Fluorophore Label-Free Light-up Near Infrared Deoxyribonucleic Acid Nanosensor for Monitoring Extracellular Potassium Levels.

Fluorescent DNA nanosensors have been widely used due to their unique advantages, among which the near-infrared (NIR) imaging mode can provide deeper penetration depth and lower biological background for the nanosensors. However, efficient NIR quenchers require ingenious design, complex synthesis, and modification, which severely limit the development of NIR DNA nanosensors. Label-free strategies based on G-quadruplex (G4) and NIR G4 dyes were first introduced into in situ extracellular imaging, and a novel NIR sensing strategy for the specific detection of extracellular targets is proposed. The strategy avoids complex synthesis and site-specific modification by controlling the change of the NIR signal through the formation of a G4 nanostructure. A light-up NIR DNA nanosensor based on potassium ion (K+)-sensitive G4 chain PS2.M was constructed to verify the strategy. PS2.M forms a stable G4 nanostructure in the presence of K+ and activates the NIR G4 dye CSTS, thus outputting NIR signals. The nanosensor can rapidly respond to K+ with a linear range of 5-50 mM and has good resistance to interference. The nanosensor with cholesterol can provide feedback on the changes in extracellular K+ concentration in many kinds of cells, serving as a potential tool for the study of diseases such as epilepsy and cancer, as well as the development of related drugs. The strategy can be potentially applied to the NIR detection of a variety of extracellular targets with the help of functional DNAs such as aptamer and DNAzyme.

Synthetic Biology-based Construction of Unnatural Perylenequinones with Improved Photodynamic Anticancer Activities.

The construction of structural complexity and diversity of natural products is crucial for drug discovery and development. To overcome high dark toxicity and poor photostability of natural photosensitizer perylenequinones (PQs) for photodynamic therapy, herein, we aim to introduce the structural complexity and diversity to biosynthesize the desired unnatural PQs in fungus Cercospora through synthetic biology-based strategy. Thus, we first elucidate the intricate biosynthetic pathways of class B PQs and reveal how the branching enzymes create their structural complexity and diversity from a common ancestor. This enables the rational reprogramming of cercosporin biosynthetic pathway in Cercospora to generate diverse unnatural PQs without chemical modification. Among them, unnatural cercosporin A displays remarkably low dark toxicity and high photostability with retention of great photodynamic anticancer and antimicrobial activities. Moreover, it is found that, unlike cercosporin, unnatural cercosporin A could be selectively accumulated in cancer cells, providing potential targets for drug development. Therefore, this work provides a comprehensive foundation for preparing unnatural products with customized functions through synthetic biology-based strategies, thus facilitating drug discovery pipelines from nature.

Bone marrow mesenchymal stem cell-derived exosomes attenuate the maturation of dendritic cells and reduce the rejection of allogeneic transplantation.

BACKGROUND: Bone mesenchymal stem cell (BMSC)-derived exosomes (B-exos) are attractive for applications in enabling alloantigen tolerance. An in-depth mechanistic understanding of the interaction between B-exos and dendritic cells (DCs) could lead to novel cell-based therapies for allogeneic transplantation. OBJECTIVES: To examine whether B-exos exert immunomodulatory effects on DC function and maturation. MATERIAL AND METHODS: After mixed culture of BMSCs and DCs for 48 h, DCs from the upper layer were collected to analyze the expression levels of surface markers and mRNAs of inflammation-related cytokines. Then, before being collected to detect the mRNA and protein expression levels of indoleamine 2,3-dioxygenase (IDO), the DCs were co-cultured with B-exos. Then, the treated DCs from different groups were co-cultured with naïve CD4+ T cells from the mouse spleen. The proliferation of CD4+ T cells and the proportion of CD4+CD25+Foxp3+ T cells were analyzed. Finally, the skins of BALB/c mice were transplanted to the back of C57 mice in order to establish a mouse allogeneic skin transplantation model. RESULTS: The co-culture of DCs with BMSCs downregulated the expression of the major histocompatibility complex class II (MHC-II) and CD80/86 costimulatory molecules on DCs. Moreover, B-exos increased the expression of IDO in DCs treated with lipopolysaccharide (LPS). The proliferation of CD4+CD25+Foxp3+ T cells increased when cultured with B-exos-exposed DCs. Finally, mice recipients injected with B-exos-treated DCs had significantly prolonged survival after receiving the skin allograft. CONCLUSIONS: Taken together, these data suggest that the B-exos suppress the maturation of DCs and increase the expression of IDO, which might shed light on the role of B-exos in inducing alloantigen tolerance.

Self-assembly of DNA nanospheres with controllable size and self-degradable property for enhanced antitumor chemotherapy.

Controllable size, self-degradability and targeting property are important for a precise improvement of anticancer effects and reduction of side effects of drug vehicles. Here, a series of DNA nanospheres with controllable size and self-degradation ability were constructed through the hybridization of two i-motif strands and two linker strands for targeted cancer therapy. DNA nanospheres with different sizes were fabricated by regulating the linker sequence, and their pH-responsive self-degradation property was realized by the introduction of the i-motif strand. Moreover, the ZY11 aptamer was introduced to endow the DNA nanospheres with targeting property toward SMMC-7721 cancer cells. The results revealed that the appropriate size of DNA nanospheres (80 nm) highly promoted the internalization by mammalian cells. The results of DLS, AFM and CD spectra showed that the DNA nanospheres were stable in a physiological environment but they self-degraded in a slightly acidic environment due to the existence of the i-motif strand. Moreover, the fluorescence of DOX@AP-NSs2 was triple at pH = 5.0 than at pH = 7.4, which further confirmed the pH-responsive drug release performance. The above results proved that the use of DOX@AP-NSs2 is a promising approach to accelerate the rapid release of drugs into the tumors and avoid drug leakage into the normal tissue. The results at a cellular level and in vivo confirmed the pH-responsive targeted antitumor effect. Hence, the novel DNA nanospheres with controllable size and self-degradable property represent a potential tool for targeted drug delivery and cancer therapy.

Identification of two chickpea multidrug and toxic compound extrusion transporter genes transcriptionally upregulated upon aluminum treatment in root tips.

Aluminum (Al) toxicity poses a significant challenge for the yield improvement of chickpea, which is an economically important legume crop with high nutritional value in human diets. The genetic basis of Al-tolerance in chickpea remains unclear. Here, we assessed the Al-tolerance of 8 wild Cicer and one cultivated chickpea (PBA Pistol) accessions by measuring the root elongation in solution culture under control (0 µM Al3+) and Al treatments (15, 30 µM Al3+). Compared to PBA Pistol, the wild Cicer accessions displayed both tolerant and sensitive phenotypes, supporting wild Cicer as a potential genetic pool for Al-tolerance improvement. To identify potential genes related to Al-tolerance in chickpea, genome-wide screening of multidrug and toxic compound extrusion (MATE) encoding genes was performed. Fifty-six MATE genes were identified in total, which can be divided into 4 major phylogenetic groups. Four chickpea MATE genes (CaMATE1-4) were clustered with the previously characterized citrate transporters MtMATE66 and MtMATE69 in Medicago truncatula. Transcriptome data showed that CaMATE1-4 have diverse expression profiles, with CaMATE2 being root-specific. qRT-PCR analyses confirmed that CaMATE2 and CaMATE4 were highly expressed in root tips and were up-regulated upon Al treatment in all chickpea lines. Further measurement of carboxylic acids showed that malonic acid, instead of malate or citrate, is the major extruded acid by Cicer spp. root. Protein structural modeling analyses revealed that CaMATE2 has a divergent substrate-binding cavity from Arabidopsis AtFRD3, which may explain the different acid-secretion profile for chickpea. Pangenome survey showed that CaMATE1-4 have much higher genetic diversity in wild Cicer than that in cultivated chickpea. This first identification of CaMATE2 and CaMATE4 responsive to Al3+ treatment in Cicer paves the way for future functional characterization of MATE genes in Cicer spp., and to facilitate future design of gene-specific markers for Al-tolerant line selection in chickpea breeding programs.

Nanoflare Couple: Multiplexed mRNA Imaging and Logic-Controlled Combinational Therapy.

Theranostics, which combines both diagnostic and therapeutic capabilities in one dose, has always been an intractable challenge in personalized cancer treatment. Herein, a versatile nanotheranostic platform "nanoflare couple (NC)" has been developed for in situ multiplex cancer-related mRNA imaging and subsequent logic-controlled aggregation of gold nanoparticles, leading to gene therapy and photothermal therapy upon irradiation with infrared light. As a proof of concept, TK1 and survivin mRNAs that are highly expressed in most tumor tissues are selected as endogenous cancer indicators and therapy triggers to design the NC. Mice bearing breast cancer cells MCF-7 are prepared as a model to test its efficacy. The in vitro and in vivo assays validate that the NC show the capability for multiplexed mRNA imaging and high efficiency for logic-controlled combinational therapy of breast cancer.

Discovery of the Biosynthetic Pathway of Beticolin 1 Reveals a Novel Non-Heme Iron-Dependent Oxygenase for Anthraquinone Ring Cleavage.

This study used light-mediated comparative transcriptomics to identify the biosynthetic gene cluster of beticolin 1 in Cercospora. It contains an anthraquinone moiety and an unusual halogenated xanthone moiety connected by a bicyclo[3.2.2]nonane. During elucidation of the biosynthetic pathway of beticolin 1, a novel non-heme iron oxygenase BTG13 responsible for anthraquinone ring cleavage was discovered. More importantly, the discovery of non-heme iron oxygenase BTG13 is well supported by experimental evidence: (i) crystal structure and the inductively coupled plasma mass spectrometry revealed that its reactive site is built by an atypical iron ion coordination, where the iron ion is uncommonly coordinated by four histidine residues, an unusual carboxylated-lysine (Kcx377) and water; (ii) Kcx377 is mediated by His58 and Thr299 to modulate the catalytic activity of BTG13. Therefore, we believed this study updates our knowledge of metalloenzymes.

Fabrication, GSH-responsive drug release, and anticancer properties of thioctic acid-based intelligent hydrogels.

Injectable hydrogels are potential local drug delivery systems since they contain plenty of water and soft like biological tissues. Such hydrogels could be injected directly into the tumor site where the drug is released under the tumor microenvironment. However, drug loaded hydrogels for cancer treatment based on lipoic acid (natural small molecule) have not been exploited. Here, a novel poly(lipoic acid)-poly(ethylene glycol) (PEG-PTA) hydrogels were prepared through a two-step reaction. The hydrogels contained disulfide bonds, so they could be degraded via the thiol exchange reaction with the abundant GSH in the tumor microenvironment, and subsequently release the drug. The results in vitro and at cellular level showed that the hydrogels were degraded and released the drugs only in the presence of GSH. Therefore, the injectable GSH-responsive hydrogels are promising to be served as an intelligent drug delivery system for cancer treatment.

Capsule-like molecular imprinted polymer nanoparticles for targeted and chemophotothermal synergistic cancer therapy.

Selective cancer cell targeting, controlled drug release, easy construction and multiple therapeutic modalities are some of the desirable characteristics of drug delivery systems. We designed and built simple capsule-like molecular imprinted polymer (MIP)-based nanoparticles for targeted and chemo-photothermal synergistic cancer therapy. Using dopamine (DA) as functional monomer, cross-linking agent as well as photo-thermal agent, ZIF-8 (zeoliticimidazolate framework-8) as drug carrier, epitope of EGFR (epidermal growth factor receptor) as template molecules, molecular imprinted polymer (MIP) drug carrier was constructed. The ability of MIP layer to bind to EGFR epitope endowed the MD (DOX@MIP) particles to recognize EGFR-overexpressing cancer cells, while the pH-responsiveness and photothermal conversion ability of PDA (polydopamine) achieved chemo-photothermal synergistic effects upon NIR irradiation. Taken together, the MD nanoparticles integrated cancer cell targeting recognition, intelligent drug release, biocompatibility and chemo-photothermal effects, and is therefore a promising tool for targeted cancer therapy with minimal toxicity to normal cells, as well as tumor imaging.

How useful is sentinel lymph node biopsy for the status of lymph node metastasis in cT1N0M0 gastric cancer? A systematic review and meta-analysis.

Sentinel lymph node biopsy (SLNB) is intriguing because it is expected to further expand the indication of endoscopic resection (ER) for cT1N0M0 gastric cancer and as an additional operation for post-ER gastric cancer. The aim of our study was to perform a systematic review and meta-analysis on the feasibility and diagnostic value of SLNB technique in patients with cT1N0M0 gastric cancer. Eligible studies were systematically searched in PubMed, Embase, and Cochrane Library databases from inception to April 2020. A random-effect model was used to pool the data, and subgroup analysis was used to explain the heterogeneities. A total of 22 clinical studies (1993 patients with cT1N0M0 gastric cancer) were included. The pooled SLN identification rate, sensitivity, specificity, and diagnostic odds ratio with 95% confidence intervals were 0.99 (0.99-1.00), 0.92 (0.88-0.95), 1.00 (1.00-1.00), and 832.8 (395.5-1753.6), respectively. The summary receiver operator characteristic displayed a test accuracy of 99.3%. Subgroup analysis found an improved SLN sensitivity for studies with the mean number of SLNs > 4 and studies stained with a combination of hematoxylin-eosin with immunohistochemistry (HE + IHC). Further, studies using the basin dissection were associated with a higher SLN identification rate. The current meta-analysis provides data that favors the use of SLNB for predicting the status of lymph node metastasis in patients with cT1N0M0 gastric cancer. However, establishing standard procedure and suitable criteria for further application and optimization of SLNB is urgently needed.

A 1232 bp upstream sequence of glutamine synthetase 1b from Eichhornia crassipes is a root-preferential promoter sequence.

BACKGROUND: Glutamine synthetase (GS) acts as a key enzyme in plant nitrogen (N) metabolism. It is important to understand the regulation of GS expression in plant. Promoters can initiate the transcription of its downstream gene. Eichhornia crassipes is a most prominent aquatic invasive plant, which has negative effects on environment and economic development. It also can be used in the bioremediation of pollutants present in water and the production of feeding and energy fuel. So identification and characterization of GS promoter in E. crassipes can help to elucidate its regulation mechanism of GS expression and further to control its N metabolism. RESULTS: A 1232 bp genomic fragment upstream of EcGS1b sequence from E. crassipes (EcGS1b-P) has been cloned, analyzed and functionally characterized. TSSP-TCM software and PlantCARE analysis showed a TATA-box core element, a CAAT-box, root specific expression element, light regulation elements including chs-CMA1a, Box I, and Sp1 and other cis-acting elements in the sequence. Three 5'-deletion fragments of EcGS1b upstream sequence with 400 bp, 600 bp and 900 bp length and the 1232 bp fragment were used to drive the expression of ß-glucuronidase (GUS) in tobacco. The quantitative test revealed that GUS activity decreased with the decreasing of the promoter length, which indicated that there were no negative regulated elements in the EcGS1-P. The GUS expressions of EcGS1b-P in roots were significantly higher than those in leaves and stems, indicating EcGS1b-P to be a root-preferential promoter. Real-time Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analysis of EcGS1b gene also showed higher expression in the roots of E.crassipes than in stems and leaves. CONCLUSIONS: EcGS1b-P is a root-preferential promoter sequence. It can specifically drive the transcription of its downstream gene in root. This study will help to elucidate the regulatory mechanisms of EcGS1b tissue-specific expression and further study its other regulatory mechanisms in order to utilize E.crassipes in remediation of eutrophic water and control its overgrowth from the point of nutrient metabolism.

A water-soluble selenium-enriched polysaccharide produced by Pleurotus ostreatus: Purification, characterization, antioxidant and antitumor activities in vitro.

The development and application of new selenium-enriched polysaccharides has become a critical topic in recent years. In this study, a natural selenium-enriched polysaccharide fraction (Se-POP-21) produced by Pleurotus ostreatus was purified, characterized, and investigated the antioxidant and antitumor activities in vitro. The Se-POP-21 was mainly composed of mannose, glucose, galactose and arabinose, with a molar ratio of 18.01:2.40:26.15:7.34, of which molecular weight was 15,888 Da and the selenium content was 5.31 µg/g. Spectral analysis demonstrated that Se-POP-21 represented a non-triple helix pyranopolysaccharide and selenium occurred in the form of C-O-Se and SeO. Molecular size and morphology studies showed that Se-POP-21 exhibited a spherical shape with a particle size distribution between 100 and 200 nm, even though Se-POP-21 aggregates were also found with a size between 500 and 600 nm. In addition, Se-POP-21 showed strong scavenging capacity to DPPH and hydroxyl radical. More, cell experiments showed that Se-POP-21 could reduce viability of A549, SKOV3, HepG2 and MCF-7 cells, induce apoptosis and inhibit metastasis of A549 cells. A potential mechanism was that Se-POP-21 inhibited the epithelial-to-mesenchymal transition of cancer cells. Se-POP-21 featured no significant effect on normal cells. Se-POP-21 showed great potential to develop into a natural antioxidant or low-toxic antitumor drug.

Dually acid- and GSH-triggered bis(ß-cyclodextrin) as drugs delivery nanoplatform for effective anticancer monotherapy.

The intrinsic poor solubility and limited load capacity of ß-cyclodextrins (ß-CDs) results in reduced bioavailability, rendering the material unsuitable in complex biological environments. In this work, a pair of ß-CDs was methylated and covalently linked with acid-sensitive acylhydrazone and GSH-sensitive disulfide bonds to ensure a precise drug release pattern. The hydrophobic anticancer drug doxorubicin (Dox) was encapsulated inside the hydrophobic core of bis(ß-CD) via hydrophobic association with loading capacity of 24% in weight and a hydrodynamic size of about 100 nm. When exposed to acidic and reductive environments, the acylhydrazone and disulfide bonds were found to be cleaved, resulting in Dox release. Using fluorescence imaging and flow cytometry analysis, the designed bis(ß-CD) were determined to activate the drug release behavior by specific intracellular stimuli (pH and GSH). In vivo studies demonstrated specific drug delivery characteristics and controlled drug release behaviors in the tumor sites, giving rise to high antitumor activity and low toxicity. Taken in concert, this dual stimuli-responsive bis(ß-CD) with superior amphiphilicity and biocompatibility features showed great potential for future clinical applications.

Physicochemical characterization and antitumor activity in vitro of a selenium polysaccharide from Pleurotus ostreatus.

Selenium-enriched polysaccharides have been gaining great attention for their antitumor activity in recent years. In this study, a novel selenium polysaccharide fraction (Se-POP-3) produced by Pleurotus ostreatus was characterized and its antitumor activity explored at cellular level. Results showed that Se-POP-3 has 25.9 µg/g of selenium, an average molecular weight of 16,106 Da, and is mainly composed of mannose, glucose and galactose with a molar ratio of 1.7:49.6:2.4. Spectra analysis revealed Se-POP-3 as a pyranopolysaccharide linked by α-glycoside bonds in the main chain, and selenium may occur in the form of COSe and SeO. A single sphere of Se-POP-3 has 50-60 nm in aqueous solution, even though it can agglomerate to form larger spherical structures. In vitro experiments with cancer and normal cell lines showed that Se-POP-3 can induce apoptosis and inhibit migration of cancer cells. Potential anticancer mechanism is that Se-POP-3 can disrupt the Bax/Bcl-2 protein ratio and inhibit the epithelial-to-mesenchymal transition (EMT) in cancer cells. Se-POP-3 showed no significant effect on the growth of normal cell lines. Se-POP-3 showed great potential as a broad-spectrum antitumor agent and dietary supplement.

A nanoprobe for ratiometric imaging of glutathione in living cells based on the use of a nanocomposite prepared from dual-emission carbon dots and manganese dioxide nanosheets.

A ratiometric fluorescence assay for glutathione (GSH) was developed. The novel assay is based on a nanoprobe composed of manganese dioxide nanosheets (MnO2 NS) and dual-emission carbon dots (de-CDs) with intrinsic GSH-response property. After construction of the nanoprobe, two emission peaks of de-CDs were suppressed to varying degrees by MnO2 NS. The suppression was relieved and the two emission peaks recovered proportionally when MnO2 NS was decomposed by GSH, thus realizing the ratiometric assay for micromolar GSH. The intrinsic responsiveness of de-CDs to millimolar GSH broadens the analytical range of the nanoprobe. An appropriate precursor, calcon-carboxylic acid, was screened out to synthesize de-CDs via one-step hydrothermal treatment. The de-CD@MnO2 NS nanoprobe can measure GSH concentrations through the fluorescence intensity ratio between 435 and 516 nm excited at 365 nm. The range of response was from 1 µM to 10 mM and the detection limit reached 0.6 µM (3σ criterion). Benefiting from its good biocompatibility, the proposed nanoprobe has excellent applicability for intracellular GSH imaging.Graphical abstract Schematic representation of glutathione (GSH) ratiometric detection. The nanoprobe is prepared from dual-emission carbon dots (de-CDs) and manganese dioxide nanosheets (MnO2 NS). GSH removes quenching effect by decomposing MnO2 NS and induces intrinsic response of de-CDs, which realizes ratiometric detection.

Intelligent Nanoprobe: Acid-Responsive Drug Release and In Situ Evaluation of Its Own Therapeutic Effect.

The design of an intelligent nanoprobe capable of intracellular controlled release of apoptosis inducers and subsequent high-fidelity imaging of the drug-induced apoptosis is highly desirable for precise cancer treatment. Herein, we report an intelligent nanoprobe that combined therapeutic and imaging functions in one agent. Briefly, a gold nanoparticle is designed to be conjugated with acid-responsive DNA duplexes (Dox intercalates in this region) and caspase-3-specific cleavable peptides (labeled with fluorophore). We demonstrated that the nanoprobe could efficiently deliver an anticancer drug (Dox) into cancer cells and achieve acid-responsive drug release. Furthermore, the apoptotic process was in situ-monitored by detection of fluorescence through the cleavage of the peptide linker by caspase-3, which is one of the executioner caspases involved in apoptosis. This newly developed nanoprobe could serve as a theranostic agent for targeted responsive chemotherapy and also provide feedback apoptosis imaging of the self-therapeutic effect.

Micelles via self-assembly of amphiphilic beta-cyclodextrin block copolymers as drug carrier for cancer therapy.

We developed intelligent, star-shaped amphiphilic ß-cyclodextrin (ß-CD) co-polymer nanocarriers to circumvent the poor drug loading and water-solubility of ß-CD. The secondary hydroxyl groups of ß-CD were methylated to improve solubility, and the primary hydroxyl groups were conjugated with mPEG-b-PCL-SH through disulfide linkage to amplify the hydrophobic cavity and enhance the stability of the nanocarrier. A series of amphiphilic ß-CD block copolymers (CCPPs) differing in molecular weights were synthesized that could self-assemble into core-shell nanospheres measuring 50-70 nm in water. The different CCPP carriers were screened for their drug loading, encapsulation and release efficiencies, and CCPP-2 showed the highest drug loading capacity of 31.9% by weight. These nanocarriers accumulated at the tumor site through the EPR effect and released the drug in a controlled manner in the reductive tumor microenvironment, with negligible premature leakage and side effects. Therefore, CCPP-2 shows significant potential as a smart and efficient nanovehicle for anticancer drug delivery.

ß-Cyclodextrin coated and folic acid conjugated magnetic halloysite nanotubes for targeting and isolating of cancer cells.

The study developed a simple, effective and inexpensive strategy for capturing, enriching and detecting circulating tumor cells (CTCs) by using folic acid (FA) as the targeting molecule instead of antibodies. This work constructed magnetic halloysite nanotubes (MHNTs) coated with biocompatible ß-cyclodextrin (CD), and conjugated to FA via a PEG-Ad linker, to specifically capture the FA receptor (FR)-overexpressing cancer cells. The capture efficiencies of MHNTs@ß-CD@Ad-PEG-FA for the Skov3, Hela and A549 cancer cells were 96.3%, 97.0% and 95.6% respectively. In addition, the nanoparticles were able to capture very low numbers of the cancer cells (25-500 cells/mL) from PBS and whole blood, as well as selectively capture the cancer cells over normal HEK 293 T cells. Furthermore, the captured cells were viable and grew normally in vitro, indicating the future potential of downstream analyses. This approach can be adapted for different CTCs, once the tumor-specific surface markers are identified and the efficacy of targeting ligands is established. Taken together, FA-conjugated MHNTs nanoparticles are a highly promising tool for isolating CTCs for the diagnosis and treatment of cancer.

Amphipathic ß-cyclodextrin nanocarriers serve as intelligent delivery platform for anticancer drug.

A novel glutathione-responsive (GSH-responsive) star-like amphiphilic polymer (C12H25)14-ß-CD-(S-S-mPEG)7 (denoted as CCSP) was designed for efficient antitumor drug delivery. The amphiphilic ß-cyclodextrin (ß-CD) self-polymerize in water to form a sphere with a diameter of 40-50 nm. The secondary hydroxyl groups of ß-CD were modified by dodecyl to form a hydrophobic core and the primary hydroxyl groups of ß-CD were decorated with PEG through disulfide bond to form a hydrophilic shell. Since the hydrophobic cavity of ß-CD was maintained, the hydrophobic core formed by dodecyl as well as cavity of ß-CD provided CCSP with a loading content as high as 39.6 wt%. Importantly, DOX@CCSP exhibited low drug leakage and negligible cytotoxicity in non-reductive physiological environment, while it showed rapid release and high cytotoxicity in reductive tumorous environment via the breakage of disulfide bond. In view of the above-mentioned advantages of DOX@CCSP nanocarriers such as high loading content, proper size, favorable stimulus-response release performance and low leakage, it is believed that CCSP may offer great potential to be used as an intelligent nanocarrier for anticancer drug delivery.

Fumigant and repellent activities of essential oil extracted from Artemisia dubia and its main compounds against two stored product pests.

The major chemical constituents of the essential oil extracted from Artemisia dubia wall. ex Bess. (Family: Asteraceae) were found as terpinolene (19.02%), limonene (17.40%), 2,5-etheno[4.2.2]propella-3,7,9-triene (11.29%), isoelemicin (11.05%) and p-cymene-8-ol (5.93%). Terpinolene and limonene were separated as main components from the essential oil. The essential oil showed fumigant toxicity against Tribolium castaneum and Liposcelis bostrychophila with LC50 values of 49.54 and 0.74 mg/L, respectively. The essential oil and isolated compounds of A. dubia showed repellency activities against both insects. Terpinolene and limonene showed the fumigant toxicity against T. castaneum. Terpinolene showed obvious fumigant toxicity against L. bostrychophila. The results indicated that the essential oil of A. dubia had potential to be developed into natural insecticides for controlling stored product pests.