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The first organocatalytic asymmetric synthesis of an advanced intermediate of (+)-sarain A was achieved. This approach featured the employment of an organocatalytic asymmetric Michael addition reaction and a nitrogen-to-carbon chirality transfer to forge three chiral centers, as well as a catalytic hydrosilylation for the chemoselective reduction of a key lactam intermediate. The tricyclic intermediate contained all the required functionalities for elaborating into (+)-sarain A.
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The combination of transition-metal catalysis and organocatalysis increasingly offers chemists opportunities to realize diverse unprecedented chemical transformations. By combining iridium with chiral thiourea catalysis, direct enantioselective reductive cyanation and phosphonylation of secondary amides have been accomplished for the first time for the synthesis of enantioenriched chiral α-aminonitriles and α-aminophosphonates. The protocol is highly efficient and enantioselective, providing a novel route to the synthesis of optically active α-functionalized amines from the simple, readily available feedstocks. In addition, the reactions are scalable and the thiourea catalyst can be recycled and reused.
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In the version of this article initially published, in Volume 21, issue 3, the first affiliation (affiliation number 1) was incorrectly stated as "Department of Pathology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey". The correct affiliation is "Department of Oncology, Shaoxing People's Hospital ,Shaoxing Hospital of Zhejiang University, Shaoxing 312000,China'. This error appeared only in the PubMed database and not in the print form of the Journal.
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PURPOSE: To investigate the in vitro and in vivo antitumor effects of amarogentin in SNU-16 human gastric cancer cells as well as in nude mice xenograft model. The effects of this compound on cell apoptosis, cell cycle phase distribution and PI3K/Akt and m-TOR signalling pathways were also studied in detail. METHODS: MTT assay was used to study the effect of amarogentin on SNU-16 cell viability while clonogenic assay indicated the effect of the compound on colony formation tendency of these cells. Phase contrast microscopy revealed the effect on cellular morphology while flow cytometry was engaged to study the effects on cell apoptosis and cell cycle arrest. SNU-16 cancer cells were subcutaneously inoculated into nude mice to investigate the in vivo antitumor effects of amarogentin. RESULTS: Amarogentin induced potent, dose-dependent as well as time-dependent cytotoxic effects on the growth of SNU-16 human gastric cancer cells. Amarogentin also inhibited the colony forming capability of these tumor cells and its treatment led to morphological alterations in these cells in which the cells became withered and rounded, detached from one another and adopted irregular shapes while floating freely in the culture medium. In comparison to untreated control cells, the amarogentin treated cells with 10, 50 and 75 µM exhibited 32.5, 45.2 and 57.1 % apoptotic cells, respectively. Amarogentin induced potent and dose-dependent G2/M cell cycle arrest in these cells and led to downregulation of m-TOR, p-PI3K, PI3K, p-Akt and Akt and upregulation of cyclin D1 and cyclin E protein expressions. The tumor tissues obtained from the amarogentin-treated mice were much smaller than the tumor tissues derived from the control group. CONCLUSION: Amarogentin exerts potent in vitro and in vivo antitumor effects in SNU-16 cell model as well as in nude mice xenograft model. These antitumor effects were found to be mediated through apoptosis induction, G2/M cell cycle arrest and downregulation of PI3K/Akt/m-TOR signalling pathways.
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Apoptose/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Iridoides/farmacologia , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Neoplasias Gástricas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy for patients with locally advanced unresectable extrahepatic cholangiocarcinoma. METHODS: Thirty-eight patients with locally advanced unresectable extrahepatic cholangiocarcinoma admitted in Shaoxing People's Hospital from February 2007 to February 2012 were enrolled in the study. They were randomized into sequential chemoradiotherapy (n=19) or concurrent chemoradiotherapy group (n=19). All patients were treated with intensity modulated radiation therapy (IMRT). Patients in concurrent chemoradiotherapy group received the regimen of gemcitabine plus oxaliplatin. Tumor response and adverse effects were observed periodically. The primary end points were disease progression-free survival (PFS) and overall survival (OS). RESULTS: The response rates of sequential chemoradiotherapy and concurrent chemoradiotherapy groups were 42.1% (8/19) and 63.2% (12/19). The disease control rates of them were 78.9% (15/19) and 84.2% (16/19))ï¼ respectively. The median PFS of sequential chemoradiotherapy group and concurrent chemoradiotherapy group was 8.3 (95%CI: 7.6-9.0) and 10.4 months (95%CI: 9.4-11.4, P=0.037), and the median OS in two groups were 14.2 (95%CI: 12.6-15.8) and 15.6 months (95%CI: 14.2-17.0, P=0.095), respectively. The major adverse reactions were controllable hematology toxicity and gastrointestinal reaction. There was no significant difference in incidence of adverse reactions between two groups (P>0.05). CONCLUSION: Sequential chemoradiotherapy and concurrent chemoradiotherapy may improve PFS and OS in patients with locally advanced unresectable extrahepatic cholangiocarcinoma, and both are well-tolerated. In addition, concurrent chemoradiotherapy might provide additional PFS benefit and would be preferable.
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Neoplasias dos Ductos Biliares/terapia , Quimiorradioterapia , Colangiocarcinoma/terapia , Ductos Biliares Intra-Hepáticos/patologia , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Humanos , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina , Taxa de Sobrevida , GencitabinaRESUMO
The design simulation and fabrication results of a bandpass filter based on micro-electro-mechanical system (MEMS) switches are presented in this paper. The MEMS filter element consists of a MEMS capacitance switch and two resonant rings that are fixed onto coplanar waveguide lines through anchor points. The micromachine characteristics of the filter could be optimized to change the center frequency from 8.5 to 12 GHz by improving the geometrical parameters; other electrical parameters of the filter, such as stopband rejection, insertion loss, and return loss at each center frequency, were simulated and calculated. In order to evaluate the MEMS filter design methodology, a filter working at 10.5 GHz fabricated with an aluminum top electrode was used, and it displayed a low insertion loss of 1.12 dB and a high stopband rejection of 28.3 dB. Compared with the simulation results, these proposed filter showed better electrical performance. Our results demonstrated that the filter with the integrated RF MEMS switch not only provides the benefit of reduced size compared with a traditional filter, but also improves stopband rejection, insertion loss, and return loss.
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The catalytic reductive condensation reactions of tertiary amides with active methylene compounds leading to multifunctionalized non-N-containing products is described. The reactions proceed through sequential iridium-catalyzed hydrosilylation of the amides followed by acid-mediated condensation with the active methylene compounds. This scalable method is broad in scope and shows remarkable chemoselectivity for the amide group in the presence of several sensitive or even more reactive functionalities such as ester, cyano, nitro, silyl dienol ether, and ketone.
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OBJECTIVE: To reveal the neuroprotective effect and the underlying mechanisms of a mixture of the main components of Panax notoginseng saponins (TSPN) on cerebral ischemia-reperfusion injury and oxygen-glucose deprivation/reoxygenation (OGD/R) of cultured cortical neurons. METHODS: The neuroprotective effect of TSPN was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry and live/dead cell assays. The morphology of dendrites was detected by immunofluorescence. Middle cerebral artery occlusion (MCAO) was developed in rats as a model of cerebral ischemia-reperfusion. The neuroprotective effect of TSPN was evaluated by neurological scoring, tail suspension test, 2,3,5-triphenyltetrazolium chloride (TTC) and Nissl stainings. Western blot analysis, immunohistochemistry and immunofluorescence were used to measure the changes in the Akt/mammalian target of rapamycin (mTOR) signaling pathway. RESULTS: MTT showed that TSPN (50, 25 and 12.5 µ g/mL) protected cortical neurons after OGD/R treatment (P<0.01 or P<0.05). Flow cytometry and live/dead cell assays indicated that 25 µ g/mL TSPN decreased neuronal apoptosis (P<0.05), and immunofluorescence showed that 25 µ g/mL TSPN restored the dendritic morphology of damaged neurons (P<0.05). Moreover, 12.5 µ g/mL TSPN downregulated the expression of Beclin-1, Cleaved-caspase 3 and LC3B-II/LC3B-I, and upregulated the levels of phosphorylated (p)-Akt and p-mTOR (P<0.01 or P<0.05). In the MCAO model, 50 µ g/mL TSPN improved defective neurological behavior and reduced infarct volume (P<0.05). Moreover, the expression of Beclin-1 and LC3B in cerebral ischemic penumbra was downregulated after 50 µ g/mL TSPN treatment, whereas the p-mTOR level was upregulated (P<0.05 or P<0.01). CONCLUSION: TSPN promoted neuronal survival and protected dendrite integrity after OGD/R and had a potential therapeutic effect by alleviating neurological deficits and reversing neuronal loss. TSPN promoted p-mTOR and inhibited Beclin-1 to alleviate ischemic damage, which may be the mechanism that underlies the neuroprotective activity of TSPN.
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Isquemia Encefálica , Fármacos Neuroprotetores , Panax notoginseng , Traumatismo por Reperfusão , Saponinas , Animais , Proteína Beclina-1 , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Glucose , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/tratamento farmacológico , Mamíferos/metabolismo , Neuroproteção , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Oxigênio , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Traumatismo por Reperfusão/metabolismo , Saponinas/farmacologia , Saponinas/uso terapêutico , Serina-Treonina Quinases TOR/metabolismoRESUMO
The Editors of JBUON issue an Expression of Concern to 'Amarogentin secoiridoid inhibits in vivo cancer cell growth in xenograft mice model and induces apoptosis in human gastric cancer cells (SNU-16) through G2/M cell cycle arrest and PI3K/Akt signalling pathway', by Jian-Guo Zhao, Ling Zhang, Xiao-Jun Xiang, Feng Yu, Wan-li Ye, Dong-Ping Wu, Jian-Fang Wang, Jian-Ping Xiong, JBUON 2016;21(3):609-617; PMID:27569081. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.
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We disclose that following activation with trifluoromethanesulfonyl anhydride, secondary N-arylamides undergo smooth intermolecular dehydrative [4 + 2] aza-annulation with alkenes under mild conditions to give 3,4-dihydroquinolines, amenable to further functionalization. Meanwhile, conditions have been established to allow divergent one pot synthesis of tetrahydroquinolines and quinolines as well as tricyclic analogues from N-arylamides.
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OBJECTIVE: To investigate the expression of NOB1 in colorectal cancer and its relationship with the clinicopathological characteristics. METHODS: The expression of NOB1 was detected immunohistochemically in 60 primary colorectal cancer tissues and the corresponding normal epithelia (3.0 cm away from the cancer margin) and graded according to the staining intensity and the percentage of positively stained tumor cells. RESULTS: NOB1 overexpression was found in 32 of the 60 cases (53.3%). NOB1 overexpression in the adjacent non-neoplastic tissues was found in 10 of the cases (16.7%), a rate significantly lower than that in the cancer tissues (P<0.05). NOB1 expression was not correlated to such tumor characteristics as gender, age, histological differentiation grade, depth of invasion and lymph node metastasis (P>0.05). CONCLUSIONS: NOB1 expression is higher in colorectal cancer than in normal colorectal tissues, suggesting its involvement in the tumorigenesis and progression of colorectal cancer.
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Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Proteínas Nucleares/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neoplasias Colorretais/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Proteínas de Ligação a RNA/genéticaRESUMO
Severe water erosion in the key loess hilly area is affected by the coupling role of rainfall and earth surface features. In this study, rainfall simulation techniques at the micro-plot scale (1.2 m x 1.2 m; 2 m x 1.2 m) was used as the basic measures, the relations between rainfall depth, intensity and runoff-erosion under different plant morphology features as well as micro-landscape positions were quantified and analyzed. Several key findings were captured. Firstly, rainfall depth and intensity both affected water erosion significantly, while the role of the rainfall intensity was more important than that of the depth. Secondly, a strong negative correlation was found between the antecedent soil moisture content and the generation timing of surface runoff, while water erosion had a positive relation with the antecedent soil moisture. Thirdly, different plant morphology and micro-landscape positions of shrub plant (seabuckthorn) played different roles leading to different rates of surface runoff and soil erosion. Dominated by a rainfall intensity ranging from 50 to 60 mm x h(-1), runoff coefficient in those micro-plots covered by seabuckthorn was about 5%-8%, and changed into 25%, 45% and 63% in grassland-plots, bared plots covered by biological-crust and bared plots without any coverage, respectively. Fourthly, the specific landscape position of seabuckthorn in the plots was also found to play a key role in affecting water erosion processes, and seabuckthorn at the lower landscape position, rather than the upper and middle position, played a better buffering role in reducing runoff and soil loss.
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Altitude , Conservação dos Recursos Naturais/métodos , Chuva , Solo , Movimentos da Água , China , Simulação por Computador , Monitoramento Ambiental/métodos , Hippophae/crescimento & desenvolvimento , Poaceae/crescimento & desenvolvimentoRESUMO
Soil crusts are distributed extensively in the Chinese Loess Plateau and play key roles in surface hydrological processes. In this study, a typical loess hilly region in Anjiagou catchment, Dingxi city, Gansu province was selected as the study region, and soil crusts in the catchment were investigated. Then, the hydrological effect of soil crusts was studied by using multi-sampling and hydrological monitoring experiments. Several key results were shown as follows. Firstly, compared with bared soil without crust cover, soil crusts can greatly reduce the bulk density, improve the porosity of soil, and raise the holding capacity of soil moisture which ranges from 1.4 to 1.9 times of that of bared soil. Secondly, the role of soil crust on rainfall interception was very significant. Moss crust was found to be strongest on rainfall interception, followed by synantectic crusts and lichen crusts. Bared soil without covering crusts was poorest in resisting rainfall splash. Thirdly, hydrological simulation experiments indicate that soil crusts play a certain positive role in promoting the water infiltration capacity, and the mean infiltration rate of the crusted soil was 2 times higher than that of the no-crust covered soils. While the accumulated infiltrated water amounts was also far higher than that of the bared soil.
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Cianobactérias/metabolismo , Ecossistema , Solo/química , Água/análise , Altitude , China , Hidrologia , Líquens/metabolismo , Microbiologia do SoloRESUMO
A phase II clinical trial was performed to evaluate the efficacy and safety of gefitinib on pretreated Chinese female non-small-cell lung cancer (NSCLC) patients. Chinese female patients with locally advanced or metastatic NSCLC who failed at least one platinum-based chemotherapy received gefitinib monotherapy (250 mg/day) between April 2002 and January 2010. The primary endpoint was overall response rate (ORR), and secondary endpoints were overall survival (OS) and progression-free survival (PFS). Of the 40 evaluable female patients, the ORR was 62.5%. All patients have responded with one (2.5%) complete response, 24 (60%) partial response, 12 (30%) stable disease, and 3 (7.5%) progressive disease. The OS and PFS were 20 months (95% CI: 11.9-28 months) and 13 months (95% CI: 8.0-17.9 months), respectively. Survival (OS and PFS) were longer in patients with good performance status and in patients older than 65 years (P < 0.05). The most frequently observed toxicities were rash/dry skin (80%), diarrhea (42.5%), and vomiting/anorexia (32.5%). Four patients developed grade 3 toxicities (rash and diarrhea) but did not require either dose reduction or discontinuation. Gefitinib is a highly effective and well-tolerated agent for Chinese women with pretreated advanced NSCLC.