Synthesis of a cysteine functional covalent organic framework via facile click reaction for the efficient solid phase extraction of substituted p-phenylenediamine-derived quinones.

N,N'-Substituted p-phenylenediamine quinones (PPD-Qs) are the emerging toxicant, which transform from the rubber tire antioxidant N,N'-substituted p-phenylenediamines (PPDs). Because of their potential toxic and widespread occurrence in the environment, PPD-Qs have received great attention. However, efficiently extracting PPD-Qs from complex samples is still a challenge. Herein, a cysteine functional covalent organic framework (Cys-COF) designed according to the "donor-acceptor" sites of hydrogen bonding of PPD-Qs was synthesized via click reaction and then used as solid-phase extraction (SPE) adsorbent. Cys-COF can form the seven-member ring adsorption structure with PPD-Qs via hydrogen bonding. The adsorption mechanism was tentatively revealed by density functional theory (DFT). After optimizing the Cys-COF-SPE parameters, PPD-Qs were efficiently extracted from water, soil, sediment, and fish, followed by detection using ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The Cys-COF-SPE-UHPLC-MS/MS method exhibited ideal linearity (R2 ≥ 0.9932), high relative recoveries (80.4-111 %), and low limits of detection (0.0001-0.0013 ng mL-1). In addition, the bioconcentration kinetics in goldfish provides a feasible platform to investigate the toxicity and accumulated ability of PPD-Qs.

Measurements of Thermal Resistance Across Buried Interfaces with Frequency-Domain Thermoreflectance and Microscale Confinement.

Confined geometries are used to increase measurement sensitivity to thermal boundary resistance at buried SiO2 interfaces with frequency-domain thermoreflectance (FDTR). We show that radial confinement of the transducer film and additional underlying material layers prevents heat from spreading and increases the thermal penetration depth of the thermal wave. Parametric analyses are performed with finite element methods and used to examine the extent to which the thermal penetration depth increases as a function of a material's effective thermal resistance and the degree of material confinement relative to the pump beam diameter. To our surprise, results suggest that the measurement technique is not always the most sensitive to the largest thermal resistor in a multilayer material. We also find that increasing the degree to which a material is confined improves measurement sensitivity to the thermal resistance across material interfaces that are buried 10s of µm to mm below the surface. These results are used to design experimental measurements of etched, 200 nm thick SiO2 films deposited on Al2O3 substrates, and offer an opportunity for thermal scientists and engineers to characterize the thermal resistance across a broader range of material interfaces within electronic device architectures that have historically been difficult to access via experiment.

A novel surface marker CD49d promotes TNF expression in oyster agranulocytes by mediating the MAPK pathway.

CD49d, encoded by the gene Integrin α4, is a significant member of cell adhesion receptors, which is widely expressed in various immune cells to trigger immune responses against invading pathogens. In the present study, the expression of CgCD49d and its regulatory role in TNF expression were investigated in the Pacific oyster Crassostrea gigas. There were five Int-alpha domains, an Integrin_alpha2 region and a unique FG-GAP repeat region inserted identified in CgCD49d. CgCD49d transcript was specifically expressed in haemocytes, and its mRNA expression level in haemocytes increased after LPS and Vibrio splendidus stimulation. After CgCD49d was blocked by using its antibody, the phosphorylation level of CgJNK in the MAPK signaling pathway and CgTNF transcripts decreased significantly post V. splendidus stimulation. After phosphorylation level of CgJNK was inhibited by using its inhibitor, the nuclear translocation of CgRel was restrained and CgTNF transcripts also decreased significantly post V. splendidus stimulation. Furthermore, CgCD49d was found to be mainly expressed in the agranulocyte subpopulation, and Alexa Fluor 488-conjugated CgCD49d antibody labeled agranulocytes with a circle of green fluorescence signals on CgCD49d+ agranulocyte surface under Confocal microscopy, which accounted for 24.9 ± 4.53% of total haemocytes. Collectively, these results suggested that CgCD49d promoted TNF expression in oyster haemocytes against bacterial invasion by mediating MAPK pathway, and it could be used as a surface marker to type and sort a subset of agranulocyte subpopulation among haemocytes.

Favoritism or bias? Cooperation and competition under different intergroup relationships: evidence from EEG hyperscanning.

Cooperation and competition are the most common forms of social interaction in various social relationships. Intergroup relationships have been posited to influence individuals' interpersonal interactions significantly. Using electroencephalography hyperscanning, this study aimed to establish whether intergroup relationships influence interpersonal cooperation and competition and the underlying neural mechanisms. According to the results, the in-group Coop-index is better than the out-group, whereas the out-group Comp-index is stronger than the in-group. The in-group functional connectivity between the frontal-central region and the right temporoparietal junction in the ß band was stronger in competition than cooperation. The out-group functional connectivity between the frontal-central region and the left temporoparietal junction in the α band was stronger in cooperation than competition. In both cooperation and competition, the in-group exhibited higher interbrain synchronization between the prefrontal cortex and parietal region in the θ band, as well as between the frontal-central region and frontal-central region in the α band, compared to the out-group. The intrabrain phase-locking value in both the α and ß bands can effectively predict performance in competition tasks. Interbrain phase-locking value in both the α and θ bands can be effectively predicted in a performance cooperation task. This study offers neuroscientific evidence for in-group favoritism and out-group bias at an interpersonal level.

Indole-3-acetic acid ameliorates dextran sulfate sodium-induced colitis via the ERK signaling pathway.

Microbiota-derived catabolism of nutrients is closely related to ulcerative colitis (UC). The level of indole-3-acetic acid (IAA), a microbiota-dependent metabolite of tryptophan, was decreased significantly in the feces of UC patients. Thus supplementation with IAA could be a potential therapeutic method for ameliorating colitis. In this work, the protective effect of supplementation with IAA on dextran sulfate sodium (DSS)-induced colitis was evaluated, and the underlying mechanism was elucidated. The results indicated that the administration of IAA significantly relieved DSS-induced weight loss, reduced the disease activity index (DAI), restored colon length, alleviated intestinal injury, and improved the intestinal tight junction barrier. Furthermore, IAA inhibited intestinal inflammation by reducing the expression of proinflammatory cytokines and promoting the production of IL-10 and TGF-ß1. In addition, the ERK signaling pathway is an important mediator of various physiological processes including inflammatory responses and is closely associated with the expression of IL-10. Notably, IAA treatment induced the activation of extracellular signal-regulated kinase (ERK), which is involved in the progression of colitis, while the ERK inhibitor U0126 attenuated the beneficial effects of IAA. In summary, IAA could attenuate the clinical symptoms of colitis, and the ERK signaling pathway was involved in the underlying mechanism. Supplementation with IAA could be a potential option for preventing or ameliorating UC.

Skin irritation assessment and potential mechanism of Capparis spinosa L. fruits.

ETHNOPHARMACOLOGICAL RELEVANCE: In China, Capparis spinosa L. fruits (CSF) are often used topically in Uyghur folk medicine in treating rheumatic diseases with remarkable efficacy. However, it has noticed severe skin irritation after a short time application with high dose of CSF, which limited long-term clinical use. To date, there is almost no research related to skin irritation of CSF. AIM OF THE STUDY: This study was intended to perform the first systematic assessment of morphological and histological changes in skin after stimulation with CSF. Furthermore, potential irritant components in CSF and related mechanisms were explored by in vitro transdermal techniques, network pharmacology, molecular docking, and experimental validation. MATERIALS AND METHODS: Skin changes after single and multiple stimulations with CSF were observed and subjected to skin irritation response scoring, irritation strength assessment, and histopathological analysis. In addition, in vitro transdermal technology, liquid chromatography-mass spectrometry (LC-MS) method, network pharmacology, molecular docking, and experimental validation were used to further exploit underlying skin irritant components and possible mechanisms of action. RESULTS: CSF induced significant morphological (erythema and edema) and histological (epidermal thickening and inflammatory infiltration) changes in skin of mice, which were similar to the clinical presentation of irritation contact dermatitis (ICD). The ethyl acetate fraction of CSF (CFEAF) was the main source of CSF-induced skin irritation. Kaempferol, flazin, and gallic acid were potential major irritant compounds. Moreover, CFEAF, kaempferol, flazin, and gallic acid could increase the levels of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and interleukin-17A (IL-17A) to promote skin inflammation. The potential mechanism of CSF-induced skin irritation may be activation of the nuclear factor kappa-B (NF-κB) signaling pathway, including phosphorylation of NF-κB p65 (p65) and nuclear factor-kappa B inhibitor alpha (IκBα). CONCLUSION: Kaempferol, flazin, and gallic acid are potential skin irritant components from CSF. Altogether, they induce skin irritation responses through promoting the release of the inflammatory factors TNF-α and ICAM-1, as well as activating the NF-κB signaling pathway. In addition, IL-17A may be an important pro-inflammatory factor in skin irritation.

Effect of different fertilization strategies on the yield, quality of Euryales Semen and soil microbial community.

Introduction: Euryales Semen, a medicinal herb widely utilized in Asia, faces a critical constraint in its production, primarily attributed to fertilizer utilization. Understanding the impact of different fertilization schemes on Euryales Semen (ES) planting and exploring the supporting mechanism are crucial for achieving high yield and sustainable development of the ES planting industry. Methods: In this study, a field plot experiment was conducted to evaluate the effects of four different fertilization treatments on the yield and quality of ES using morphological characteristics and metabolomic changes. These treatments included a control group and three groups with different organic fertilizer to chemical fertilizer ratios (3:7, 5:5, and 7:3). The results of this study revealed the mechanisms underlying the effect of the different treatments on the yield and quality of Euryales Semen. These insights were achieved through analyses of soil physicochemical properties, soil enzyme activity, and soil microbial structure. Results: We found that the quality and yield of ES were the best at a ratio of organic fertilizer to chemical fertilizer of 7:3. The optimality of this treatment was reflected in the yield, soil available nitrogen, soil available phosphorus, and soil enzyme activity of ES. This ratio also increased soil microbial diversity, resulting in an increase and decrease in Proteobacteria and Firmicutes abundances, respectively. In addition, linear discriminant analysis showed that Chloroflexi, Gammaproteobacteria, and Hypocreales-incertae-sedis were significantly enriched in the ratio of organic fertilizer to chemical fertilizer of 7:3. Variance partitioning analysis showed that the soil properties, enzyme activities, and their interactions cumulatively can explain 90.80% of the differences in Euryales Semen yield and metabolome. In general, blending organic and chemical fertilizers at a 7:3 ratio can enhance soil fertility, boost Euryales Semen yield and quality, and bring forth conditions that are agriculturally beneficial to microbial (bacteria and fungi) dynamics. Discussion: This study initially revealed the scientific connotation of the effects of different fertilization patterns on the planting of Euryales Semen and laid a theoretical foundation for the study of green planting patterns of Euryales Semen with high quality and yield.

Mechanism of optical limiting in metalloporphyrins under visible continuous radiation.

Here, we present an experimental investigation on the nonlinear optical (NLO) and optical limiting properties of metalloporphyrin compounds (Cu-1-OH, Zn-1-OH, Cu-1-E and Zn-1-E) using spatial self-phase modulation (SSPM) method in the visible range. It is found that all of the samples show a large self-defocusing effect at 532 nm, which is attributed to the thermal nonlinear optical effects with negative nonlinear refractive index coefficient n2 due to the relatively high absorption at 532 nm. In contrast, at 780 nm where absorption is weak for both Zn- and Cu-porphyrins, Zn-porphyrins still exhibit visible self-defocusing while Cu-porphyrins do not show any nonlinear diffraction pattern. Such a phenomenon can be explained by the Kerr effect of Cu-porphyrins at 780 nm. As the thermal nonlinear optical effects (of negative n2) at 780 nm are reduced due to the low absorption, the Kerr effect with positive n2 becomes comparable and the overall nonlinearity is reduced. The Kerr effect of Cu-porphyrins is stronger than that of Zn-porphyrins because of the enhanced π-electron delocalization effect as Cu(II) has a variable number of valence electrons and incompletely filled d atomic orbitals. Finally, the optical limiting performance of Zn-porphyrins is demonstrated as a representative and its dependence on sample position is examined. This work not only enriches the understanding of the physical mechanism of optical limiting in porphyrin materials, but also provides a significant reference to improve the third-order NLO coefficient by adjusting the structure of compounds.

Metabolite profiling and transcriptomic analyses demonstrate the effects of biocontrol agents on alkaloid accumulation in Fritillaria thunbergii.

BACKGROUND: During Fritillaria thunbergii planting, pests and diseases usually invade the plant, resulting in reduced yield and quality. Previous studies have demonstrated that using biocontrol agents can effectively control grubs and affect the steroid alkaloids content in F. thunbergii. However, the molecular regulatory mechanisms underlying the differences in the accumulation of steroid alkaloids in response to biocontrol agents remain unclear. RESULTS: Combined transcriptomic and metabolic analyses were performed by treating the bulbs of F. thunbergii treated with biocontrol agents during planting. Otherwise, 48 alkaloids including 32 steroid alkaloids, 6 indole alkaloids, 2 scopolamine-type alkaloids, 1 isoquinoline alkaloid, 1 furoquinoline alkaloid, and 6 other alkaloids were identified. The content of steroidal alkaloids particularly peimine, peiminine, and veratramine, increased significantly in the group treated with the biocontrol agents. Transcriptome sequencing identified 929 differential genes using biocontrol agents, including 589 upregulated and 340 downregulated genes. Putative biosynthesis networks of steroid alkaloids have been established and combined with differentially expressed structural unigenes, such as acetyl-CoA C-acetyl-transferase, acelyl-CoAC-acetyltransferase3-hydroxy-3-methylglutaryl-coenzyme A synthase, 1-deoxy-D-xylulose-5-phosphate reductor-isomerase, 2-C-methyl-D-erythritol-4-phosphate cytidylyltransferase and 4-hydroxy-3-methylbut-2-enyl diphosphate reductase. In addition, biological processes such as amino acid accumulation and oxidative phosphorylation were predicted to be related to the synthesis of steroid alkaloids. Cytochrome P450 enzymes also play crucial roles in the steroid alkaloid synthesis. The transcription factor families MYB and bHLH were significantly upregulated after using biocontrol agents. CONCLUSIONS: Biocontrol agents increased the steroid alkaloids accumulation of steroid alkaloids by affecting key enzymes in the steroid alkaloid synthesis pathway, biological processes of oxidative phosphorylation and amino acid synthesis, cytochrome P450 enzymes, and transcription factors. This study revealed the mechanism underlying the difference in steroidal alkaloids in F. thunbergii after using biocontrol agents, laying the groundwork for future industrial production of steroid alkaloids and ecological planting of medicinal materials in the future.

Glehnia littoralis Fr. Schmidtex Miq.: A systematic review on ethnopharmacology, chemical composition, pharmacology and quality control.

ETHNOPHARMACOLOGICAL RELEVANCE: Glehnia littoralis Fr. Schmidtex Miq. is a well-known perennial herb that is used in traditional medicine in China, Japan and Korea. G. littoralis has the effects of treating the lungs with heat, nourishing yin and blood, and acting as an expectorant. Traditional Chinese medicine (TCM) prescriptions containing G. littoralis have various clinical applications, such as clearing heat, relieving coughs, treating hepatic fibrosis, resolving phlegm, and treating esophagitis. AIM OF THE REVIEW: This paper aims to provide a comprehensive and productive review of G. littoralis, mainly including traditional application, ethnopharmacology, chemical composition, pharmacological activities, and quality control. MATERIALS AND METHODS: Literature search was conducted through the Web of Science, ScienceDirect, Springer Link, PubMed, Baidu Scholar, CNKI, and WanFang DATA by using the keywords "Glehnia littoralis", "Radix Glehniae", "Bei Shashen", "Clinical application", "Chemical composition", "Quality control" and "pharmacological action". In addition, information was collected from relevant ancient books, reviews, and documents (1980-2022). RESULTS: G. littoralis is a traditional Chinese herbal medicine with great clinical value and rich resources. More than 186 components, including coumarins, lignans, polyacetylenes, organic acids, flavonoids, and terpenoids, have been isolated and identified from G. littoralis. The pharmacological activities of more than half of these chemicals are yet unknown. Polyacetylenes and coumarins are the most important bioactive compounds responsible for pharmacological activities, such as antiproliferative, anti-oxidation, anti-inflammatory, antibacterial, antitussive, immune regulation and analgesic. In this study, the progress in chemical analysis of G. littoralis, including thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (MS), and HPLC-MS, were summarized. CONCLUSION: In this paper reviewed the previous literature regarding ethnopharmacological, phytochemical, pharmacological, and quality evaluation of the processing of G. littoralis was reviewed, providing potential reference information for future investigation and clinical applications. However, research on the relationship between chemical constituents and traditional uses of G. littoralis is lacking, and the comprehensive pharmacological effects and mechanisms of G. littoralis require further detailed exploration. In addition, an efficient method for chemical profiling is still unavailable to obtain potent bioactive markers for quality control. Perfect quality standards, which are also the basis for further drug development of G. littoralis, are urgently needed to ensure its quality and clinical application.

Quantitative Analysis of the Cu Element Enhanced by AgNPs in a Single Microsized Suspended Particle Based on Optical Trapping-LIBS and Machine Learning.

Extremely severe and persistent particulate pollution caused by industrialization and urbanization impacts air quality, regional and global climates, and human health. The unstable and complex spectral signal of laser-induced breakdown spectroscopy (LIBS) with minimal feature information and interference signals considerably influences the accuracy of qualitative and quantitative analysis. In response to overcome this phenomenon, in this work, quantitative analysis of Cu element enhanced by silver nanoparticles (AgNPs) in a single microsized suspended particle was proposed herein using optical trapping-LIBS and machine learning method was proposed. Initially, the optimal AgNPs enhancement conditions were optimized. The LIBS spectra of 15 polluted black carbon samples were collected and various spectral pretreatment methods were compared to optimize the LIBS spectra. Variable selection methods include variable importance measurement (VIM), variable importance projection (VIP), VIM-successive projections algorithm (VIM-SPA), VIM-genetic algorithm (VIM-GA), and VIM-mutual information (VIM-MI). Finally, several hybrid variable selection methods were implemented in random forest (RF) calibration models. In particular, a wavelet transform (WT)-VIM-SPA-RF calibration model has constructed under the WT spectral pretreatment method and the selected and optimized input variables (VIM-SPA). Results elucidate that the WT-VIM-SPA-RF calibration model (R2P = 0.9858, MREP = 0.0396) have the best prediction performance than the WT-RF and Raw-RF models in predicting the Cu level in a single microsized black carbon particle. Compared to the WT-RF and Raw-RF models, MREP values decreased by 37% and 62%, respectively. The values of RSD, RPD, and RER of this calibration model are 2.8%, 8.39%, and 17.79%, respectively. The aforementioned results demonstrate that the WT-VIM-SPA-RF calibration model with accuracy, stability, and robustness is a promising approach for improving the quantitative accuracy of the Cu level in carbon black particles.

Chemical profiling and quantification analysis of flavonoids in different varieties of Euryales Semen by ultra-high-performance liquid chromatography with tandem mass spectrometry.

Euryales Semen was a traditional Chinese medicine, which has been commonly used to treat spermatorrhea, enuresis, and frequent urination. Flavonoids were a critical ingredient in determining the function and quality of Euryales Semen. At present, no effective method has been established for the qualitative of Euryales Semen flavonoids. In this study, an ultra-high-performance liquid chromatography-quadrupole-time of flight-mass spectrometry method was established for flavonoids. By comparison with standard or literature data, 32 flavonoid compounds have been identified in Euryales Semen. Based on the qualitative results, an ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectroscopy method was developed for the main components, and the linearity, the limit of detection, limit of quantification, repeatability, precision, stability, and recovery of the method were verified. The principal component analysis and the hierarchical clustering heatmaps analysis showed that the 30 batches of samples were distinctly separated into the North Gordon Euryale and South Gordon Euryale, and the measured contents of the six flavonoids in North Gordon Euryale were more abundant than in South Gordon Euryale, especially isoquercitrin, hesperetin, and quercetin. It provided a scientific basis for the quality control of Euryales Semen and a theoretical basis for the rational utilization of Euryales Semen resources.

Individual Micron-Sized Aerosol Qualitative Analysis-Combined Raman Spectroscopy and Laser-Induced Breakdown Spectroscopy by Optical Trapping in Air.

The attribution of single particle sources of atmospheric aerosols is an essential problem in the study of air pollution. However, it is still difficult to qualitatively analyze the source of a single aerosol particle using noncontact in situ techniques. Hence, we proposed using optical trapping to combine gated Raman spectroscopy with laser-induced breakdown spectroscopy (LIBS) in a single levitated micron aerosol. The findings of the spectroscopic imaging indicated that the particle plasma formed by a single particle ablation with a pulsed laser within 7 ns deviates from the trapped particle location. The LIBS acquisition field of view was expanded using the 19-bundle fiber, which also reduces the fluctuation of a single particle signal. In addition, gated Raman was utilized to suppress the fluorescence and increase the Raman signal-to-noise ratio. Based on this, Raman can measure hard-to-ionize substances with LIBS, such as sulfates. The LIBS radical can overcome the restriction that Raman cannot detect ionic chemicals like fluoride and chloride in halogens. To test the capability of directly identifying distinctive feature compounds utilizing spectra, we detected anions using Raman spectroscopy and cations using LIBS. Four typical mineral aerosols are subjected to precise qualitative evaluations (marble, gypsum, baking soda, and activated carbon adsorbed potassium bicarbonate). To further validate the application potential for substances with indistinctive feature discrimination, we employed machine learning algorithms to conduct a qualitative analysis of the coal aerosol from ten different origin regions. Three data fusion methodologies (early fusion, intermediate fusion, and late fusion) for Raman and LIBS are implemented, respectively. The accuracy of the late fusion model prediction using StackingClassifier is higher than that of the LIBS data (66.7%) and Raman data (86.1%) models, with an average accuracy of 90.6%. This research has the potential to provide online single aerosol analysis as well as technical assistance for aerosol monitoring and early warning.

Simultaneous determination of cordycepin and its metabolite 3'-deoxyinosine in rat whole blood by ultra-high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole orbitrap high-resolution accurate mass spectrometry and its application to accurate pharmacokinetic studies.

Cordycepin from Cordyceps possesses excellent pharmacological properties, including anti-inflammation and anti-tumor effects, therefore representing a potential alternative medicine. However, doubts about the pharmacokinetic results of cordycepin had been raised in the previous study due to its rapid deamination. The organic solvent methanol was immediately added to terminate the degradation of cordycepin in anticoagulated blood samples and enable the accurate evaluation of pharmacokinetics in vivo. A sensitive and selective ultra-high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole orbitrap high-resolution accurate mass spectrometry method was developed and validated to simultaneously determine cordycepin and its deamination metabolite 3'-deoxyinosine using 2-chloroadenosine as an internal standard in rat whole blood. The calibration curves of cordycepin and 3'-deoxyinosine showed excellent linearity within the concentration range of 1.05-10 000.00 ng/ml with acceptable accuracy, precision, selectivity, recovery, matrix effect, and stability. This method was successfully applied to the pharmacokinetic study of cordycepin and its metabolite in rat blood. The effect of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride on the pharmacokinetics of cordycepin was investigated. In summary, the reliable pharmacokinetic parameters of cordycepin and its deamination metabolite 3'-deoxyinosine in rat blood were successfully elucidated. Erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride considerably prolonged the half-life of cordycepin in vivo.

The in vitro/in vivo metabolic pathways analysis of lobetyol, lobetyolin, and lobetyolinin, three polyacetylenes from Codonopsis Radix, by UHPLC-Q/TOF-MS and UHPLC-MS/MS.

Polyacetylenes, lobetyol, lobetyolin and lobetyolinin, are responsible for antitumor, antioxidant, anti-inflammatory, immunomodulatory activities of Codonopsis Radix. However, their metabolic pathways are still unknown. The study was purposed to investigate the metabolism of three polyacetylenes in vitro and in vivo by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Moreover, a rapid, sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantitative and semi-quantitative determination of lobetyol and its 12 metabolites to investigate the metabolic stability and metabolic phenotypes. A total of 47, 30 and 34 metabolites of lobetyol, lobetyolin and lobetyolinin were found in all samples. These metabolites are produced through extensive pathways, mainly involving oxidation, glucuronidation and glutathione conjugation. Lobetyol showed good metabolic stability in liver microsomes. The results of both recombinant human CYP enzymes and chemical inhibition experiments confirmed that CYP2C19, 1A1, 2C9, and 1A2 are the major isozymes mediating lobetyol metabolism.

Multi-element Quantitative Analysis of Single Micro-sized Suspended Particles in Air with High Accuracy Based on Random Forest and Variable Selection Strategies.

The chemical compositions of atmospheric particles have been studied for several decades, and the traditional techniques for particle analysis usually require time-consuming sample preparation. Within this study, simultaneous quantitative detection of multiple metallic species (Zn, Cu, and Ni) in single micro-sized suspended particles was investigated by combining random forest (RF) and variable selection strategies. Laser-induced breakdown spectra of 15 polluted black carbon samples were applied for establishing the RF model, and the movmean smoothing spectral pretreatment method and variable selection methods [variable importance measurement (VIM), genetic algorithm (GA), and variable importance projection (VIP)] were proposed. Finally, the optimized RF calibration model with the evaluation indicators of mean relative error (MRE), root-mean-square error (RMSE), and coefficient of determination (R2) was constructed based on the optimal input variables and model parameters. Compared with the univariate regression method, the VIP-RF (Zn) and VIM-RF (Cu and Ni) models showed a better correlation relationship (Rp2 = 0.9662 for Zn, Rp2 = 0.9596 for Cu, and Rp2 = 0.9548 for Ni). For Zn, Cu, and Ni, the values of RMSEP (RMSE of prediction) decreased by 116.44, 68.94, and 102.10 ppm, while the values of MREP (MRE of prediction) decreased by 67, 55, and 48%, respectively. The values of ratio of prediction to deviation (RPD) of VIP-RF (Zn), VIM-RF (Cu), and VIM-RF (Ni) models were 5.4, 5.0, and 4.7, respectively. The performance of this combined approach displays a notable accuracy improvement in the quantitative analysis of single particles, suggesting that it is a promising tool for real-time air particulate matter pollution monitoring and control in the future.

Neural Basis of the Implicit Learning of Complex Artificial Grammar with Nonadjacent Dependencies.

The capacity for the implicit learning/processing of complex grammar with nonadjacent dependencies is an important feature of human language learning. In this fMRI study, using an implicit AGL paradigm, we explored the neural basis of the implicit learning of the nonadjacent dependency rule, disentangling from sequence-based chunk knowledge (i.e., local sequential regularities or substring) by focusing on the low chunk strength items (which were naturally less similar to training strings), based on tracking neural responses during training and test phases. After listening to and memorizing a series of strings of 10 syllables generated from nonadjacent artificial grammar in the training phase, participants implicitly acquired the knowledge of grammar and chunks. Regarding grammaticality, Broca's area was specifically related to low chunk strength grammatical strings relative to nongrammatical strings in the test phase. This region showed decreased activity with time in the training phase, and a lesser decrease in activity was associated with higher performance in grammar learning. Furthermore, Broca's area showed significantly higher strength of functional connectivity with the left superior temporal gyrus in the low chunk strength grammatical string compared with nongrammatical strings, and this functional connectivity increased with the training time. For the chunks, the performance of accurate discrimination of high chunk strength from low chunk strength nongrammatical strings was predicted by hippocampal activity in the training phase. Converging evidence from the training and test phases showed that Broca's area and its functional connectivity with the left superior temporal gyrus were engaged in the implicit learning/processing of the nonadjacent dependency rule, separating the effects of chunks.

Serum pharmacochemistry and pharmacokinetics of major components after oral administration of Luhong recipe in rats using ultra-performance liquid chromatography-tandem mass spectrometry.

Luhong recipe (LHR) is has been used as an empirical prescription for treating chronic heart failure for long, with safety, reliability, and significant efficacy. However, its pharmacokinetics has not yet been studied. This study aims to establish a ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous analysis of epimedin A, epimedin B, epimedin C, icariin, psoralen, and isopsoralen in rat plasma and apply it to the pharmacokinetic study of LHR after oral administration. These six analytes were ionized using positive electrospray ionization (ESI+ ). The MS/MS transitions used for monitoring are successively converted to m/z 839.3 → 369.1, m/z 809.2 → 369.1, m/z 823.3 → 369.1, m/z 677.2 → 205.2, m/z 187.1 → 115.2, and m/z 230 → 120.9. Linearity, precision, accuracy, stability, matrix effect, and recovery of the established method were within the acceptable range. The method was suitable for the determination of six analytes after oral administration of LHR. The pharmacokinetic results showed that the time to reach the peak concentration (Tmax ) was from 0.17 to 13.5 h, the peak concentration (Cmax ) was 109.23-980 ng/mL, the area under the concentration-time curve (AUC[0 - t] ) was 65.48-8846.08 ng·h/mL, and the apparent distribution volume (Vd) was 24,772-896,132 mL/kg. These results provided a meaningful basis for formulating the clinical dose regimen of LHR.

Rapid and Simultaneous Quantification of Six Aristolochic Acids and Two Lignans in Asari Radix et Rhizoma Using Ultra-Performance Liquid Chromatography-Triple Quadrupole Tandem Mass Spectrometry.

Asari Radix et Rhizoma (AR) is a widely-used Chinese herbal medicine containing multiple active lignans and rare nephrotoxic components-aristolochic acids derivatives (AAs). However, the current quality control method carried out by Chinese Pharmacopoeia has defects in trace AAs detection and insufficient marker ingredients, which is unable to comprehensively evaluate the efficacy and safety of AR. To improve the quality control method of AR, a rapid, sensitive, and reliable chromatographic analytic method based on ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry (UHPLC-QqQ-MS) was established for the simultaneous analysis of multiple AAs and lignans in AR samples. Positive electrospray ionization mode with multiple reaction monitoring (MRM) was applied for the detection of the eight analytes. The method showed available linearity (R 2 ≥ 0.991), the limit of quantification (2-5 ng/mL), precision (RSD <8.12%), and accuracy (89.78-112.16%). A total of 6 AAs and 2 lignans were quantified for their content in 15 AR samples. The content of AA-IVa, AA-VIIa, and aristololactam I (AL-I) was much higher than the AA-I controlled by pharmacopoeia. Considering the potential toxicity of AAs, AA-IVa, AA-VIIa, and AL-I should also be controlled in AR. A considerable amount of active sesamin was detected in AR, suggesting that it could be added as a quality marker for the quality control of AR. The newly developed analytical method could be applied for the fast evaluation of toxic AA's content and quality during quality control of AR or preparations containing AR.

The antinociceptive and anti-inflammatory potential and pharmacokinetic study of significant alkamides ingredients from Asarum Linn.

ETHNOPHARMACOLOGICAL RELEVANCE: Asari Radix et Rhizoma (ARR), including 3 major plants of genus Asarum Linn, A. heterotropoides Fr. Schmidt var. mandshuricum (Maxim.) Kitag., A. sieboldii Miq. f. sieboldii and A. sieboldii Miq f. seoulense (Nakai) C. Y. Cheng et C. S. Yang, is one of the most important traditional herbal medicine in Asia with tremendous pharmacological activities. For a long time, researchers focus attention on studing asarinin and essential oils, the indicating ingredients of ARR, but paid less attention to another characteristic component, alkamides. The role of alkamides in the major efficacy of ARR medication remains to be elucidated. AIM OF THE STUDY: This study aims to investigate the contribution of alkamides in the efficacy of ARR according to the evaluation of antinociceptive and anti-inflammatory effects and in vivo pharmacokinetics processes. MATERIALS AND METHODS: For pharmacodynamic study, the analgesic and anti-inflammatory effects of alkamides-enriched fraction (ARRA) were comparatively evaluated by writhing test, hot plate test, and ear swelling test in mice after oral administration. For pharmacokinetic study, an UHPLC-MS/MS method was developed for the simultaneous determination of N-isobutyl-2E,4E,8Z,10Z/E-dodecatetraenamide (DDA) and other 6 major characteristic ingredients of ARR in rat plasma. The analytical method was validated and successfully applied to the pharmacokinetic study of ARR extract and DDA. RESULTS: Pharmacodynamic study show that the ARR and ARRA can significantly inhibit the writhing times of mice caused by acetic acid administration, increase the pain threshold of thermal stimulation, and inhibit xylene treated ear swelling degree by reduce PGE2 and TNF-α levels in the inflamed tissue. For pharmacokinetic study, the pharmacokinetic parameters of Vd/F and CL/F after intravenous administration in rats of DDA are 63.94 ± 32.12 L/kg and 0.33 ± 0.06 L/min/kg, respectively. The plasma drug concentration declined with the T1/2 value of 2.25 ± 0.96 h, and the MRT0-∞ was 2.23 ± 1.02 h. The absolute bioavailability of DDA after oral administration was calculated as 10.73%. DDA, methyleugenol, and asarinin have relatively high AUC0-∞ values when the ethanol and water extract of ARR is orally administered. CONCLUSIONS: ARRA is a kind of active ingredients with potential analgesic and anti-inflammatory effects that played a significant role in the major efficacy of ARR. DDA, the major compound of ARRA, has a high level of exposure in vivo, which could be is suitable for the pharmacokinetic marker or new quality marker of ARR.