Scutellarin alleviates microglia-mediated neuroinflammation and apoptosis after ischemic stroke through the PI3K/AKT/GSK3ß signaling pathway.

Microglia are resident immune cells in the central nervous system that are rapidly activated to mediate neuroinflammation and apoptosis, thereby aggravating brain tissue damage after ischemic stroke (IS). Although scutellarin has a specific therapeutic effect on IS, the potential target mechanism of its treatment has not been fully elucidated. In this study, we explored the potential mechanism of scutellarin in treating IS using network pharmacology. Lipopolysaccharide (LPS) was used to induce an in vitro BV-2 microglial cell model, while middle cerebral artery occlusion (MCAO) was used to induce an in vivo animal model. Our findings indicated that scutellarin promoted the recovery of cerebral blood flow in MCAO rats at 3 days, significantly different from that in the MCAO group. Western blotting and immunofluorescence revealed that scutellarin treatment of BV-2 microglial cells resulted in a significant reduction in the protein expression levels and incidence of cells immunopositive for p-NF-κB, TNF-α, IL-1ß, Bax, and C-caspase-3. In contrast, the expression levels of p-PI3K, p-AKT, p-GSK3ß, and Bcl-2 were further increased, significantly different from those in the LPS group. The PI3K inhibitor LY294002 had similar effects to scutellarin by inhibiting neuroinflammation and apoptosis in activated microglia. The results of the PI3K/AKT/GSK3ß signaling pathway and NF-κB pathway in vivo in MCAO models induced microglia at 3 days were consistent with those obtained from in vitro cells. These findings indicate that scutellarin plays a neuroprotective role by reducing microglial neuroinflammation and apoptosis mediated by the activated PI3K/AKT/GSK3ß/NF-κB signaling pathway.

Phospholipid and glycerolipid metabolism as potential diagnostic biomarkers for acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is characterized as a systemic inflammatory condition posing challenges in diagnosis and prognosis assessment. Lipid metabolism abnormalities, especially triacylglycerol (TAG) levels, have been reported, indicating their potential as biomarkers in acute pancreatitis. However, the performance of the TAG cycle, including phospholipid and glycerolipid metabolism, in AP patients has not yet been reported. METHODS: This study enrolled 91 patients with acute biliary pancreatitis (ABP), 27 with hyperlipidaemic acute pancreatitis (HLAP), and 58 healthy controls (HCs), and their plasma phospholipid and glycerolipid levels were analyzed through liquid chromatography‒mass spectrometry. The phospholipid and glycerolipid contents of plasma collected from AP patients on the first, third, and seventh days of hospitalization were also measured. An orthogonal partial least squares discriminant analysis model served to differentiate the ABP, HLAP and HC groups, and potentially diagnostic lipids were evaluated via receiver operating characteristic curves in both the test and validation sets. Correlations between clinical data and lipids were conducted using Spearman's method. Clustering via the 'mfuzz' R package and the Kruskal‒Wallis H test were conducted to monitor changes during hospitalization. RESULTS: Compared with those in HCs, the levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidic acid (PA) were lower in AP patients, whereas the levels of phosphatidylinositol (PI) and phosphatidylglycerol (PG) showed the opposite trend. Interestingly, TAG levels were positively correlated with white blood cell counts in ABP patients, and TAGs containing 44-55 carbon atoms were highly correlated with plasma TAG levels in HLAP patients. Phospholipid levels exhibited an inverse correlation with AP markers, in contrast to glycerolipids, which demonstrated a positive correlation with these markers. Additionally, PE (O-16:0/20:4) and PE (18:0/22:6) emerged as potential biomarkers because of their ability to distinguish ABP and HLAP patients from HCs, showing area under the curve (AUC) values of 0.932 and 0.962, respectively. PG (16:0/18:2), PG (16:0/20:4), PE (P-16:0/20:2), PE (P-18:2/18:2), PE (P-18:1/20:3), PE (P-18:1/20:4), PE (O-16:0/20:4), and TAG (56:6/FA18:0) were significantly changed in ABP patients who improved. For HLAP patients, PC (18:0/20:3), TAG (48:3/FA18:1), PE (P-18:0/16:0), and TAG (48:4/FA18:2) showed different trends in patients with improvement and deterioration, which might be used for prognosis. CONCLUSIONS: Phospholipids and glycerolipids were found to be potential biomarkers in acute pancreatitis, which offers new diagnostic and therapeutic insights into this disease.

Effect of scutellarin on BV-2 microglial-mediated apoptosis in PC12 cells via JAK2/STAT3 signalling pathway.

Previous studies have shown that scutellarin inhibits the excessive activation of microglia, reduces neuronal apoptosis, and exerts neuroprotective effects. However, whether scutellarin regulates activated microglia-mediated neuronal apoptosis and its mechanisms remains unclear. This study aimed to investigate whether scutellarin can attenuate PC12 cell apoptosis induced by activated microglia via the JAK2/STAT3 signalling pathway. Microglia were cultured in oxygen-glucose deprivation (OGD) medium, which acted as a conditioning medium (CM) to activate PC12 cells, to investigate the expression of apoptosis and JAK2/STAT3 signalling-related proteins. We observed that PC12 cells apoptosis in CM was significantly increased, the expression and fluorescence intensity of the pro-apoptotic protein Bax and apoptosis-related protein cleaved caspase-3 were increased, and expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) was decreased. Phosphorylation levels and fluorescence intensity of the JAK2/STAT3 signalling pathway-related proteins JAK2 and STAT3 decreased. After treatment with scutellarin, PC12 cells apoptosis as well as cleaved caspase-3 and Bax protein expression and fluorescence intensity decreased. The expression and fluorescence intensity of Bcl-2, phosphorylated JAK2, and STAT3 increased. AG490, a specific inhibitor of the JAK2/STAT3 signalling pathway, was used. Our findings suggest that AG490 attenuates the effects of scutellarin. Our study revealed that scutellarin inhibited OGD-activated microglia-mediated PC12 cells apoptosis which was regulated via the JAK2/STAT3 signalling pathway.

A nitrogen-doped carbon nanosheet composited platinum-cobalt single atom alloy catalyst for effective hydrogen evolution reaction.

An electrocatalyst with ultra-small PtCo single atom alloy species evenly dispersed on nitrogen-doped ultra-thin carbon nanosheets (PtCo SAA/NC) was designed. The introduction of single-atom Pt not only maximizes the atomic utilization efficiency of Pt species, but also synergistically enhances the charge transfer characteristics of Co cluster surfaces, thereby increasing the migration and evolution rate of hydrogen ions. The PtCo SAA/NC catalyst exhibits a Tafel slope of 42 mV dec-1 and a low overpotential of 45 mV at 10 mA cm-2 in 0.5 M H2SO4 solution.

Scutellarin Attenuates Microglia Activation in LPS-Induced BV-2 Microglia via miRNA-7036a/MAPT/PRKCG/ERK Axis.

Scutellarin is an herbal agent which can exert anti-neuroinflammatory effects in activated microglia. However, it remains uncertain if it can inhibit microglia-mediated neuroinflammation by regulating miRNAs. This study sought to elucidate the upstream regulatory mechanisms by endogenous microRNAs and its target gene in activated microglia in lipopolysaccharide (LPS)-induced BV-2 microglia. Results show that scutellarin suppressed the expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and inducible nitric oxide synthase (iNOS) significantly in LPS-stimulated BV-2 microglia. As with the results of miRNAs function classification in vitro, the expression levels of mir-7036a-5p are upregulated in LPS-activated BV-2 microglia, but are downregulated by scutellarin. Rescue experiments indicated that mir-7036a-5p is a pro-inflammatory factor in activated BV-2 microglia. mir-7036a-5p agomir promoted the expression of phosphorylated tau proteins (p-tau), protein kinase C gamma type (PRKCG), extracellular regulated protein kinases (ERK1/2), but the is reversed by mir-7036a-5p antagomir in vitro. It is shown here that mir-7036a-5p is involved in microglia-mediated inflammation in LPS-induced BV-2 microglia. More important is the novel finding that scutellarin mitigated microglia inflammation by down-regulating the mir-7036a-5p/MAPT/PRKCG/ERK signaling pathway.

Adsorption, boiling or membrane filtration for disinfection by-product removal: How to make our drinking water safer?

Disinfection by-products (DBPs) generated in drinking water have become a global concern due to their potential harm to human health. Nevertheless, there are few studies about different point-of-use water treatments in household drinking water. The study aims to compare the effectiveness of three point-of-use water treatments: adsorption, boiling, and membrane filtration. The experimental results showed that the initial average concentration of volatile DBPs and non-volatile DBPs for tap water were 63.71 µg/L and 6.33 µg/L. The removal efficiency of DBPs for adsorption which were 75.6 % (the filter volumes from 0 L to 20 L) and 45.4 % (the filter volumes from 20 L to 50 L) during the service life of the filter element (50 L). Boiling had a high removal efficiency for volatile DBPs like trihalomethanes (THMs), haloacetaldehydes (HALs), haloacetonitriles (HANs), and haloketones (HKs) (90.5 %, 100 %, 100 %, and 100 %, respectively). However, boiling had a low removal efficiency which was 15 % in removing non-volatile DBPs like haloacetic acids (HAAs). Membrane filtration had a middle removal efficiency for THMs, HAAs, HALs, HKs, and HANs (45.3 %, 75.2 %, 46.5 %, 47.6 %, and 100 %, respectively). Through analysis of the correlation between dissolved organic matter (DOM) removal efficacy and DBP removal efficiency, it was found that the strongest correlation was observed between UV254 and DBP removal efficiency. Boiling showed a lower estimated cytotoxicity of DBPs compared to adsorption and membrane filtration. Cancer risk assessment of DBPs was below the specified risk range for three point-of-use water treatments. This study provides a reference for choosing point-of-use water treatments in household drinking water.

Analysis of soil pollution characteristics and influencing factors based on ten electroplating enterprises.

The electroplating industry encompasses various processes and plating types that contribute to environmental pollution, which has led to growing public concern. To investigate related soil pollution in China, the study selected 10 sites with diverse industrial characteristics distributed across China and collected 1052 soil samples to determine the presence of industrial priority pollutants (PP) based on production process and pollutant toxicity. The factors influencing site pollution as well as proposed pollution prevention and control approaches were then evaluated. The results indicate the presence of significant pollution in the electroplating industry, with ten constituents surpassing the risk screening values (RSV). The identified PP consist of Cr(VI), zinc (Zn), nickel (Ni), total chromium (Cr), and petroleum hydrocarbons (C10-C40). PP contamination was primarily observed in production areas, liquid storage facilities, and solid zones. The vertical distribution of metal pollutants decreased with soil depth, whereas the reverse was true for petroleum hydrocarbons (C10-C40). Increase in site production time was strongly correlated with soil pollution, but strengthening anti-seepage measures in key areas can effectively reduce the soil exceedance standard ratio. This study serves as a foundation for conceptualizing site repair technology in the electroplating industry and offers a reference and methodology for pollution and source control in this and related sectors.

A clinical nomogram for predicting small bowel obstruction after extubation after radical resection of esophageal cancer and jejunostomy.

BACKGROUND: Small bowel obstruction after extubation is among the most serious complications of radical esophageal cancer and jejunostomy resection. This study aimed to explore the risk factors and treatment methods for small bowel obstruction after extubation and construct a predictive model to guide its clinical management. METHODS: Clinical data for 514 patients who underwent esophagectomy with jejunostomy for esophageal cancer were collected. A nomogram was constructed using the independent risk factors for small bowel obstruction after extubation determined on multivariable logistic regression analysis, and a subgroup analysis was performed of the treatment methods for the 61 patients with small bowel obstruction after extubation. RESULTS: The nomogram incorporated the independent risk factors for small bowel obstruction after extubation (gastrointestinal function recovery [P < .001], postoperative albumin reduction ratio [P = .009], and serious postoperative complications [P < .001]) in the multivariable logistic regression analysis. The final model had an area under the curve of 0.829 (95% confidence interval, 0.775-0.883). The calibration plots demonstrated high concordance between the predicted and actual probabilities. The model demonstrated excellent discriminatory power for internal and time validation, with adjusted C-statistics of 0.821 and 0.810 (95% confidence interval, 0.686-0.933), respectively. In the subgroup analysis, an abnormal anion gap (P = .016) and low serum albumin level (P = .005) were associated with recurrent small bowel obstruction. The model's area under the curve was 0.815 (95% confidence interval, 0.683-0.948). The probability of recurrence among patients with small bowel obstruction after extubation was 78.3% when the 2 risk factors were present. CONCLUSION: The clinical nomogram based on small bowel obstruction after extubation predictors recommends aggressive surgical intervention for patients with small bowel obstruction after extubation and an abnormal anion gap and low serum albumin level at admission.

Exosomal DLX6-AS1 from hepatocellular carcinoma cells induces M2 macrophage polarization to promote migration and invasion in hepatocellular carcinoma through microRNA-15a-5p/CXCL17 axis.

BACKGROUND: Hepatocellular carcinoma (HCC) cells-secreted exosomes (exo) could stimulate M2 macrophage polarization and promote HCC progression, but the related mechanism of long non-coding RNA distal-less homeobox 6 antisense 1 (DLX6-AS1) with HCC-exo-mediated M2 macrophage polarization is largely ambiguous. Thereafter, this research was started to unearth the role of DLX6-AS1 in HCC-exo in HCC through M2 macrophage polarization and microRNA (miR)-15a-5p/C-X-C motif chemokine ligand 17 (CXCL17) axis. METHODS: DLX6-AS1, miR-15a-5p and CXCL17 expression in HCC tissues and cells were tested. Exosomes were isolated from HCC cells with overexpressed DLX6-AS1 and co-cultured with M2 macrophages. MiR-15a-5p/CXCL17 down-regulation assays were performed in macrophages. The treated M2 macrophages were co-cultured with HCC cells, after which cell migration, invasion and epithelial mesenchymal transition were examined. The targeting relationships between DLX6-AS1 and miR-15a-5p, and between miR-15a-5p and CXCL17 were explored. In vivo experiment was conducted to detect the effect of exosomal DLX6-AS1-induced M2 macrophage polarization on HCC metastasis. RESULTS: Promoted DLX6-AS1 and CXCL17 and reduced miR-15a-5p exhibited in HCC. HCC-exo induced M2 macrophage polarization to accelerate migration, invasion and epithelial mesenchymal transition in HCC, which was further enhanced by up-regulated DLX6-AS1 but impaired by silenced DLX6-AS1. Inhibition of miR-15a-5p promoted M2 macrophage polarization to stimulate the invasion and metastasis of HCC while that of CXCL17 had the opposite effects. DLX6-AS1 mediated miR-15a-5p to target CXCL17. DLX6-AS1 from HCC-exo promoted metastasis in the lung by inducing M2 macrophage polarization in vivo. CONCLUSION: DLX6-AS1 from HCC-exo regulates CXCL17 by competitively binding to miR-15a-5p to induce M2 macrophage polarization, thus promoting HCC migration, invasion and EMT.

Genistein protects against acetaminophen-induced liver toxicity through augmentation of SIRT1 with induction of Nrf2 signalling.

Previous studies suggest that genistein protects liver from acetaminophen (APAP)-induced injury, however, the detailed mechanism of the process is still incompletely. Therefore, present study was to investigate the potential mechanism of the genistein mediated protection against APAP-induced hepatotoxicity. As shown, supplementation with 150 mg/kg genistein greatly alleviated the increase in serum alanine aminotransferase (ALT) activity, aspartate aminotransferase (AST) activity, hepatic malondialdehyde (MDA) contents, and reversed the decrease in hepatic GSH levels in response to overdose APAP. At the same time, hepatic SIRT1 protein and activity were markedly upregulated in mouse receiving genistein. However, the amelioration was almost abolished by the knockdown of hepatic SIRT1 expression using lentivirus carrying specific shRNA targeting SIRT1. These results were further validated by histopathology examination. Moreover, depletion of hepatic SIRT1 prevented the accumulation of Nrf2 in nucleus and the upregulation of the antioxidant gene expression in the presence of genistein and/or APAP. Concomitantly, the induced mRNA expression of UDP-glucuronosyltransferases (UGTs) by genistein was largely dependent on the SIRT1 expression and activity. Together, our results support the notion that the strong elevation of SIRT1 expression and activity may represent a potential mechanism of protection against APAP-induced liver injury by genistein.

Temporal effect of MgO reactivity on the stabilization of lead contaminated soil.

Elevated soil lead (Pb) concentrations are a global concern owing to the toxic effects of this heavy metal. Solidification/stabilization (S/S) of soils using reagents like Portland cement (PC) is a common approach for the remediation of Pb contaminated sites. However, it has been reported that under long-term field conditions, the performance of PC treatments can diminish significantly. Therefore, novel reagents that provide longer-term stabilization performance are needed. In this study, four magnesium oxide (MgO) products of different reactivity values were applied (5 wt%) to a Pb contaminated clayey soil. The short-term (1-49 days) and long-term (25-100 years) temporal stabilization effects were investigated by laboratory incubation and accelerated ageing methods, respectively. The concentration of Pb in Toxicity Characterization Leaching Procure (TCLP) leachate was ~14 mg/L for the untreated soil; ~1.8 times higher than the TCLP regulatory level (5 mg/L). Only one day after treatment with MgO, the leachate concentration was reduced to below the regulatory level (a reduction of 69.4%-83.2%), regardless of the MgO type applied. However, in the long-term accelerated ageing experiments, only treatments using the most reactive MgO type could provide leachate concentrations that were consistently below the TCLP threshold throughout the 100 years of simulated ageing. The soil treated with the MgO of lowest reactivity was the first to exceed the regulatory level, at simulated year 75. It is thus demonstrated that MgO reactivity has a significant effect on its long-term effectiveness for contaminated soil stabilization. This is attributed to differences in their specific surface area and readiness to carbonate, which may facilitate the immobilization of Pb in the long term. It is also noteworthy that compared to PC, reactive MgO is more environmentally friendly owing to lower energy consumption and reduced CO2 emissions during its manufacture.

Degradation of DDTs in thermal desorption off-gas by pulsed corona discharge plasma.

Thermal desorption has been widely employed to treat soils contaminated with chlorinated organics. The off-gas of thermal desorption must be treated to avoid secondary pollution. In this study, the treatment of DDTs in thermal desorption off-gas by pulsed corona discharge plasma was investigated. The effects of important operation parameters, including energy density, gas temperature, humidity, and O2 content, on DDTs degradation were investigated. The main degradation products were also studied. The DDTs degradation efficiency increased with the increase in energy density, gas temperature, and O2 content. The degradation efficiency of DDTs was achieved to 84.6% when the initial concentration, energy density, and gas flow rate were 2.0 mg/m3, 17.8 J/L, and 3.0 L/min, respectively. Maximum DDTs degradation efficiency was observed when the gas was at 5% relative humidity. The main degradation products identified were DM, phenol, benzene, acetic acid, and formic acid. It was calculated that 87% of chlorine in the degraded DDTs was converted into chloride ion.

[Emission Characteristics of VOCs from Typical Restaurants in Beijing].

Using the EPA method, emission of volatile organic compounds (VOCs) , sampled from barbecue, Chinese and Western fast-food, Sichuan cuisine and Zhejiang cuisine restaurants in Beijing was investigated. VOCs concentrations and components from different cuisines were studied. The results indicated that based on the calibrated baseline ventilation volume, the VOCs emission level from barbecue was the highest, reaching 12.22 mg · m(-3), while those from fast-food of either Chinese or Western, Sichuan cuisine and Zhejiang cuisine were about 4 mg · m(-3). The components of VOCs from barbecue were different from those in the other cuisines, which were mainly propylene, 1-butene, n-butane, etc. The non-barbecue cuisines consisted of high concentration of alcohols, and Western fast-food contained relatively high proportion of aldehydes and ketones organic compounds. According to emission concentration of baseline ventilation volume, barbecue released more pollutants than the non-barbecue cuisines at the same scale. So, barbecue should be supervised and controlled with the top priority.

[Degradation of nonylphenol and short chain nonylphenol polyethoxylates in soil].

Biodegradation of nonylphenolic estrogens in soil and sludge-amended soil were investigated. Biodegradations of nonylphenol (NP), nonylphenol monoethoxylate (NPEO1) and nonylphenol diethoxylates (NPEO2) followed the first-order kinetics, and the degradation rates were enhanced when the temperature was increased. Spiked NP, NPEO1 and NPEO2 (with the concentration of 100, 50 and 100 mg x kg(-1), respectively) could be degraded completely in 45 days at the temperature of 30 degrees C. NP presented a higher degradation rates in soil than NPEO1 and NPEO2 under the same condition. The amended sludge enhanced the biodegradation of NPEO1 and NPEO2 in soil, while it inhibited that of NP.