Self-Assembled CuCo2S4 Nanoparticles for Efficient Chemo-Photothermal Therapy of Arterial Inflammation.

Cardiovascular disease caused by atherosclerosis (AS) seriously affects human health. Photothermal therapy (PTT) brings hope to the diagnosis and treatment of AS, with the development of nanotechnology. To improve treatment efficiency, self-assembled CuCo2S4 nanocrystals (NCs) were developed as a drug-delivery nanocarrier, triggered by near-infrared (NIR) light for efficient chemophotothermal therapy of arterial inflammation. The as-prepared self-assembled CuCo2S4 NCs exhibited excellent biocompatibility and a very high chloroquine (CL)-loading content. In addition, the self-assembled CuCo2S4 NCs/CL nanocomposites showed good photothermal performance, due to strong absorption in the NIR region, and the release of CL from the NCs/CL nanocomposites was driven by NIR light. When illuminated by NIR light, both PTT from the NCs and chemotherapy from the CL were simultaneously triggered, resulting in killing macrophages with a synergistic effect. Moreover, chemo-photothermal therapy with CuCo2S4 NCs/CL nanocomposites showed an effective therapeutic effect for arterial inflammation, in vivo. Our work demonstrated that chemo-photothermal therapy could be a promising strategy for the treatment of arterial inflammation against atherosclerosis.

A nanoselenium-coating biomimetic cytomembrane nanoplatform for mitochondrial targeted chemotherapy- and chemodynamic therapy through manganese and doxorubicin codelivery.

The cell membrane is widely considered as a promising delivery nanocarrier due to its excellent properties. In this study, self-assembled Pseudomonas geniculate cell membranes were prepared with high yield as drug nanocarriers, and named BMMPs. BMMPs showed excellent biosafety, and could be more efficiently internalized by cancer cells than traditional red cell membrane nanocarriers, indicating that BMMPs could deliver more drug into cancer cells. Subsequently, the BMMPs were coated with nanoselenium (Se), and subsequently loaded with Mn2+ ions and doxorubicin (DOX) to fabricate a functional nanoplatform (BMMP-Mn2+/Se/DOX). Notably, in this nanoplatform, Se nanoparticles activated superoxide dismutase-1 (SOD-1) expression and subsequently up-regulated downstream H2O2 levels. Next, the released Mn2+ ions catalyzed H2O2 to highly toxic hydroxyl radicals (·OH), inducing mitochondrial damage. In addition, the BMMP-Mn2+/Se nanoplatform inhibited glutathione peroxidase 4 (GPX4) expression and further accelerated intracellular reactive oxygen species (ROS) generation. Notably, the BMMP-Mn2+/Se/DOX nanoplatform exhibited increased effectiveness in inducing cancer cell death through mitochondrial and nuclear targeting dual-mode therapeutic pathways and showed negligible toxicity to normal organs. Therefore, this nanoplatform may represent a promising drug delivery system for achieving a safe, effective, and accurate cancer therapeutic plan.

Transcriptome Analysis of Cordyceps militaris Reveals Genes Associated With Carotenoid Synthesis and Identification of the Function of the Cmtns Gene.

Cordyceps militaris, a valuable edible and medicinal fungus, has attracted increasing attention because of its various bioactive ingredients. However, the biosynthetic pathway of C. militaris carotenoids is still unknown due to lack of transcriptome information. To uncover genes related to the biosynthesis of C. militaris carotenoids, the transcriptomes of mycelia CM10_D cultured under dark conditions and mycelia CM10_L cultured under light exposure conditions were sequenced. Compared with mycelia CM10_D, 866 up-regulated genes and 856 down-regulated genes were found in mycelia CM10_L. Gene ontology (GO) analysis of differentially expressed genes (DEGs) indicated that DEGs were mainly classified into the "metabolic process," "membrane," and "catalytic activity" terms. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs suggested that DEGs were mainly enriched in "metabolic pathways," "MAPK signaling pathway-yeast," and "biosynthesis of secondary metabolites." In addition, the carotenoid content of the Cmtns gene deletion mutant (ΔCmtns) was significantly lower than that of the wild-type C. militaris CM10, while the carotenoid content of the complementary strain (ΔCmtns-c) of the Cmtns gene was not significantly different from that of C. militaris CM10, suggesting that the Cmtns gene significantly affected the biosynthesis of carotenoids in C. militaris. These results potentially pave the way for revealing the biosynthetic pathway of carotenoids and improving carotenoids production in C. militaris.

Anxiolytic and anti-depressant effects of hydroalcoholic extract from Erythrina variegata and its possible mechanism of action.

BACKGROUND: Erythrina variegata has been widely used as a traditional medicine. OBJECTIVE: The study was designed to evaluate the anxiolytic and anti-depressant effects of an extract from Erythrina variegata. METHODS: The extract was evaluated for anxiolytic and anti-depressant action using the elevated plus maze, light/dark box, open field, forced swimming and tail suspension tests in mice. The mechanism of action was further elucidated using high-performance liquid chromatography with fluorescence detection methods to assay the levels of five neurotransmitters in brain. RESULTS: The extract exhibited significant increase in the percentage of the open arms entries and the time spent in the open arms in the elevated plus maze test. The results of the light/dark box test revealed a significant increase in the amount of time spent in the light chamber. Extract- treated mice also produced significant increase in the number of crossings and rearings in the open field test. In the forced swimming and tail suspension tests, the extract was able to promote significant decrease in the immobility time. In addition, the extract significantly altered the levels of five neurotransmitters in the brain tissue. CONCLUSION: These findings suggest that Erythrina variegata presents potential anxiolytic and anti-depressant activity, and the mechanism may be related to the alteration of neurotransmitter levels.

[Effects of plateau zokor disturbance and restoration years on soil nutrients and microbial functional diversity in alpine meadow].

To explore the dynamic process of restoration succession in degraded alpine meadow that had been disturbed by plateau zokors in the eastern Tibetan Plateau, we examined soil nutrients and microbial functional diversity using conventional laboratory analysis and the Biolog-ECO microplate method. Our study showed that: 1) The zokors disturbance significantly reduced soil organic matter, total nitrogen, available nitrogen and phosphorus contents, but had no significant effects on soil total phosphorus and potassium contents; 2) Soil microbial carbon utilization efficiency, values of Shannon, Pielou and McIntosh indexes increased with alpine meadow restoration years; 3) Principal component analysis (PCA) showed that carbohydrates and amino acids were the main carbon sources for maintaining soil microbial community; 4) Redundancy analysis ( RDA) indicated that soil pH, soil organic matter, total nitrogen, available nitrogen, and total potassium were the main factors influencing the metabolic rate of soil microbial community and microbial functional diversity. In summary, variations in soil microbial functional diversity at different recovery stages reflected the microbial response to aboveground vegetation, soil microbial composition and soil nutrients.

Terpene and lignan glycosides from the twigs and leaves of an endangered conifer, Cathaya argyrophylla.

Labdane diterpene glycosides cathargyroside A and cathargyroside B, monoterpene glycosides vervenone-10-O-ß-D-glucopyranoside and vervenone-10-O-ß-D-apiofuranosyl-(1″→6')-ß-D-glucopyranoside, as well as lignan glycosides cedrusinin-4-O-α-L-rhamnopyranoside and (+)-cyclo-olivil-9'-O-ß-D-xylopyranoside, along with 39 known compounds, were obtained from the methanol extract of the twigs and leaves of Cathaya argyrophylla. These compounds were identified mainly by analyzing their NMR and MS data. Almost all of these compounds were hitherto unknown in this genus. The isolated compounds were screened against Candida albicans and Staphylococcus aureus for antimicrobial assay, and against K562, HT-29, BEL-7402, SGC-7901, B16, BGC-823, U251 and A549 cancer cell lines for cytotoxic activities. One compound showed antimicrobial activity against C. albicans, and four of them displayed cytotoxicity. Similarity analysis on the chemical constituents of the genera Cathaya, Picea and Pinus supported their close phylogenetic relationships.

Antimicrobial, cytotoxic lignans and terpenoids from the twigs of Pseudolarix kaempferi.

Seven new compounds, including four lignans, (+)-(8S,8'S)-9,9'-dibenzoylsecoisolariciresinol (1), (+)-(8S*,8'R*)-4,4'-dimethyloxomatairesinol (2), (+)-(7S*,8R*,8'R*,9'S*)-9'-n-butoxytsugacetal (3), and pseudolarkaemin A (4), a pyronane glycoside, pseudolarkaemin B (5), an ent-beyerene glycoside, pseudolarkaemin C (6), and a triterpene, 25-epi-pseudolarolide Q (7), along with 25 known compounds (8­32) were isolated from the twigs of Pseudolarix kaempferi. Their structures were elucidated mainly by the analysis of their NMR and MS data. Pseudolarolide C acid (24) was isolated for the first time as a natural product. All compounds were evaluated for antimicrobial activity against Candida albicans and Staphylococcus aureus, and cytotoxic activity against K562, HT-29, B16, BGC-823, BEL-7402, SGC-7901, U251, and A549 cancer cell lines were assayed. Results indicated that the new compounds 3, 7, and some known compounds showed antimicrobial and cytotoxic activities.