ABSTRACT
Objective.Depression is a common chronic mental disorder characterized by high rates of prevalence, recurrence, suicide, and disability as well as heavy disease burden. An accurate diagnosis of depression is a prerequisite for treatment. However, existing questionnaire-based diagnostic methods are limited by the innate subjectivity of medical practitioners and subjects. In the search for a more objective diagnostic methods for depression, researchers have recently started to use deep learning approaches.Approach.In this work, a deep-learning network, named adaptively multi-time-window graph convolutional network (GCN) with long-short-term memory (LSTM) (i.e. AMGCN-L), is proposed. This network can automatically categorize depressed and non-depressed people by testing for the existence of inherent brain functional connectivity and spatiotemporal features contained in electroencephalogram (EEG) signals. AMGCN-L is mainly composed of two sub-networks: the first sub-network is an adaptive multi-time-window graph generation block with which adjacency matrices that contain brain functional connectivity on different time periods are adaptively designed. The second sub-network consists of GCN and LSTM, which are used to fully extract the innate spatial and temporal features of EEG signals, respectively.Main results.Two public datasets, namely the patient repository for EEG data and computational tools, and the multi-modal open dataset for mental-disorder analysis, were used to test the performance of the proposed network; the depression recognition accuracies achieved in both datasets (using tenfold cross-validation) were 90.38% and 90.57%, respectively.Significance.This work demonstrates that GCN and LSTM have eminent effects on spatial and temporal feature extraction, respectively, suggesting that the exploration of brain connectivity and the exploitation of spatiotemporal features benefit the detection of depression. Moreover, the proposed method provides effective support and supplement for the detection of clinical depression and later treatment procedures.
Subject(s)
Depression , Depressive Disorder, Major , Humans , Depression/diagnosis , Memory, Short-Term , Brain , ElectroencephalographyABSTRACT
Treatments with abiotic elicitors can efficiently induce the accumulation of specialized metabolites in plants. We used a combined omics approach to analyze the elicitation effects of MeJa, AgNO3, and PEG on camptothecin (CPT) biosynthesis in Camptotheca acuminata plantlets. Untargeted analyses revealed that treatments with MeJa, AgNO3, and PEG significantly inhibited the photosynthetic pathway and promoted carbon metabolism and secondary metabolic pathways. The CPT levels increased by 78.6, 73.3, and 50.0% in the MeJa, AgNO3, and PEG treatment groups, respectively. Using C. acuminata plantlets after elicitation treatment, we mined and characterized 15 new alkaloids, 25 known CPT analogs and precursors, 9 iridoid biosynthetic precursors, and 15 tryptamine biosynthetic precursors based on their MS/MS fragmentation spectra. Using 32 characterized genes involved in CPT biosynthesis as bait, we mined 12 prioritized CYP450 genes from the 416 CYP450 candidates that had been identified based on co-expression analysis, conserved domain analysis, and their elicitation-associated upregulation patterns. This study provides a comprehensive perspective on CPT biosynthesis in C. acuminata plantlets after abiotic elicitation. The findings enable us to elucidate the previously unexplored CYP450-mediated oxidation steps for CPT biosynthesis.
ABSTRACT
To improve the drug-ability of celastrol, a series of PEGylation celastrol (PEGC) were designed and synthesized by conjugation with different kinds of polyethylene glycols (PEGs) with celastrol. Most of PEGCs could easily dissolve in water. In particular, one of them (DC1000) could be dispersed in water to form nanoparticles by self-assembly. The cytotoxic evaluation of PEGCs revealed that some of PEGCs showed more potent cytotoxicity than celastrol, and the molecular weight of PEG parts in PEGCs had apparent influence on their cytotoxic activity. Anti-tumor evaluation in vivo showed DC1000 had higher tumor inhibition rate and better safety than celastrol by intravenous administration with equivalent molar weight. These results revealed PEGylation might be an efficient and economical method to improve the water solubility and safety of celastrol and similar natural products.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Nanoparticles/chemistry , Polyethylene Glycols/chemistry , Triterpenes/chemistry , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Pentacyclic Triterpenes , Solubility , Water/chemistryABSTRACT
A series of 3-carbamate and 29-ester celastrol derivatives (compounds 1-26) were designed and synthesized. These analogues were evaluated for their cytotoxic activities against several cancer cell lines. Cytotoxicity data revealed that the properties of substituents and substitution position had important influence on cytotoxic activity. Modification of C-3 hydroxyl with size-limited groups did not reduce the activity obviously. The introduction of polarity group like piperazine could improve the solubility. Compound 23 was chosen to further evaluate anti-tumor efficacy in vivo. It showed higher inhibition rate and better safety than celastrol during in vivo experiment by intragastric administration. The preliminary antitumor studies of compound 23in vivo showed that it might be promising for the development of new antitumor agents.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Triterpenes/chemistry , Triterpenes/pharmacology , A549 Cells , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Cell Survival/drug effects , Drug Design , Drug Screening Assays, Antitumor , Esterification , Humans , Mice, Nude , Neoplasms/drug therapy , Neoplasms/pathology , Pentacyclic Triterpenes , Structure-Activity Relationship , Triterpenes/chemical synthesis , Triterpenes/therapeutic useABSTRACT
A homologous sequence was amplified from resurrection plant Selaginella pulvinta by RACE technique, proved to be the full-length cDNA of trehalose-6-phosphate synthase gene by homologous alignment and yeast complementation assay, and nominated as SpTPS1 gene. The open reading frame of this gene was truncated 225bp at the 5'-end, resulting the N-terminal truncation modification of 75 amino acids for its encoding protein. The TPS1 deletion mutant strain YSH290 of the brewer's yeast transformed by the truncated gene SpTPS1Δ and its original full-length version restored growth on the medium with glucose as a sole carbon source and displayed growth curves with no significant difference, indicating their encoding proteins functioning as TPS enzyme. The TPS activity of the mutant strain transformed by the truncated gene SpTPS1Δ was about six fold higher than that transformed by its original version, reasoning that the extra N-terminal extension of the full-length amino acid sequence acts as an inhibitory domain to trehalose synthesis. However, the trehalose accumulation of the mutant strain transformed by the truncated gene SpTPS1Δ was only 8% higher than that transformed by its original version. This result is explained by the feedback balance of trehalose content coordinated by the comparative activities between trehalose synthase and trehalase. The truncated gene SpTPS1Δ is suggested to be used in transgenic operation, together with the inhibition of trehalase activity by the application of validamycin A or genetic deficiency of the endogenous trehalase gene, for the enhancement of trehalose accumulation and improvement of abiotic tolerance in transgenic plants.
Subject(s)
Amino Acid Sequence , Glucosyltransferases/metabolism , Plant Proteins/metabolism , Selaginellaceae/enzymology , Sequence Deletion , Cloning, Molecular , Genetic Complementation Test , Glucosyltransferases/genetics , Mutation , Open Reading Frames/physiology , Plant Proteins/genetics , Saccharomyces cerevisiae/enzymology , Saccharomyces cerevisiae/genetics , Selaginellaceae/genetics , Trehalose/genetics , Trehalose/metabolismABSTRACT
To overcome the low efficiency of agronomic protection from maize dwarf mosaic disease, susceptible maize inbred line was transformed by Agrobacterium tumefaciens harboring hpRNA expression vectors containing inverted-repeat sequences of different lengths targeting coat protein gene (CP) of maize dwarf mosaic virus (MDMV). After PCR screening and Southern blotting, the flanking sequences of the integration sites were amplified by thermal asymmetric interlaced PCR (TAIL-PCR) and used for analysis of T-DNA integration patterns. The T2 plant lines were evaluated for their MDMV resistance in field inoculation trials under two environments. Of the nineteen T2 plant lines positive in Southern blotting, six were evaluated as resistant to MDMV, and four of them had resistance non-significantly different from the highly resistant control "H9-21", while the resistance of the other eleven was proved to be significantly improved when compared to their non-transformed parent line. These improvements in MDMV resistance were verified by the relative amount of virus CP gene expression measured by quantitative real time PCR. Comparing the results of Southern blotting and TAIL-PCR analysis, different integration patterns of one or two copies of the inverted-repeat sequences were identified from non-repetitive and repetitive sequences of the maize genome. The MDMV resistance mediated by RNA interference is relative to the length of the inverted-repeat sequence, the copy number of T-DNA integration and the repeatability of integration sites. A longer hpRNA expression construct shows more efficiency than a shorter one.