A DMAP‐N‐oxide, featuring an α‐amino acid as the chiral source, was developed, synthesized and applied in asymmetric Steglich rearrangement. A series of O‐acylated azlactones afforded C‐acylated ...azlactones possessing a quaternary stereocenter in high yields (up to 97 % yield) and excellent enantioselectivities (up to 97 % ee). Compared to the widespread use of pyridine nitrogen, which serves as the nucleophilic site in the asymmetric acyl transfer reaction, we discovered that chiral DMAP‐N‐oxides, in which the oxygen now acts as the nucleophilic site, are efficient acyl transfer catalysts. Our finding might open a new door for the development of chiral DMAP‐N‐oxides for asymmetric acyl transfer reactions.
A DMAP‐N‐oxide, featuring an α‐amino acid as the chiral source, was developed, synthesized and applied in asymmetric Steglich rearrangement. A series of O‐acylated azlactones afforded C‐acylated azlactones possessing a quaternary stereocenter in high yields (up to 97 % yield) and excellent enantioselectivities (up to 97 % ee).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Bifunctional chiral DMAP-N-oxides have been reported for the highly enantioselective rearrangement of indolyl carbonates. Using 2.5 mol% of chiral DMAP-N-oxide, diverse oxindoles containing an ...all-carbon quaternary stereocenter were obtained in excellent yields (up to 98% yield) with high enantioselectivities (up to 96% ee). Compared to the widespread use of chiral DMAP and isothiourea catalysts, in which the nitrogen atom serves as a nucleophilic site, we found that chiral DMAP-N-oxides, which utilize the oxygen atom as a nucleophilic site, were also efficient organocatalysts in this rearrangement.
Premature delivery is one of the direct factors that affect the early development and safety of infants. Its direct clinical manifestation is the change of uterine contraction intensity and ...frequency. Uterine Electrohysterography(EHG) signal collected from the abdomen of pregnant women can accurately and effectively reflect the uterine contraction, which has higher clinical application value than invasive monitoring technology such as intrauterine pressure catheter. Therefore, the research of fetal preterm birth recognition algorithm based on EHG is particularly important for perinatal fetal monitoring. We proposed a convolution neural network(CNN) based on EHG fetal preterm birth recognition algorithm, and a deep CNN model was constructed by combining the Gramian angular difference field(GADF) with the transfer learning technology. The structure of the model was optimized using the clinical measured term-preterm EHG database. The classification accuracy of 94.38% and
value of 97.11% were achieved. The experi
In this work, a double-gate-all-around tunneling field-effect transistor is proposed. The performance of the novel device is studied by numerical simulation. The results show that with a thinner body ...and an additional core gate, the novel device achieves a steeper subthreshold slope, less susceptibility to the short channel effect, higher on-state current, and larger on/off current ratio than the traditional gate-all-around tunneling field-effect transistor. The excellent performance makes the proposed structure more attractive to further dimension scaling.
Novel therapeutic strategies are urgently needed for patients with a delayed diagnosis of pancreatic ductal adenocarcinoma (PDAC) in order to improve their chances of survival. Recent studies have ...shown potent anti-neoplastic effects of curcumin and its analogues. In addition, the role of histone methyltransferases on cancer therapeutics has also been elucidated. However, the relationship between these two factors in the treatment of pancreatic cancer remains unknown. Our working hypothesis was that L48H37, a novel curcumin analog, has better efficacy in pancreatic cancer cell growth inhibition in the absence of histone-lysine N-methyltransferase 2D (KMT2D).
To determine the anti-cancer effects of L48H37 in PDAC, and the role of KMT2D on its therapeutic efficacy.
The viability and proliferation of primary (PANC-1 and MIA PaCa-2) and metastatic (SW1990 and ASPC-1) PDAC cell lines treated with L48H37 was determined by CCK8 and colony formation assay. Apoptosis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) levels, and cell cycle profile were determined by staining the cells with Annexin-V/7-AAD, JC-1, DCFH-DA, and PI respectively, as well as flow cytometric acquisition.
migration was assessed by the wound healing assay. The protein and mRNA levels of relevant factors were analyzed using Western blotting, immunofluorescence and real time-quantitative PCR. The in situ expression of KMT2D in both human PDAC and paired adjacent normal tissues was determined by immunohistochemistry.
tumor xenografts were established by injecting nude mice with PDAC cells. Bioinformatics analyses were also conducted using gene expression databases and TCGA.
L48H37 inhibited the proliferation and induced apoptosis in SW1990 and ASPC-1 cells in a dose- and time-dependent manner, while also reducing MMP, increasing ROS levels, arresting cell cycle at the G2/M stages and activating the endoplasmic reticulum (ER) stress-associated protein kinase RNA-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/activating transcription factor 4 (ATF4)/CHOP signaling pathway. Knocking down ATF4 significantly upregulated KMT2D in PDAC cells, and also decreased L48H37-induced apoptosis. Furthermore, silencing KMT2D in L48H37-treated cells significantly augmented apoptosis and the ER stress pathway, indicating that KMT2D depletion is essential for the anti-neoplastic effects of L48H37. Administering L48H37 to mice bearing tumors derived from control or KMT2D-knockdown PDAC cells significantly decreased the tumor burden. We also identified several differentially expressed genes in PDAC cell lines expressing very low levels of KMT2D that were functionally categorized into the extrinsic apoptotic signaling pathway. The KMT2D high- and low-expressing PDAC patients from the TCGA database showed similar survival rates,but higher KMT2D expression was associated with poor tumor grade in clinical and pathological analyses.
L48H37 exerts a potent anti-cancer effect in PDAC, which is augmented by KMT2D deficiency.
A DMAP‐N‐oxide, featuring an α‐amino acid as the chiral source, was developed, synthesized and applied in asymmetric Steglich rearrangement. A series of O‐acylated azlactones afforded C‐acylated ...azlactones possessing a quaternary stereocenter in high yields (up to 97 % yield) and excellent enantioselectivities (up to 97 % ee). Compared to the widespread use of pyridine nitrogen, which serves as the nucleophilic site in the asymmetric acyl transfer reaction, we discovered that chiral DMAP‐N‐oxides, in which the oxygen now acts as the nucleophilic site, are efficient acyl transfer catalysts. Our finding might open a new door for the development of chiral DMAP‐N‐oxides for asymmetric acyl transfer reactions.
Ein DMAP‐N‐Oxid mit einer α‐Aminosäure als chirale Quelle wurde entwickelt und für eine asymmetrische Steglich‐Umlagerung verwendet. Eine Reihe von O‐acylierten Azlactonen lieferte C‐acylierte Azlactone mit einem quartären Stereozentrum in hohen Ausbeuten (bis 97 %) und mit exzellenten Enantioselektivitäten (bis 97 % ee).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Tanshinone IIA (Tan IIA) is a Traditional Chinese Medicine commonly used in Asian and Western countries for the prevention and treatment of cardiovascular disorders, such as atherosclerosis. ...Endothelial dysfunction and associated inflammatory processes have a critical role in the development of atherosclerosis. Endothelial progenitor cells (EPCs) have been demonstrated to be involved in certain aspects of the endothelial repair process. The present study aimed to investigate the putative protective effects of Tan IIA on EPCs injured by tumor necrosis factor-α (TNF-α). The potential effects of Tan IIA on TNF-α-stimulated EPC proliferation, migration, adhesion, in vitro tube formation ability and paracrine activity were investigated in the current study. The results indicated that TNF-α impaired EPC proliferation, migration, adhesion capacity and vasculogenesis ability in vitro as well as promoted EPC secretion of inflammatory cytokines, including monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and soluble CD40 ligand (sCD40L). However, Tan IIA was able to reverse these effects. In conclusion, these findings demonstrated that Tan IIA may have the potential to protect EPCs against damage induced by TNF-α. Therefore, these results may provide evidence for the pharmacological basis of Tan IIA and its potential use in the prevention and treatment of early atherosclerosis associated with EPC and endothelial damage.
AIM：To determine the effects of curcumin,（-）-epigallocatechin-3-gallate （EGCG）,lovastatin,and their combinations on inhibition of esophageal cancer.METHODS：Esophageal cancer TE-8 and SKGT-4 cell ...lines were subjected to cell viability methyl thiazolyl tetrazolium and tumor cell invasion assays in vitro and tumor formation and growth in nude mouse xenografts with or without curcumin,EGCG and lovastatin treatment.Gene expression was detected using immunohistochemistry and Western blotting in tumor cell lines,tumor xenografts and human esophageal cancer tissues,respectively.RESULTS：These drugs individually or in combinations significantly reduced the viability and invasion capacity of esophageal cancer cells in vitro.Molecularly,these three agents reduced the expression of phosphorylated extracellular-signal-regulated kinases （Erk1/2）,c-Jun and cyclooxygenase-2 （COX-2）,but activated caspase 3 in esophageal cancer cells.The nude mouse xenograft assay showed that EGCG and the combinations of curcumin,EGCG and lovastatin suppressed esophageal cancer cell growth and reduced the expression of Ki67,phosphorylated Erk1/2 and COX-2.The expression of phosphorylated Erk1/2 and COX-2 in esophageal cancer tissue specimens was also analyzed using immunohistochemistry.The data demonstrated that 77 of 156 （49.4%） tumors expressed phosphorylated Erk1/2 and that 121 of 156 （77.6%） esophageal cancers expressed COX-2 protein.In particular,phosphorylated Erk1/2 was expressed in 23 of 50 （46%） cases of esophageal squamous cell carcinoma （SCC） and in 54 of 106 （50.9%） cases of adenocarcinoma,while COX-2 was expressed in 39 of 50 （78%） esophageal SCC and in 82 of 106 （77.4%） esophageal adenocarcinoma.CONCLUSION：The combinations of curcumin,EGCG and lovastatin were able to suppress esophageal cancer cell growth in vitro and in nude mouse xenografts,these drugs also inhibited phosphorylated Erk1/2,c-Jun and COX-2 expression.
Background： Spontaneous coronary artery dissection （SCAD） is a nonatherosclerotic but a rare and extremely dangerous clinical entity, it has a high prevalence in young female population with acute ...myocardial infarction （AMI）. The previous reports were restricted to other countries＇ population, but rare in China. Hence, this study aimed to focus on the characteristics of SCAD as a cause of young female AMI population in Jiangsu, China. Methods： This study enrolled young female AMI patients aged ≤50 years who underwent coronary angiography （CAG） and intracoronary imaging in our center between January 2013 and December 2016. Their clinical presentations, risk factors, and CAG characteristics were analyzed. Results： A total of 60 young l＇emale AMI （〈7 days） patients were enrolled. From their CAG and intracoronary imaging results, the prevalence of SCAD in young female AMI population was 35% （21/60）, the prevalence of coronary atherosclerostic heart disease was 65% （39/60）. In the SCAD group, 43% （9/21） presented with non-ST-elevation myocardial infarction （NSTEM1） and the remainder presenting as STEMI. SCAD usually occurred in a single vessel （20/21, 95%）, especially in left anterior descending artery （14/21, 67%）. Eighteen patients （18/21, 86%） underwent conservative treatment, whereas the remaining three patients （3/21, 14%） underwent percutaneous coronary intervention. Regarding the angiographic results of SCAD lesions, intramural hematoma was discriminated in 95% （20/21）, and Type I imaging was observed in 5% （1/21）, Type l I was observed in 67% （14/21）, and Type Ⅲ was 29% （6/21）. The average stenosis in the group was 76.9% - 20.6%, and the mean lesion length was 36.6 ± 8.6 ±m. Conclusions： SCAD has a high prevalence in young female AMI population in Jiangsu, China. Discriminating the cause of AMI in young female population is very important.
In this work, a double-gate-all-around tunneling field-effect transistor is proposed. The performance of the novel device is studied by numerical simulation. The results show that with a thinner body ...and an additional core gate, the novel device achieves a steeper subthreshold slope, less susceptibility to the short channel effect, higher on-state current, and larger on/off current ratio than the traditional gate-all-around tunneling field-effect transistor. The excellent performance makes the proposed structure more attractive to further dimension scaling.
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