Modular Assembly of Pyrrolo[3,4-c]isoquinolines through Rh-Catalyzed Cascade C-H Activation/Annulation of O-Methyl Aryloximes with Maleimides.

An efficient and practical strategy for the construction of pyrrolo[3,4-c]isoquinolines via Rh(III)-catalyzed cascade C-H activation and subsequential annulation process from easily available O-methyl aryloximes and maleimides has been disclosed. This facile protocol does not require any inert atmosphere protection with good efficiency in a low loading of catalyst and exhibits good functional group tolerance and broad substrate scope. Notably, the as-prepared products show potential photophysical properties.

A rhodium-catalyzed cascade C-H activation/annulation strategy for the expeditious assembly of pyrrolidinedione-fused 1,2-benzothiazines.

A cascade annulation strategy triggered by rhodium(III)-catalyzed C-H activation has been reported for the expeditious assembly of pyrrolidinedione-fused 1,2-benzothiazines from free NH-sulfoximines with maleimides under mild conditions. Without the need for inert atmosphere protection, a broad range of sulfoximines with maleimides were well tolerated, producing diverse fused-thiazine derivatives in moderate to good yields. Additionally, the late-stage transformation of the target product demonstrated the potential synthetic value of this protocol.

Neutrophil extracellular traps contribute to tissue plasminogen activator resistance in acute ischemic stroke.

Circulating neutrophil extracellular traps (NETs) resistant to t-PA have not been studied completely although NETs in thrombi may contribute to tissue plasminogen activator (t-PA) resistance. This research intended to elucidate whether circulating NETs are associated with t-PA resistance and the underlying mechanism. The levels of NETs were detected in the circulating neutrophils, ischemic brain tissue of acute ischemic stroke (AIS) patients, and transient middle cerebral artery occlusion (tMCAO) models. NET formation in blood, thrombi, and ischemic brain tissue of mice were analyzed by immunofluorescence. Exposed phosphatidylserine (PS) was assessed using flow cytometry and confocal microscopy. Procoagulant activity (PCA) was evaluated using fibrin formation assays, thrombin, and purified coagulation complex. The plasma levels of NETs in AIS patients were significantly higher than those in healthy individuals. After thrombolysis, a significant increase was noted in NET markers in no-improvement patients, while the changes in improvement patients were not significant. Importantly, NETs were decorated with von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1) in the blood and thrombi, which could reverse the fibrinolytic effects. In addition, NETs activated platelets (PLTs) and endothelial cells (ECs), stimulating a procoagulant phenotype and facilitating vWF and PAI-1 release. DNase I, activated protein C (APC), and sivelestat markedly inhibited these effects. Furthermore, targeting NETs protected mice from tMCAO-induced cerebral ischemia, possibly by regulating vWF and PAI-1. In summary, NETs may contribute to t-PA resistance in AIS through activation of PLTs and ECs. Strategies against NETs may present a promising therapeutic approach to improve the thrombolysis efficiency of t-PA in AIS patients.

Neutrophil extracellular traps enhance procoagulant activity and thrombotic tendency in patients with obstructive jaundice.

BACKGROUND & AIMS: Patients with obstructive jaundice (OJ) are considered to be prothrombotic with increased risk of thromboembolism complications. The role of neutrophil extracellular traps (NETs) in procoagulant activity (PCA) and thrombosis risk in patients with OJ is unclear. In this study, we investigated NETs formation in OJ patients and the role of elevated unconjugated bilirubin (UCB) in inducing NETs, resulting in enhanced PCA and endothelial injury. METHODS: NETs of OJ patients and healthy controls were measured. NETs PCA was assessed via coagulation time (CT), fibrin formation and purified coagulation complex production assays. Visualization of NETs and mitochondrial reactive oxygen species (MitoROS) were performed with a fluorescence microscope. We further used confocal microscopy to quantify the exposure of phosphatidylserine (PS), fibrin strands and FVa/Xa on Human umbilical vein endothelial cells (HUVECs). RESULTS: Assessment of NETs components levels revealed greater NETs production in OJ patients than in healthy controls. Importantly, OJ-NETs were responsible for enhanced PCA. UCB induced NETs formation via MitoROS accumulation and mitochondrial mobilization. HUVECs cocultured with OJ NETs lost their cell-cell junctions and consequently converted to a procoagulant phenotype. The PCA was attenuated by using DNase I alone or in combination with lactadherin. CONCLUSIONS: Our results suggest that UCB-induced NETs play a prominent role in promoting the hypercoagulable and prothrombotic state in OJ patients. The increased MitoROS accumulation in neutrophils initiated NETosis. NETs are promising targets for indicating or improving coagulation disorders in OJ patients.

Rh(III)-Catalyzed Cascade Nucleophilic Addition/Annulation of 2-Diazo-1,3-diketones with 1,3-Dicarbonyl Compounds To Access 6,7-Dihydrobenzofuran-4(5H)-ones.

A Rh(III)-catalyzed cascade nucleophilic addition/intramolecular annulation of 2-diazo-1,3-diketones with 1,3-dicarbonyl compounds (e.g., 1,3-diketones and ß-keto esters) is achieved to afford 6,7-dihydrobenzofuran-4(5H)-ones in up to 91% yields. Notably, a wide range of substrates and functional groups were well-tolerated under the optimized reaction conditions to give desired products in moderate to excellent yields with release of N2 and H2O as byproducts. Moreover, the method described is scalable and adaptable to late-stage functionalization.

Synthesis of unsymmetrical urea derivatives via one-pot sequential three-component reactions of cyclic 2-diazo-1,3-diketones, carbodiimides, and 1,2-dihaloethanes.

A novel and efficient multicomponent reaction of cyclic 2-diazo-1,3-diketones, carbodiimides, and 1,2-dihaloethanes has been developed, and it leads to unsymmetrical urea derivatives with good yields in a single operation. This transformation involves the cascade formation of C-X (X = Cl, Br, I), C-N and C[double bond, length as m-dash]O bonds through halogenation, nucleophilic addition, ring-opening, and enol-ketone tautomerization processes. This protocol is step- and atom-economical; 1,2-dihaloethane was used as an easily available halogenated reagent, and it is amenable to different functional groups.

Cartilage regeneration of adipose-derived stem cells in a hybrid scaffold from fibrin-modified PLGA.

Adipose-derived stem cells (ASCs) appear to be a useful stem cell population, which has been shown to possess multipotentiality. The aim of this study was to evaluate the utility of ASCs in tissue-engineered cartilage using a hybrid scaffold from fibrin-modified PLGA scaffold. ASCs were isolated from rabbit adipose tissue. The PLGA scaffold was prepared by low-temperature deposition technology and the hybrid scaffold was fabricated by a freeze-drying method. When ASCs were seeded onto fibrin-modified PLGA scaffold in vitro, enhanced cellular viability was observed compared to unmodified PLGA scaffold. The analysis of proteoglycan and collagen II revealed that fibrin-modified scaffold succeeded in inducing ASCs to differentiate into chondrocytes in vitro. A preliminary study on cartilage regeneration was also performed in vivo. Observation of histology and immunoblotting demonstrated that ASCs containing the hybrid scaffold promoted cartilage regeneration in the defects of articular cartilage much better than other groups. These results indicated that ASCs containing the hybrid scaffold are a more effective way to potentially enhance articular cartilage regeneration.

Ru(II)/Ir(III)-Catalyzed C-H Bond Activation/Annulation of Cyclic Amides with 1,3-Diketone-2-diazo Compounds: Facile Access to 8H-Isoquinolino[1,2-b]quinazolin-8-ones and Phthalazino[2,3-a]cinnoline-8,13-diones.

Efficient access to 8H-isoquinolino[1,2-b]quinazolin-8-ones and phthalazino[2,3-a]cinnoline-8,13-diones through cyclic amide-directed Ru(II)/Ir(III)-catalyzed C-H bond activation, has been developed. Consecutive C-H bond activation, carbene insertion, and condensation annulation processes were realized, affording 8H-isoquinolino[1,2-b]quinazolin-8-one and phthalazino[2,3-a]cinnoline-8,13-dione derivatives in good-to-excellent yields under mild conditions, with H2O and N2 being generated as the only byproducts.

[Trends of microalgal biotechnology: a view from bibliometrics].

Microalgae is a single-cell organism with the characteristics of high light energy utilization rate, fast growth rate, high-value bioactive components and high energy material content. Therefore, microalgae has broad application prospects in food, feed, bioenergy, carbon sequestration, wastewater treatment and other fields. In this article, the microalgae biotechnology development in recent years were fully consulted, through analysis from the literature and patent. The progress of microalgal biotechnology at home and abroad is compared and discussed. Furthermore, the project layout, important achievements and development bottlenecks of microalgae biotechnology in our country were also summarized. At last, future development directions of microalgae biotechnology were discussed.

Medium screening and optimization for photoautotrophic culture of Chlorella pyrenoidosa with high lipid productivity indoors and outdoors.

Medium screening and optimization is one of the most important preconditions for photoautotrophic cultivation of microalgae. Although, it has been widely conducted indoors, little work performed outdoors. There are enormous differences between indoor and outdoor conditions, especially for light intensity, temperature and their diurnal or annual fluctuations, which would greatly influence microalgae growth. No data shows whether the differences would lead to different results on medium screening and optimization. In present study, medium screening for the photoautotrophic cultivation of Chlorella pyrenoidosa was carried out indoors and outdoors firstly, and then the selected medium was optimized. The results showed that F-Si medium is the optimum both under indoor and outdoor conditions. Based on F-Si medium, nutrients were optimized as follows: NaNO3 500mgl(-1), NaH2PO4·2H2O 7.7mgl(-1) and FeCl3·6H2O 6.30mgl(-1). With the optimized medium, the biomass, lipid content and productivity were all significantly higher both indoors and outdoors.