[Optimization and identification of potential targets of obacunone against sepsis].

OBJECTIVE: To investigate the molecular characteristics of obacunone, and to screen and identify potential targets of obacunone against sepsis. METHODS: The pharmacological parameters and molecular characteristics of obacunone were analyzed with the aid of the Traditional Chinese Medicine Systems Pharmacology Database Analysis Platform (TCMSP). The potential targets of obacunone against sepsis were screened using SwissTargetPrediction and Drug Repositioning and Adverse Drug Reaction Chemical-Protein Interactome (DRAR-CPI) software, with a Z'-score < -0.5. The anti-sepsis targets of obacunone were selected by Online Mendelian Inheritance in Man (OMIM), Comparative Toxicogenomics Database (CTD) and Therapeutic Target Database (TTD). The anti-sepsis potential target was identified by molecular docking software. RESULTS: The oral bioavailability of obacunone was 81.58% and the drug-likeness was 0.57 indicating that obacunone showed good drug formation. A total of 242 potential targets were screened through SwissTargetPrediction and DRAR-CPI software, 13 targets were directly related to sepsis. Cathepsin G (CTSG), caspase-1 (CASP1), S100 calcium binding protein A9 (S100A9), protein C (inactivator of coagulation factors V a and VIII a, PROC), mitogen-activated protein kinase 1 (MAPK1), glucose-6-phosphate dehydrogenase (G6PD), interleukin-10 (IL-10), migration inhibitory factor (MIF), complement C5a receptor 1 (C5AR1), caspase-3 (CASP3), CXC chemokine receptor 2 (CXCR2), thrombin receptor (F2R), nicotinamide phosphoribosyltransferase (NAMPT) were identified as the potential targets for anti-sepsis of obacunone by molecular docking software, the free binding energies were -32.55, 1.26, -30.00, 300.08, -31.88, -30.29, -21.38, -30.79, 16 777.84, -21.80, 6 443.36, -20.38, -23.47 kJ/mol, respectively. CONCLUSIONS: Obacunone can inhibit blood coagulation and improve inflammatory response by regulating PROC and F2R. It regulates MIF, S100A9, G6PD and IL-10 to play a role in immune response. It regulates CTSG, CASP1, MAPK1, C5AR1 and CASP3 to protect sepsis-damaged organs. By regulating CXCR2, it can reduce the excessive migration of neutrophils to the site of inflammation, alleviate tissue damage. By regulating NAMPT, it improves cellular energy status, reduces oxidative stress, and protects cells from damage.

COVID-19 Misinformation Detection: Machine-Learned Solutions to the Infodemic.

Background: The volume of COVID-19-related misinformation has long exceeded the resources available to fact checkers to effectively mitigate its ill effects. Automated and web-based approaches can provide effective deterrents to online misinformation. Machine learning-based methods have achieved robust performance on text classification tasks, including potentially low-quality-news credibility assessment. Despite the progress of initial, rapid interventions, the enormity of COVID-19-related misinformation continues to overwhelm fact checkers. Therefore, improvement in automated and machine-learned methods for an infodemic response is urgently needed. Objective: The aim of this study was to achieve improvement in automated and machine-learned methods for an infodemic response. Methods: We evaluated three strategies for training a machine-learning model to determine the highest model performance: (1) COVID-19-related fact-checked data only, (2) general fact-checked data only, and (3) combined COVID-19 and general fact-checked data. We created two COVID-19-related misinformation data sets from fact-checked "false" content combined with programmatically retrieved "true" content. The first set contained ~7000 entries from July to August 2020, and the second contained ~31,000 entries from January 2020 to June 2022. We crowdsourced 31,441 votes to human label the first data set. Results: The models achieved an accuracy of 96.55% and 94.56% on the first and second external validation data set, respectively. Our best-performing model was developed using COVID-19-specific content. We were able to successfully develop combined models that outperformed human votes of misinformation. Specifically, when we blended our model predictions with human votes, the highest accuracy we achieved on the first external validation data set was 99.1%. When we considered outputs where the machine-learning model agreed with human votes, we achieved accuracies up to 98.59% on the first validation data set. This outperformed human votes alone with an accuracy of only 73%. Conclusions: External validation accuracies of 96.55% and 94.56% are evidence that machine learning can produce superior results for the difficult task of classifying the veracity of COVID-19 content. Pretrained language models performed best when fine-tuned on a topic-specific data set, while other models achieved their best accuracy when fine-tuned on a combination of topic-specific and general-topic data sets. Crucially, our study found that blended models, trained/fine-tuned on general-topic content with crowdsourced data, improved our models' accuracies up to 99.7%. The successful use of crowdsourced data can increase the accuracy of models in situations when expert-labeled data are scarce. The 98.59% accuracy on a "high-confidence" subsection comprised of machine-learned and human labels suggests that crowdsourced votes can optimize machine-learned labels to improve accuracy above human-only levels. These results support the utility of supervised machine learning to deter and combat future health-related disinformation.

Optimization of Total Polar Compounds Quantification in Frying Oils by Low-field Nuclear Magnetic Resonance.

To improve the accuracy of total polar compounds (TPC) quantification in frying oils by low-field nuclear magnetic resonance (LF-NMR), an optimized statistical method was proposed. The method uses a specially designed sequence to detect the NMR signal in frying oils, and establishes the TPC prediction model by partial least squares (PLS) regression on relaxation properties extracted from the NMR signal. Compared with inversion recovery (IR) and Carr-Purcell-Meiboom-Gill (CPMG) sequences, the designed sequence provides more relaxation information. The experimental result shows that the proposed method is more accurate than reported methods that are based on longitudinal and transverse relaxation times in the TPC quantification of frying oils.