I2-Mediated [6 + 1] Annulation of Alkynes with MsONH3OTf: Direct Synthesis of Benzo[b]azepines.

The synthesis of benzo[b]azepines using protonated aminating reagent (MsONH3OTf) and alkynes through I2-mediated [6 + 1] annulation reaction has been developed. This protocol features excellent functional group tolerance and mild reaction conditions and affords the benzo[b]azepines in moderate to good yields under metal-free reaction conditions.

Toxicological effects of fipronil on laying hens and its residue elimination in eggs.

Eighty 24-week-old laying hens were divided into eight groups, seven given a single oral dose per chicken with 7 dosing levels from 13.6 to 137 mg/kg body weight (bw) and one serving as sham control. The hens were observed for 28 days for clinical abnormalities, egg yield, and body weight. Egg samples from groups of low-to-medium doses were analyzed for residues of fipronil and its metabolites by LC-MS/MS. Blood and organ samples from hens of the group receiving 63.3 mg/kg bw were collected for hematochemical and histopathological analysis. We found that the median lethal dose (LD50) of fipronil was 74 mg/kg bw for laying hens. No death occurred, and there were no obvious changes in body weight and egg production in the hens receiving doses at or below 20 mg/kg bw. In the hens that survived exposure to the dose at 63.3 mg/kg bw, there was significant reduction in body weight and egg yield; histopathological changes in the liver and kidney; and increased levels of creatine, urea, glutamate oxaloacetate transferase, and glutamate pyruvic transaminase. Fipronil-sulfone was the residual marker in eggs with significantly higher concentrations and longer withdrawal periods than its maternal compound. We conclude that fipronil is efficiently transformed into fipronil-sulfone in the body with subsequent excretion into eggs. More attention should be paid to the potential food safety risk of fipronil-sulfone because of its persistence in eggs.

Synthesis of Benzimidazo[2,1-a]isoquinoline and Indolo[2,1-a]isoquinoline Derivatives via Copper-Catalyzed Silylation/Methylation of 2-Arylindoles and 2-Arylbenzimidazoles.

A one-pot method for the synthesis of silylsubstituted/methylsubstituted indolo[2,1-a]isoquinolin-6(5H)-ones and benzimidazo[2,1-a]isoquinoline-6(5H)-ones via copper(II)-initiated silylation/methylation of 2-arylindoles and 2-arylbenzimidazoles was developed. In this procedure, the C-Si bond and C-C bond were constructed by radical addition and cyclization. A series of 2-arylindole and 2-arylbenzimidazole derivatives were facilely transformed to indolo[2,1-a]isoquinolines and benzimidazo[2,1-a]isoquinolines in 39-83% yields.

Scleral Buckling with Viscoelastics or Gas Injection for Bulging Retinal Detachments: A Retrospective Cohort Study.

OBJECTIVE: To examine the use of a viscoelastic agent instead of air in the vitreous cavity during surgery for scleral buckling. METHODS: This was a retrospective cohort study of patients who underwent scleral buckling surgery for bulging rhegmatogenous retinal detachment (RRD) at Ningbo Eye Hospital from 07/2016 to 12/2019. The patients were grouped into drainage, air injection, cryotherapy and explant (DACE) and drainage, viscoelastic injection, cryotherapy, and explant (DVCE) groups, which were comparatively assessed. RESULTS: There were 25 and 22 patients in the DVCE and DACE groups, respectively. The surgery was significantly shorter with DVCE than DACE (P < 0.05), with less intraoperative external pressure adjustment (P < 0.05). BCVA was lower in the DVCE group at 1 week compared with the DACE group (P < 0.05). Successful retinal reattachment was observed in 92.0% and 81.8% of the DVCE and DACE groups, respectively (P < 0.05). Cases requiring laser replenishing after the operation were less in the DVCE group compared with the DACE group (P < 0.05). There were no differences in complications and intraocular pressure between the two groups (all P < 0.05). CONCLUSION: DVCE has better operative characteristics and faster vision recovery than DACE, with similar outcomes.

The relationship between plasma serglycin levels and the diagnosis of diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR), a microvascular complication which is closely related to diabetes, remains the leading cause of vision loss around the world among older adults. Serglycin (SRGN) was known as a hematopoietic cell granule proteoglycan, exerting its function in the formation of mast cell secretory granules and mediates the storage of various compounds in secretory vesicles. The present study illustrates the potential clinical value and experimental mechanisms of SRGN in the DR. METHODS: Firstly, the mRNA expression and protein expression of SRGN in plasma samples from NPDR, PDR patients, type 2 diabetes mellitus (T2Dm) cases, and healthy controls were measured by qPCR and Western blotting assays, respectively. Then, the potentials of SRGN functioning as a diagnostic indicator in DR were verified by the receiver operating characteristic (ROC) analysis. We established in vitro DR model of human retinal endothelial cells through high-glucose treatment. The expression of SRGN and its mechanisms of regulating cellular processes were illustrated subsequently. RESULTS: Our data revealed that SRGN was dramatically upregulated in NPDR and PDR cases compared with healthy controls and T2DM patients; meanwhile, the expression of SRGN was further increased in the PDR group with regard to the NPDR group. Furthermore, the ROC analysis demonstrated that SRGN could distinguish the DR cases from type 2 diabetes mellitus (T2DM) patients and healthy controls with the area under the curve (AUC) of 0.7680 (95% CI = 0.6780 ~ 0.8576, sensitivity = 47.27%, specificity = 100%, cutoff value = 1.4727) and 0.8753 (95% CI = 0.8261 ~ 0.9244, sensitivity = 69.23%, specificity = 100%, cutoff value = 1.6923), respectively. In vitro high-glucose treatment showed that the SRGN expressions were dramatically increased. The loss of SRGN could partially counteract the inhibition of HREC proliferation caused by high-glucose stimulation. Meanwhile, SRGN knockdown could reverse the promotion of HREC apoptosis induced by high glucose as well. CONCLUSIONS: Consequently, our study implied that SRGN might serve as a promising biomarker with high specificity and sensitivity in the DR diagnosis and progression.

Dispersive Liquid-Liquid Microextraction Combined with Microwave Demulsification for Determination of FAME Residuals in Biodiesel Wastewater.

Biodiesel consists of various fatty acid methyl esters (FAMEs) that are mainly produced through transesterification of plant oil or animal fat. It is essential for biodiesel to be purified utmostly to meet its product standard before being traded, while the universal purification method has been water washing. However, water washing inevitably causes the residual of FAMEs in wastewater, which represents a loss of industrial profits. For the purpose of determination and monitoring of the FAME profile in wastewater, there is a necessity to develop a fast and reliable approach with small volume of sample in need. Hence, in this study, a combination of dispersive liquid-liquid microextraction (DLLME) and microwave demulsification is applied for the enrichment of residual FAMEs in water, followed by qualitative and quantitative analyses using gas chromatography-mass spectrometry. The results indicate that the optimal extractant in DLLME approach is toluene. And the optimal parameters are 20 mL of water sample, 80 µL of toluene as the extractant, 60 s of ultrasonic irradiation duration, 200 W of microwave power and 2 min of microwave irradiation duration. The standard curves and linear equations obtained with these conditions are used for the quantitative analysis of biodiesel wastewater, which reveals that there was 50.35 mg·L-1 of the total FAME residuals in wastewater. To the best of our knowledge, it is for the first time that the combined technique of DLLME and microwave demulsification is applied in determination of residual FAMEs in water samples. The proposed method corresponds to small volumes of sample and extractant and short analytical period. It also has the potential to be extended to the analysis of other water pollutants.

Microwave-assisted-demulsification dispersive liquid-liquid microextraction for the determination of triazole fungicides in water by gas chromatography with mass spectrometry.

A novel microwave-assisted-demulsification dispersive liquid-liquid microextraction technique was established for determination of three triazole fungicides in environmental water samples by gas chromatography with mass spectrometry. Importantly, microwave irradiation has been applied in demulsification to achieve the phase separation and enrichment of triazole fungicides in water samples successfully with low-density toluene as extractant. The experimental variables, including microwave power, microwave time, ultrasonic time, type and volume of extraction solvent, and effect of salting out were investigated. Under the optimized conditions, the method showed good linearity for myclobutanil, tebuconazole, and difenoconazole in the range of 1-100 µg/L. The limits of detection and the limits of quantification were within the range of 0.14-0.27 and 0.47-0.90 µg/L, respectively. The suitable enrichment factors for three triazole pesticides were in the range of 425-636. The recoveries were between 89.3 and 108.7%, and the relative standard deviations were from 5.4 to 8.6%. Finally, environmental water samples were used to verify the applicability of the proposed method for analysis of triazole fungicides targets. It can be concluded that the developed microwave-assisted-demulsification dispersive liquid-liquid microextraction gas chromatography with mass spectrometry method was a rapid, efficient, reliable, and environmental friendly way for analysis of triazole fungicides in water.

Inhibition of migration and invasion by berberine via inactivation of PI3K/Akt and p38 in human retinoblastoma cell line.

BACKGROUND: As a clinically important natural isoquinoline alkaloid, berberine has been reported to possess various pharmacological effects. OBJECTIVES: This study was aimed to investigate the effect of berberine on cell migration and invasion in human retinoblastoma (Rb) cells. MATERIAL AND METHODS: The cytotoxicity of berberine was estimated by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. After being stimulated with berberine under various concentrations, the cell migration and invasion were evaluated by transwell assay. Then, the expression levels of epithelial-mesenchymal transition (EMT) markers were determined by quantitative reverse transcription PCR (qRT-PCR) and western blot analysis. Furthermore, the phosphorylation levels of protein kinase B (Akt) and p38 were detected by western blot analysis. Finally, the effect of phosphatidylinositol-3-kinase (PI3K) and p38 inhibitors on cell migration and invasion was estimated by transwell assay. Untreated cells acted as control for all the experiments. RESULTS: The concentrations of berberine for further studies were controlled in a range of 0 to 100 µM. The cell migration and invasion were both suppressed by berberine in a dose-dependent manner compared to the control (p < 0.05 or p < 0.001). Berberine remarkably down-regulated expression of E-cadherin and up-regulated expression of vimentin and α-SMA compared to the control (p < 0.01 or p < 0.001). Furthermore, the phosphorylation levels of Akt and p38 were both down-regulated by berberine in comparison to the control. Furthermore, the addition of berberine accompanied by LY294002 or SB203580 significantly suppressed cell migration and invasion compared to the addition of berberine alone (p < 0.05). CONCLUSIONS: Berberine suppressed cell migration and invasion via inactivation of PI3K/Akt and p38.

Pd-Catalyzed Ligand-Free Synthesis of Arylated Heteroaromatics by Coupling of N-Heteroaromatic Bromides with Iodobenzene Diacetate, Iodosobenzene, or Diphenyliodonium Salts.

An efficient method for synthesizing arylated heteroaromatics has been reported via Pd-catalyzed ligand-free cross-coupling of N-heteroaromatic bromides with iodine(III) reagents under mild conditions. Iodobenzene diacetate, iodosobenzene, and diphenyliodonium salts act as ideal arylated sources in this reaction, producing bioactive aromatic-substituted pyridines and quinolines in moderate to high yields.