Gallic acid improves color quality and stability of red wine via physico-chemical interaction and chemical transformation as revealed by thermodynamics, real wine dynamics and benchmark quantum mechanical calculations.

The aim of this study was to explore the copigmentation effect of gallic acid on red wine color and to dissect its mechanism at the molecular level. Three-dimensional studies, e.g., in model wine, in real wine and in silico, and multiple indicators, e.g., color, spectrum, thermodynamics and phenolic dynamics, were employed. The results showed that gallic acid significantly enhanced the color quality and stability of red wine. Physico-chemical interactions and chemical transformations should be the most likely mechanism, and physico-chemical interactions are also a prerequisite for chemical transformations. QM calculations of the physico-chemical interactions proved that the binding between gallic acid and malvidin-3-O-glucoside is a spontaneous exothermic reaction driven by hydrogen bonding and dispersion forces. The sugar moiety of malvidin-3-O-glucoside and the phenolic hydroxyl groups of gallic acid affect the formation of hydrogen bonds, while the dispersion interaction was related to the stacking of the molecular skeleton.

Intermolecular interactions between malvidin-3-O-glucoside and caffeic acid: Structural and thermodynamic characterization and its effect on real wine color quality.

The copigmentation effect between malvidin-3-O-glucoside and caffeic acid was comprehensive inquiry on the model wine solution, theoretical simulation and real wine. Thermodynamic parameters were determined by UV/Visible spectroscopy and Isothermal titration calorimetry (ITC). Theoretical data were obtained employing a dispersion-corrected density functional approach. The effects in real wines were investigated by adding the caffeic acid during different fermentation periods. Results shown that the copigmentation reaction between caffeic acid and malvidin-3-O-glucoside is a spontaneous exothermic reaction driven by hydrogen bonding and dispersions forces. Computations show that the polyhydroxyl sugar moiety and phenolic hydroxyl groups are the key active sites. The addition of caffeic acid in post-alcohol fermentation samples evidences an improving color characteristics in the wine.

Comprehensive effect of Naoxintong capsule combined with Western medicine on coronary heart disease after percutaneous coronary intervention: a meta-analysis.

Aims: To systematically evaluate the comprehensive effect of combining Naoxintong capsule (NXT) with Western medicine (WM) on coronary heart disease post-percutaneous coronary intervention (PCI). Methods: Randomized controlled trials (RCTs) of NXT for patients with CHD after PCI were systematically searched across multiple databases, including the Cochrane Library, PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Database (VIP), and Wan Fang, from inception until 31 January 2023. Study selection, data extraction, and quality assessment were performed by two independent reviewers. The quality of the included studies was evaluated using version 2 of the Cochrane risk-of-bias tool (RoB 2), and data analysis was performed using R4.2.2. Results: Fifteen RCTs conducted between 2011 and 2022 and involving 1,551 patients were identified, with 774 and 777 patients in the experimental and control groups respectively. It was found that the NXT and WM combination was superior to the WM therapy alone in terms of the effective clinical rate (odds ratio [OR] = 4.69, 95% confidence interval [CI] = 2.13-10.30), effective rate in electrocardiogram (OR = 6.92, 95% CI = 3.44-13.92), effective rate in angina (OR = 5.90, 95% CI = 3.04-11.46), left ventricular ejection fraction (mean difference [MD] = 4.94, 95% CI = 2.89-6.99), brain natriuretic peptide (MD = -294.00, 95% CI = -584.60 to -3.39), creatine kinase-MB (MD = -7.82, 95% CI = -13.26 to -2.37), major adverse cardiovascular events (OR = 0.24, 95% CI = 0.14-0.43), maximum platelet aggregation rate (MD = -8.33, 95% CI = -11.64 to -5.01), and Chinese medicine evidence score (OR = 9.79, 95% CI = 3.57-26.85). However, there was no significant difference in cardiac troponin I level reduction (MD = -0.13, 95% CI = 0.35-0.09) or the occurrence of adverse medicine events (OR = 0.92, 95% CI = 0.41-2.05). Meta-regression and subgroup analyses indicated that NXT capsule dosage, treatment duration, and patient baseline characteristics contributed to the heterogeneity. Conclusion: A combination of NXT and WM can improve clinical outcomes in patients undergoing PCI. However, further studies are needed to confirm the reliability and safety of this combined treatment approach. Systematic Review Registration: PROSPERO, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=369174, Identifier CRD42022369174.

Study on the Mechanism of Competing Endogenous Network of 'Scutellaria barbata D.Don-Houttuynia cordata- Radix Scutellariae' in the Treatment of NSCLC based on Bioinformatics, Molecular Dynamics and Experimental Verification.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Traditional Chinese medicine, known for its multi-target and multi-pathway characteristics, offers a potential treatment approach for NSCLC. OBJECTIVE: This study aimed to explore the mechanism of the competitive endogenous network of 'Scutellaria barbata D.Don-Houttuynia cordata-Radix Scutellariae' in treating NSCLC through bioinformatics analysis and in vitro experiments. MATERIALS AND METHODS: Various databases and ceRNA networks were utilized to collect and screen components and target genes, molecular docking and molecular dynamics simulations to determine the binding ability of ligand-receptor complexes. In vitro experiments were conducted to validate the effects of active ingredients of 'Scutellaria barbata D.Don-Houttuynia cordata- Radix Scutellariae' on non-small cell lung cancer cell line A549. RESULTS: The key target proteins CCL2, EDN1, MMP9, PPARG, and SPP1 were docked well with their corresponding TCM ligands. Among the ligand-receptor complexes, MMP9-Luteolin and MMP9-Quercetin demonstrated the weaking binding force, while the SPP1-Quercetin complex, associated with NSCLC prognosis, exhibited stable structure formation through hydrogen bond interaction during MD simulation. In vitro experiments confirmed the inhibitory effect of Quercetin on SPP1 expression, as well as the proliferation and migration of A549 cells. CONCLUSION: The findings suggest that 'Scutellaria barbata D.Don-Houttuynia cordata-Radix Scutellariae' may potentially treat lung cancer by suppressing the expression of SPP1. This study provides valuable insights and novel research directions for understanding the mechanism of traditional Chinese medicine in combating lung cancer.

Study on analgesic effect of Shentong Zhuyu Decoction in neuropathic pain rats by network pharmacology and RNA-Seq.

ETHNOPHARMACOLOGICAL RELEVANCE: Shentong Zhuyu Decoction (STZYD) is a traditional prescription for promoting the flow of Qi and Blood which is often used in the treatment of low back and leg pain clinicall with unclear mechanism. Neuropathic pain (NP) is caused by disease or injury affecting the somatosensory system. LncRNAs may play a key role in NP by regulating the expression of pain-related genes through binding mRNAs or miRNAs sponge mechanisms. AIM OF THE STUDY: To investigate the effect and potential mechanism of STZYD on neuropathic pain. METHODS: Chronic constriction injury (CCI) rats, a commonly used animal model, were used in this study. The target of STZYD in NP was analyzed by network pharmacology, and the analgesic effect of STZYD in different doses (H-STZYD, M-STZYD, L-STZYD) on CCI rats was evaluated by Mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL). Meanwhile, RNA-seq assay was used to detect the changed mRNAs and lncRNAs in CCI rats after STZYD intervention. GO analysis, KEGG pathway analysis, and IPA analysis were used to find key target genes and pathways, verified by qPCR and Western Blot. The regulatory effect of lncRNAs on target genes was predicted by co-expression analysis and ceRNA network construction. RESULTS: We found that STZYD can improve hyperalgesia in CCI rats, and H-STZYD has the best analgesic effect. The results of network pharmacological analysis showed that STZYD could play an analgesic role in CCI rats through the MAPK/ERK/c-FOS pathway. By mRNA-seq and lncRNA-seq, we found that STZYD could regulate the expression of Cnr1, Cacng5, Gucy1a3, Kitlg, Npy2r, and Grm8, and inhibited the phosphorylation level of ERK in the spinal cord of CCI rats. A total of 27 lncRNAs were associated with the target genes and 30 lncRNAs, 83 miRNAs and 5 mRNAs participated in the ceRNA network. CONCLUSION: STZYD has the effect of improving hyperalgesia in CCI rats through the MAPK/ERK/c-FOS pathway, which is related to the regulation of lncRNAs to Cnr1 and other key targets.

The influence of placenta microbiota of normal term pregnant women on immune regulation during pregnancy.

BACKGROUND: The concerted regulation of placenta microbiota and the immune responses secures the occurrence and development of pregnancy, while few studies reported this correlation. This study aimed to explore the relationship between the placenta microbiota and immune regulation during pregnancy. METHODS: Twenty-six healthy pregnant women scheduled for elective cesarean section in the First Affiliated Hospital of Jinan University who met the inclusion criteria were recruited. Placenta and peripheral venous blood samples were collected. Microbiota in placental tissue was detected using high-throughput sequencing. Flow cytometry was used to detect immune cells in placental tissue and peripheral venous blood. ELISA and Luminex liquid chip technology were used to detect the content of cytokines in placental tissue and peripheral venous blood, respectively. RESULTS: The placental microbiota has stimulating effects on the local immunity of the placenta and mainly stimulates the placental balance ratio CD56 + CD16 + /CD56 + CD16 and the placental macrophages, that is, it plays the role of immune protection and supporting nutrition. The stimulating effect of placental microbiota on maternal systemic immunity mainly induces peripheral Treg cells and B lymphocytes. CONCLUSION: The placental microbiota may be an important factor mediating local immune regulation in the placenta, and placental microbiota participates in the regulatory function of the maternal immune system.

Direct access to carbamates via acylation of arylamines with dialkyl azodicarboxylates under metal-free conditions.

A novel C-N coupling of various arylamines with dialkyl azodicarboxylates under metal-free conditions for the rapid assembly of carbamates has been achieved. This established protocol features mild reaction conditions, simple operation, broad substrate scope, moderate to excellent yields and good tolerance of functional groups. Moreover, the potential synthetic utility of products was exemplified by a series of intriguing chemical operations.

Integration of microbiota and metabolomics reveals the analgesic mechanisms of emodin against neuropathic pain.

BACKGROUND AND OBJECTIVE: Neuropathic pain (NeP) induced dysbiosis of intestinal microbiota in chronic constriction injury (CCI) rats. Emodin has analgesic effect but the detailed mechanism is not clear at the present time. This study aims to explore the underling mechanism of action of emodin against NeP with in CCI model. METHODS: Male SD rats (180-220 g) were randomly divided into three groups: sham group, CCI group, and emodin group. Behavioral tests were performed to evaluate the therapeutic effects of emodin on CCI model. Feces and spinal cords of all rats were collected 15 days after surgery. 16S rDNA sequencing, untargeted metabolomics, qPCR and ELISA were performed. RESULTS: Mechanical withdrawal thresholds (MWT), thermal withdrawal latency (TWL) and Sciatic functional index (SFI) in emodin group were significantly higher than CCI group (P < 0.05). Emodin not only inhibited the expression of pro-inflammatory cytokines in the spinal cords and colonic tissue, but also increased the expression of tight junction protein in colonic tissue. 16S rDNA sequencing showed that emodin treatment changed the community structure of intestinal microbiota in CCI rats. Untargeted metabolomics analysis showed that 33 differential metabolites were screened out between CCI group and emodin group. After verification, we found that emodin increased the level of S-adenosylmethionine (SAM) and Histamine in the spinal cord of CCI rats. CONCLUSION: Emodin was effective in relieving neuropathic pain, which is linked to inhibition inflammatory response, increasing the proportion of beneficial bacteria and beneficial metabolites.

Checkerboard corner detection method based on neighborhood linear fitting.

To improve the calibration accuracy of a vision measurement system, a checkerboard corner detection method based on linear fitting of the checkerboard local contour is proposed. First, by binarization and morphological dilation of the checkerboard image, the coordinates of two adjacent vertices of adjacent dark squares are obtained; the midpoint of the two vertices is taken as the reference point; the reference dotted array is obtained; and the Zernike moment subpixel method is used to obtain the checkerboard contour data points in the neighborhood of each reference point. Finally, the contour points are classified according to the orientation based on the reference points; two intersecting lines are fitted; and the intersection of the two lines is exactly the corner point that we want to find. A camera calibration experiment was conducted on the same group of checkerboard images. The results show that the calibration results of the corner points obtained based on this method are highly consistent with the OpenCV library function method and the MATLAB Toolbox calibration method, and the reprojection error is smaller. At the same time, it is robust to changes in the light source brightness.

Identification and validation of risk score model based on gene set activity as a diagnostic biomarker for endometriosis.

Objective: The enigmatic nature of Endometriosis (EMS) pathogenesis necessitates investigating alterations in signaling pathway activity to enhance our comprehension of the disease's characteristics. Methods: Three published gene expression profiles (GSE11691, GSE25628, and GSE7305 datasets) were downloaded, and the "combat" algorithm was employed for batch correction, gene expression difference analysis, and pathway enrichment difference analysis. The protein-protein interaction (PPI) network was constructed to identify core genes, and the relative enrichment degree of gene sets was evaluated. The Lasso regression model identified candidate gene sets with diagnostic value, and a risk scoring diagnostic model was constructed for further validation on the GSE86534 and GSE5108 datasets. CIBERSORT was used to assess the composition of immune cells in EMS, and the correlation between EMS diagnostic value gene sets and immune cells was evaluated. Results: A total of 568 differentially expressed genes were identified between eutopic and ectopic endometrium, with 10 core genes in the PPI network associated with cell cycle regulation. Inflammation-related pathways, including cytokine-receptor signaling and chemokine signaling pathways, were significantly more active in ectopic endometrium compared to eutopic endometrium. Diagnostic gene sets for EMS, such as homologous recombination, base excision repair, DNA replication, P53 signaling pathway, adherens junction, and SNARE interactions in vesicular transport, were identified. The risk score's area under the curve (AUC) was 0.854, as indicated by the receiver operating characteristic (ROC) curve, and the risk score's diagnostic value was validated by the validation cohort. Immune cell infiltration analysis revealed correlations between the risk score and Macrophages M2, Plasma cells, resting NK cells, activated NK cells, and regulatory T cells. Conclusion: The risk scoring diagnostic model, based on pathway activity, demonstrates high diagnostic value and offers novel insights and strategies for the clinical diagnosis and treatment of Endometriosis.

[A preliminary study on the effects of fecal microbiota transplantation on the intestinal microecology of patients with severe pneumonia during the convalescence period].

OBJECTIVE: To investigate the effects of fecal microbiota transplantation (FMT) on intestinal microbiome and organism in patients with severe pneumonia during the convalescence period. METHODS: A prospective non-randomized controlled study was conducted. From December 2021 to May 2022, patients with severe pneumonia during the convalescence period who received FMT (FMT group) and patients with severe pneumonia during the convalescence period who did not receive FMT (non-FMT group) admitted to the First Affiliated Hospital of Guangzhou Medical University were enrolled. The differences of clinical indicators, gastrointestinal function and fecal traits between the two groups were compared 1 day before and 10 days after enrollment. The 16S rDNA gene sequencing technology was used to analyze the changes of intestinal flora diversity and different species in patients with FMT before and after enrollment, and metabolic pathways were analyzed and predicted by Kyoto Encyclopedia of Genes and Genomes database (KEGG). Pearson correlation method was used to analyze the correlation between intestinal flora and clinical indicators in FMT group. RESULTS: The level of triacylglycerol (TG) in FMT group was significantly decreased at 10 days after enrollment compared with before enrollment [mmol/L: 0.94 (0.71, 1.40) vs. 1.47 (0.78, 1.86), P < 0.05]. The level of high-density lipoprotein cholesterol (HDL-C) in non-FMT group was significantly decreased at 10 days after enrollment compared with before enrollment (mmol/L: 0.68±0.27 vs. 0.80±0.31, P < 0.05). There were no significant differences in other clinical indexes, gastrointestinal function or fecal character scores between the two groups. Diversity analysis showed that the α diversity indexes of intestinal flora in FMT group at 10 days after enrollment were significantly higher than those in non-FMT group, and ß diversity was also significantly different from that in non-FMT group. Differential species analysis showed that the relative abundance of Proteobacteria at the level of intestinal flora in FMT group at 10 days after enrollment was significantly lower than that in non-FMT group [8.554% (5.977%, 12.159%) vs. 19.285% (8.054%, 33.207%), P < 0.05], while the relative abundance of Fusobacteria was significantly higher than that in non-FMT group [6.801% (1.373%, 20.586%) vs. 0.003% (0%, 9.324%), P < 0.05], and the relative abundance of Butyricimonas, Fusobacterium and Bifidobacterium at the genus level of the intestinal flora was significantly higher than that in non-FMT group [Butyricimonas: 1.634% (0.813%, 2.387%) vs. 0% (0%, 0.061%), Fusobacterium: 6.801% (1.373%, 20.586%) vs. 0.002% (0%, 9.324%), Bifidobacterium: 0.037% (0%, 0.153%) vs. 0% (0%, 0%), all P < 0.05]. KEGG metabolic pathway analysis showed that the intestinal flora of FMT group was changed in bisphenol degradation, mineral absorption, phosphonate and phosphinate metabolism, cardiac muscle contraction, Parkinson disease and other metabolic pathways and diseases. Correlation analysis showed that Actinobacteria and prealbumin (PA) in intestinal flora of FMT group were significantly positively correlated (r = 0.53, P = 0.043), Bacteroidetes was positively correlated with blood urea nitrogen (BUN; r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Firmicutes was positively correlated with BUN (r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Fusobacteria was significantly positively correlated with immunoglobulin M (IgM; r = 0.71, P = 0.003), Proteobacteria was significantly positively correlated with procalcitonin (PCT; r = 0.63, P = 0.012) and complement C4 (r = 0.56, P = 0.030). CONCLUSIONS: FMT can reduce TG level, reconstruct intestinal microecological structure, change body metabolism and function, and alleviate inflammatory response by reducing the relative abundance of harmful bacteria in patients with severe pneumonia during the convalescence period.

Ocular emotion discrimination disorders in self-limited epilepsy patients with centrotemporal spikes complicated with electrical status epilepticus during sleep: A pediatric neuropsychological study.

OBJECTIVE: We investigated the characteristics and factors influencing eye emotion recognition in self-limited epilepsy patients with centrotemporal spikes (SeLECTS) complicated with electrical status epilepticus during sleep (ESES). METHODS: We selected SeLECTS (n = 160) patients treated in the outpatient and inpatient departments of Anhui Children's Hospital from September 2020 to January 2022. According to the video electroencephalogram monitoring slow-wave index (SWI), SeLECTS patients with SWI < 50% were assigned into the typical SeLECTS group (n = 79), and patients with SWI ≥ 50% were assigned into the ESES group (n = 81). Patients in the two groups were assessed by The Eye Basic Emotion Discrimination Task (EBEDT) and The Eye Complex Emotion Discrimination Task (ECEDT), respectively. Comparisons were made with age-, sex- and education level-matched healthy control participants. The correlation between the characteristics of emotional discrimination disorder in the eye area and the clinical influencing factors was analyzed in ESES group, and p ≤ .050 was the threshold for significance. RESULTS: Relative to the healthy control group, scores of sadness and fear in the typical SeLECTS group were markedly lower (p = .018, p = .023), while differences in scores of disgust, happiness, surprise, and anger were not significantly different between the groups (p = .072, p = .162, p = .395, p = .380, respectively). Compared with the healthy control group, the ESES group had significantly low scores in recognition of sadness, fear, disgust, and surprise (p = .006, p = .016, p = .043 and p = .038, respectively). However, differences in recognition of happiness and anger between the groups were not significant (p = .665 and p = .272). Univariate logistic analysis showed that the score of eye recognition for sadness in the ESES group was affected by age of onset, SWI, ESES duration and number of seizures. The score of eye recognition for fear was mainly affected by SWI, while the score of eye recognition for disgust was affected by SWI and number of seizures. The surprised eye emotion recognition score was mainly affected by the number of seizures. Variables with p < .1 were considered to be independent variables of multivariable ordered logistic regression. Multivariate logistic analysis showed that sadness emotion recognition was mainly affected by SWI and ESES duration, while disgust was mainly affected by SWI. CONCLUSION: The typical SeLECTS group showed impaired emotion (sadness and fear) recognition function in the eye area. The ESES group was associated with more intense emotional (sadness, fear, disgust, and surprise) recognition impairment in the eye region. The higher the SWI, the younger the onset age and the longer the duration of ESES, while the more the number of seizures, the more serious the impairment of emotional recognition function in the affected eye area.

Characteristics and Mechanisms of Phosphorous Adsorption by Peanut Shell-Derived Biochar Modified with Magnesium Chloride by Ultrasonic-Assisted Impregnation.

Recovery of phosphate (P) from sludge, domestic wastewater, and industrial wastewater is beneficial for overcoming the problem of shortage of P rock resources. In this study, Mg-functionalized peanut shell-derived biochar was prepared by ultrasound-assisted impregnation. The obtained Mg-laden biochar had a higher content of Mg, a larger specific surface area, and more porosity. The prepared Mg-modified biochar exhibited excellent adsorption properties of phosphorus. Modified biochar has a higher amount of adsorbed P than raw biochar. The capacity of P adsorption by modified biochar was 30.48-114.24% higher than that by raw biochar. Moreover, the Mg-laden biochar can be applied in a wide working environment (pH: 2-10; temperature range: 15-40 °C). This study not only develops a new strategy for the preparation of high-capacity P adsorbents but also provides a new green use for agricultural peanut shells.

Vortex coagulation treatment of oilfield wastewater.

In this study, the traditional coagulation process was optimized and a method of vortex coagulation for wastewater treatment was proposed for the first time. The process discards the sedimentation method used in traditional coagulation and uses agitation to bring flocs up. These flocs can then be stuck by the filter cotton fixed in wastewater, and the filter cotton and flocs can act as net capturing several times under the action of agitation. It is worth noting that the filter cotton and flocs can synergistically adsorb the suspended and organic pollutants from wastewater. The results showed that the chemical oxygen demand (COD) removal of vortex coagulation could reach 82%, which was 10% higher than that of the traditional coagulation under the same coagulant dosing. In addition, the flocs in conventional coagulation and vortex coagulation were analyzed by IR spectroscopy and XRD, which showed that the mixing process did not destroy the chemical structure of the flocs. Compared with the conventional method, this process does not require a sedimentation tank, which can avoid the investment of equipment construction in this area. The effects of coagulant dosage, pH, stirring speed, and stirring time on the wastewater treatment effects were explored in the experiment.

Environment-friendly bio-based controlled-release phosphate fertilizer with waste kitchen oil as coating material: Preparation, characterization, and mechanisms.

Recently, Bio-based polyurethane controlled-release fertilizers (BPCF) have been developed rapidly owing to their environmental friendliness, renewability, and low cost. However, the unsatisfying controlled release prohibits their large-scale direct application in agricultural production. Here, we prepared bio-based controlled-release phosphate (P) fertilizers using harmful waste kitchen oils (WKO) as coating materials. The membrane shell surface was modified with multi-walled carbon nanotubes (CNT), and superhydrophobic controlled-release phosphorus fertilizers (SCRF) were obtained. After CNT modification, the controlled release period of SCRF was greatly improved. Phosphorus released period of SCRF reached over 67 d while that of BPCF was merely ∼49 d. Additionally, the surface energy, cracks, roughness, microstructure, cross-linking degree, etc., of the membrane shells were measured. The results showed that CNT greatly improved the hydrophobic properties of the membrane shells. The findings indicated the application of modified WKO with great agricultural value in preparing environment-friendly BPCFs.

Highly Chemoselective Synthesis of Azaarene-Equipped CF3-Tertiary Alcohols under Metal-Free Conditions and Their Fungicidal Activities.

A highly chemoselective reaction between α,ß-unsaturated trifluoromethyl ketones with azaarenes under metal-free conditions was carried out, affording a range of valuable azaarene-equipped CF3-tertiary alcohols in moderate to excellent yields (up to 95% yield) with good tolerance of functional groups, and their structures were confirmed by NMR, HRMS, and X-ray diffraction for validation. This method features simple reaction conditions (only solvent), high atom- and step-economy, and broad substrate scope. Moreover, most of the target products exhibited promising fungicidal activities, and compound 3al exhibited 91.65% fungicidal activity against R. solani, with an EC50 value of 0.18 mg/mL.

Synthesis of Novel Indole Schiff Base Compounds and Their Antifungal Activities.

A series of novel indole Schiff base derivatives (2a-2t) containing a 1,3,4-thiadiazole scaffold modified with a thioether group were synthesized, and their structures were confirmed using FT-IR, 1H NMR, 13C NMR, and HR-MS. In addition, the antifungal activity of synthesized indole derivatives was investigated against Fusarium graminearum (F. graminearum), Fusarium oxysporum (F. oxysporum), Fusariummoniliforme (F.moniliforme), Curvularia lunata (C. lunata), and Phytophthora parasitica var. nicotiana (P. p. var. nicotianae) using the mycelium growth rate method. Among the synthesized indole derivatives, compound 2j showed the highest inhibition rates of 100%, 95.7%, 89%, and 76.5% at a concentration of 500 µg/mL against F. graminearum, F. oxysporum, F.moniliforme, and P. p. var. nicotianae, respectively. Similarly, compounds 2j and 2q exhibited higher inhibition rates of 81.9% and 83.7% at a concentration of 500 µg/mL against C. lunata. In addition, compound 2j has been recognized as a potential compound for further investigation in the field of fungicides.

COVID-19 vaccination for patients with benign childhood epilepsy with centrotemporal spikes.

AIM: There is a high demand for information on COVID-19 vaccination for patients with childhood epilepsy with centrotemporal spikes (BECTS). Patients with this condition need a stable, daily life; unfortunately, the decision of vaccination is not easy for their parents. We evaluated patients with BECTS for symptoms and seizure control after COVID-19 vaccination. METHODS: We asked the caregivers of all patients who visited our hospital to report their vaccination status, and if vaccinated, their experience in terms of adverse effects and seizure control after the second dose of the four Chinese-approved COVID-19 vaccines. RESULTS: Seventy-seven children had received their second COVID-19 vaccine dose: 58 of 77 (75.3%) received Sinopharm (Beijing): BBIBP-CorV (Vero cells) and 16 (20.8%) received CanSino: Ad5-nCoV. Twenty of seventy-seven (25.97%) patients with BECTS reported having side effects; all effects were mild that could be relieved themselves. For Sinopharm (Beijing): BBIBP-CorV (Vero cells), the most frequent local side effect reported by the parents was pain at the site of injection (17.24%) and systematic side effect was fatigue (15.52%). For CanSino: Ad5-nCoV, the most reported local side effect was pain at the site of injection (6.25%). All parents reported that their child's side effects could be relieved by themselves. No patient reported status epilepticus or exacerbation of a pre-existing condition. If non-vaccinated, the cause of hesitation was explored: 40% of parents worried about inducing seizures, 19% of parents worried about vaccine side effects, 32% of parents worried about the vaccine-antiepileptic drug interactions, and 9% of parents feared for their child's physical condition. More than 34.1% of parents accepted that the decision to get the vaccine for their child was difficult. Over 90% of parents believe that research on the safety and tolerability of vaccination would help them to make the decision. CONCLUSION: Our data suggest that COVID-19 vaccination is well tolerated and safe in patients below 18 years of age having BECTS, thereby supporting the recommendation of vaccination.

Angiotensin II-induced miR-31-5p upregulation promotes vascular smooth muscle cell proliferation and migration.

Angiotensin II (Ang II) plays a central role in vascular smooth muscle cell (VSMC) proliferation and migration, being key to regulate vascular function and promote vascular remodeling in cardiovascular diseases. We recently showed that miR-31-5p promoted oxidative stress in spontaneously hypertensive rats. In this study, we aim to investigate whether miR-31-5p and fibronectin type III domain-containing 5 (FNDC5) contribute to Ang II-induced VSMC proliferation and migration. Experiments were performed in primary VSMCs of wide-type (WT) and FNDC5-/- mice as well as the rat A7r5 cell line. We found that Ang II increased miR-31-5p level, reduced FNDC5 expression and stimulated VSMC proliferation and migration, which were aggravated by miR-31-5p mimic, and prevented by miR-31-5p inhibitor in VSMCs. The Ang II-induced VSMC proliferation were prevented by exogenous FNDC5 in both WT and FNDC5-/- mice, while the effects were more significant in FNDC5-/- mice. Furthermore, exogenous FNDC5 reversed the effects of miR-31-5p mimic on VSMC proliferation and migration in Ang II-treated VSMCs. Meanwhile, FNDC5 deficiency prevented the effects of miR-31-5p inhibitor on VSMC proliferation and migration in Ang II-treated VSMCs. In conclusion, our findings demonstrate that the miR-31-5p upregulation and the following FNDC5 downregulation contribute to Ang II-induced VSMC proliferation and migration.

Network Pharmacology Experiments Show That Emodin Can Exert a Protective Effect on MCAO Rats by Regulating Hif-1α/VEGF-A Signaling.

Modern pharmacological studies have shown that emodin, the main effective component of rhubarb, has good anti-inflammatory and antioxidant effects, but its pharmacodynamic mechanism remains unclear yet. This study aims to elucidate the multitarget action mechanism of emodin in ischemic stroke through network pharmacology and in vivo experiments. Sprague-Dawley rats were randomly divided into control (normal saline), sham (normal saline), model (normal saline), and emodin groups (n = 9 per group). Emodin was administered at 40 mg/kg/d for 3 consecutive days. The rats were subjected to middle cerebral artery occlusion for 2 h, followed by reperfusion for 24 h to establish the cerebral ischemia-reperfusion injury. To search for relevant studies in databases, emodin, ischemic stroke, and stroke were used as keywords. Subsequently, protein-protein interaction networks and complex disease target networks were established, and an enrichment analysis and molecular docking of core targets were performed. Gene expression was detected through western blotting and reverse-transcription polymerase chain reaction. Localization and expression of proteins were detected through immunohistochemistry. Furthermore, the neurological function, 2,3,5-triphenyltetrazolium chloride staining, levels of brain tissue inflammatory factors, the role of the blood-brain barrier (BBB), and relevant signaling pathways were assessed in vivo. The molecular docking of core targets revealed that the docking between vascular endothelial growth factor A (VEGF-A) and emodin was the most efficient. Emodin pretreatment decreased the neurological score from 2.875 to 1.125. Moreover, emodin inhibited the degradation of occludin and claudin-5 caused by matrix metalloprotein kinase (MMP)-2/MMP-9, thereby protecting the BBB. Additionally, related proteins such as hypoxia-inducible factor-1α/VEGF-A and nuclear factor kappa B were down-regulated. Thus, emodin may play a protective role during cerebral ischemia reperfusion through mediation of the Hif-1α/VEGF-A signaling pathway to inhibit the expression of inflammatory factors.