Abstract
Scalar coupling constant (SCC), directly measured by nuclear magnetic resonance (NMR) spectroscopy, is a key parameter for molecular structure analysis, and widely used to predict unknown ...molecular structure. Restricted by the high cost of NMR experiments, it is impossible to measure the SCC of unknown molecules on a large scale. Using density functional theory (DFT) to theoretically calculate the SCC of molecules is incredibly challenging, due to the cost of substantial computational time and space. Graph neural networks (GNN) of artificial intelligence (AI) have great potential in constructing molecul
ar-like topology models, which endows them the ability to rapidly predict SCC through data-driven machine learning methods, and avoiding time-consuming quantum chemical calculations. With a priori knowledge of angles, we propose a graph angle-attention neural network (GAANN) model to predict SCC by means of some easily accessible related information. GAANN, with a multilayer message-passing network and a self-attention mechanism, can accurately simulate the molecular-like topological structure and predict molecular properties. Our simulations show that the prediction accuracy by GAANN, with the log(MAE) = −2.52, is close to that by DFT calculations. Different from conventional AI methods, GAANN combining the AI method with quantum chemistry theory (Karplus equation) has a strong physicochemical interpretability about angles. From an AI perspective, we find that bond angle has the highest correlation with the SCC among all angle features (dihedral angle, bond angle, geometric angles) about multiple coupling types in the small molecule datasets.
It is well-recognized that the gut microbiota (GM) is crucial for gut function, metabolism, and energy cycles. The GM also has effects on neurological outcomes via many mechanisms, such as metabolite ...production and the gut-brain axis. Emerging evidence has gradually indicated that GM dysbiosis plays a role in several neurological diseases, such as Parkinson's disease (PD), Alzheimer's disease, depression, and multiple sclerosis. Several studies have observed that PD patients generally suffer from gastrointestinal disorders and GM dysbiosis prior to displaying motor symptoms, but the specific link between the GM and PD is not clearly understood. In this review, we aim to summarize what is known regarding the correlation between the GM and PD pathologies, including direct, and indirect evidence.
Evidence of the gut microbiota influencing neurodegenerative diseases has been reported for several neural diseases. However, there is little insight regarding the relationship between the gut ...microbiota and prion disease. Here, using fecal samples of 12 prion-infected mice and 25 healthy controls, we analyzed the structure of the gut microbiota and metabolic changes by 16S rRNA sequencing and LC-MS–based metabolomics respectively as multi-omic analyses. Additionally, SCFAs and common amino acids were detected by GC–MS and UPLC respectively. Enteric changes induced by prion disease affected both structure and abundances of the gut microbiota. The gut microbiota of infected mice displayed greater numbers of Proteobacteria and less Saccharibacteria at the phylum level and more Lactobacillaceae and Helicobacteraceae and less Prevotellaceae and Ruminococcaceae at the family level. A total of 145 fecal metabolites were found to be significantly different in prion infection, and most (114) of these were lipid metabolites. Using KEGG pathway enrichment analysis, we found that 3 phosphatidylcholine (PC) compounds significantly decreased and 4 hydrophobic bile acids significantly increased. Decreases of 8 types of short-chain acids (SCFAs) and increases of Cys and Tyr and decreases of His, Trp, and Arg were observed in prion infection. Correlation analysis indicated that the gut microbiota changes observed in our study may have been the shared outcome of prion disease. These findings suggest that prion disease can cause significant shifts in the gut microbiota. Certain bacterial taxa can then respond to the resulting change to the enteric environment by causing dramatic shifts in metabolite levels. Our data highlight the health impact of the gut microbiota and related metabolites in prion disease.
•Altered compositions of gut microbiota were found in prion disease infectious mice.•Related metabolites, amino acids and short chain fatty acids were changed significantly with prion disease.•Based on multi-omics analyses, related gut bacterial communities and metabolites were associated with the prion disease.
Prion diseases caused by the cellular prion protein (PrP
) conversion into a misfolded isoform (PrP
) are associated with multiple mitochondrial damages. We previously reported mitochondrial dynamic ...abnormalities and cell death in prion diseases via modulation of a variety of factors. Optic atrophy 1 (OPA1) is one of the factors that control mitochondrial fusion, mitochondrial DNA (mtDNA) maintenance, bioenergetics, and cristae integrity. In this study, we observed downregulation of OPA1 in prion disease models in vitro and in vivo, mitochondria structure damage and dysfunction, loss of mtDNA, and neuronal apoptosis. Similar mitochondria findings were seen in OPA1-silenced un-infected primary neurons. Overexpression of OPA1 not only alleviated prion-induced mitochondrial network fragmentation and mtDNA loss, decrease in intracellular ATP, increase in ADP/ATP ratio, and decrease in mitochondrial membrane potential but also protected neurons from apoptosis by suppressing the release of cytochrome c from mitochondria to cytosol and activation of the apoptotic factor, caspase 3. Our results demonstrated that overexpression of OPA1 alleviates prion-associated mitochondrial network fragmentation and cristae remodeling, mitochondrial dysfunction, mtDNA depletion, and neuronal apoptosis, suggesting that OPA1 may be a novel and effective therapeutic target for prion diseases.
The current diagnosis method for Creutzfeldt-Jakob disease (CJD) is post-mortem examination, so early detection of CJD has been historically problematic. Auxiliary detection of CJD based on changes ...in levels of components of the cerebrospinal fluid (CSF) has become a focus of research. In other neurodegenerative diseases such as Alzheimer's disease (AD), cell-free mitochondrial DNA (mtDNA) in the CSF of patients may serve as a biomarker that could facilitate early diagnosis and studies of the mechanisms underlying the disease.
In this study, the cell-free mitochondrial DNA in the CSF of patients with sCJD and control patients was compared by digital droplet PCR.
The cell-free mitochondrial DNA copy number in the CSF of sCJD patients was significantly increased in comparison with that of the control group, and this difference was pathologically related to CJD.
Therefore, we speculate that changes in cerebrospinal fluid mitochondrial DNA copy number play an important role in the study of CJD mechanism and diagnosis.
Prion diseases are neurodegenerative diseases associated with neuron damage and behavioral disorders in animals and humans. Melatonin is a potent antioxidant and is used to treat a variety of ...diseases. We investigated the neuroprotective effect of melatonin on prion-induced damage in N2a cells. N2a cells were pretreated with 10 μM melatonin for 1 hour followed by incubation with 100 μM PrP
for 24 hours. Melatonin markedly alleviated PrP
-induced apoptosis of N2a cells, and inhibited PrP
-induced mitochondrial abnormality and dysfunction, including mitochondrial fragmentation and overproduction of reactive oxygen species (ROS), suppression of ATP, reduced mitochondrial membrane potential (MMP), and altered mitochondrial dynamic proteins dynamin-related protein 1 (DRP1) and optic atrophy protein 1 (OPA1). Our findings identify that pretreatment with melatonin prevents the deleterious effects of PrPSc on mitochondrial function and dynamics, protects synapses and alleviates neuron damage. Melatonin could be a novel and effective medication in the therapy of prion diseases.
Elemental selenium is one of the dominant selenium species in soil, but the mechanism of its uptake by plants is still unclear. In this study, nanoparticles of elemental selenium (SeNPs) with ...different sizes were prepared, and their uptake and transformation in wheat (
L.) were analyzed in hydroponic experiments by HPLC-ICP-MS. We found that the SeNPs can be absorbed by wheat seedlings, and the process is energy independent. The addition of aquaporins inhibitor caused 92.5 and 93.4% inhibition of chemosynthesized SeNPs (CheSeNPs) and biosynthesized SeNPs (BioSeNPs) absorption by wheat roots, respectively. The 40 nm SeNPs uptake by wheat roots was 1.8-fold and 2.2-fold higher than that of 140 and 240 nm, respectively. The rate of SeNPs uptake in wheat was much slower than that of selenite Se (IV), and CheSeNPs were more efficiently absorbed than BioSeNPs. The SeNPs were rapidly oxidized to Se (IV) and converted to organic forms selenocystine (SeCys
), se-methyl-selenocysteine (MeSeCys), and selenomethionine (SeMet) after they were absorbed by wheat roots. Additionally, we demonstrated that the aquaporin function in some way is related to the absorption of SeNPs. The particle size and synthesis method of the SeNPs affected their uptake rates by plants. Taken together, our results provide a deep understanding of the SeNPs uptake mechanism in plants.
Selenium is an essential element for mammals and Se-methylselenocysteine was considered as most beneficial Se forms for humans. To better understand Se biofortification in mushrooms and find ...biosynthetic Se-methylselenocysteine resource, we evaluated the effects of selenate, selenite, and selenium nanoparticles on the growth and development of Hypsizygus marmoreus, and analyzed their uptake and biotransformation in this edible mushroom. Our results showed the fruiting bodies yield was not affected by these inorganic Se forms at 0.5–40.0 μg g−1, and Se in caps was higher than that in stipes. The mycelia growth was more sensitive to selenite than selenate and SeNPs. The absorbed inorganic Se forms were converted to selenomethionine (9.0%–54.8%) and selenocystine (26.3%–79.2%) in mycelia, and to selenomethionine (51.8%–76.3%), Se-methylselenocysteine (18.8%–39.4%), and selenocystine (2.2%–3.1%) in fruiting body. The health beneficial Se-methylselenocysteine accounted for 18.8%, 39.4%, and 22.5% of the total Se content in fruiting bodies supplied by selenate, selenite, and SeNPs, respectively. The results, for the first time, revealed that SeNPs was converted to organic forms of Se in mushroom and the H. marmoreus will be a good resource for Se-methylselenocysteine biosynthesis. Altogether, the findings indicate that Se-enriched H. marmoreus is a novel Se food-based source for human beings.
•H. marmoreus mycelium was more tolerable to selenate and SeNPs than selenite.•SeNPs could be absorbed and transformed into organic Se species.•MeSeCys was one of the dominating Se species in fruiting bodies.•Se-enriched H. marmoreus is a novel food-based source of Se.
Selenium (Se) is an essential trace element with multiple functions that may help mitigate adverse health conditions.
Cordyceps militaris
is an edible mushroom with medicinal properties. The ...experiment was conducted under artificial cultivation, with five Se concentrations (0, 5, 10, 20, and 40 μg g
−1
) and three forms of Se (selenate, selenite, and selenomethionine).
C. militaris
can absorb inorganic from the substrate and convert it to organic Se compounds (selenocystine, selenomethionine, and an unknown species) in fruiting bodies. Compared with the control treatment, Se applications (40 μg g
−1
selenate and selenite) significantly increased the Se concentration in fruiting bodies by 130.9 and 128.1 μg g
−1
, respectively. The biofortification with selenate and selenite did not affect fruiting body production, in some case, but did enhance the biological efficiency. Moreover, the abundance of cordycepin and adenosine increased, while the amino acid contents remained relatively stable. Meanwhile, Se-biofortified
C. militaris
showed effective antioxidant activities. These results suggest that Se-biofortified
C. militaris
fruiting bodies may enhance human and animal health when it was included as part of a healthy diet or used as Se supplements.
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