Ultrasound-Chargeable Persistent Luminescence Nanoparticles to Generate Self-Propelled Motion and Photothermal/NO Therapy for Synergistic Tumor Treatment.

Cancer phototherapy indicates advantages in ease of manipulation, negligible drug resistance, and spatiotemporal control but is confronted with challenges in tumor cell accessibility and intermittent light excitation. Herein, we propose a strategy with persistent luminescence (PL)-excited photothermal therapy (PTT), concurrent thermophoresis-propelled motion, and PL-triggered NO release, where PL emission is chargeable by ultrasonication for readily applicable to deep tumors. Mechanoluminescent (ML) nanodots of SrAl2O4:Eu2+ (SAOE) and PL nanodots of ZnGa2O4:Cr3+ (ZGC) were deposited on mesoporous silicates to obtain mSZ nanoparticles (NPs), followed by partially coating with polydopamine (PDA) caps and loading NO donors to prepare Janus mSZ@PDA-NO NPs. The ML emission bands of SAOE nanodots overlap with the excitation band of ZGC, and the persistent near-infrared (NIR) emission could be repeatedly activated by ultrasonication. The PL emission acts as an internal NIR source to produce a thermophoretic force and NO gas propellers to drive the motion of Janus NPs. Compared with the commonly used intermittent NIR illumination at both 660 and 808 nm, the persistent motion of ultrasound-activated NPs enhances cellular uptake and long-lasting PTT and intracellular NO levels to combat tumor cells without the use of any chemotherapeutic drugs. The ultrasound-activated persistent motion promotes intratumoral accumulation and tumor distribution of PTT/NO therapeutics and exhibits significantly higher tumor growth inhibition, longer animal survival, and larger intratumoral NO levels than those who experience external NIR illumination. Thus, this study demonstrates a strategy to activate PL emissions and construct PL-excited nanomotors for phototherapy in deep tissues.

Pyroelectric Janus nanomotors to promote cell internalization and synergistic tumor therapy.

The tumor diffusion and cell internalization are the major obstacles to improving delivery efficacy of therapeutic agents. External electric fields have shown strong effect on the cell membrane polarization and fluidity, but usually need complicated power management circuits. Herein, in situ generation of microelectric field on nanoparticles (NPs) is proposed to overcome these delivery barriers. Janus tBT@PDA-CPT NPs were developed through partially coating of polydopamine (PDA) caps on pyroelectric tetragonal BaTiO3 (tBT) NPs and then camptothecin (CPT) conjugation via disulfide linkages. For comparison, cBT@PDA-CPT NPs were prepared from non-pyroelectric cubic BaTiO3 (cBT) as control. Near-infrared (NIR) illumination on PDA caps of the Janus NPs produces asymmetric thermophoretic force to drive NP motion for tumor accumulation, deep tissue penetration and effective cell interaction. Photothermally created temperature variations on tBT NPs build pyroelectric potentials to selectively change the membrane potential of tumor cells other than normal cells and exhibit a dominated role in enhancing tumor cell internalization and cytotoxicity. The combination index analysis confirms the synergistic effect of pyroelectric dynamic therapy (PEDT), chemotherapy and photothermal therapy (PTT), leading to full inhibition of tumor growth and noticeable extension of animal survival at significant lower CPT doses. The mild PTT/PEDT, the reduced CPT dose and the selective toxicity to tumor cells have achieved favorable treatment safety after tBT@PDA-CPT/NIR treatment. Therefore, in response to the differences in membrane potentials and glutathione levels between tumor and normal cells, we have demonstrated a concise design to achieve thermophoresis-driven motion, pyroelectric potential-enhanced cell internalization and PTT/PEDT/chemotherapy-synergized antitumor treatment.

[Substitution mode of rare and endangered Chinese medicinal materials and research strategy of multi-component replacement].

Rare and endangered Chinese medicinal materials are the material basis for innovation and development of Chinese medicinal materials and their curative effects are remarkable. However, the resources are in shortage due to various man-made or natural factors such as rising demand, overexploitation and environmental degradation. Therefore, finding alternatives is a feasible and effective solution. This study systematically sorted out the list of rare and endangered Chinese medicinal materials, and combed relevant policies and regulations. According to existing research, the substitution model of rare and endangered Chinese medicinal materials was constructed from the theoretical level. In view of the slow search for substitutes, the failure to follow the basic theory of traditional Chinese medicine in the process of research and development, the difficulty in breaking through technologies and the incomplete guarantee of the clinical efficacy of substitutes, a multi-component replacement was proposed to replace the originals with more effective components from a wide range of sources. This study was expected to promote the study on the substitutes of rare and endangered Chinese medicinal materials to step into a new stage.

Substitution mode of rare and endangered Chinese medicinal materials and research strategy of multi-component replacement / 中国中药杂志

Rare and endangered Chinese medicinal materials are the material basis for innovation and development of Chinese medicinal materials and their curative effects are remarkable. However, the resources are in shortage due to various man-made or natural factors such as rising demand, overexploitation and environmental degradation. Therefore, finding alternatives is a feasible and effective solution. This study systematically sorted out the list of rare and endangered Chinese medicinal materials, and combed relevant policies and regulations. According to existing research, the substitution model of rare and endangered Chinese medicinal materials was constructed from the theoretical level. In view of the slow search for substitutes, the failure to follow the basic theory of traditional Chinese medicine in the process of research and development, the difficulty in breaking through technologies and the incomplete guarantee of the clinical efficacy of substitutes, a multi-component replacement was proposed to replace the originals with more effective components from a wide range of sources. This study was expected to promote the study on the substitutes of rare and endangered Chinese medicinal materials to step into a new stage.

Biochar and organic fertilizer drive the bacterial community to improve the productivity and quality of Sophora tonkinensis in cadmium-contaminated soil.

Excessive Cd accumulation in soil reduces the production of numerous plants, such as Sophora tonkinensis Gagnep., which is an important and widely cultivated medicinal plant whose roots and rhizomes are used in traditional Chinese medicine. Applying a mixture of biochar and organic fertilizers improved the overall health of the Cd-contaminated soil and increased the yield and quality of Sophora. However, the underlying mechanism between this mixed fertilization and the improvement of the yield and quality of Sophora remains uncovered. This study investigated the effect of biochar and organic fertilizer application (BO, biochar to organic fertilizer ratio of 1:2) on the growth of Sophora cultivated in Cd-contaminated soil. BO significantly reduced the total Cd content (TCd) in the Sophora rhizosphere soil and increased the soil water content, overall soil nutrient levels, and enzyme activities in the soil. Additionally, the α diversity of the soil bacterial community had been significantly improved after BO treatment. Soil pH, total Cd content, total carbon content, and dissolved organic carbon were the main reasons for the fluctuation of the bacterial dominant species. Further investigation demonstrated that the abundance of variable microorganisms, including Acidobacteria, Proteobacteria, Bacteroidetes, Firmicutes, Chloroflexi, Gemmatimonadetes, Patescibacteria, Armatimonadetes, Subgroups_ 6, Bacillus and Bacillus_ Acidiceler, was also significantly changed in Cd-contaminated soil. All these alterations could contribute to the reduction of the Cd content and, thus, the increase of the biomass and the content of the main secondary metabolites (matrine and oxymatrine) in Sophora. Our research demonstrated that the co-application of biochar and organic fertilizer has the potential to enhance soil health and increase the productivity and quality of plants by regulating the microorganisms in Cd-contaminated soil.

[Overview of research and development of polypeptide drugs and traditional Chinese medicine-peptides].

Peptide is a compound consisting of 2-50 amino acids, which is intermediate between small molecule and protein. It is characterized by a variety of biological activities, easy absorption, strong specific targeting, and few side effects and has become one of the hotspots in biomedical research in recent years. Chinese medicine contains a large number of peptides. The traditional processing methods such as decocting and boiling can effectively boost peptides to exert their due biological activities. At present, however, the research on Chinese medicinal components in laboratory generally employs high-concentration alcohol extraction method, which may cause the peptides to be ignored in many natural Chinese medicines. Substantial studies have revealed that the peptides in Chinese medicine are important material basis responsible for the traditional efficacy. Based on years of research and literature retrieval, this study put forward the concept of "traditional Chinese medicine(TCM)-peptides", referring to the components consisting of two or more amino acids with molecular weight between small molecules and proteins that can express the efficacy of Chinese medicine. Furthermore, this study also summarized the extraction and separation of TCM-peptides, and structure determination methods and routes, predicted the research prospect of modern research methods of TCM-peptides based on "holistic view" and big data. The artificial intelligence prediction was combined with high-throughput screening technology to improve the discovery efficiency and accuracy of TCM-peptides, and holographic images between TCM-peptides and biological targets were established to provide references for the innovative drug design and related health product development of TCM-peptides based on TCM theories.

[Digestive properties of flavonoid components in Xiaoer Chiqiao Qingre Granules in simulated infant gastrointestinal environment].

This study aimed to elucidate the digestive characteristics of flavonoid components in Xiaoer Chiqiao Qingre Granules(XECQ) in the gastrointestinal environment of infants. An in vitro model was established to simulate the gastric and intestinal environment of infants. UPLC was used to analyze the content change of flavonoid components in XECQ, and their overall content was integrated through the mass fraction weight coefficient method. UPLC-Q-TOF-MS was employed to determine the digestive products of flavonoid components in gastrointestinal fluids and their metabolic pathways. The results showed that in the process of digestion, 11 digestion products were generated by oxidation, reduction, deglycosylation, methylation and other phase Ⅰ metabolism. From flavonoid content and component changes, it was found that the flavonoid components in XECQ were relatively stable in the gastric fluid, while their content in the intestinal fluid was first increased and then maintained stable. This was mainly because flavonoid components were released from proteins, polysaccharides and other macromolecular substances during gastrointestinal digestion. In addition, phase Ⅰ metabolism occurred, but with relatively low metabolic rate, resulting in their stable content. This study preliminarily explored the digestive characteristics of flavonoid components in XECQ in the infant gastrointestinal environment, which laid a foundation for further studying the absorption, transport and metabolism of pharmacodynamics components in XECQ, and facilitated the study of the biopharmaceutical pro-perties of pediatric Chinese medicine.

Eucommia ulmoides Oliver's Multitarget Mechanism for Treatment of Ankylosing Spondylitis: A Study Based on Network Pharmacology and Molecular Docking.

Background: Eucommia ulmoides Oliver (EU) is a plant used in Chinese medicine as a medicinal herb to treat autoimmune and inflammatory conditions. We used network pharmacology to examine the active ingredients and estimate the main targets and pathways affected by EU when it is used to treat ankylosing spondylitis (AS). Materials and Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to search for active ingredients in EU and their target proteins. The GeneCards Database was used to find AS-related targets. The targets from the EU and AS searches that coincided were selected by constructing a Venn diagram. Then, a STRING network platform and Cytoscape software were used to analyse the protein-protein interaction (PPI) network and key targets. The strong affinity between EU and its targets was confirmed using molecular docking techniques. The Gene Ontology and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis of overlapping targets was performed using the database for annotation, visualization, and integrated discovery online tool. Results: The number of active ingredients against AS in EU was discovered to be 28. Major targets against AS in the PPI network and core targets analyses were identified as IL-1B, PTGS2, IL-8, nMMP-9, CCL2, MYC, and IL-2. Furthermore, molecular docking studies showed the strong affinity between EU's bioactive molecules and their AS targets. Enrichment analysis revealed that active ingredients from EU were involved in a variety of biological processes, including the response to molecules derived from bacteria, extracellular stimuli, nutrient levels, and the regulation of reactive oxygen species, all of which are mediated by interleukin-17, TNF-α, and other signalling pathways. Conclusion: The therapy for AS using EU involves a multitarget, multipathway, and multiselection mechanism that includes anti-inflammatory and analgesic effects. This study provides a theoretical basis for future research into targeted molecular therapies for AS.

Recent progress on in-situ chemical oxidation for the remediation of petroleum contaminated soil and groundwater.

Accidental oil leaks and spills can often result in severe soil and groundwater pollution. In situ chemical oxidation (ISCO) is a powerful and efficient remediation technology. In this review, the applications and recent advances of three commonly applied in-situ oxidants (hydrogen peroxide, persulfate, and permanganate), and the gap in remediation efficiency between lab-scale and field-scale applications is critically assessed. Feasible improvements for these measures, especially solutions for the 'rebound effect', are discussed. The removal efficiencies reported in 108 research articles related to petroleum-contaminated soil and groundwater were analyzed. The average remediation efficiency of groundwater (82.7%) by the three oxidants was higher than that of soil (65.8%). A number of factors, including non-aqueous phase liquids, adsorption effect, the aging process of contaminants, low-permeability zones, and vapor migration resulted in a decrease in the remediation efficiency and caused the residual contaminants to rebound from 19.1% of the original content to 57.7%. However, the average remediation efficiency of ISCO can be increased from 40.9% to 75.5% when combined with other techniques. In the future, improving the utilization efficiency of reactive species and enhancing the contact efficiency between oxidants and petroleum contaminants will be worthy of attention. Multi-technical combinations, such as the ISCO coupled with phase-transfer, viscosity control, controlled release or natural attenuation, can be effective methods to solve the rebound problem.

[Research on artificial substitutes of rare and endangered animal medicinal materials and industrialization].

Rare and endangered animal medicine, a kind of important Chinese medicine, plays an irreplaceable role in the prevention and treatment of serious acute and chronic diseases and major diseases. Due to resource limitation and depletion and the increasing demand, rare and endangered medicinal animal resources have been drastically reduced or even extinct, which threatens the inheritance of traditional Chinese medicine, the integrity of clinical medicine, and the development of the traditional Chinese medicine industry. For the protection and sustainable utilization of Chinese medicinal resources, artificial substitutes came into being. However, there is still a lack of systematic research on the pharmacological effects and clinical applications of artificial substitutes and whether they can completely replace the original medicinal materials in clinical practice. Therefore, this study focuses on the status quo of rare and endangered animal medicinal materials and their artificial substitutes that have been marketed. To be specific, the two were compared and whether the artificial substitutes can completely replace the original medicinal materials was analyzed. In addition, constructive suggestions on the industrialization of artificial substitutes were put forward, which was expected to promote the sustainable development of Chinese medicinal resources.

[History and application of foreign medicinal resources serving healthcare industry].

Foreign medicinal resources have always been an important part of Chinese medicine and have made great contributions to the development of the Chinese medical and health industry. Since the opening of the Silk Road in the Han Dynasty, foreign medicinal resources have been introduced for different purposes, some of which have become Chinese medicine in clinical practice and are still in use today.Today, foreign medicinal resources also serve the Big Health industry in China. They are introduced and applied to the fields in the Big Health industry, such as food, cosmetics, health products, decoction pieces, and daily chemical products. With the integration and development of the "Healthy China" initiative, more foreign resources will enter the Big Health industry. This paper retrospectedthe history of foreign medicinal resources serving the ancient medical and health industry, reviewedits current development under the Big Health industry, summarizedthe experience of foreign medicinal resources serving the ancient medical and health industry, as well as the development and problems of new foreign medicinal resources, and put forward some suggestions to provide ideas for the development and application of foreign medicinal resources under the Big Health industry.

Application Analysis of Radial Basis Function Neural Network Algorithm of Genetic Algorithm for Environmental Restoration and Treatment Effect Evaluation of Decommissioned Uranium Tailings Ponds.

A new analysis method for the environmental stability of uranium tailing ponds is established in this paper, and the stability intervals and environmental stability rates of indicators are defined in precise mathematical language and analyzed with examples. The results show that the overall environmental stability of this uranium tailings pond is still in a poor state after the first phase of decommissioning treatment, and special decommissioning treatment should be carried out for factors such as pH and radionuclides Po and Pb. Using the powerful nonlinear mapping function of the artificial neural network, a radial basis function neural network algorithm was constructed to predict the environmental stability of the uranium tailing pond. It provides a new feasible method for the comprehensive evaluation technology of uranium tailings ponds. Accuracy in DOA Estimation. The research work in this paper mainly analyzed the environmental stabilization process and stability of decommissioned uranium tailings ponds, proposed a new concept of environmental stability with ecological and environmental protection concepts and gave it a new connotation, established an environmental stability evaluation index system for decommissioned uranium tailings ponds through index screening by using rough set theory, comprehensively considered the influence of environmental factors such as external wastewater and exhaust gas, and realized the multifactor. The system of evaluation indexes for the stability of decommissioned uranium tailings ponds was established by combining multiple factors, and the long-term monitoring and modeling of the environmental stabilization process of decommissioned uranium tailings ponds was carried out by using mathematical methods. The results show that the RBFNN-GA algorithm can reduce the training error of the random radial basis function neural network, improve the generalization ability of the network, and make it capable of handling large data sets.

Kellerin from Ferula sinkiangensis exerts neuroprotective effects after focal cerebral ischemia in rats by inhibiting microglia-mediated inflammatory responses.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferula sinkiangensis K. M. Shen is a traditional Chinese medicine that has a variety of pharmacological properties relevant to neurological disorders and inflammations. Kellerin, a novel compound extracted from Ferula sinkiangensis, exerts a strong anti-neuroinflammatory effect by inhibiting microglial activation. Microglial activation plays a vital role in ischemia-induced brain injury. However, the potential therapeutic effect of kellerin on focal cerebral ischemia is still unknown. AIM OF THE STUDY: To explore the effect of kellerin on cerebral ischemia and clarify its possible mechanisms, we applied the middle cerebral artery occlusion (MCAO) model and the LPS-activated microglia model in our study. MATERIALS AND METHODS: Neurological outcome was examined according to a 4-tiered grading system. Brain infarct size was measured using TTC staining. Brain edema was calculated using the wet weight minus dry weight method. Neuron damage and microglial activation were observed by immunofluorescence in MCAO model in rats. In in vitro studies, microglial activation was examined by flow cytometry and the viability of neuronal cells cultured in microglia-conditioned medium was measured using MTT assay. The levels of pro-inflammatory cytokines were measured by qRT-PCR and ELISA. The proteins involved in NF-κB signaling pathway were determined by western blot. Intracellular ROS was examined using DCFH-DA method and NADPH oxidase activity was measured using the NBT assay. RESULTS: We found that kellerin improved neurological outcome, reduced brain infarct size and decreased brain edema in MCAO model in rats. Under the pathologic conditions of focal cerebral ischemia, kellerin alleviated neuron damage and inhibited microglial activation. Moreover, in in vitro studies of LPS-stimulated BV2 cells kellerin protected neuronal cells from being damaged by inhibiting microglial activation. Kellerin also reduced the levels of pro-inflammatory cytokines, suppressed the NF-κB signaling pathway, and decreased ROS generation and NADPH oxidase activity. CONCLUSIONS: Our discoveries reveal that the neuroprotective effects of kellerin may largely depend on its inhibitory effect on microglial activation. This suggests that kellerin could serve as a novel anti-inflammatory agent which may have therapeutic effects in ischemic stroke.

Safety and Efficacy of Ginkgo-Damole and Nitroglycerin or Sodium Nitroprusside on Hypertensive Cerebropathies: A Meta-Analysis.

OBJECTIVE: To systematically evaluate the safety and efficacy of ginko-damole combined with nitroglycerin or unitary sodium nitroprusside on hypertensive cerebropathy. METHODS: Four Chinese databases (VIP, CBM, Wanfang database, and CNKI database) and three English databases (Cochrane, PubMed, and EMBASE) were used to screen randomised controlled trials (RCTs) on treatments of hypertensive cerebropathy using both ginko-damole and nitroglycerin or unitary sodium nitroprusside. Outcomes included clinical effect, blood pressure after treatment, and adverse effects. These indicators were then analysed statistically using the RevMan 5.3 and Stata 12.0 software. RESULTS: Altogether, 16 RCTs including 1507 patients with hypertensive cerebropathy were included in the present meta-analysis, of which, 755 patients treated with combined ginko-damole and nitroglycerin were included in the observation group and 752 patients treated with sodium nitroprusside were included in the control group. The curative effect of the observation group was significantly better than that of the control group (RR: 1.115 [1.077, 1.155], p < 0.05). DBPs of the observation and control groups were both lower after treatment, and no significant difference was observed between the observation and control groups (MD: -1.072 [-2.578, 0.434], p > 0.05). SBPs in the observation group were significantly lower than those in the control group (MD: -2.842 [-5.222, -0.462], p < 0.05). The probability of adverse response in both groups did not differ significantly (RR: 0.752 [0.412, 1.374], p > 0.05). CONCLUSION: Compared with sodium nitroprusside, the combined ginkgo-damole and nitroglycerin could better control blood pressure in patients with hypertensive cerebropathy and showed enhanced clinical effects and improved safety. However, due to poor quality of the included studies, results of the present meta-analysis should be confirmed by more stringent RCTs.

Kellerin alleviates cognitive impairment in mice after ischemic stroke by multiple mechanisms.

Ischemic stroke is a global disease with high disability and mortality rates. Cognitive impairment is one of the major clinical features of ischemic stroke, and microglia-mediated inflammation has been shown to be an important contributor to the pathogenesis of ischemic stroke. Kellerin, extracted from Ferula sinkiangensis, was previously shown to inhibit microglial activation and exert a strong anti-neuroinflammatory effect. However, there is no report of the potential therapeutic effect of kellerin on ischemic stroke by targeting microglial cells. In this study, we wanted to examine the effects of kellerin on ischemic stroke in the bilateral common carotid artery occlusion (BCCAO) model and the lipopolysaccharide (LPS)-activated microglia model. We found that kellerin alleviated cognitive impairment, decreased neuronal loss, suppressed microglial activation, and transformed microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype in BCCAO mice. Moreover, in in vitro studies, we found that kellerin regulated microglial polarization and inhibited the NLRP3 and MAPK signaling pathways after LPS treatment. These findings provide a new understanding of the function of kellerin in ischemic stroke, and suggest that kellerin could be a potential therapeutic agent for the treatment of ischemic stroke.

Gomisin M2 from Baizuan suppresses breast cancer stem cell proliferation in a zebrafish xenograft model.

Gomisin M2 isolated from Schisandra viridis A. C. Smith has potential anti-tumor effects on certain cancers, including breast cancer. However, only a few investigations have been conducted on the effects of Gomisin M2 on breast cancer stem cells (CSCs), which have the ability to self-renew and differentiate, as a possible strategy to resolve cancer cell resistance to apoptosis and to improve treatments. It is essential to investigate the effects of Gomisin M2 on breast cancer stem cells (BCSCs). In this study, we enriched breast cancer stem cells with CD44+/CD24- from MDA-MB-231 and HCC1806 cells through magnetic-activated cell sorting and cultured these in serum-free medium. The ability of Gomisin M2 to kill breast cancer stem cells was evaluated in vitro and in vivo. Gomisin M2 significantly inhibited the proliferation of the triple-negative breast cancer cell lines and mammosphere formation in breast CSCs and downregulated the Wnt/ß-catenin self-renewal pathway. Moreover, Gomisin M2 induced apoptosis and blocked the mitochondrial membrane potential of BCSCs. Gomisin M2 suppressed the proliferation of MDA-MB-231 and HCC1806 xenografts in zebrafish. Together, these findings suggest that the anti-BCSC activity of Gomisin M2 could become a promising starting point for the discovery of novel BCSC-targeting drugs.

Transcriptome analysis of Panax zingiberensis identifies genes encoding oleanolic acid glucuronosyltransferase involved in the biosynthesis of oleanane-type ginsenosides.

MAIN CONCLUSION: Oleanolic acid glucuronosyltransferase (OAGT) genes synthesizing the direct precursor of oleanane-type ginsenosides were discovered. The four recombinant proteins of OAGT were able to transfer glucuronic acid at C-3 of oleanolic acid that yields oleanolic acid 3-O-ß-glucuronide. Ginsenosides are the primary active components in the genus Panax, and great efforts have been made to elucidate the mechanisms underlying dammarane-type ginsenoside biosynthesis. However, there is limited information on oleanane-type ginsenosides. Here, high-performance liquid chromatography analysis demonstrated that oleanane-type ginsenosides (particularly ginsenoside Ro and chikusetsusaponin IV and IVa) are the abundant ginsenosides in Panax zingiberensis, an extremely endangered Panax species in southwest China. These ginsenosides are derived from oleanolic acid 3-O-ß-glucuronide, which may be formed from oleanolic acid catalyzed by an unknown oleanolic acid glucuronosyltransferase (OAGT). Transcriptomic analysis of leaves, stems, main roots, and fibrous roots of P. zingiberensis was performed, and a total of 46,098 unigenes were obtained, including all the identified homologous genes involved in ginsenoside biosynthesis. The most upstream genes were highly expressed in the leaves, and the UDP-glucosyltransferase genes were highly expressed in the roots. This finding indicated that the precursors of ginsenosides are mainly synthesized in the leaves and transported to different parts for the formation of particular ginsenosides. For the first time, enzyme activity assay characterized four genes (three from P. zingiberensis and one from P. japonicus var. major, another Panax species with oleanane-type ginsenosides) encoding OAGT, which particularly transfer glucuronic acid at C-3 of oleanolic acid to form oleanolic acid 3-O-ß-glucuronide. Taken together, our study provides valuable genetic information for P. zingiberensis and the genes responsible for synthesizing the direct precursor of oleanane-type ginsenosides.

Antiviral activity of aconite alkaloids from Aconitum carmichaelii Debx.

Four diterpenoid alkaloids, namely, (a) hypaconitine, (b) songorine, (c) mesaconitine and (d) aconitine, were isolated from the ethanol root extract of Aconitum carmichaelii Debx. The antiviral activities of these alkaloids against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) were evaluated. Antiviral activity test in vivo showed that compounds a and c, which were C19-diterpenoid alkaloids, showed inactivation efficacy values of 82.4 and 85.6% against TMV at 500 µg/mL, respectively. By contrast, compound c presented inactivation activity of 52.1% against CMV at 500 µg/mL, which was almost equal to that of the commercial Ningnanmycin (87.1% inactivation activity against TMV and 53.8% inactivation activity against CMV). C19-Diterpenoid alkaloids displayed moderate to high antiviral activity against TMV and CMV at 500 µg/mL, dosage plays an important role in antiviral activities. This paper is the first report on the evolution of aconite diterpenoid alkaloids for antiviral activity against CMV.

Mapping genes for drug chronotherapy.

Genome-wide association studies have been increasingly used to map and characterize genes that contribute to interindividual variation in drug response. Some studies have integrated the pharmacokinetic (PK) and pharmacodynamic (PD) processes of drug reactions into association mapping, gleaning new insight into how genes determine the dynamic relationship of drug effect and drug dose. Here, we present an evolutionary framework by which two distinct concepts, chronopharmacodynamics and heterochrony (describing variation in the timing and rate of developmental events), are married to comprehend the pharmacogenetic architecture of drug response. The resulting new concept, heterochronopharmacodynamics (HCPD), can better interpret how genes influence drug efficacy and drug toxicity according to the circadian rhythm of the body and changes in drug concentration.

[Study on herbal textual evolution and flavonoids and their pharmacological of Spatholobi Caulis].

Spatholobi Caulis, the vine stem of Spatholobus suberectus and widely used in China and Southeast Asian nations, has the effects on nourishing the blood and promoting blood flow, regulating menstruation and relieving pain, and invigorating the nerves. Through consulting the herbal textual and local chronicles, we summarized the original textual research and medicinal evolution on Spatholobi Caulis to analyze the changes of varieties in different historical periods. Further, the major active ingredient in Spatholobi Caulis was discussed. According to the literature to date, 60 flavonoids compounds have been isolated and could be divided into isoflavones, dihydroflavones, flavanols, dihydroflavonols, procyaninides, chalcones, pterocarpans, isoflavanols, isoflavanones and aurone according to their molecular structures. These indicative ingredients in Spatholobi Caulis showed pharmacological activities on regulation of the blood system, anti-tumor, anti-oxidation, anti-virus, anti-bacteria and inhibition of melanin deposition. This review will provide reference and basis for the sustainable use of resources and industry development on Spatholobi Caulis.