Cross-modal credibility modelling for EEG-based multimodal emotion recognition.

Objective.The study of emotion recognition through electroencephalography (EEG) has garnered significant attention recently. Integrating EEG with other peripheral physiological signals may greatly enhance performance in emotion recognition. Nonetheless, existing approaches still suffer from two predominant challenges: modality heterogeneity, stemming from the diverse mechanisms across modalities, and fusion credibility, which arises when one or multiple modalities fail to provide highly credible signals.Approach.In this paper, we introduce a novel multimodal physiological signal fusion model that incorporates both intra-inter modality reconstruction and sequential pattern consistency, thereby ensuring a computable and credible EEG-based multimodal emotion recognition. For the modality heterogeneity issue, we first implement a local self-attention transformer to obtain intra-modal features for each respective modality. Subsequently, we devise a pairwise cross-attention transformer to reveal the inter-modal correlations among different modalities, thereby rendering different modalities compatible and diminishing the heterogeneity concern. For the fusion credibility issue, we introduce the concept of sequential pattern consistency to measure whether different modalities evolve in a consistent way. Specifically, we propose to measure the varying trends of different modalities, and compute the inter-modality consistency scores to ascertain fusion credibility.Main results.We conduct extensive experiments on two benchmarked datasets (DEAP and MAHNOB-HCI) with the subject-dependent paradigm. For the DEAP dataset, our method improves the accuracy by 4.58%, and the F1 score by 0.63%, compared to the state-of-the-art baseline. Similarly, for the MAHNOB-HCI dataset, our method improves the accuracy by 3.97%, and the F1 score by 4.21%. In addition, we gain much insight into the proposed framework through significance test, ablation experiments, confusion matrices and hyperparameter analysis. Consequently, we demonstrate the effectiveness of the proposed credibility modelling through statistical analysis and carefully designed experiments.Significance.All experimental results demonstrate the effectiveness of our proposed architecture and indicate that credibility modelling is essential for multimodal emotion recognition.

Chaihu Guizhi Ganjiang Decoction attenuates nonalcoholic steatohepatitis by enhancing intestinal barrier integrity and ameliorating PPARα mediated lipotoxicity.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a prominent cause of liver-related death that poses a threat to global health and is characterized by severe hepatic steatosis, lobular inflammation, and ballooning degeneration. To date, no Food and Drug Administration-approved medicine is commercially available. The Chaihu Guizhi Ganjiang Decoction (CGGD) shows potential curative effects on regulation of blood lipids and blood glucose, mitigation of organism inflammation, and amelioration of hepatic function. However, the overall regulatory mechanisms underlying its effects on NASH remain unclear. PURPOSE: This study aimed to investigate the efficiency of CGGD on methionine- and choline-deficient (MCD)-induced NASH and unravel its underlying mechanisms. METHODS: A NASH model of SD rats was established using an MCD diet for 8 weeks, and the efficacy of CGGD was evaluated based on hepatic lipid accumulation, inflammatory response, and fibrosis. The effects of CGGD on the intestinal barrier, metabolic profile, and differentially expressed genes (DEGs) profile were analyzed by integrating gut microbiota, metabolomics, and transcriptome sequencing to elucidate its mechanisms of action. RESULTS: In MCD-induced NASH rats, pathological staining demonstrated that CGGD alleviated lipid accumulation, inflammatory cell infiltration, and fibrosis in the hepatic tissue. After CGGD administration, liver index, liver weight, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) contents, liver triglycerides (TG), and free fatty acids (FFAs) were decreased, meanwhile, it down-regulated the level of proinflammatory mediators (TNF-α, IL-6, IL-1ß, MCP-1), and up-regulated the level of anti-inflammatory factors (IL-4, IL-10), and the expression of liver fibrosis markers TGFß, Acta2, Col1a1 and Col1a2 were weakened. Mechanistically, CGGD treatment altered the diversity of intestinal flora, as evidenced by the depletion of Allobaculum, Blautia, norank_f_Erysipelotrichaceae, and enrichment of the probiotic genera Roseburia, Lactobacillus, Lachnoclostridium, etc. The colonic histopathological results indicated that the gut barrier damage recovered in the CGGD treatment group, and the expression levels of colonic short-chain fatty acids (SCFAs)-specific receptors FFAR2, FFAR3, and tight junction (TJs) proteins ZO-1, Occludin, Claudin-1 were increased compared with those in the model group. Further metabolomic and transcriptomic analyses suggested that CGGD mitigated the lipotoxicity caused by glycerophospholipid and eicosanoid metabolism disorders by decreasing the levels of PLA2G4A, LPCAT1, COX2, and LOX5. In addition, CGGD could activate the inhibitory lipotoxic transcription factor PPARα, regulate the proteins of FABP1, APOC2, APOA2, and LPL to promote fatty acid catabolism, and suppress the TLR4/MyD88/NFκB pathway to attenuate NASH. CONCLUSION: Our study demonstrated that CGGD improved steatosis, inflammation, and fibrosis on NASH through enhancing intestinal barrier integrity and alleviating PPARα mediated lipotoxicity, which makes it an attractive candidate for potential new strategies for NASH prevention and treatment.

Integration of metabolomics and transcriptomics reveals that Da Chuanxiong Formula improves vascular cognitive impairment via ACSL4/GPX4 mediated ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Da Chuanxiong Formula (DCX) is a traditional herbal compound composed of Gastrodia elata Bl. and Ligusticum chuanxiong Hort, which could significantly enhance blood circulation and neuroprotection, showing promise in treating Vascular Cognitive Impairment (VCI). AIM OF STUDY: This study aims to elucidate the potential of DCX in treating VCI and its underlying mechanism. MATERIALS AND METHODS: Firstly, the cognitive behavior level, blood flow changes, and brain pathology changes were evaluated through techniques such as the Morris water maze, step-down, laser speckle, coagulation analysis, and pathological staining to appraise the DCX efficacy. Then, the DCX targeting pathways were decoded by merging metabolomics with transcriptomics. Finally, the levels of reactive oxygen species (ROS), Fe2+, and lipid peroxidation related to the targeting signaling pathways of DCX were detected by kit, and the expression levels of mRNAs or proteins related to ferroptosis were determined by qPCR or Western blot assays respectively. RESULTS: DCX improved cognitive abilities and cerebral perfusion significantly, and mitigated pathological damage in the hippocampal region of VCI model rats. Metabolomics revealed that DCX was able to call back 33 metabolites in plasma and 32 metabolites in brain samples, and the majority of the differential metabolites are phospholipid metabolites. Transcriptomic analysis revealed that DCX regulated a total of 3081 genes, with the ferroptosis pathway exhibiting the greatest impact. DCX inhibited ferroptosis of VCI rates by decreasing the levels of ferrous iron, ROS, and malondialdehyde (MDA) while increasing the level of superoxide dismutase (SOD) and glutathione (GSH) in VCI rats. Moreover, the mRNA and protein levels of ACSL4, LPCAT3, ALOX15, and GPX4, which are related to lipid metabolism in ferroptosis, were also regulated by DCX. CONCLUSION: Our research findings indicated that DCX could inhibit ferroptosis through the ACSL4/GPX4 signaling pathway, thereby exerting its therapeutic benefits on VCI.

AutoEER: automatic EEG-based emotion recognition with neural architecture search.

Objective.Emotion recognition based on electroencephalography (EEG) is garnering increasing attention among researchers due to its wide-ranging applications and the rise of portable devices. Deep learning-based models have demonstrated impressive progress in EEG-based emotion recognition, thanks to their exceptional feature extraction capabilities. However, the manual design of deep networks is time-consuming and labour-intensive. Moreover, the inherent variability of EEG signals necessitates extensive customization of models, exacerbating these challenges. Neural architecture search (NAS) methods can alleviate the need for excessive manual involvement by automatically discovering the optimal network structure for EEG-based emotion recognition.Approach.In this regard, we propose AutoEER (AutomaticEEG-basedEmotionRecognition), a framework that leverages tailored NAS to automatically discover the optimal network structure for EEG-based emotion recognition. We carefully design a customized search space specifically for EEG signals, incorporating operators that effectively capture both temporal and spatial properties of EEG. Additionally, we employ a novel parameterization strategy to derive the optimal network structure from the proposed search space.Main results.Extensive experimentation on emotion classification tasks using two benchmark datasets, DEAP and SEED, has demonstrated that AutoEER outperforms state-of-the-art manual deep and NAS models. Specifically, compared to the optimal model WangNAS on the accuracy (ACC) metric, AutoEER improves its average accuracy on all datasets by 0.93%. Similarly, compared to the optimal model LiNAS on the F1 Ssore (F1) metric, AutoEER improves its average F1 score on all datasets by 4.51%. Furthermore, the architectures generated by AutoEER exhibit superior transferability compared to alternative methods.Significance.AutoEER represents a novel approach to EEG analysis, utilizing a specialized search space to design models tailored to individual subjects. This approach significantly reduces the labour and time costs associated with manual model construction in EEG research, holding great promise for advancing the field and streamlining research practices.

Nitrogen removal characteristics of biofilms in each area of a full-scale AAO oxidation ditch process.

Plastic carriers were installed in different areas of a full-scale anaerobic/anoxic/aerobic (AAO) oxidation ditch process, and the dynamics of nitrogen removal, biofilm morphologies, and microorganism species were investigated. The results showed that the biofilm at the front of the aerobic area (dissolved oxygen [DO] = 0.93 mg L-1) provided the best denitrification, with specific nitrate and nitrite reduction rates of 10.16 and 3.78 mg·(g·h)-1, respectively. The biofilm in the middle of the aerobic area (DO = 1.27 mg L-1) exhibited the best nitrification performance, with a maximum specific ammonia oxidation rate of 3.21 mg·(g·h)-1. The biofilm at the end of the aerobic area (DO = 0.01 mg L-1) exhibited the highest anammox potential with a maximum specific anammox rate of 0.67 mg·(g·h)-1. No correlation was observed between the specific nitrogen removal rates and abundance of nitrogen-removing microorganisms at the genus level. Biofilm denitrification during the process was primarily completed by heterotrophic denitrifying bacteria (Thauera, Acinetobacter, Hyphomicrobium, and Thermomonas). Aerobic denitrifying bacteria (0.19% Thauera and 0.34% Hyphomicrobium) were identified as the main denitrifying bacteria in the middle of the aerobic area. The dominant nitrifying microorganisms in the middle of the aerobic area were Nitrosomonas (0.50%) and Nitrospira (1.04%). A biofilm in the end of the aerobic area exhibited specific anammox potential, which may have been related to the dominance of 0.024% Candidatus Brocadia. Kinetic analysis revealed that adding plastic carriers to the front and middle of the aerobic area contributed to stable nitrogen removal efficiency.

[Effect of Danhong Injection on platelet metabolites based on metabonomics technology].

The effect of Danhong Injection on the endogenous metabolites of rabbit platelets was analyzed by the liquid chromatography-mass spectrometry( LC-MS) based metabonomic approach. Anti-platelet aggregation was detected after Danhong Injection treatment and the changes of platelet metabolites were analyzed by metabonomics. Principal component analysis( PCA) and partial least squares discriminant analysis( PLS-DA) were performed to investigate the effect of Danhong Injection on endogenous metabolites of platelets,characterize the biomarkers,and explore the relevant pathways and the underlying mechanism. As demonstrated by the pharmacodynamic results,Danhong Injection of different doses and concentrations antagonized platelet aggregation in a dose-and concentration-dependent manner. In contrast to the control group,25 differential metabolites such as nicotinic acid,nicotinic acid riboside,and hypoxanthine were screened out after platelets were treated by Danhong Injection. These metabolites,serving as important biomarkers,were mainly enriched in the nicotinic acid-niacinamide metabolic pathway and purine metabolic pathway. This study explored the therapeutic mechanism of Danhong Injection from a microscopic perspective by metabonomics,which is expected to provide a new idea for the investigation of platelet-related mechanisms.

[Analysis and comparison of metabolic processes of salvianolic acid A and salvianolic acid B in rats based on UHPLC-LTQ-Orbitrap MS technology].

The metabolites of salvianolic acid A and salvianolic acid B in rats were analyzed and compared by ultra-high-perfor-mance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS). After the rats were administrated by gavage, plasma at different time points and urine within 24 hours were collected to be treated by solid phase extraction(SPE), then they were gradient eluted by Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) and 0.1% formic acid solution(A)-acetonitrile(B) mobile phase system, and finally all biological samples of rats were analyzed under negative ion scanning mode. By obtaining the accurate relative molecular mass and multi-level mass spectrometry information of metabolites, combined with the characteristic cleavage law of the reference standard and literature reports, a total of 30 metabolites, including salvianolic acid A and B, were identified. Among them, there were 24 metabolites derived from salvianolic acid A, with the main metabolic pathways including ester bond cleavage, dehydroxylation, decarboxylation, hydrogenation, methylation, hydroxylation, sulfonation, glucuronidation, and their multiple reactions. There were 15 metabolites of salvianolic acid B, and the main biotransformation pathways were five-membered ring cracking, ester bond cleavage, decarboxylation, dehydroxylation, hydrogenation, methylation, sulfonation, glucuronidation, and their compound reactions. In this study, the cross-metabolic profile of salvianolic acid A and B was elucidated completely, which would provide reference for further studies on the basis of pharmacodynamic substances and the exploration of pharmacological mechanism.

Characteristics of nutrients removal under partial denitrification initiated by different initial nitrate concentration.

The partial denitrification (PD) is a very promising process developed in the last decade, to study the comprehensive influence of influent carbon to nitrogen (C/N) on the activated sludge system under PD, six sequencing batch reactors (SBRs) were operated in parallel at C/N of 2.75, 3.30, 4.13, 5.50, 8.25 and 16.50, the nitrogen removal, phosphorus removal and sludge settleability of PD were investigated. The results showed that PD was observed treating synthetic wastewater in all the six SBRs, and the nitrite accumulation rate (NAR) was highest at C/N of 5.50 (NAR of 82.30%). However, due to the alternate inhibition of NO2--N and free nitrous acid (FNA) produced by a limited carbon source, both the sludge settleability and phosphorus removal deteriorated. The average SVI at C/N of 8.25 was 130% lower than C/N of 3.30, and the average amount of PO43--P released at C/N of 16.5 was 189% higher than C/N of 2.75. Kinetic analysis showed that the denitrification kinetics of PD and complete denitrification were similar, and the nitrite accumulation was caused by the difference between nitrate reduction rate and nitrite reduction rate. Variations of on-line parameters (pH and ORP) revealed that nitrite accumulation could be indicated by judging the nitrate turning point and nitrite turning point on pH and ORP curves, which provided guidance for the setup of PD.

Enhanced denitrification of secondary effluent using composite solid carbon source based on agricultural wastes and synthetic polymers.

Solid-phase denitrification is a promising approach to enhance nitrate removal. In this work, polybutylene succinate (PBS) and peanut shell (PS) (with crosslinked polyvinyl alcohol-sodium alginate (PVA-SA) as carrier) were used to prepare a composite solid carbon source (3P) to denitrify the secondary effluent. The results showed that for carbon release performance, 3P had not only a large release of organics, like PS, but also the excellent sustainability of PBS. Among the short chain fatty acids released by PBS, PS, PVA-SA and 3P, the percentages of acetic acid were 59.42%, 72.54%, 72.29% and 92.11%, respectively. When 3P was used as external carbon source, denitrification performance could be enhanced with effluent dissolved organic carbon lower than 20 mg/L. The prepared 3P could improve denitrification, from both microbial and kinetic aspects. The relative abundance of Gammaproteobacteria increased from 39.32% to 43.58%, and the half saturation constant of the fitting Monod equation was 21.28 mg/L. The prepared 3P is an ideal carbon source for secondary effluent denitrification. Using multiple crosslinking methods to produce carrier is an effective way to show the properties of each material.

Nitrification characteristics of long-term idle aerobic activated sludge during domestication.

Nitrite accumulation usually occurred when domesticating the idle aerobic activated sludge. A sequencing batch reactor (SBR) was used to investigate whether the short-cut nitrification sludge could be cultivated using the idle sludge as inoculated sludge. The results showed that the nitrification process consisted of three stages. In the first stage, the activity of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) were very low with almost no nitrification performance. In the second stage, the activity of AOB started to recover with the effluent NH4+-N gradually decreased to 0.29 mg L-1, while NOB was alternately inhibited by free ammonia (FA), free nitrous acid (FNA), and nitrite. The effluent NOx--N was mainly NO2--N with an average nitrite accumulation ratio of 74.00%. In the third stage, the nitrification altered from short-cut nitrification to complete nitrification, and the nitrification kinetics of AOB and NOB were both well-fitted to the Monod equation (R2 > 0.92). The variations of effluent pH and ORP between cycles could indicate the recovery stage of the nitrifying ability. Through monitoring the curves of effluent pH and ORP, when the domestication process is between the pH peak and ORP plateau, the short-cut nitrification sludge could be cultivated. This study revealed the mechanism of nitrite accumulation during the domestication of long-term idle aerobic activated sludge, and established a control strategy to accelerate the domestication.

Comprehensive metabolism study of swertiamarin in rats using ultra high-performance liquid chromatography coupled with Quadrupole-Exactive Orbitrap mass spectrometry.

Swertiamarin, a natural ingredient with potent pharmacological activities in the iridoid glycoside family, had been reported to have significant therapeutic effects on a variety of human diseases.In this study, a systematic and efficient strategy based on UHPLC-Q-Exactive Orbitrap mass spectrometry was established to reveal the metabolic profile of swertiamarin in rat urine, plasma, and faeces.First of all, post-acquisition data-mining methods, including multiple mass defect filters (MMDFs) and high-resolution extracted ion chromatograms (HREICs), were developed to screen the metabolite candidates of swertiamarin from the complete mass scan data sets.Second, according to the diagnostic product ions (DPIs), neutral loss fragments (NLFs), chromatographic retention time, accurate mass measurement and calculated Clog P values, all metabolite candidates were rapidly identified.As a consequence, 49 metabolites altogether, including archetype compound, were preliminarily characterised. The corresponding in vivo biotransformation processes, such as dehydration, dehydrogenation, hydroxylation, hydrogenation, methylation, sulphonation, N-acetylcysteine (NAC) formation, N-heterocyclisation and their composite reactions, were all discovered in the study.In conclusion, our results not only detailedly elucidated many new metabolites and metabolic pathways of swertiamarin, but also provided a reference for further study of its pharmacological mechanism and evaluation of its safety.

[Analysis of carnosic acid metabolites in rats by UHPLC-Q-Exactive MS].

A method of ultra-high performance liquid chromatography coupled with quadrupole/electrostatic field Obitrap high-resolution mass spectrometry(UHPLC-Q-Exactive MS) was established to comprehensively identify the metabolites of carnosic acid in rats. After oral gavage of carnosic acid CMC-Na suspension in rats, urine, plasma and feces samples were collected and pretreated by solid phase extraction(SPE). Acquity UPLC BEH C_(18 )column(2.1 mm×100 mm, 1.7 µm) was used with 0.1% formic acid solution(A)-acetonitrile(B) as the mobile phase for the gradient elution. Biological samples were analyzed by quadrupole/electrostatic field Obitrap high-resolution mass spectrometry in positive and negative ion mode. Based on the accurate molecular mass, fragment ion information, and related literature reports, a total of 28 compounds(including carnosic acid) were finally identified in rat samples. As a result, the main metabolic pathways of carnosic acid in rats are oxidation, hydroxylation, methylation, glucuronide conjugation, sulfate conjugation, S-cysteine conjugation, glutathione conjugation, demethylation, decarbonylation and their composite reactions. The study showed that the metabolism of carnosic acid in rats could be efficiently and comprehensively clarified by using UHPLC-Q-Exactive MS, providing a reference for clarifying the material basis and metabolic mechanism of carnosic acid.

Comprehensive Screening and Identification of Phillyrin Metabolites in Rats Based on UHPLC-Q-Exactive Mass Spectrometry Combined with Multi-Channel Data Mining.

Phillyrin, a well-known bisepoxylignan, has been shown to have many critical pharmacological activities. In this study, a novel strategy for the extensive acquisition and use of data was established based on UHPLC-Q-Exactive mass spectrometry to analyze and identify the in vivo metabolites of phillyrin and to elucidate the in vivo metabolic pathways of phillyrin. Among them, the generation of data sets was mainly due to multichannel data mining methods, such as high extracted ion chromatogram (HEIC), diagnostic product ion (DPI), and neutral loss filtering (NLF). A total of 60 metabolites (including the prototype compound) were identified in positive and negative ion modes based on intuitive and useful data such as the standard's cleavage rule, accurate molecular mass, and chromatographic retention time. The results showed that a series of biological reactions of phillyrin in vivo mainly included methylation, hydroxylation, hydrogenation, sulfonation, glucuronidation, demethylation, and dehydrogenation and their composite reactions. In summary, this study not only comprehensively explained the in vivo metabolism of phillyrin, but also proposed an effective strategy to quickly analyze and identify the metabolites of natural pharmaceutical ingredients in nature.