Mitigation of gestational diabetes-induced endothelial dysfunction through FGF21-NRF2 pathway activation involving L-Cystine.

Gestational diabetes mellitus (GDM) disrupts glucolipid metabolism, endangering maternal and fetal health. Despite limited research on its pathogenesis and treatments, we conducted a study using serum samples from GDM-diagnosed pregnant women. We performed metabolic sequencing to identify key small molecule metabolites and explored their molecular interactions with FGF21. We also investigated FGF21's impact on GDM using blood samples from affected women. Our analysis revealed a novel finding: elevated levels of L-Cystine in GDM patients. Furthermore, we observed a positive correlation between L-Cystine and FGF21 levels, and found that L-Cystine induces NRF2 expression via FGF21 for a period of 96 h. Under high glucose (HG) conditions, FGF21 upregulates NRF2 and downstream genes NQO1 and EPHX1 via AKT phosphorylation induced by activation of IRS1, enhancing endothelial function. Additionally, we confirmed that levels of FGF21, L-Cystine, and endothelial function at the third trimester were effectively enhanced through appropriate exercise and diet during pregnancy in GDM patients (GDM + ED). These findings suggest FGF21 as a potential therapeutic agent for GDM, particularly in protecting endothelial cells. Moreover, elevated L-Cystine via appropriate exercise and diet might be a potential strategy to enhance FGF21's efficacy.

Neurovascular coupling dysfunction associated with cognitive impairment in presbycusis.

The neuropathological mechanism underlying presbycusis remains unclear. This study aimed to illustrate the mechanism of neurovascular coupling associated with cognitive impairment in patients with presbycusis. We assessed the coupling of cerebral blood perfusion with spontaneous neuronal activity by calculating the correlation coefficients between cerebral blood flow and blood oxygen level-dependent-derived quantitative maps (amplitude of low-frequency fluctuation, fractional amplitude of low-frequency fluctuation, regional homogeneity, degree centrality). Four neurovascular coupling metrics (cerebral blood flow-amplitude of low-frequency fluctuation, cerebral blood flow-fractional amplitude of low-frequency fluctuation, cerebral blood flow-regional homogeneity and cerebral blood flow-degree centrality) were compared at the global and regional levels between the presbycusis group and the healthy control group, and the intrinsic association between the altered neurovascular coupling metrics and the neuropsychological scale was further analysed in the presbycusis group. At the global level, neurovascular coupling was significantly lower in the presbycusis group than in the control group and partially related to cognitive level. At the regional level, neurovascular biomarkers were significantly elevated in three brain regions and significantly decreased in one brain region, all of which involved the Papez circuit. Regional neurovascular coupling provides more information than global neurovascular coupling, and neurovascular coupling dysfunction within the Papez circuit has been shown to reveal the causes of poor cognitive and emotional responses in age-related hearing loss patients.

Combination of static and dynamic neural imaging features to distinguish sensorineural hearing loss: a machine learning study.

Purpose: Sensorineural hearing loss (SNHL) is the most common form of sensory deprivation and is often unrecognized by patients, inducing not only auditory but also nonauditory symptoms. Data-driven classifier modeling with the combination of neural static and dynamic imaging features could be effectively used to classify SNHL individuals and healthy controls (HCs). Methods: We conducted hearing evaluation, neurological scale tests and resting-state MRI on 110 SNHL patients and 106 HCs. A total of 1,267 static and dynamic imaging characteristics were extracted from MRI data, and three methods of feature selection were computed, including the Spearman rank correlation test, least absolute shrinkage and selection operator (LASSO) and t test as well as LASSO. Linear, polynomial, radial basis functional kernel (RBF) and sigmoid support vector machine (SVM) models were chosen as the classifiers with fivefold cross-validation. The receiver operating characteristic curve, area under the curve (AUC), sensitivity, specificity and accuracy were calculated for each model. Results: SNHL subjects had higher hearing thresholds in each frequency, as well as worse performance in cognitive and emotional evaluations, than HCs. After comparison, the selected brain regions using LASSO based on static and dynamic features were consistent with the between-group analysis, including auditory and nonauditory areas. The subsequent AUCs of the four SVM models (linear, polynomial, RBF and sigmoid) were as follows: 0.8075, 0.7340, 0.8462 and 0.8562. The RBF and sigmoid SVM had relatively higher accuracy, sensitivity and specificity. Conclusion: Our research raised attention to static and dynamic alterations underlying hearing deprivation. Machine learning-based models may provide several useful biomarkers for the classification and diagnosis of SNHL.

Exposure to Chloropropanols and Their Fatty Acid Esters and Glycidyl Fatty Acid Esters in the Sixth Total Diet Study - China, 2016-2019.

What is already known about this topic?: Chloropropanols, along with their fatty acid esters and glycidyl fatty acid esters (GEs), are prevalent contaminants in a variety of processed foods, posing potential health risks to humans. What is added by this report?: In the Sixth China Total Diet Study (TDS), 3-monochloropropane-1,2-diol esters (3-MCPD esters) and GEs were identified as the predominant chloropropanols and their esters in composite food samples. Vegetables (47.0%) and cereals (15.4%) were the major contributors to exposure among the 12 food categories evaluated. What are the implications for public health practice?: The Sixth China TDS highlighted concerns regarding potential health risks associated with dietary exposure to GEs. This study underscores the need for further attention in devising practical strategies to mitigate dietary exposure to GEs.

Aberrant Intra- and Inter-Network Connectivity in Idiopathic Sudden Sensorineural Hearing Loss with Tinnitus.

BACKGROUND: Idiopathic Sudden Sensorineural Hearing Loss (ISSNHL) is related to alterations in brain cortical and subcortical structures, and changes in brain functional activities involving multiple networks, which is often accompanied by tinnitus. There have been many in-depth research studies conducted concerning ISSNHL. Despite this, the neurophysiological mechanisms of ISSNHL with tinnitus are still under exploration. OBJECTIVE: The study aimed to investigate the neural mechanism in ISSNHL patients with tinnitus based on the alterations in intra- and inter-network Functional Connectivity (FC) of multiple networks. METHODS: Thirty ISSNHL subjects and 37 healthy subjects underwent resting-state functional Magnetic Resonance Imaging (rs-fMRI). Independent Component Analysis (ICA) was used to identify 8 Resting-state Networks (RSNs). Furthermore, the study used a two-sample t-test to calculate the intra-network FC differences, while calculating Functional Network Connectivity (FNC) to detect the inter-network FC differences. RESULTS: By using the ICA approach, tinnitus patients with ISSNHL were found to have FC changes in the following RSNs: CN, VN, DMN, ECN, SMN, and AUN. In addition, the interconnections of VN-SMN, VN-ECN, and ECN-DAN were weakened. CONCLUSION: The present study has demonstrated changes in FC within and between networks in ISSNHL with tinnitus, providing ideas for further study on the neuropathological mechanism of the disease.

Genome-wide association study and haplotype analysis reveal novel candidate genes for resistance to powdery mildew in soybean.

Powdery mildew disease (PMD) is caused by the obligate biotrophic fungus Microsphaera diffusa Cooke & Peck (M. diffusa) and results in significant yield losses in soybean (Glycine max (L.) Merr.) crops. By identifying disease-resistant genes and breeding soybean accessions with enhanced resistance, we can effectively mitigate the detrimental impact of PMD on soybeans. We analyzed PMD resistance in a diversity panel of 315 soybean accessions in two locations over 3 years, and candidate genes associated with PMD resistance were identified through genome-wide association studies (GWAS), haplotype analysis, qRT-PCR, and EMS mutant analysis. Based on the GWAS approach, we identified a region on chromosome 16 (Chr16) in which 21 genes form a gene cluster that is highly correlated with PMD resistance. In order to validate and refine these findings, we conducted haplotype analysis of 21 candidate genes and indicated there are single nucleotide polymorphisms (SNPs) and insertion-deletions (InDels) variations of Glyma.16G214000, Glyma.16G214200, Glyma.16G215100 and Glyma.16G215300 within the coding and promoter regions that exhibit a strong association with resistance against PMD. Subsequent structural analysis of candidate genes within this cluster revealed that in 315 accessions, the majority of accessions exhibited resistance to PMD when Glyma.16G214300, Glyma.16G214800 and Glyma.16G215000 were complete; however, they demonstrated susceptibility to PMD when these genes were incomplete. Quantitative real-time PCR assays (qRT-PCR) of possible candidate genes showed that 14 candidate genes (Glyma.16G213700, Glyma.16G213800, Glyma.16G213900, Glyma.16G214000, Glyma.16G214200, Glyma.16G214300, Glyma.16G214500, Glyma.16G214585, Glyma.16G214669, Glyma.16G214700, Glyma.16G214800, Glyma.16G215000, Glyma.16G215100 and Glyma.16G215300) were involved in PMD resistance. Finally, we evaluated the PMD resistance of mutant lines from the Williams 82 EMS mutations library, which revealed that mutants of Glyma.16G214000, Glyma.16G214200, Glyma.16G214300, Glyma.16G214800, Glyma.16G215000, Glyma.16G215100 and Glyma.16G215300, exhibited sensitivity to PMD. Combined with the analysis results of GWAS, haplotypes, qRT-PCR and mutants, the genes Glyma.16G214000, Glyma.16G214200, Glyma.16G214300, Glyma.16G214800, Glyma.16G215000, Glyma.16G215100 and Glyma.16G215300 were identified as highly correlated with PMD resistance. The candidate genes identified above are all NLR family genes, and these discoveries deepen our understanding of the molecular basis of PMD resistance in soybeans and will be useful for guiding breeding strategies.

Multiple salary comparisons, distributive justice, and employee withdrawal.

Salary comparison has well-established implications for employees' attitudes and behaviors at work. Yet how employees process information about simultaneous comparisons, particularly when internal and external comparison information is incongruent, remains controversial. In this article, we draw from the model of dispositional attribution and equity theory to predict how the incongruence of internal and external salary comparisons affects perceptions of distributive justice and subsequent employee withdrawal behavior. We hypothesized that the effect of salary comparisons on perceived distributive justice follows a hierarchically restrictive schema in which a lower salary in comparison to a referent has a greater effect than a higher salary. This further affects employee withdrawal (neglect, turnover intention, and voluntary turnover). We also propose that the effects of salary comparisons are bounded by employees' zero-sum construal of success. Three studies were conducted to test our hypotheses: a quasi-experimental study and two time-lagged field studies. Consistent with our hypotheses, we observed that, when comparison information was incongruent, underpayment compared with others more strongly affected perceived distributive justice than overpayment did. The subsequent impact on perceived distributive justice was negatively related to employee withdrawal. As expected, the effect of incongruent salary comparison information was stronger for employees with lower zero-sum construal of success. The theoretical and practical implications of these findings are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

An Organic Optoelectronic Synapse with Multilevel Memory Enabled by Gate Modulation.

Artificial synaptic devices are emerging as contenders for next-generation computing systems due to their combined advantages of self-adaptive learning mechanisms, high parallel computation capabilities, adjustable memory level, and energy efficiency. Optoelectronic devices are particularly notable for their responsiveness to both voltage inputs and light exposure, making them attractive for dynamic modulation. However, engineering devices with reconfigurable synaptic plasticity and multilevel memory within a singular configuration present a fundamental challenge. Here, we have established an organic transistor-based synaptic device that exhibits both volatile and nonvolatile memory characteristics, modulated through gate voltage together with light stimuli. Our device demonstrates a range of synaptic behaviors, including both short/long-term plasticity (STP and LTP) as well as STP-LTP transitions. Further, as an encoding unit, it delivers exceptional read current levels, achieving a program/erase current ratio exceeding 105, with excellent repeatability. Additionally, a prototype 4 × 4 matrix demonstrates potential in practical neuromorphic systems, showing capabilities in the perception, processing, and memory retention of image inputs.

CDK1 promotes the phosphorylation of KIFC1 to regulate the tumorgenicity of endometrial carcinoma.

OBJECTIVE: This study aims to clarify the mechanical action of cyclin-dependent protein kinase 1 (CDK1) in the development of endometrial carcinoma (EMCA), which may be associated with the phosphorylation of kinesin family member C1 (KIFC1) and further activate the PI3K/AKT pathway. METHODS: The protein and gene expression of CDK1 in EMCA tissues and tumor cell lines were evaluated by western blot, quantitative polymerase chain reaction, and immunohistochemistry staining. Next, Cell Counting Kit-8 and colony formation assay detected cell survival and proliferation. Cell migration and invasion were measured by Transwell assay. Cell apoptosis and cell cycle were tested by flow cytometry. Immunofluorescence staining of γH2AX was used to evaluate DNA damage, respectively. Subsequently, a co-immunoprecipitation assay was used to detect the interaction between CDK1 and KIFC1. The phosphorylated protein of KIFC1 and PI3K/AKT was detected by western blot. Finally, the effect of CDK1 on the tumor formation of EMCA was evaluated in a nude mouse xenograft model. RESULTS: CDK1 was highly expressed in EMCA tumor cell lines and tissues, which contributed to cell survival, proliferation, invasion, and migration, inhibited cell apoptosis, and induced DNA damage of EMCA cells dependent on the phosphorylation of KIFC1. Moreover, the CDK1-KIFC1 axis further activated PI3K/AKT pathway. Finally, CDK1 knockdown repressed tumor formation of EMCA in vivo. CONCLUSION: We report that increased CDK1 promotes tumor progression and identified it as a potential prognostic marker and therapeutic target of EMCA.

Simultaneous Analysis of Nicarbazin, Diclazuril, Toltrazuril, and Its Two Metabolites in Chicken Muscle and Eggs by In-Syringe Dispersive Solid-Phase Filter Clean-Up Followed by Liquid Chromatography-Tandem Mass Spectrometry.

Nicarbazin (NICA) and triazine anticoccidial drugs (diclazuril (DIZ) and toltrazuril (TOZ)) are the primary strategy for preventing and treating coccidiosis. To prevent the development of drug resistance and mitigate the potential chronic toxicity to humans resulting from prolonged exposure, a liquid chromatography-tandem mass spectrometry method with high reliability and sensitivity was developed to determine NICA, DIZ, TOZ, and its two metabolites in chicken muscle and eggs. Upon establishing the extraction conditions involving 10 mL of acetonitrile and 10 min of sonication, in-syringe dispersive solid-phase extraction with silica was performed in combination with n-hexane clean-up. The selection of isotope peaks of precursor ions and low-mass range scanning allowed the two transitions for the quantification of all compounds. The limits of detection for DIZ and NICA were both 0.1 µg/kg, and for TOZ and metabolites, they were 0.3 µg/kg; the limits of quantitation were 0.3 and 1 µg/kg, respectively. The linear range was 0.25-50 ng/mL with a correlation coefficient r > 0.999. The average recoveries at three spiking levels in muscle and eggs were 90.1-105.2% and 94.0-103.7% with the relative standard deviations of 3.0-8.1% and 3.1-14.4%, respectively. The precision, accuracy, and stability were evaluated by three quality control samples.

Ultralow Loading Copper-Intercalated MoO3 Nanobelts with High Activity against Antibiotic-Resistant Bacteria.

In recent years, the infection rate of antibiotic resistance has been increasing year by year, and the prevalence of super bacteria has posed a great threat to human health. Therefore, there is an urgent need to find new antibiotic alternatives with long-term inhibitory activity against a broad spectrum of bacteria and microorganisms in order to avoid the proliferation of more multidrug-resistant (MDR) bacteria. The presence of natural van der Waals (vdW) gaps in layered materials allows them to be easily inserted by different guest species, providing an attractive strategy for optimizing their physicochemical properties and applications. Here, we have successfully constructed a copper-intercalated α-MoO3 nanobelt based on nanoenzymes, which is antibacterial through the synergistic effect of multiple enzymes. Compared with α-MoO3, MoO3-x/Cu nanobelts with a copper loading capacity of 2.11% possess enhanced peroxidase (POD) catalytic activity and glutathione (GSH) depletion, indicating that copper intercalation significantly improves the catalytic performance of the nanoenzymes. The MoO3-x/Cu nanobelts are effective in inducing POD and oxidase (OXD) and catalase (CAT) activities in the presence of H2O2 and O2, which resulted in the generation of large amounts of reactive oxygen species (ROS), which were effective in bacterial killing. Interestingly, MoO3-x/Cu nanobelts can serve as glutathione oxidase (GSHOx)-like nanoenzymes, which can deplete GSH in bacteria and thus significantly improve the bactericidal effect. The multienzyme-catalyzed synergistic antimicrobial strategy shows excellent antimicrobial efficiency against ß-lactamase-producing Escherichia coli (ESBL-E. coli) and methicillin-resistant Staphylococcus aureus (MRSA). MoO3-x/Cu exhibits excellent spectral bactericidal properties at very low concentrations (20 µg mL-1). Our work highlights the wide range of antibacterial and anti-infective biological applications of copper-intercalated MoO3-x/Cu nanobelt catalysts.

Perovskite for Electrocatalytic Oxygen Evolution at Elevated Temperatures.

The development of advanced electrolysis technologies such as anion exchange membrane water electrolyzer (AEMWE) is central to the vision of a sustainable energy future. Key to the realization of such AEMWE technology lies in the exploration of low-cost and high-efficient catalysts for facilitating the anodic oxygen evolution reaction (OER). Despite tremendous efforts in the fundamental research, most of today's OER works are conducted under room temperature, which deviates significantly with AEMWE's operating temperature (50-80 °C). To bridge this gap, it is highly desirable to obtain insights into the OER catalytic behavior at elevated temperatures. Herein, using the well-known perovskite catalyst Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF) as a proof of concept, the effect of temperature on the variation in OER catalytic activity and stability is evaluated. It is found that the BSCF's activity increases with increasing temperature due to enhanced lattice oxygen participation promoting the lattice oxygen-mediated OER process. Further, surface amorphization and cation leaching of BSCF become more pronounced as temperature increases, causing a somewhat attenuated OER stability. These new understandings of the fundamental OER catalysis over perovskite materials at industrial-relevant temperature conditions are expected to have strong implications for the research of OER catalysts to be deployed in practical water electrolyzers.

Tinnitus classification based on resting-state functional connectivity using a convolutional neural network architecture.

OBJECTIVES: Many studies have investigated aberrant functional connectivity (FC) using resting-state functional MRI (rs-fMRI) in subjective tinnitus patients. However, no studies have verified the efficacy of resting-state FC as a diagnostic imaging marker. We established a convolutional neural network (CNN) model based on rs-fMRI FC to distinguish tinnitus patients from healthy controls, providing guidance and fast diagnostic tools for the clinical diagnosis of subjective tinnitus. METHODS: A CNN architecture was trained on rs-fMRI data from 100 tinnitus patients and 100 healthy controls using an asymmetric convolutional layer. Additionally, a traditional machine learning model and a transfer learning model were included for comparison with the CNN, and each of the three models was tested on three different brain atlases. RESULTS: Of the three models, the CNN model outperformed the other two models with the highest area under the curve, especially on the Dos_160 atlas (AUC = 0.944). Meanwhile, the model with the best classification performance highlights the crucial role of the default mode network, salience network, and sensorimotor network in distinguishing between normal controls and patients with subjective tinnitus. CONCLUSION: Our CNN model could appropriately tackle the diagnosis of tinnitus patients using rs-fMRI and confirmed the diagnostic value of FC as measured by rs-fMRI.

[Determination of tetrodotoxin in urine by liquid chromatography-tandem mass spectrometry with internal standard calibration].

OBJECTIVE: An analytical method was developed for tetrodotoxin(TTX) in urine by liquid chromatography-tandem mass spectrometry(LC-MS/MS) with internal standard calibration. METHODS: TTX in the sample was extracted with the mixture of acetic acid/methanol/acetonitrile(0.005 mL/0.8 mL/1.8 mL), cleaned by solid phase extraction(SPE) with cation exchange cartridge, eluted with 50% acetonitrile/water containing 0.3% hydrochloric acid, and neutralized with ammonia. The extract was separated by a Waters XBridge~(TM) BEH Amide column(150 mm×3.0mm, 1.7 µm) and measured by MS/MS. By optimizing sample extraction and SPE cleanup conditions, the problems of low recovery and strong suppression effects of MS signal for TTX in urine were resolved when cleaned with cation exchange cartridge. RESULTS: Quantitatively calibrated by the internal standard of Kasugamycin, good linear relationship was found for TTX in urine at the range of 0.2-200 µg/L with the correlation coefficient(r~2) of 0.997. The limits of detection and quantitation for TTX in sample matrix were 0.1 and 0.2µg/L, respectively. The average recoveries at three spiking levels(0.2, 10.0 and 200 µg/L) were 89.3%-95.3% with relative standard deviation(n=6) less than 5.1%. The concentrations of TTX in urine from 11 poisoning patients were 0.4-138 µg/L. The detection rate was 100% in urine collected within 3 days after poisoning. CONCLUSION: The established method was simple, accurate and sensitive. It can provide reliable technical support for the rapid treatment of TTX poisoning events and the study of toxin metabolism in vivo.

Eubacterium rectale is a potential marker of altered gut microbiota in psoriasis and psoriatic arthritis.

Previous studies have profiled the gut microbiota among psoriatic patients compared to that among healthy individuals. However, a comprehensive understanding of the magnitude, direction, and detailed compositional and functional profiles remains limited. Additionally, research exploring the gut microbiota in the context of both plaque psoriasis (PsO) and psoriatic arthritis (PsA) is lacking. To assess the taxonomic and functional characteristics of the gut microbiota in PsO and PsA patients and investigate potential links between the gut microbiota and disease pathogenesis. We collected fecal samples from 70 psoriatic patients (44 PsO and 26 PsA) and 25 age- and gender-matched healthy controls (HC) and employed deep metagenomic sequencing to characterize their gut microbiota. We noted significant alternations in the gut microbiota compositions of both PsO and PsA patients compared to those of HC. Despite limited effect sizes in alpha diversity (12.3% reduction of microbial richness but unchanged evenness in psoriatic patients) and beta diversity (disease accounts for 3.5% of total variations), we consistently observed substantial reductions of Eubacterium rectale in both PsO and PsA patients, with PsA patients exhibiting even lower levels of E. rectale than PsO patients. Additionally, two Alistipes species were also depleted in psoriatic patients. These microorganisms are known to play crucial roles in carbohydrate metabolism pathways, mainly producing short-chain fatty acids with anti-inflammatory effects. Overall, our observations supplemented the profiling of altered gut microbiota in patients with PsO and PsA at the species level and described a link between the dominant short-chain fatty acid-producing bacterial species and systemic immunity in psoriatic patients. IMPORTANCE: In this observational clinical study with sufficient sample size and metagenomic sequencing to profile the gut microbiota, we identified consistent signals of the depleted abundance of Eubacterium rectale and related functional genes among psoriatic patients, including those with psoriatic arthritis. E. rectale may serve as an ecologically important functional unit in the gut microbiota, holding potential as a diagnostic marker and target for therapeutic interventions to achieve lasting effects. Our findings provide comprehensive gut microbiota profiling in psoriasis, resolving previous contradictions and generating new hypotheses for further investigation. These insights may significantly impact psoriasis management and related conditions.

Contamination Status and Acute Dietary Exposure Assessment of Paralytic Shellfish Toxins in Shellfish in the Dalian Area of the Yellow-Bohai Sea, China.

The Yellow-Bohai Sea is an important semi-enclosed continental shelf marginal seas with an intensive aquaculture industry in China. The current study analyzed the contamination status and the time variations of paralytic shellfish toxins (PSTs) in shellfish between 2019 and 2020 from the Yellow-Bohai Sea in the Dalian area and estimated the acute health risks to consumers in China. A total of 199 shellfish samples (including 34 Pacific oysters, 25 Mediterranean blue mussels, 34 Manila clams, 36 bay scallops, 34 veined rapa whelks and 36 bloody clams) were analyzed from four representative aquaculture zones around the Yellow-Bohai Sea in Dalian. Among the samples, scallops and blood clams were the shellfish species with the highest detection rate of PSTs (94.4%), and the highest level of PSTs was detected in scallops with 3953.5 µg STX.2HCl eq./kg (µg STX.2HCL equivalents per kg shellfish tissue), followed by blood clams with 993.4 µg STX.2HCl eq./kg. The contents of PSTs in shellfish showed a time variation trend, and autumn was the season of concern for PST contamination in Dalian. For general Chinese consumers, the probability of acute health risks to shellfish consumers from dietary exposure to PSTs was around 13%. For typical consumers in coastal areas of China, especially those with higher shellfish intake, there was an acute health risk associated with exposure to PSTs through shellfish consumption during the occurrence of harmful algal blooms. It is suggested that the government continue to strengthen the monitoring of the source of PSTs and the monitoring of harmful algal blooms and give reasonable advice on shellfish consumption for consumers in coastal areas, such as not eating scallop viscera.

[Mechanism of acteoside in prevention and treatment of gouty arthritis based on liver metabolomics].

This study aims to reveal the effect of acteoside on gouty arthritis(GA) in rats based on liver metabolomics. The ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to search for the potential biomarkers and metabolic pathways. SD rats were randomly assigned into blank, model, colchicine(0.3 mg·kg~(-1)), and high-, medium-, low-dose(200, 100, and 50 mg·kg~(-1), respectively) acteoside groups(n=7). The rats were administrated once a day for 7 continuous days. Monosodium urate(MSU) was used to induce GA model in rats during administration. The degree of joint swelling and pathological changes of synovial tissue in rats were observed, and the levels of interleukin(IL)-1ß, IL-18 and tumor necrosis factor(TNF)-α in the synovial tissue of rats were measured. UPLC-Q-TOF-MS was employed to collect rat liver data, and Progenesis QI and EZ info were used for data analysis. Human Metabolomics Database(HMDB) and Kyoto Encyclopedia of Genes and Genomes(KEGG) were employed to predict the potential biomarkers and metabolic pathways. The results showed that acteoside alleviated joint swelling, reduced synovial tissue damage, and lowered the levels of inflammatory cytokines in GA rats. A total of 19 common biomarkers were identified, 17 of which can be regulated by acteoside. Seven metabolic pathways were enriched, such as glycerophospholipid metabolism, linoleic acid metabolism, and taurine and hypotaurine metabolism, among which glycerophospholipid metabolism was strongly disturbed. The metabolomics analysis suggested that acteoside may down-regulate the expression of inflammatory cytokines and alleviate the symptoms of GA rats by regulating glycerophospholipid metabolism, linoleic acid metabolism, and taurine and hypotaurine metabolism. The findings provide a reference for future research and development of acteoside.

Who are you after psychedelics? A systematic review and a meta-analysis of the magnitude of long-term effects of serotonergic psychedelics on cognition/creativity, emotional processing and personality.

This systematic review and a meta-analysis synthesised the results from contemporary, randomized and non-randomized controlled studies to assess lasting (one week minimum) changes on cognition/creativity, emotional processing and personality from serotonergic psychedelics. PubMed, Embase and PsycInfo were searched in July 2022. Risk of bias was assessed using Rob 2.0 and ROBINS-I. Ten studies met the eligibility criteria which involved 304 participants. No statistically significant effects were found for the majority outcome measures across the three constructs. A meta-analysis of emotional recognition outcomes found an overall significant effect for faster reaction times in the active treatment groups for disgust (SMD=-0.63, 95% CI=[-1.01 to -0.25], I2 = 65%) and sadness (SMD=-0.45, 95% CI=[-0.85 to -0.06], I2 = 60%). Future research should include larger samples, better control conditions, standardized doses and longer follow-up periods to confirm these preliminary findings.

Integrating network pharmacology and renal metabonomics to reveal the protective mechanism of resveratrol on gouty nephropathy.

Resveratrol (Res) has been demonstrated to have beneficial effects on gouty nephropathy (GN). However, the mechanisms of Res on GN remain unclear. This study aimed to investigate the mechanisms of Res on GN. In this study, network pharmacology technology was used to predict the Res targets in the prevention and treatment of GN. Renal metabonomics was used to identify differential metabolites in kidney tissue of GN model rats. Finally, molecular docking technology was used to verify the binding ability of Res to key targets. Metabonomics analysis showed that 24 potentially important metabolites were involved in the prevention and treatment of GN with Res. After exposure to Res, metabolite levels normalized. The network pharmacology analysis showed that 24 key targets were involved in the prevention and treatment of GN disease. According to the metabolite-gene network diagram, we identified two core genes, PTGS1 and PTGS2, and found that both were involved in the arachidonic acid metabolism pathway. Molecular docking further verified the affinity of Res binding to PTGS1 and PTGS2. In conclusion, the mechanism of Res against GN may be the regulation of arachidonic acid metabolism through the regulation of PTGS 1 and PTGS 2.