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[This corrects the article DOI: 10.1371/journal.pone.0243082.].[This corrects the article DOI: 10.1371/journal.pone.0243082.].

In this paper, we report the synthesis of spirocyclopropane-containing 4H-pyrazolo[1,5-a]indoles 6a–e via alkylative dearomatization and intramolecular N-imination of indole–O-(methylsulfonyl)oxime 11. Starting materials tryptophol (7) and 2-bromocyclopetanone (8) were reacted in the presence of HBF[sub.4]·OEt[sub.2], providing 1,2,3,5,6,11-hexahydrocyclopenta[2,3]oxepino[4,5-b]indole (9) in a 63% yield. Compound 9 was reacted with hydroxylamine hydrochloride to afford oxime 10 (65% yield), which was subsequently bis-methanesulfonated to form 11 in a 85% yield. Heating 11 with various alcohols in the presence of N,N-diisopropylethylamine (DIPEA) triggered the alkylative dearomatization and intramolecular N-imination, forming the spirocyclopropane and 4H-pyrazolo[1,5-a]indole structures in the targets 6a–e with 67–84% yields.

CACNA1C encodes the pore-forming α1C subunit of the L-type Ca[sup.2+] channel, Cav1.2. Mutations and polymorphisms of the gene are associated with neuropsychiatric and cardiac disease. Haploinsufficient Cacna1c+/− rats represent a recently developed model with a behavioral phenotype, but its cardiac phenotype is unknown. Here, we unraveled the cardiac phenotype of Cacna1c+/− rats with a main focus on cellular Ca[sup.2+] handling mechanisms. Under basal conditions, isolated ventricular Cacna1c+/− myocytes exhibited unaltered L-type Ca[sup.2+] current, Ca[sup.2+] transients (CaTs), sarcoplasmic reticulum (SR) Ca[sup.2+] load, fractional release, and sarcomere shortenings. However, immunoblotting of left ventricular (LV) tissue revealed reduced expression of Cav1.2, increased expression of SERCA2a and NCX, and augmented phosphorylation of RyR2 (at S2808) in Cacna1c+/− rats. The β-adrenergic agonist isoprenaline increased amplitude and accelerated decay of CaTs and sarcomere shortenings in both Cacna1c+/− and WT myocytes. However, the isoprenaline effect on CaT amplitude and fractional shortening (but not CaT decay) was impaired in Cacna1c+/− myocytes exhibiting both reduced potency and efficacy. Moreover, sarcolemmal Ca[sup.2+] influx and fractional SR Ca[sup.2+] release after treatment with isoprenaline were smaller in Cacna1c+/− than in WT myocytes. In Langendorff-perfused hearts, the isoprenaline-induced increase in RyR2 phosphorylation at S2808 and S2814 was attenuated in Cacna1c+/− compared to WT hearts. Despite unaltered CaTs and sarcomere shortenings, Cacna1c+/− myocytes display remodeling of Ca[sup.2+] handling proteins under basal conditions. Mimicking sympathetic stress with isoprenaline unmasks an impaired ability to stimulate Ca[sup.2+] influx, SR Ca[sup.2+] release, and CaTs caused, in part, by reduced phosphorylation reserve of RyR2 in Cacna1c+/− cardiomyocytes.

A regioselective one-pot method for the synthesis of 1-ethyl 2,4-dihydrochromene[3,4-c]pyrroles in 63–94% yields from available 2-phenyl-, 2-trifluoro(trichloro)methyl- or 2-phenyl-2-(trifluoromethyl)-3-nitro-2H-chromenes and ethyl isocyanoacetate through the Barton–Zard reaction in ethanol at reflux for 0.5 h, using K[sub.2]CO[sub.3] as a base, has been developed.

Fusarium basal rot of onions causes large losses during storage of commercial production of onion bulbs, which in turn adversely affects the food market situation in the off-season period. There are no data on the composition of Fusarium spp., which causes onion basal rot in the Russian Federation. Therefore, our research was aimed at Fusarium spp. causing onion basal rot in the Moscow Region of the Russian Federation and studying the pathogenicity of these species for the host plant. We studied 20 isolates of Fusarium spp. collected from affected mature bulbs and seed bulbs. Species identification of the isolates was carried out using analysis of the nucleotide sequences of the three genetic loci ITS, tef1 and rpb2, as well as was based on the macro- and micromorphological characteristics of these isolates. As a result, the species F. annulatum (F. fujikuroi species complex), F. oxysporum (F. oxysporum species complex), F. acuminatum (F. tricinctum species complex) and F. solani (F. solani species complex) were identified to involve in the pathogenesis of Fusarium basal rot. We have shown for the first time that the species F. annulatum and F. acuminatum are highly aggressive and capable of causing onion basal rot. The predominant species were F. annulatum and F. oxysporum. The proportion of these species in the total number of analyzed isolates was 60% and 25%, respectively. The largest proportion (33%) of highly aggressive on mature bulbs isolates was found in the species F. annulatum. The data obtained provide practical insights for developing strategies to manage Fusarium fungi responsible for onion basal rot Moscow Region of the Russian Federation. In addition, data about species composition and aggressive isolates may be used in onion breeding for resistance to Fusarium basal rot.

Background Activated neutrophils can create structures known as neutrophil extracellular traps (NETs/ETs) consisting of nuclear components and granules. The ETOsis phenomenon leads to activating the platelets and coagulation factors. Accordingly, coagulation and fibrinolysis can be promoted. Resveratrol (RSV) is a botanical antioxidant with anti-inflammatory and anti-leukemia effects. The present study was conducted to assess the effect of RSV on the occurrence of ETOsis in the NB4 cell line. Methods Human acute promyelocytic leukemia cell line (NB4) were stimulated and treated by lipopolysaccharides (LPS) and RSV, respectively. Sytox green and a fluorescent microscope were used to assess the ETOsis in NB4 cells. Furthermore, the expression level of peptidylarginine deiminase 4 (PAD4) gene and the occurrence of ETOsis in NB4 cells were evaluated by real-time PCR and flow cytometry, respectively. Moreover, an enzyme-linked immunosorbent assay (ELISA) kit was utilized to measure tumor necrosis factor-[alpha] (TNF-[alpha]) cytokine. Results Following treatment with RSV, a significant decrease in PAD4 gene expression and TNF-[alpha] cytokine concentration in the supernatant of NB4 cell line culture medium was observed. Besides, the amount of ETOsis in the NB4 cells treated with LPS and RSV decreased. Conclusion The findings demonstrated that RSV can inhibit the process of ETOsis in NB4 cells. By inhibiting the process of ETOsis, RSV may be able to reduce the bleeding and, consequently, the failure after treatment in acute promyelocytic leukemia (APL) patients.

Activated neutrophils can create structures known as neutrophil extracellular traps (NETs/ETs) consisting of nuclear components and granules. The ETOsis phenomenon leads to activating the platelets and coagulation factors. Accordingly, coagulation and fibrinolysis can be promoted. Resveratrol (RSV) is a botanical antioxidant with anti-inflammatory and anti-leukemia effects. The present study was conducted to assess the effect of RSV on the occurrence of ETOsis in the NB4 cell line. Human acute promyelocytic leukemia cell line (NB4) were stimulated and treated by lipopolysaccharides (LPS) and RSV, respectively. Sytox green and a fluorescent microscope were used to assess the ETOsis in NB4 cells. Furthermore, the expression level of peptidylarginine deiminase 4 (PAD4) gene and the occurrence of ETOsis in NB4 cells were evaluated by real-time PCR and flow cytometry, respectively. Moreover, an enzyme-linked immunosorbent assay (ELISA) kit was utilized to measure tumor necrosis factor-[alpha] (TNF-[alpha]) cytokine. Following treatment with RSV, a significant decrease in PAD4 gene expression and TNF-[alpha] cytokine concentration in the supernatant of NB4 cell line culture medium was observed. Besides, the amount of ETOsis in the NB4 cells treated with LPS and RSV decreased. The findings demonstrated that RSV can inhibit the process of ETOsis in NB4 cells. By inhibiting the process of ETOsis, RSV may be able to reduce the bleeding and, consequently, the failure after treatment in acute promyelocytic leukemia (APL) patients.

In the Dinaric Karst, Alpioniscus (Illyrionethes) is the taxon with the largest number of troglobiotic species (19), one of which is new and described here: A. busljetai sp. nov., found in two caves in the coastal area of North Dalmatia. Both caves are threatened by human activities (IUCN threats 1.1, 9.1.1).