Toxicokinetics of MDMA and Its Metabolite MDA in Rats.

OBJECTIVES: To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine (MDMA) and its metabolite 4,5-methylene dioxy amphetamine (MDA) in rats after single and continuous administration of MDMA, providing reference data for the forensic identification of MDMA. METHODS: A total of 24 rats in the single administration group were randomly divided into 5, 10 and 20 mg/kg experimental groups and the control group, with 6 rats in each group. The experimental group was given intraperitoneal injection of MDMA, and the control group was given intraperitoneal injection of the same volume of normal saline as the experimental group. The amount of 0.5 mL blood was collected from the medial canthus 5 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h after administration. In the continuous administration group, 24 rats were randomly divided into the experimental group (18 rats) and the control group (6 rats). The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5, 7, 9, 11, 13, 15, 17 mg/kg per day, respectively, while the control group was given the same volume of normal saline as the experimental group by intraperitoneal injection. On the eighth day, the experimental rats were randomly divided into 5, 10 and 20 mg/kg dose groups, with 6 rats in each group. MDMA was injected intraperitoneally, and the control group was injected intraperitoneally with the same volume of normal saline as the experimental group. On the eighth day, 0.5 mL of blood was taken from the medial canthus 5 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h after administration. Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels, and statistical software was employed for data analysis. RESULTS: In the single-administration group, peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration, respectively, with the largest detection time limit of 12 h. In the continuous administration group, peak concentrations were reached at 30 min and 1.5 h after administration, respectively, with the largest detection time limit of 10 h. Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows: T=10.362C-1.183, R2=0.974 6; T=7.397 3C-0.694, R2=0.961 5 (T: injection time; C: concentration ratio of MDMA to MDA in plasma). CONCLUSIONS: The toxicokinetic data of MDMA and its metabolite MDA in rats, obtained through single and continuous administration, including peak concentration, peak time, detection time limit, and the relationship between concentration ratio and administration time, provide a theoretical and data foundation for relevant forensic identification.

Bioinspired Hierarchical Self-Assembled Nanozyme for Efficient Antibacterial Treatment.

Along with the rapid development and ever-deepening understanding of nanoscience and nanotechnology, nanomaterials hold promise to mimic the highly evolved biological exquisite nanostructures and sophisticated functions. Here, inspired by the ubiquitous antibacterial nanostructures on the wing surfaces of some insects, a NiCo2 O4 nanozyme with self-adaptive hierarchical nanostructure is developed that can capture bacteria of various morphotypes via the physico-mechanical interaction between the nanostructure and bacteria. Moreover, the developed biomimetic nanostructure further exhibits superior peroxidase-like catalytic activity, which can catalytically generate highly toxic reactive oxygen species that disrupt bacterial membranes and induce bacterial apoptosis. Therefore, the mechano-catalytic coupling property of this NiCo2 O4 nanozyme allows for an extensive and efficient antibacterial application, with no concerns of antimicrobial resistance. This work suggests a promising strategy for the rational design of advanced antibacterial materials by mimicking biological antibiosis.

A pH-responsive ultrathin Cu-based nanoplatform for specific photothermal and chemodynamic synergistic therapy.

Noninvasive tumor therapy requires a new generation of bionanomaterials towards sensitive response to the unique tumor microenvironment to achieve accurate and effective treatment. Herein, we have developed a tumor therapy nanoplatform by immobilizing natural glucose oxidase (GOD) onto Cu-based layered double hydroxide (CuFe-LDH) nanosheets, which for the first time integrates acid-enhanced photothermal therapy (PTT), and pH-responsive and heat-facilitated chemodynamic therapy (CDT) simultaneously. As demonstrated by EXAFS and HRTEM, CuFe-LDH nanosheets possess a considerable number of defects caused by different acid conditions, resulting in a significantly acid-enhanced photothermal conversion efficiency (83.2% at pH 5.4 vs. 46.0% at pH 7.4). Moreover, GOD/CuFe-LDH nanosheets can convert a cascade of glucose into hydroxyl radicals (˙OH) under tumor acid conditions, which is validated by a high maximum velocity (V max = 2.00 × 10-7 M) and low Michaelis-Menten constant (K M = 12.01 mM). With the combination of PTT and CDT, the tumor tissue in vivo is almost eliminated with low-dose drug injection (1 mg kg-1). Therefore, this novel pH-responsive Cu-based nanoplatform holds great promise in tumor-specific CDT/PTT synergistic therapy.

Application of generated mask method based on Mask R-CNN in classification and detection of melanoma.

OBJECTIVE: Melanoma is a type of malignant skin cancer with high mortality, and its incidence is increasing rapidly in recent years. At present, the best treatment is surgical resection after early diagnosis. However, due to the high visual similarity between melanoma and benign melanocytic nevus, coupled with the scarcity and imbalance of data, traditional methods are difficult to achieve good recognition and detection results. Similarly, many machine learning methods have been applied to the task of skin disease detection and classification. However, the accuracy and sensitivity of the experiments are still not satisfactory. Therefore, this paper proposed a method to identify melanoma more efficiently and accurately. METHOD: We implemented a Mixed Skin Lesion Picture Generate method based on Mask R-CNN (MSLP-MR) to solve the problem of data imbalance. Besides, we designed a melanoma detection framework of Mask-DenseNet+ based on MSLP-MR. This method used Mask R-CNN to introduce the method of mask segmentation, and combined with the idea of ensemble learning to integrate multiple classifiers for weighted prediction. Compared with the ablation experiments, the accuracy, sensitivity and AUC of the proposed network classification are improved by 2.56%, 29.33% and 0.0345. RESULT: The experimental results on the ISIC dataset shown that the accuracy of the algorithm is 90.61%, the sensitivity reaches 78.00%, which is higher than the original methods; the specificity reaches 93.43%; and the AUC reaches 0.9502. CONCLUSION: The method is feasible and effective, and achieves the preliminary goal of melanoma detection. It is greatly improved the detection accuracy and reached the level of visual diagnosis of doctors.

Recent advances in innovative strategies for enhanced cancer photodynamic therapy.

Photodynamic therapy (PDT), a non-invasive therapeutic modality, has received increasing attention owing to its high selectivity and limited side effects. Although significant clinical research progress has been made in PDT, the breadth and depth of its clinical application have not been fully realized due to the limitations such as inadequate light penetration depth, non-targeting photosensitizers (PSs), and tumor hypoxia. Consequently, numerous investigations put their emphasis on innovative strategies to overcome the aforementioned limitations and enhance the therapeutic effect of PDT. Herein, up-to-date advances in these innovative methods for PDT are summarized by introducing the design of PS systems, their working mechanisms and application examples. In addition, current challenges of these innovative strategies for clinical application, and future perspectives on further improvement of PDT are also discussed.

Chemodynamic/photothermal synergistic therapy based on Ce-doped Cu-Al layered double hydroxides.

The combination of chemodynamic therapy (CDT) with photothermal therapy (PTT) is an efficacious strategy in cancer treatment to acquire satisfactory therapy efficiency in the endogenous redox reaction and external laser induction. In this work, we have designed Ce doped Cu-Al layered double hydroxide (CAC-LDH) ultrathin them through a bottom-up synthesis method, and further loaded them with indocyanine green (ICG). The synthesized ICG/CAC-LDH was used as a Fenton-catalyst and photothermal agent. With the Fenton activity, the ICG/CAC-LDH nanosheets could decompose H2O2 and exhibit a low KM value (1.57 mM) and an ultra-high Vmax (4.88 × 10-6 M s-1) value. Due to the presence of oxidized metal ions, ICG/CAC-LDH could induce intracellular GSH depletion and reduce Cu2+ and Ce4+ to Cu+ and Ce3+, respectively. The generated Cu+ and Ce3+ further reacted with local H2O2 to generate toxic hydroxyl radicals (˙OH) via the Fenton reaction. Owing to the obviously enhanced absorption of ICG/CAC-LDH at 808 nm, the photothermal efficiency of ICG/CAC-LDH increased significantly compared with ICG (ΔT = 34.7 °C vs. 28.3 °C). In vitro studies substantiate the remarkable CDT/PTT efficacy, with complete apoptosis of HepG2 cancer cells (the cell viability is less than 2%) treated with 25 µg mL-1 of ICG/CAC-LDH. Furthermore, ICG/CAC-LDH could also act as a contrast agent for cancer magnetic resonance imaging (MRI) and photoacoustic imaging (PAI). These results demonstrate the potential of ICG/CAC-LDH as an integrated agent for dual-modal imaging and synergistic CDT/PTT.

Application of Zero-Dimensional Nanomaterials in Biosensing.

Zero-dimensional (0D) nanomaterials, including graphene quantum dots (GQDs), carbon quantum dots (CQDs), fullerenes, inorganic quantum dots (QDs), magnetic nanoparticles (MNPs), noble metal nanoparticles, upconversion nanoparticles (UCNPs) and polymer dots (Pdots), have attracted extensive research interest in the field of biosensing in recent years. Benefiting from the ultra-small size, quantum confinement effect, excellent physical and chemical properties and good biocompatibility, 0D nanomaterials have shown great potential in ion detection, biomolecular recognition, disease diagnosis and pathogen detection. Here we first introduce the structures and properties of different 0D nanomaterials. On this basis, recent progress and application examples of 0D nanomaterials in the field of biosensing are discussed. In the last part, we summarize the research status of 0D nanomaterials in the field of biosensing and anticipate the development prospects and future challenges in this field.

A concise total synthesis and PPAR activation activity of hericerin from Hericium erinaceum.

Hericerin is an isoindolinone meroterpenoid alkaloid isolated from medicinal mushroom Hericium erinaceum with some bioactivities. Herein, a concise total synthesis of hericerin was described, with four steps and 30% overall yield starting from commercially available methyl 3-hydroxy-5-methoxybenzoate and geranyl bromide. A comprehensive effect of hericerin on HepG2 cell line was observed and confirmed by transcriptomic analysis. Furthermore, hericerin was found to be a new PPARγ agonist.

Terphenyl derivatives and terpenoids from a wheat-born mold Aspergillus candidus.

A new p-terphenyl derivative aspergicandidusin A (1), a new cleistanthane diterpenoid 6-deoxyaspergiloid C (13), and 12 known compounds (2-12, and 14) were isolated from the mold Aspergillus candidus. The structures of the new compounds were elucidated by spectral analysis of NMR and MS data. The absolute configuration of C-1 in 13 was determined via the circular dichroism data of the [Rh2(OCOCF3)4] complex. Compounds 2-8 and 11 showed moderate inhibitory activity against K562 cell lines with the IC50 value in the range from 17.9 to 46.3 µM. Compound 13 exhibited moderate cytotoxicity against HepG2 cells with the IC50 value of 47.7 µM. Compounds 11 and 12 exhibited moderate activity against the growth of S. aureus with MIC value of 6.25 µM, respectively.