Visible-Light-Promoted Trifluoromethylthiolation and Trifluoromethylselenolation of 1,4-Dihydropyridines.

We report a metal-free trifluoromethylthiolation and trifluoromethylselenolation of 1,4-dihydropyridines with S-(trifluoromethyl) 4-methylbenzenesulfonothioate and Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate under visible light irradiation. This transformation was tolerated with a wide range of functional groups and provided an alternative and green strategy for the synthesis of trifluoromethylthioesters and trifluoromethylselenoesters.

An integrated microbiome and metabolomic analysis identifies immunoenhancing features of Ganoderma lucidum spores oil in mice.

Ganoderma lucidum (Leyss. ex Fr.) Karst. is a valuable dietary supplement used worldwide for promoting health as well as a medicinal fungus for handling fatigue, immunological disorders, and cancer. Previous studies have revealed the immunoenhancing effect of G. lucidum and the polysaccharide extract, with potential involvement of gut microbiome. The oil of G. lucidum spores (GLSO)is one of the well-known G. lucidum-related products. However, there is little evidence supporting the immune promotion activity and the underlying mechanisms. The present study aims to investigate the immunoenhancing effect of GLSO in mice. GLSO enhanced macrophage phagocytosis and NK cell cytotoxicity of mice. Further microbiome and metabolomics studies showed that GLSO induced structural rearrangement of gut microbiota, mediating alterations in a wide range of metabolites. By clustering, multivariate and correlation analysis, the immunoenhancing effect of GLSO was found to be highly correlated with elevated abundance of several bacterial genera (Lactobacillus, Turicibacter and Romboutsia) and species (Lactobacillus_intestinalis and Lactobacillus_reuteri), and decreased level of Staphylococcus and Helicobacter, which resulted in the regulation of a range of key metabolites such as dopamine, prolyl-glutamine, pentahomomethionine, leucyl-glutamine, l-threonine, stearoylcarnitine, dolichyl ß-d-glucosyl phosphate, etc. These results provide new insights into the understanding of the modulatory effect of GLSO on immune system.

Enhanced Humidity Sensitivity with Silicon Nanopillar Array by UV Light.

The sensitivity of silicon nanopillar array for relative humidity (RH) with UV illumination was investigated in this work. The silicon nanopillar array was prepared by nanosphere lithography. Electrical measurements were performed on its sensing performance with and without UV irradiation. It was found that UV light improved the humidity sensitivity with different UV light wavelengths and power. The sensor response and recovery time were reduced. Furthermore, the turn-on threshold voltage and the operating voltage both decreased. These sensing characteristics can mainly be attributed to the electron-hole pairs generated by UV light. These electron-hole pairs promote the adsorption and desorption processes. The results indicate that silicon nanopillar array materials with UV irradiation might be competitive as novel sensing materials for fabricating humidity sensors with high performances.

Fabrication of Ordered SnO2 Nanostructures with Enhanced Humidity Sensing Performance.

Ordered SnO2 nanostructures were prepared as humidity sensors by nanosphere lithography with the magnetron sputtering technique. The X-ray diffraction patterns of SnO2 nanostructures show that all intense diffraction peaks correspond to the crystallographic planes of SnO2. The Atomic Force Microscope (AFM) mage shows that these SnO2 nanostructures exhibited a classic honeycomb structure. The resistance of this sensor was measured to show that the resistance of the sensor decreases with an increase from lower relative humidity (RH) to higher RH. Additionally, the longest response/recovery time was 32 s/42 s for 11-96% RH. The hysteresis for the SnO2 nanostructure sensor was <5%.

[Consideration about chemistry, manufacture and control (CMC) key problems in simplified registration of classical traditional Chinese medicine excellent prescriptions].

As an outstanding representative of traditional Chinese medicine(TCM) prescriptions accumulated from famous TCM doctors' clinical experiences in past dynasties, classical TCM excellent prescriptions (cTCMeP) are the most valuable part of TCM system. To support the research and development of cTCMeP, a series of regulations and measures were issued to encourage its simplified registration. There is still a long-way to go because many key problems and puzzles about technology, registration and administration in cTCMeP R&D process are not resolved. Based on the analysis of registration and management regulations of botanical drug products in FDA of USA and Japan, and EMA of Europe, the possible key problems and countermeasures in chemistry, manufacture and control (CMC) of simplified registration of cTCMeP were analyzed on the consideration of its actual situation. The method of "reference decoction extract by traditional prescription" (RDETP) was firstly proposed as standard to evaluate the quality and preparation uniformity between the new developing product under simplified registration and traditional original usages of cTCMeP, instead of Standard Decoction method in Japan. "Totality of the evidence" approach, mass balance and bioassay/biological assay of cTCMeP were emphatically suggested to introduce to the quality uniformity evaluation system in the raw drug material, drug substance and final product between the modern product and traditional decoction.

Transcriptional data mining of Salvia miltiorrhiza in response to methyl jasmonate to examine the mechanism of bioactive compound biosynthesis and regulation.

Salvia miltiorrhiza is a Chinese herb with significant pharmacologic effects because of the bioactive compounds of tanshinones and phenolic acids. Methyl jasmonate (MeJA) has been used as an effective elicitor to enhance the production of these compounds. However, the molecular mechanism of MeJA-mediated tanshinone and salvianolic acid biosynthesis remains unclear. The transcriptional profiles of S. miltiorrhiza leaves at 12 h (T12) after MeJA elicitation and mock-treated leaves (T0) were generated using the Illumina deep RNA sequencing (RNA-seq) strategy to detect the changes in gene expression in response to MeJA. In total, 37 647 unique sequences were obtained from about 21 million reads, and 25 641 (71.53%) of these sequences were annotated based on the blast searches against the public databases. A total of 5287 unique sequences were expressed differentially between the samples of T0 and T12, which covered almost all the known genes involved in tanshinone and phenolic acid biosynthesis in S. miltiorrhiza. Many of the transcription factors (e.g. MYB, bHLH and WRKY) and genes involved in plant hormone biosynthesis and signal transduction were expressed differentially in response to the MeJA induction. Importantly, three and four candidate cytochrome P450s (P450s) that could be involved in the tanshinone and phenolic acid biosynthesis, respectively, were selected from the RNA-seq data based on co-expressed pattern analysis with SmCPS1/SmKSL1 and SmRAS, which are the key genes responsible for biosynthesis. This comprehensive investigation of MeJA-induced gene expression profiles can shed light on the molecular mechanisms of the MeJA-mediated bioactive compound biosynthesis and regulation in S. miltiorrhiza.

Anion-exchange and anthracene-encapsulation within copper(II) and manganese(II)-triazole metal-organic confined space in a single crystal-to-single crystal transformation fashion.

A new multidentate ligand 1-(9-(1H-1,2,4-triazol-1-yl)anthracen-10-yl)-1H-1,2,4-triazole (tatrz) was designed and synthesized. Using tatrz as a building block, three novel coordination frameworks, namely, {[Cu(tatrz)2(NO3)2]·(CH3OH)·4H2O}n (1), {[Cu(tatrz)2(H2O)2](BF4)2}n (2), and [Mn(tatrz)2(SCN)2(CH3OH)]·2H2O (3) can be isolated. Anion-exchange experiment indicates that NO3(-) anions in the two-dimensional (2D) copper framework of 1 can be completely exchanged by ClO4(-) in an irreversible single crystal-to-single crystal (SC-SC) transformation fashion, as evidenced by the anion-exchange products of {[Cu(tatrz)2(H2O)2](ClO4)2·4CH3OH} (1a). Further, if 1a was employed as a precursor in N,N-dimethylformamide (DMF), an isomorphic solvate of {[Cu(tatrz)2(DMF)2](ClO4)2·2H2O}n (1b) can be generated during the reversible dynamic transformation process. When 1 was immersed in CH3OH, a distinct 2D layer {[Cu(tatrz)2(NO3)2]·4.4CH3OH·0.6H2O}n (1c) was isolated. Interestingly, the solvent-exchange conversion is also invertible between 1 and 1c, which exhibits spongelike dynamic behavior with retention of crystalline integrity. If the 2-fold interpenetrating three-dimensional (3D) framework 2 is selected, it can be transformed into another 2-fold interpenetrating 3D framework {[Cu(tatrz)2(H2O)2](ClO4)2·5.56H2O}n (2a) in a reversible SC-SC transformation fashion. However, when the light yellow crystals of mononuclear complex 3 were exposed to trichloromethane containing aromatic organic anthracene (atan), through our careful observation, the crystals of 3 were dissolved and reassembled into dark brown crystals of 2D crystalline coordination framework {[Mn(tatrz)2(SCN)2]·(atan)}n (3a). X-ray diffraction revealed that in 3a, atan acting as an organic template was encapsulated in the confined space of the 2D grid. Luminescent measurements illustrate that 3a is the first report of multidimensional polymers based on triazole derivatives as luminescent probes of Mg(2+).

Total glucosides of Rhizoma Smilacis Glabrae: a therapeutic approach for psoriasis by regulating Th17/Treg balance.

Total glucosides of Rhizoma Smilacis Glabrae (RSG) are selective immunosuppressants that exhibit primary efficacy in the treatment of rheumatoid arthritis through targeted inhibition of activated T cells. In this study, we aimed to investigate the potential application of RSG in the treatment of psoriasis and elucidate its mechanism of action and material basis. Our findings revealed significant improvements upon administration of RSG in an imiquimod (IMQ)-induced psoriasis model. These improvements were characterized by a remarkable increase in the number of tail scales in mice and a substantial amelioration of skin erythema, ulceration, and flaking. By transcriptome sequencing and T-cell flow sorting assay, we identified notable effects of RSG on the modulation of various cellular processes. Specifically, RSG prominently down-regulated the Th17/Treg ratio in damaged skin tissues and reduced the proportion of G2 phase cells. Furthermore, RSG exhibited a stimulatory effect on the proliferation and differentiation of epithelial cells. Of particular interest, we discovered that ß-sitosterol, sitostenone, stigmasterol, smiglanin, and cinchonain Ib displayed potent inhibitory effects on the IL-17-mediated inflammatory response in HaCaT cells. In summary, our study highlights the therapeutic potential of RSG in the treatment of psoriasis, attributed to its ability to regulate the Th17/Treg balance. These findings contribute to the development of new indications for RSG and provide a solid theoretical foundation for further exploration in this field.

Widely quasi-quantitative analysis of both metabolites and tryptic peptides in animal-originated medicinal materials: Bufonis Venenum as a case.

It is challenging to achieve in-depth quality analysis for animal-originated medicinal materials (AMMs) owing to containing abundant metabolites and proteins. RPLC-MS/MS intrinsically bears the ability to simultaneously monitor metabolites and peptides. Hence, its potential towards merging quasi-quantitative metabolomics and tryptic proteomics characterization is therefore assessed in current study, and a well-known AMM namely Bufonis Venenum (BV, Chinese name: Chansu) was employed as a proof-of-concept. Qualitative information of metabolites was acquired by RPLC-Qtof-MS and translated to plausible structures through careful "spectrum-to-structure" analysis. Bottom-up proteomics was conducted to characterize the tryptic peptidome using nanoLC-QExactive HF orbitrap-MS. Quantitative MS/MS parameters of either metabolites (72 ones) or tryptic peptides (28 unique peptides) were optimized using online energy-resolved MS and applied to configure RPLC-selected-reaction monitoring (RPLC-SRM) program. Ultimately, SRM response of each analyte was converted to quasi-content by serially diluting a so-called universal metabolome standard (UMS) solution and building regressive calibration curve set to achieve widely quasi-quantitative metabolomics and proteomics. Although being sourced from identical species, significant differences occurred among the metabolite and protein profiles between BV and toad skins, and bufadienolides (i.e., 3-(N-adipoyl-argininyl)-gamabufotalin/isomer) along with several tryptic peptides (i.e., ISGLIYEETR sourced from Histone H4) served as the primary differential variables. Above all, RPLC-SRM is a promising analytical tool for in-depth quality evaluation of AMMs, and more importantly, the workflow described here is a fit-for-purpose pipeline to merge quasi-quantitative metabolomics and bottom-up proteomics.

[Study on HPLC fingerprint of Prunella vulgaris].

OBJECTIVE: To establish HPLC fingerprint of Prunella vulgaris and provide evidence for quality control and identification of the Chinese crude drug. METHODS: The HPLC method was used, chromatography conditions were Agilent Eclipse XDB-C18 (4.6 mm x 250 mm, 5 microm) column with gradient mobile phase of acetonitrile-0.1% acetic acid, UV detection wavelength was 290 nm and the column temperature was 30 degrees C with the flow rate of 1.0 mL/min, the sample injection was 10 microL. RESULTS: HPLC fingerprints of 19 samples of Prunella vulgaris were established. 14 common peaks were selected as the fingerprint peaks in all samples. Among the obtained fingerprints, most of the detected peaks were separated effectively. 19 samples had high similarities. CONCLUSION: The established HPLC fingerprint has desirable accuracy, repeatability and stability, which can be used for one of the quality control methods of Prunella vulgaris.

Pharmacokinetics and Bioequivalence of Two Formulations of Rosuvastatin Following Single-dose Administration in Healthy Chinese Subjects Under Fasted and Fed Conditions.

The main objective of the study was to evaluate the bioequivalence of two rosuvastatin calcium tablets in healthy Chinese subjects under fasted and fed conditions. The study was carried out using a randomized, open-label, two-formulation, two-sequence, two-period, single-dose crossover design, with a washout period of 7 days. Both the fasted study and fed study enrolled 28 subjects. In each study period, the subjects were administrated a single oral dose of the test product or reference product of rosuvastatin 10 mg. Blood samples were collected from pre-dose to 72 hours after administration with 16 time points in total. Bioequivalence evaluation was performed using ln-transformed pharmacokinetic parameters of rosuvastatin, including Cmax , AUC0-t , and AUC0-∞ . In the present study, 95% confidence intervals (CIs) of test/reference geometric mean ratios (GMRs) of Cmax , AUC0-t , and AUC0-∞ under the fasted and fed conditions were all within the acceptance range of 80%-125%. Additionally, only one subject experienced one adverse event (AE). High-fat meals reduced the Cmax , AUC0-t , and AUC0-∞ , but had no significant effects on the λz, t1/2 , or Tmax of rosuvastatin. In the current study, the test product was bioequivalent to the reference product, and a single dose of rosuvastatin (10 mg) was well-tolerated. Food decreased the systemic exposure of rosuvastatin without the effects on the Tmax or elimination rate.

Analysis of the transcriptome of Panax notoginseng root uncovers putative triterpene saponin-biosynthetic genes and genetic markers.

BACKGROUND: Panax notoginseng (Burk) F.H. Chen is important medicinal plant of the Araliacease family. Triterpene saponins are the bioactive constituents in P. notoginseng. However, available genomic information regarding this plant is limited. Moreover, details of triterpene saponin biosynthesis in the Panax species are largely unknown. RESULTS: Using the 454 pyrosequencing technology, a one-quarter GS FLX titanium run resulted in 188,185 reads with an average length of 410 bases for P. notoginseng root. These reads were processed and assembled by 454 GS De Novo Assembler software into 30,852 unique sequences. A total of 70.2% of unique sequences were annotated by Basic Local Alignment Search Tool (BLAST) similarity searches against public sequence databases. The Kyoto Encyclopedia of Genes and Genomes (KEGG) assignment discovered 41 unique sequences representing 11 genes involved in triterpene saponin backbone biosynthesis in the 454-EST dataset. In particular, the transcript encoding dammarenediol synthase (DS), which is the first committed enzyme in the biosynthetic pathway of major triterpene saponins, is highly expressed in the root of four-year-old P. notoginseng. It is worth emphasizing that the candidate cytochrome P450 (Pn02132 and Pn00158) and UDP-glycosyltransferase (Pn00082) gene most likely to be involved in hydroxylation or glycosylation of aglycones for triterpene saponin biosynthesis were discovered from 174 cytochrome P450s and 242 glycosyltransferases by phylogenetic analysis, respectively. Putative transcription factors were detected in 906 unique sequences, including Myb, homeobox, WRKY, basic helix-loop-helix (bHLH), and other family proteins. Additionally, a total of 2,772 simple sequence repeat (SSR) were identified from 2,361 unique sequences, of which, di-nucleotide motifs were the most abundant motif. CONCLUSION: This study is the first to present a large-scale EST dataset for P. notoginseng root acquired by next-generation sequencing (NGS) technology. The candidate genes involved in triterpene saponin biosynthesis, including the putative CYP450s and UGTs, were obtained in this study. Additionally, the identification of SSRs provided plenty of genetic makers for molecular breeding and genetics applications in this species. These data will provide information on gene discovery, transcriptional regulation and marker-assisted selection for P. notoginseng. The dataset establishes an important foundation for the study with the purpose of ensuring adequate drug resources for this species.

Traditional Chinese Medicine Extract Properties Incorporated Energy Analysis for Membrane Concentration Processes.

This work focuses on the energy analysis of the membrane concentration systems that process traditional Chinese medicine extracts with dynamic properties incorporated, particularly for reverse osmosis (RO) and membrane distillation (MD) processes. The evaluation of process energy consumption was achieved by integrating the empirical properties correlations of Brix and other characteristics properties of the feed (e.g., density and heat capacity). The dynamic SEC analysis for RO process was largely dependent on the feed pressure, reported at 50 kWh/m3 at feed pressure of 0.9 MPa with less than 50% water removal. The occurrence of foaming at above 50% water removal caused discrepancies between the simulated flux results and the experimentally acquired results in RO, whereas the estimated dynamic SEC for MD process did not show a strong correlation with the temperatures selected in this study, ranging from 900 to 1000 kWh/m3. This approach can be adapted into the design and zoptimization for the concentration process of other herbal extracts by membrane technologies, allowing comprehensive understanding into the energy analysis in future study.

Effect of icariin on cyclic GMP levels and on the mRNA expression of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in penile cavernosum.

To further investigate the mechanisms of action of icariin (ICA), we assessed the effects of ICA on the in vitro formation of cGMP and cAMP in isolated rabbit corpus cavernosum. Isolated segments of rabbit corpus cavernosum were exposed to increasing concentrations of ICA and the dose-dependent accumulation of cGMP and cAMP was determined in the tissues samples by means of 125I radioimmunoassay. Responses of the isolated tissues preparations to ICA were compared with those obtained with the reference compounds sildenafil (Sild). Furthermore, the effects of ICA on the mRNA expression of specific cGMP-binding phosphodiesterase type V (PDE5) in rat penis were also observed. After incubation with ICA for 6 h or 14 h respectively, the levels of PDE5 mRNA were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The results showed that ICA increased cGMP concentrations directly (P < 0.05), but there was no significant effect on cAMP concentrations (P > 0.05). In the presence of sodium nitroprusside (SNP), a stimulatory agent of cGMP, both ICA and Sild increased cGMP concentrations with increasing dose (P < 0.01). Their EC50 was 4.62 (ICA) and 0.42 (Sild) micromol/L respectively. Under the same condition, ICA and Sild unaltered cAMP level significantly (P > 0.05). There were PDE5A1 and PDE5A2 mRNA expressions in rat corpus cavernosum with PDE5A2 being the dominant isoform. ICA could obviously inhibit these two isoforms mRNA expression in rat penis, and decrease PDE5A1 more pronouncedly (P < 0.01). The present study indicated that the aphrodisiac mechanisms of icariin involved the NO-cGMP signal transduction pathway, with increasing cGMP levels in the corpus cavernosum smooth muscle. The inhibitory effect of icariin on PDE5 mRNA expression, especially on PDE5A1, might account for its molecular mechanisms for its long-term activity.

The complete chloroplast genome sequence of the medicinal plant Salvia miltiorrhiza.

Salvia miltiorrhiza is an important medicinal plant with great economic and medicinal value. The complete chloroplast (cp) genome sequence of Salvia miltiorrhiza, the first sequenced member of the Lamiaceae family, is reported here. The genome is 151,328 bp in length and exhibits a typical quadripartite structure of the large (LSC, 82,695 bp) and small (SSC, 17,555 bp) single-copy regions, separated by a pair of inverted repeats (IRs, 25,539 bp). It contains 114 unique genes, including 80 protein-coding genes, 30 tRNAs and four rRNAs. The genome structure, gene order, GC content and codon usage are similar to the typical angiosperm cp genomes. Four forward, three inverted and seven tandem repeats were detected in the Salvia miltiorrhiza cp genome. Simple sequence repeat (SSR) analysis among the 30 asterid cp genomes revealed that most SSRs are AT-rich, which contribute to the overall AT richness of these cp genomes. Additionally, fewer SSRs are distributed in the protein-coding sequences compared to the non-coding regions, indicating an uneven distribution of SSRs within the cp genomes. Entire cp genome comparison of Salvia miltiorrhiza and three other Lamiales cp genomes showed a high degree of sequence similarity and a relatively high divergence of intergenic spacers. Sequence divergence analysis discovered the ten most divergent and ten most conserved genes as well as their length variation, which will be helpful for phylogenetic studies in asterids. Our analysis also supports that both regional and functional constraints affect gene sequence evolution. Further, phylogenetic analysis demonstrated a sister relationship between Salvia miltiorrhiza and Sesamum indicum. The complete cp genome sequence of Salvia miltiorrhiza reported in this paper will facilitate population, phylogenetic and cp genetic engineering studies of this medicinal plant.