Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation and antimetastasis effects on ...various types of cancers both in vitro and in vivo. Alkaloids, such as camptothecin and vinblastine, have already been successfully developed into anticancer drugs. This paper focuses on the naturally derived alkaloids with prospective anticancer properties, such as berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine, and summarizes the mechanisms of action of these compounds. Based on the information in the literature that is summarized in this paper, the use of alkaloids as anticancer agents is very promising, but more research and clinical trials are necessary before final recommendations on specific alkaloids can be made.
Eucommia ulmoides Oliver (E. ulmoides) is a popular medicinal herb and health supplement in China, Japan, and Korea, and has a variety of pharmaceutical properties. The neuroendocrine–immune (NEI) ...network is crucial in maintaining homeostasis and physical or psychological functions at a holistic level, consistent with the regulatory theory of natural medicine. This review aims to systematically summarize the chemical compositions, biological roles, and pharmacological properties of E. ulmoides to build a bridge between it and NEI-associated diseases and to provide a perspective for the development of its new clinical applications. After a review of the literature, we found that E. ulmoides has effects on NEI-related diseases including cancer, neurodegenerative disease, hyperlipidemia, osteoporosis, insomnia, hypertension, diabetes mellitus, and obesity. However, clinical studies on E. ulmoides were scarce. In addition, E. ulmoides derivatives are diverse in China, and they are mainly used to enhance immunity, improve hepatic damage, strengthen bones, and lower blood pressure. Through network pharmacological analysis, we uncovered the possibility that E. ulmoides is involved in functional interactions with cancer development, insulin resistance, NAFLD, and various inflammatory pathways associated with NEI diseases. Overall, this review suggests that E. ulmoides has a wide range of applications for NEI-related diseases and provides a direction for its future research and development.
Hexagonal boron nitride (hBN) is a remarkable two-dimensional (2D) material that hosts solid-state spins and has great potential to be used in quantum information applications, including quantum ...networks. However, in this application, both the optical and spin properties are crucial for single spins but have not yet been discovered simultaneously for hBN spins. Here, we realize an efficient method for arraying and isolating the single defects of hBN and use this method to discover a new spin defect with a high probability of 85%. This single defect exhibits outstanding optical properties and an optically controllable spin, as indicated by the observed significant Rabi oscillation and Hahn echo experiments at room temperature. First principles calculations indicate that complexes of carbon and oxygen dopants may be the origin of the single spin defects. This provides a possibility for further addressing spins that can be optically controlled.
Chemoresistance remains a major obstacle to effective treatment in patients with ovarian cancer, and recently increasing evidences suggest that miRNAs are involved in drug-resistance. In this study, ...we investigated the role of miRNAs in regulating cisplatin resistance in ovarian cancer cell line and analyzed their possible mechanisms. We profiled miRNAs differentially expressed in cisplatin-resistant human ovarian cancer cell line A2780/DDP compared with parental A2780 cells using microarray. Four abnormally expressed miRNAs were selected (miR-146a,-130a, -374a and miR-182) for further studies. Their expression were verified by qRT-PCR. MiRNA mimics or inhibitor were transfected into A2780 and A2780/DDP cells and then drug sensitivity was analyzed by MTS array. RT-PCR and Western blot were carried out to examine the alteration of MDR1, PTEN gene expression. A total of 32 miRNAs were found to be differentially expressed in A2780/DDP cells. Among them, miR-146a was down-regulated and miR-130a,-374a,-182 were upregulated in A2780/DDP cells, which was verified by RT-PCR. MiR-130a and miR-374a mimics decreased the sensitivity of A2780 cells to cisplatin, reversely, their inhibitors could resensitize A2780/DDP cells. Furthermore, overexpression of miR-130a could increase the MDR1 mRNA and P-gp levels in A2780 and A2780/DDP cells, whereas knockdown of miR-130a could inhibit MDR1 gene expression and upregulate the PTEN protein expression .In a conclusion, the deregulation of miR-374a and miR-130a may be involved in the development and regulation of cisplatin resistance in ovarian cancer cells. This role of miR-130a may be achieved by regulating the MDR1 and PTEN gene expression.
Ovarian cancer is a heterogeneous malignancy that poses tremendous clinical challenge. Based on unsupervised classification of whole-genome gene expression profiles, four molecular subtypes of ...ovarian cancer were recently identified. However, single-driver molecular events specific to these subtypes have not been clearly elucidated. We aim to characterize the regulatory mechanisms underlying the poor prognosis mesenchymal subtype of ovarian cancer using a systems biology approach, involving a variety of molecular modalities including gene and microRNA expression profiles. miR-508-3p emerged as the most powerful determinant that regulates a cascade of dysregulated genes in the mesenchymal subtype, including core genes involved in epithelial-mesenchymal transition (EMT) program. Moreover, miR-508-3p down-regulation, due to promoter hypermethylation, was directly correlated with metastatic behaviors in vitro and in vivo. Taken together, our multidimensional network analysis identified miR-508-3p as a master regulator that defines the mesenchymal subtype and provides a novel prognostic biomarker to improve management of this disease.
Saponins are glycosides with triterpenoid or spirostane aglycones that demonstrate various pharmacological effects against mammalian diseases. To promote the research and development of anticancer ...agents from saponins, this review focuses on the anticancer properties of several typical naturally derived triterpenoid saponins (ginsenosides and saikosaponins) and steroid saponins (dioscin, polyphyllin, and timosaponin) isolated from Chinese medicines. These saponins exhibit in vitro and in vivo anticancer effects, such as anti-proliferation, anti-metastasis, anti-angiogenesis, anti-multidrug resistance, and autophagy regulation actions. In addition, related signaling pathways and target proteins involved in the anticancer effects of saponins are also summarized in this work.
Moisture content (MC) influences substance transformation during composting and the function of exogenous microbial agents. Unsuitable MC could cause leaching, nutrient loss, and secondary ...contamination. In this study, chicken manure composting with varied MC (45–61%) was conducted under functional microbial agent inoculation to explore the optimum condition for composting and the potential mechanism. Due to the enhanced decomposing, nitrosation, and nitrification effect lead by the functional microorganism, treatment with the optimal MC (53%) exhibited the highest composting temperature (61 °C) and longest high-temperature period (15 days), achieving a final carbon-nitrogen ratio (C/N), humic acids and fulvic acids ratio (HA/FA), and NH4+-N/NO3−-N at 19.20, 2.00, and 0.93, respectively. After composting, the total nitrogen (TN) increased by 13.01–22.10% in the treatments with microbial agent inoculation compared with original stack, while it decreased by 7.76% in control. The highest nutrient (5.63%, 5.63–14.20% higher than the other composts) and better product safety (11.43–23.58% higher seed germination than others) were observed in treatment with MC at 53%, exceeding the Chinese national standard for organic fertilizer. Obviously, under optimum MC, microbial agent augmentation lead to high quality and safe compost products after a short composting period (25 days) without any leaching, which suggested an efficient way to promote the recycling and recovery of husbandry waste.
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•Initial moisture content at 53% is the best for bio-enhanced manure composting.•The initial moisture content of 53% effectively promoted compost quality.•Microbial agent bio-augmentation effectively promoted compost quality and safety.•The low moisture content effectively prevented leaching and nutrient loss.
Flavin adenine dinucleotide (FAD) as a cofactor is involved in numerous important metabolic pathways where the biological function is intrinsically related to its transient conformations. The ...confined space of enzymes requires FAD set in its specific intermediate conformation. However, conventional methods only detect stable conformations of FAD molecules, while transient intermediates are hidden in ensemble measurements. There still exists a challenge to uncover the transient conformation of each FAD molecule, which hinders the understanding of the structure-activity relationship of the FAD mechanism. Here, we employ the electrochemically confined space of an aerolysin nanopore to directly characterize a series of transient conformations of every individual FAD. Based on distinguishable current blockages, the "stack", "open", and four quasi-stacked FADs are clearly determined in solution, which is further confirmed by temperature-dependent experiments and mutant aerolysin assay. Combined with molecular dynamics simulations, we achieved a direct correlation between the residual current ratio (
I
/
I
0
) and FAD backbone angle. These results would facilitate further understanding of the structure-activity relationship in the flavoprotein.
Flavin adenine dinucleotide (FAD) as a cofactor is involved in numerous important metabolic pathways where the biological function is intrinsically related to its transient conformations.
Aim
Understanding the patterns and correlates of the range expansion of established alien species is crucial for predicting invasion impacts and developing effective control strategies. With ...accelerating globalization, it is key to identify the interactions of different global change processes, such as how land‐use change may influence range expansion, yet empirical studies remain limited.
Location
Liuji Town, Jiangsu Province, China.
Methods
We first divided the study area into 128 grids with a resolution of 1 × 1 km and conducted visual encounter surveys over two years for a total of 492 water bodies to explore the establishment and range expansions of a global notorious invader, the American bullfrog Lithobates catesbeianus (Shaw, 1802) (= Rana catesbeiana (Shaw, 1802)) using generalized linear mixed models. Then, we investigated the residence time of the established bullfrogs in each water body based on a questionnaire survey. We quantified the habitat loss and range expansion of the past 30 years via GIS‐based spatial analysis and explored their temporal dynamics using the breakpoint regression technique.
Results
We found that the area of suitable habitats was the most important variable positively related to the bullfrog establishment. There was a similar temporal trend of the range expansion and habitat loss, although the optimal time of habitat loss was slightly earlier than that of the great increase in bullfrog range expansion. Overall, the bullfrogs tended to expand faster with greater habitat loss after controlling for temporal non‐independence.
Main conclusions
Our results demonstrated that loss of suitable habitats may facilitate invaders with faster range expansion to occupy the remaining limited resources. Alien species might thus accelerate invasions under human‐induced land‐use modifications in the era of global change. The time lag between range expansion and habitat loss is the golden window for preventing the spread of established alien species in disturbed habitats.
A series of luminescent Ir(iii) complexes were synthesised and evaluated for their ability to act as luminescent G-quadruplex-selective probes. The Ir(iii) complex
, Ir(phq)
(phen)PF
(where phq = ...2-phenylquinoline; phen = 1,10-phenanthroline), exhibited high luminescence in the presence of G-quadruplex DNA compared to dsDNA and ssDNA, and was employed to construct a label-free G-quadruplex-based assay for hepatitis C virus NS3 helicase activity in aqueous solution. Moreover, the application of the assay for screening potential helicase inhibitors was demonstrated. To our knowledge, this is the first G-quadruplex-based assay for helicase activity.
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