Association and temporal sequence of pneumonia and gastrointestinal bleeding after acute ischemic stroke.

BACKGROUND: Stroke-associated pneumonia (SAP) and gastrointestinal bleeding (GIB) are common medical complications after stroke. The previous study suggested a strong association between SAP and GIB after stroke. However, little is known about the time sequence of SAP and GIB. In the present study, we aimed to verify the association and clarify the temporal sequence of SAP and GIB after ischemic stroke. METHODS: Patients with ischemic stroke from in-hospital Medical Complication after Acute Stroke study were analyzed. Data on occurrences of SAP and GIB during hospitalization and the intervals from stroke onset to diagnosis of SAP and GIB were collected. Multiple logistic regression was used to evaluate the association between SAP and GIB. Kruskal-Wallis test was used to compare the time intervals from stroke onset to diagnosis of SAP and GIB. RESULTS: A total of 1129 patients with ischemic stroke were included. The median length of hospitalization was 14 days. Overall, 86 patients (7.6%; 95% CI, 6.1-9.2%) developed SAP and 47 patients (4.3%; 95% CI, 3.0-5.3%) developed GIB during hospitalization. After adjusting potential confounders, SAP was significantly associated with the development of GIB after ischemic stroke (OR = 5.13; 95% CI, 2.02-13.00; P < 0.001). The median time from stroke onset to diagnosis of SAP was shorter than that of GIB after ischemic stroke (4 days vs. 5 days; P = 0.039). CONCLUSIONS: SAP was associated with GIB after ischemic stroke, and the onset time of SAP was earlier than that of GIB. It is imperative to take precautions to prevent GIB in stroke patients with SAP.

Fibrinogen-to-Albumin Ratio and Clinical Outcomes in Patients With Large Artery Atherosclerosis Stroke.

BACKGROUND: A high fibrinogen-to-albumin ratio (FAR), a novel inflammatory marker, is considered to be a prognostic marker in vascular diseases. However, the association of FAR with large artery atherosclerosis (LAA) stroke is still unknown. This study was conducted to evaluate the association between FAR levels and clinical outcomes in patients with acute LAA stroke. METHODS AND RESULTS: A total of 809 patients within 72 hours of LAA stroke were included and followed up to 1 year. FAR was calculated as fibrinogen (g/L)/albumin (g/L). The associations of FAR with clinical outcomes were assessed by multivariate Cox regression or logistic regression analysis. Clinical outcomes included stroke recurrence, all-cause death, poor functional outcome (modified Rankin Scale score 3-6), and dependence (modified Rankin Scale score 3-5). Among the 809 patients with acute LAA stroke, the median FAR was 0.075 (interquartile range, 0.064-0.087). At 1 year, 103 (12.7%) patients had stroke recurrence, 105 (13.0%) had poor functional outcome, 76 (9.8%) had dependence, and 29 (3.6%) had died. After adjusting for all confounding risk factors, a high FAR level was associated with stroke recurrence (hazard ratio, 2.57 [95% CI, 1.32-5.02]), poor functional outcome (odds ratio, 3.30 [95% CI, 1.57-6.94]), and dependence (odds ratio, 3.49 [95% CI, 1.49-8.19]). CONCLUSIONS: A high FAR level was associated with an increased risk of stroke recurrence, poor functional outcome, and dependence in patients with acute LAA stroke.

Exosomal miR-128-3p reversed fibrinogen-mediated inhibition of oligodendrocyte progenitor cell differentiation and remyelination after cerebral ischemia.

AIMS: To investigate the role of exosomal miR-128-3p in promoting fibrinogen-mediated inhibition of oligodendrocyte progenitor cell (OPC) differentiation and the therapeutic potential of exosomal miR-128-3p in cerebral ischemia. METHODS: Mouse models of middle cerebral artery occlusion (MCAO) were established as described previously. MCAO was treated with fibrinogen and exosomes by stereotactically injecting into the left stratum. Mouse cortical OPCs were used for mRNA and miRNA sequencing analysis. Exosomes were isolated from neural stem cells (NSCs) of mice. RESULTS: Fibrinogen deposition suppressed remyelination after MCAO and inhibited OPC differentiation by activating ACVR1, the bone morphogenetic protein (BMP) signaling type I receptor. In vitro, miR-sequencing and verification studies revealed that miR-128-3p is associated with BMP signaling mediated by ACVR1. Additionally, transfer of NSC-derived exosomal miR-128-3p to OPCs significantly increased myelin basic protein expression and inhibited BMP signaling. Furthermore, NSC-derived exosomal miR-128-3p protected against fibrinogen-induced demyelination related to BMP signaling, reduced the infarct volume, and improved neurological function after MCAO. CONCLUSIONS: Fibrinogen deposition inhibits remyelination after ischemic damage and NSC-derived exosomal miR-128-3p promotes OPC differentiation into OLs by suppressing BMP signaling, indicating that NSC-derived exosomal miR-128-3p represents a potential therapeutic target for ischemic stroke.

One-step synthesis of well-defined molecularly imprinted nanospheres for the class-selective recognition and separation of ß-blockers in human serum.

ß-blockers are a class of medications that are used to treat abnormal heart rhythms and hypertension. Molecularly imprinted polymers (MIPs) capable of selective recognizing and extracting ß-blockers from complex biological samples hold great promise in bioanalytical and biomedical applications, but developing such artificial receptor materials is still challenging. Herein, we introduce a simple one-step method for the synthesis of well-defined molecularly imprinted nanospheres in high yield (83.6-94.4%) via reversible addition-fragmentation chain transfer (RAFT) precipitation polymerization for the selective recognition and extraction of the ß-blockers from human serum. The prepared MIPs are characterized in terms of morphology, pore properties, binding kinetics, capacity, selectivity, and recognition mechanisms. The uniform nanoscale-imprinted layer favored the rapid mass transfer of ß-blockers. The binding studies showed the high adsorption capacity (126.8 µmol/g) and selectivity of the developed nanomaterial. The investigation on the recognition mechanism reveals that multiple driving forces participate in the binding between MIP and ß-blockers, where hydrogen bonding plays as the dominating role for the specific recognition. The MIP was successfully applied for the direct enrichment of five ß-blockers from human serum with HPLC recoveries ranging from 82.9 to 100.3% and RSD of 0.5-6.9% (n = 3).

Hydrazone bond-oriented molecularly imprinted nanocomposites for the selective separation of protein via the well-defined recognition sites.

The development of hydrazone bond-oriented epitope imprinting strategy is reported to synthesize the polymeric binders for the selective recognition of a protein-ß2-microglobulin through either its N- or C-terminal epitope. The dynamic reversibility of hydrazone bond facilitated not only the oriented assembly of the template peptide hydrazides onto the substrate but also the efficient removal of them from the imprinted cavities. The well-defined surface imprinted layer was successfully constructed through the precise control over the polymerization of silicate esters. Binding performance of the C-terminal peptide imprinted nanocomposite was significantly improved after tuning the non-covalent interactions using the sequence-matching aromatic co-monomers. The dissociation constant (Kd) between the optimized nanocomposite and epitope peptide was 0.5 µmol L-1. The nanomaterial was utilized for the selective extraction and determination of ß2-microglobulin from human urine by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and HPLC-UV with satisfied recoveries of 93.1-112.3% in a concentration range 1.0-50.0 µg⋅mL-1.

Changes in the BTK/NF-κB signaling pathway and related cytokines in different stages of neuromyelitis optica spectrum disorders.

OBJECTIVE: Neuromyelitis optica spectrum disorders (NMOSDs) are blindness-causing neuritis; their pathogenesis is still not fully elucidated. Although it has been determined that Bruton tyrosine kinase (BTK) and NF-κB are associated with NMOSD, the changes that occur in different periods remain unknown. The study aimed to demonstrate the changes in the BTK/NF-κB pathway and related chemokines in different stages of NMOSDs. METHODS: A total of 32 patients with NMOSD were selected as the experimental group, and 32 healthy volunteers were included in the control group. In this study, the BTK/NF-κB pathway and related chemokines in the cerebrospinal fluid and peripheral blood samples of patients with NMOSD were analyzed in the acute or remission phase. RESULTS: BTK, NF-κB, PI3K, IKK, CXCL2, and CXCL12 levels in the NMOSD group in the acute or remission phase were significantly higher than those in the control group (p < 0.05). CONCLUSION: The BTK/NF-κB pathway plays a vital role in the progression of NMOSD pathology. Our results shed light on its important role as a therapeutic target for NMOSD.

DIPEA-induced activation of OH- for the synthesis of amides via photocatalysis.

The development of green protocols for photocatalysis where water acts as a nucleophile, induced by a weak organic base, is difficult to achieve in organic chemistry. Herein, an efficient light-mediated strategy for the synthesis of amides in which a weak organic base acts as a reductant to induce the formation of OH- from water under metal-free conditions is reported. A mechanistic study reveals that the generation of an N,N-diisopropylethylamine (DIPEA) radical via single electron transfer (SET), with the assistance of photocatalyst, that increases the nucleophilicity of the water molecules with respect to the cyanides is essential. Moreover, the removal rate of nitrile in wastewater can be as high as 83%, indicating that this strategy has excellent potential for nitrile degradation.

Non-metal-mediated N-oxyl radical (TEMPO)-induced acceptorless dehydrogenation of N-heterocycles via electrocatalysis.

The development of protocols for direct catalytic acceptorless dehydrogenation of N-heterocycles with metal-free catalysts holds the key to difficulties in green and sustainable chemistry. Herein, an N-oxyl radical (TEMPO) acting as an oxidant in combination with electrochemistry is used as a synthesis system under neutral conditions to produce N-heterocycles such as benzimidazole and quinazolinone. The key feature of this protocol is the utilization of the TEMPO system as an inexpensive and easy to handle radical surrogate that can effectively promote the dehydrogenation reaction. Mechanistic studies also suggest that oxidative TEMPOs redox catalytic cycle participates in the dehydrogenation of 2,3-dihydro heteroarenes.

miRNA-29 aggravates myocardial infarction via inhibiting the PI3K/mTOR/HIF1α/VEGF pathway.

INTRODUCTION: MI is defined by the presence of myocardial necrosis, which is caused by acute and persistent ischemia and hypoxia of the coronary artery. In recent years, its incidence rate has been on the rise in China. METHODS: GSE34198, GSE97320 and GSE141512 datasets were download for DEG analysis. KEGG pathway analysis, GO analysis, GSEA and PPI network construction were performed. Later, target genes of candidate miRNAs were predicted. Next, echocardiography was conducted to detect the effects of miR-29 on left ventricular structure and cardiac function in vivo, and H&E staining was adopted to study the effects of miR-29 on angiogenesis and fibrosis in vivo. Furthermore, Western blotting was employed to investigate the effects of miR-29 inhibition on the expressions of proteins related to the PI3K\mTOR\ HIF-1α\VEGF pathway. RESULTS: There were 162 DEGs involved in MI. GO analysis revealed that inflammatory responses, negative regulation of apoptosis and innate immune response were the main enriched biological processes. KEGG analysis manifested that DEGs were mainly enriched in the PI3K/Akt signaling pathway, and GSEA demonstrated that they were mainly enriched in the PI3K/Akt/mTOR, HIF and VEGF pathways. Moreover, target gene prediction showed that miR-29 was lowly expressed in MI. According to Masson's trichrome staining, miR-29 inhibition promoted angiogenesis, reduced fibrosis, and increased the protein expressions of p-PI3K, p-mTOR, HIF-1α, and VEGF. CONCLUSIONS: MiR-29 may play an important role in the growth and development of MI. After inhibition of miR-29, the PI3K/mTOR/HIF-1α/VEGF pathway is activated to alleviate MI.

Baseline or 90-day fibrinogen levels and long-term outcomes after ischemic stroke or TIA: Results from the China national stroke registry â ¢.

BACKGROUND AND AIMS: Elevated fibrinogen levels have been observed in patients with acute ischemic stroke, but the association of fibrinogen with stroke outcomes is still undefined. We aimed to assess the association between baseline or 90-day fibrinogen levels and long-term outcomes in patients with ischemic stroke or transient ischemic attack (TIA). METHODS: Using data from the China National Stroke Registry Ⅲ, this substudy included 10 518 patients within 7 days (baseline) of onset and 6268 patients at 90 days of recovery. Multivariate Cox regression and logistic regression analyses were used to assess the associations of fibrinogen with poor functional outcome (modified Rankin Scale score 3-6), dependence (modified Rankin Scale score 3-5), all-cause death, and stroke recurrence at 1 year. RESULTS: Fibrinogen levels at 90 days were higher than those at baseline (443.5 mg/dl versus 393.7 mg/dl; p < 0.001). A high baseline fibrinogen level was associated with poor functional outcome (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.35-1.97) and dependence (OR, 1.68; 95% CI, 1.36-2.09) after adjusting for all confounding risk factors. In contrast, further adjustment for high-sensitivity C-reactive protein attenuated the association between baseline fibrinogen level and all-cause death or stroke recurrence. Furthermore, a high 90-day fibrinogen level was also associated with poor functional outcome (OR, 1.46; 95% CI, 1.07-2.00) and dependence (OR, 1.43; 95% CI, 1.03-1.98) after adjusting for all confounding risk factors. CONCLUSIONS: High baseline and 90-day fibrinogen levels were associated with outcomes in patients with ischemic stroke or TIA.

Plasma Levels of Homocysteine is Associated with Liver Fibrosis in Health Check-Up Population.

OBJECT: Studies have shown a link between homocysteine (Hcy) and heart diseases, kidney diseases, cerebrovascular diseases, liver diseases, and other pathological conditions. However, the relationship between Hcy and liver fibrosis (LF) is unclear. Here, we studied the link between plasma Hcy concentration and LF. METHODS: We determined and recorded the plasma Hcy concentration, general biochemical parameters, and liver stiffness measurement (LSM) in 1582 subjects, followed by statistical data analyses. RESULTS: During different stages of LF, we found a considerable difference (p <0.001 unless specified) in body mass index (BMI), sex, age, Hcy, the levels of alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT; P = 0.012), triglycerides (TG; P = 0.006), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBS), and platelet count (PLT). There was a strong association between the plasma Hcy concentration and the serum biomarkers of LF (P <0.001) and the values of LSM (P <0.001). CONCLUSION: The plasma Hcy concentration was substantially different among different stages of LF. The higher the plasma Hcy concentration, the more evident was the degree of LF.

Development and validation of a nomogram to better predict hypertension based on a 10-year retrospective cohort study in China.

Background: Hypertension is a highly prevalent disorder. A nomogram to estimate the risk of hypertension in Chinese individuals is not available. Methods: 6201 subjects were enrolled in the study and randomly divided into training set and validation set at a ratio of 2:1. The LASSO regression technique was used to select the optimal predictive features, and multivariate logistic regression to construct the nomograms. The performance of the nomograms was assessed and validated by AUC, C-index, calibration curves, DCA, clinical impact curves, NRI, and IDI. Results: The nomogram140/90 was developed with the parameters of family history of hypertension, age, SBP, DBP, BMI, MCHC, MPV, TBIL, and TG. AUCs of nomogram140/90 were 0.750 in the training set and 0.772 in the validation set. C-index of nomogram140/90 were 0.750 in the training set and 0.772 in the validation set. The nomogram130/80 was developed with the parameters of family history of hypertension, age, SBP, DBP, RDWSD, and TBIL. AUCs of nomogram130/80 were 0.705 in the training set and 0.697 in the validation set. C-index of nomogram130/80 were 0.705 in the training set and 0.697 in the validation set. Both nomograms demonstrated favorable clinical consistency. NRI and IDI showed that the nomogram140/90 exhibited superior performance than the nomogram130/80. Therefore, the web-based calculator of nomogram140/90 was built online. Conclusions: We have constructed a nomogram that can be effectively used in the preliminary and in-depth risk prediction of hypertension in a Chinese population based on a 10-year retrospective cohort study. Funding: This study was supported by the Hebei Science and Technology Department Program (no. H2018206110).

Ponesimod modulates the Th1/Th17/Treg cell balance and ameliorates disease in experimental autoimmune encephalomyelitis.

Sphingosine-1-phosphate receptor 1 (S1P1) plays an important role in autoimmune disease. Here, we evaluated whether ponesimod, an S1P1 modulator, affects inflammation in experimental autoimmune encephalomyelitis (EAE) and investigated Th1/Th2/Th17/Treg cell subsets. Ponesimod treatment ameliorated EAE and alleviated inflammatory infiltration. Compared with untreated EAE, ponesimod-treated mice had lower Th1 and Th17 cell numbers and higher Treg cell numbers; their IFN-γ, T-bet, IL-17, and RORγt levels as well as their pmTOR/mTOR ratio were diminished, while their TGF-ß and Foxp3 levels were enhanced. These results suggest that ponesimod modulates the Th1/Th17/Treg balance and regulates the mTOR pathway.

Vascular Risk Factors, Imaging, and Outcomes in Transient Ischemic Attack/Ischemic Stroke Patients with Neuroimaging Evidence of Probable/Possible Cerebral Amyloid Angiopathy.

BACKGROUND: In TIA/ischemic stroke patients, the clinical significance of lobar microbleeds potentially indicating cerebral amyloid angiopathy (CAA) is unknown. We assessed vascular risk factors and outcomes, including cognition, in TIA/ischemic stroke patients with neuroimaging evidence of probable/possible CAA. METHODS: This prospective cohort was conducted from August 2015 and January 2018 at 40 centers. 2625 participants were collected. Eligible participants were aged at least 55 years. Montreal Cognitive Assessment (MoCA) score is less than or equal to 26. A total of 1620 patients were included. 1604 (99.0%) and 1582 (97.7%) participants are followed up at 3 and 12 months. The primary outcomes were death or disability (mRS score, 3-6) and Montreal Cognitive Assessment (MoCA) at 3 months and 12 months. Demographic and vascular risk factors were measured at baseline (smoking, alcohol, diabetes, atrial fibrillation, hypertension, hypercholesterolemia, coronary artery disease, ischemic stroke, and transient ischemic attack). Blood samples were collected within 24 hours of admission. MRI was recommended for all patients. MoCA score was evaluated at baseline and follow-up. RESULTS: In total, 291/1620 patients with ischemic stroke/TIA (32.7% female and mean age, 67.8 years) had neuroimaging evidence of probable/possible CAA. Higher age, history of hypertension, atrial fibrillation, ischemic stroke, alcohol, and high glucose at the admission were more common in the patients. Mean MoCA changed from 21.4 at 3 months (SD 5.2) to 22.3 at 12 months (SD 4.7), difference 0.3 (SD 3.8). At the 3-month and 12-month follow-up, there were significant differences in age, education level, and sex among different cognitive groups. Higher age, lower education (less than high school), and female sex were the predictors of changing in MoCA score from 3 months to 12 months. Moreover, age (more than 66 years) and education (less than high school) are strongly associated with MoCA at 3- and 12-month follow-up. 30 of 286 (10.5%) and 37 of 281 (13.2%) patients had poor outcome of death or disability (modified Rankin Scale score, 3-6) at follow-up 3 and 12 months. Cortical superficial siderosis (cSS) was associated with higher mRS at follow-up. cSS status, cSS count 1-2, cSS strictly lobar, and strictly deep might be the risks of outcomes in adjusted analyses. CONCLUSION: This study suggested that an increasing number of vascular risk factors and imaging markers were significantly associated with outcomes of TIA/ischemic stroke patients with CAA pattern. Male, young patients with high education should get better cognitive recovery.

Identification of blood-derived candidate gene markers and a new 7-gene diagnostic model for multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a central nervous system disease with a high disability rate. Modern molecular biology techniques have identified a number of key genes and diagnostic markers to MS, but the etiology and pathogenesis of MS remain unknown. RESULTS: In this study, the integration of three peripheral blood mononuclear cell (PBMC) microarray datasets and one peripheral blood T cells microarray dataset allowed comprehensive network and pathway analyses of the biological functions of MS-related genes. Differential expression analysis identified 78 significantly aberrantly expressed genes in MS, and further functional enrichment analysis showed that these genes were associated with innate immune response-activating signal transduction (p = 0.0017), neutrophil mediated immunity (p = 0.002), positive regulation of innate immune response (p = 0.004), IL-17 signaling pathway (p < 0.035) and other immune-related signaling pathways. In addition, a network of MS-specific protein-protein interactions (PPI) was constructed based on differential genes. Subsequent analysis of network topology properties identified the up-regulated CXCR4, ITGAM, ACTB, RHOA, RPS27A, UBA52, and RPL8 genes as the hub genes of the network, and they were also potential biomarkers of MS through Rap1 signaling pathway or leukocyte transendothelial migration. RT-qPCR results demonstrated that CXCR4 was obviously up-regulated, while ACTB, RHOA, and ITGAM were down-regulated in MS patient PBMC in comparison with normal samples. Finally, support vector machine was employed to establish a diagnostic model of MS with a high prediction performance in internal and external datasets (mean AUC = 0.97) and in different chip platform datasets (AUC = (0.93). CONCLUSION: This study provides new understanding for the etiology/pathogenesis of MS, facilitating an early identification and prediction of MS.

Selective recognition of a cyclic peptide hormone in human plasma by hydrazone bond-oriented surface imprinted nanoparticles.

As a kind of artificial recognition material, molecularly imprinted polymers (MIPs) offer a promising perspective to be developed as synthetic chemical binders capable of selectively recognize biomacromolecules. However, owing to the large size and conformational flexibility of proteins and peptides, imprinting of these biomacromolecules remains a challenge. Novel imprinting strategies still need exploration for the improvement of recognition performance of MIPs. Herein, we developed a hydrazone bond-oriented surface imprinting strategy for an endogenous peptide hormone, human atrial natriuretic peptide (ANP). Surface-oriented imprinting of peptide via reversible covalent bond anchoring approach increased the orientation homogeneity of imprinted cavities as well as the utility of templates. The prepared nanoparticles exhibited high selectivity and fast recognition kinetics for ANP epitope. The dissociation constant between ANP epitope and MIP was measured as 5.3 µM. The applicability of the material in real samples was verified by the selective magnetic extraction of ANP from human plasma samples. This hydrazone bond-oriented surface imprinting strategy provides an alternative approach for the separation of peptides or proteins in complex bio-samples.

Association of Level and Increase in D-Dimer With All-Cause Death and Poor Functional Outcome After Ischemic Stroke or Transient Ischemic Attack.

Background D-dimer is involved in poor outcomes of stroke as a coagulation biomarker. We aimed to investigate the associations of the level and increase in D-dimer between baseline and 90 days with all-cause death or poor functional outcome in patients after ischemic stroke or transient ischemic attack. Methods and Results We collected data from the CNSRIII (Third China National Stroke Registry) study. The present substudy included 10 518 patients within 7 days (baseline) of ischemic stroke or transient ischemic attack and 6268 patients at 90 days. Poor functional outcome at 1 year was assessed on the basis of the modified Rankin Scale (≥3). Multivariable Cox regression or logistic regression was used to assess the association of D-dimer levels with all-cause death or poor functional outcome. D-dimer levels at 90 days were lower than those at baseline (1.4 µg/mL versus 1.7 µg/mL; P<0.001). Higher baseline D-dimer level was associated with all-cause death (adjusted hazard ratio [HR], 1.77; 95% CI, 1.25-2.52; P=0.001) and poor functional outcome (adjusted odds ratio [OR], 1.49; 95% CI, 1.23-1.80; P<0.001) during 1-year follow-up. Higher D-dimer level at 90 days was also associated with poor outcomes independently. Furthermore, an increase in D-dimer levels between baseline and 90 days was associated with all-cause death (since 90 days to 1 year after index event) (adjusted HR, 1.99; 95% CI, 1.12-3.53; P=0.019) but not with poor functional outcome (adjusted OR, 1.08; 95% CI, 0.82-1.41). Conclusions Our study shows that high level and an increase in D-dimer between baseline and 90 days are associated with poor outcomes in patients after ischemic stroke or transient ischemic attack.

Electrochemically induced synthesis of quinazolinones via cathode hydration of o-aminobenzonitriles in aqueous solutions.

An efficient and practical electrochemically catalyzed transition metal-free process for the synthesis of substituted quinazolinones from simple and readily available o-aminobenzonitriles and aldehydes in water has been accomplished. I2/base and water play an unprecedented and vital role in the reaction. By electrochemically catalysed hydrolysis of o-aminobenzonitriles, the synthesis of quinazolinones with benzaldehyde was first proposed. The synthetic utility of this method was demonstrated by gram-scale operation, as well as the preparation of bioactive N-(2,5-dichlorophenyl)-6-(2,2,2-trifluoroethoxy) pteridin-4-amine, which enables straightforward, practical and environmentally benign quinazolinone formation.

Electro-oxidative cyclization: access to quinazolinones via K2S2O8 without transition metal catalyst and base.

A K2S2O8-promoted oxidative tandem cyclization of primary alcohols with 2-aminobenzamides to synthesize quinazolinones was successfully achieved under undivided electrolytic conditions without a transition metal and base. The key feature of this protocol is the utilization of K2S2O8 as an inexpensive and easy-to-handle radical surrogate that can effectively promote the reaction via a simple procedure, leading to the formation of nitrogen heterocycles via direct oxidative cyclization at room temperature in a one-pot procedure under constant current. Owing to the use of continuous-flow electrochemical setups, this green, mild and practical electrosynthesis features high efficiency and excellent functional group tolerance and is easy to scale up.

Constant-wavelength synchronous fluorescence spectrometry for simultaneous and rapid determination of five polycyclic aromatic hydrocarbon residues in dairy products.

A new method for simultaneously determining five polycyclic aromatic hydrocarbons (PAHs) (fluorene, benzofluorene, pyrene, benzo(a)pyrene, and perylene) in dairy products using constant-wavelength synchronous fluorescence spectrometry (CWSFS) was established in this study. Acetonitrile was chosen as the extraction solvent to extract the five PAHs from the dairy products, and an ultrasound extraction method was adopted. The supernatants were filtered using a 0.45-µm microporous filter membrane and concentrated to dryness with a nitrogen dryer. The extracts were then re-dissolved in cyclohexane for analysis. To overcome interference from the background matrix and between PAHs, the difference in wavelength (Δλ) at 40 nm was chosen for CWSFS scanning. With only one single scan, the five PAHs in dairy products could be distinguished and determined using the standard curve method without the need for previous chromatographic separation of the analyte solution. Detection limits of fluorene, benzofluorene, pyrene, benzo(a)pyrene, and perylene were 0.0051 µg·L-1 , 0.016 µg·L-1 , 0.021 µg·L-1 , 0.0056 µg·L-1 , and 0.0062 µg·L-1 , respectively. Recoveries were between 85.60% and 98.42%. These five PAHs in dairy products were determined with good results and therefore expected to be a routine detection method for PAHs in dairy products.