transduction pathway (LeERF-1) and a subset of genes for shikonin formation, excretion and/or transportation (LePAL, LeC4H-2, Le4CL-1, HMGR, LePGT-1, LeDI-2, and LePS-2), which was consistent with the enhanced shikonin contents in the LeEIL-1-overexpressing hairy root lines. Conversely, LeEIL-1-RNAi dramatically repressed the expression of the above genes and significantly reduced shikonin production. Conclusions The results revealed that LeEIL-1 is a positive regulator of the biosynthesis of shikonin and its derivatives in L. erythrorhizon hairy roots. Our findings gave new insights into the molecular regulatory mechanism of ET in shikonin biosynthesis. LeEIL-1 could be a crucial target gene for the genetic engineering of shikonin biosynthesis. Electronic supplementary material The online version of this article (doi:10.1186/s12870-016-0812-6) contains supplementary material, which is available to authorized users.

Two isostructural Keggin-templated compounds containing a chair-like heptanuclear silver complex, [{Ag7(Hbtz)2(btz)4}{PM12O40}]·H2O (M = W, 1; Mo, 2) (Hbtz = benzotriazolate), have been hydrothermally synthesized and characterized by routine methods and single crystal X-ray diffraction. In the compounds 1 and 2, the Hbtz ligands present two types of coordination modes. A pentameric silver chain with two kinds of Ag⋯Ag weak interactions exists in the heptanuclear silver complex. The heptanuclear silver cations connect the polyoxoanions PM12O403− to a two-dimensional layer, and the adjacent layers are fused together by the pseudo wave-like chains, H-bonds and AgI–π interactions, constructing a three-dimensional net. Furthermore, electrochemical properties have been studied for compounds 1 and 2 and the two compounds display excellent electrocatalytic activities to the reduction of nitrite.

A new compound based on the Wells–Dawson polyoxometalate, Ag7(bbi)5(OH)(P2W18O62) (bbi = 1,1′-(1,4-butanediyl)bis(imidazole)) (1), has been hydrothermally synthesized and characterized by the normal physical methods and single-crystal X-ray diffraction. Compound 1 represents the first interpenetrating framework based on the Wells–Dawson POMs. The AgI···AgI interactions are crucial in the formation of the two individual motifs: in the first interpenetrating motif, the supported {Ag2}2+ dimers and the P2W18 polyanions form an infinite inorganic chain, then the Ag+ monomers and bbi ligands extend the chain to form a three-dimensional framework. The second motif is constructed by the Ag–bbi meso-helix chains which are stitched by the unsupported Ag7···Ag7 dimers to form a two-dimensional layer with huge loops. The electrochemical study exhibits that compound 1 could be used as electrocatalyst in the electrical reductions of bromate. In addition, compound 1 shows a photocatalytic action for degradation of RhB.

A new Wells–Dawson polyoxometalate-based compound, [CuII(2,2′-bipy)2(H2O)]3[CuI6(pz)6(P2W18O62)2] (2,2′-bipy = 2,2′-bipyridine, pz = pyrizine) (1), has been hydrothermally synthesized and characterized by routine physical methods. Compound 1 exhibits a [CuII(2,2′-bipy)2(H2O)]2+ complex-templated 3D (3,4)-connected framework with the topology of (63)(6284), which is built up by the cross-linking of porous P2W18–Cu layers and CuI–pz chains with Cu2 atoms as intersections. The transition-metal complex cation [CuII(2,2′-bipy)2(H2O)]2+ acts not only as a template locating in the voids of inorganic layers, but also as a charge-balance complex to make the 3D structure more steady. The electrochemistry property of compound 1 has also been discussed.