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61.
Jin CH Krishnaiah M Sreenu D Subrahmanyam VB Rao KS Mohan AV Park CY Son JY Sheen YY Kim DK 《Bioorganic & medicinal chemistry letters》2011,21(20):6049-6053
A series of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazoles 14a-ae, 16a, 16b, and 21a-c has been prepared and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(4-methoxyphenyl)-3-(6-methylpyridin-2-yl)-1H-pyrazole-1-carbothioamide (14n) inhibited ALK5 phosphorylation with IC(50) value of 0.57 nM and showed 94% inhibition at 100 nM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct. 相似文献
62.
Sun Jae Kwon Hak Chul Jin Soohyun Lee Myung Hee Nam Joo Hee Chung Soon Il Kwon Choong-Min Ryu Ohkmae K. Park 《The Plant journal : for cell and molecular biology》2009,58(2):235-245
Systemic resistance is induced by necrotizing pathogenic microbes and non-pathogenic rhizobacteria and confers protection against a broad range of pathogens. Here we show that Arabidopsis GDSL LIPASE-LIKE 1 (GLIP1) plays an important role in plant immunity, eliciting both local and systemic resistance in plants. GLIP1 functions independently of salicylic acid but requires ethylene signaling. Enhancement of GLIP1 expression in plants increases resistance to pathogens including Alternaria brassicicola , Erwinia carotovora and Pseudomonas syringae , and limits their growth at the infection site. Furthermore, local treatment with GLIP1 proteins is sufficient for the activation of systemic resistance, inducing both resistance gene expression and pathogen resistance in systemic leaves. The PDF1.2 -inducing activity accumulates in petiole exudates in a GLIP1-dependent manner and is fractionated in the size range of less than 10 kDa as determined by size exclusion chromatography. Our results demonstrate that GLIP1-elicited systemic resistance is dependent on ethylene signaling and provide evidence that GLIP1 may mediate the production of a systemic signaling molecule(s). 相似文献
63.
WEHI-231 and Bal 17 B cell lines are representative models for immature and mature B cells, respectively. Their regulation of cytosolic Ca(2+) concentration ([Ca(2+)](c)) was compared using fura-2 fluorescence ratiometry. The ligation of B cell antigen receptor (BCR) by anti-IgM antibody induced a slow but large increase of [Ca(2+)](c) in WEHI-231 cells while not in Bal 17 cells. The thapsigargin-induced store-operated Ca(2+) entry (SOCE) of Bal 17 cells reached a steady state which was blocked by 2-aminoethoxydiphenyl borate (2-APB). On the contrary, the thapsigargin-induced SOCE of WEHI-231 cells increased continuously, which was accelerated by 2-APB. The increase of [Ca(2+)](c) by BCR ligation was also enhanced by 2-APB in WEHI-231 cells while blocked in Bal 17 cells. The Mn(2+) quenching study showed that the thapsigargin-, or the BCR ligation-induced Ca(2+) influx pathway of WEHI-231 was hardly permeable to Mn(2+). The intractable increase of [Ca(2+)](c) may explain the mechanism of BCR-driven apoptosis of WEHI-231 cells, a well-known model of clonal deletion of autoreactive immature B cells. 相似文献
64.
65.
Shijian Jin Eric M. Fell Lucia Vina‐Lopez Yan Jing P. Winston Michalak Roy G. Gordon Michael J. Aziz 《Liver Transplantation》2020,10(20)
A highly stable phosphonate‐functionalized viologen is introduced as the redox‐active material in a negative potential electrolyte for aqueous redox flow batteries (ARFBs) operating at nearly neutral pH. The solubility is 1.23 m and the reduction potential is the lowest of any substituted viologen utilized in a flow battery, reaching ?0.462 V versus SHE at pH = 9. The negative charges in both the oxidized and the reduced states of 1,1′‐bis(3‐phosphonopropyl)‐[4,4′‐bipyridine]‐1,1′‐diium dibromide ( BPP?Vi ) effect low permeability in cation exchange membranes and suppress a bimolecular mechanism of viologen decomposition. A flow battery pairing BPP?Vi with a ferrocyanide‐based positive potential electrolyte across an inexpensive, non‐fluorinated cation exchange membrane at pH = 9 exhibits an open‐circuit voltage of 0.9 V and a capacity fade rate of 0.016% per day or 0.00069% per cycle. Overcharging leads to viologen decomposition, causing irreversible capacity fade. This work introduces extremely stable, extremely low‐permeating and low reduction potential redox active materials into near neutral ARFBs. 相似文献
66.
67.
Zhang H Cai J Dong J Zhang D Huang L Xu Z Cen P 《Applied microbiology and biotechnology》2011,92(2):295-303
Poly (β-l-malic acid) (PMLA) is a water-soluble polyester with many attractive properties in chemical industry and medicine development.
However, the low titer of PMLA in the available producer strains limits further industrialization efforts and restricts its
many potential applications. In order to solve this problem, a new strain with the distinguished high productivity of PMLA
was isolated from fresh plants samples. It was characterized as the candidate of Aureobasidium pullulans based on the morphology and phylogenetic analyses of the internal transcribed spacer sequences. After the optimization of
culture conditions, the highest PMLA concentration (62.27 g l−1) could be achieved in the shake flask scale. In addition, the contribution of the carbon flux to exopolysaccharide (EPS)
and PMLA could be regulated by the addition of CaCO3 in the medium. This high-level fermentation process was further scaled up in the 10 l benchtop fermentor with a high PMLA
concentration (57.2 g l−1) and productivity (0.35 g l−1 h−1), which are the highest level in all the literature. Finally, the suitable acid hydrolysis conditions of PMLA were also investigated
with regard to the production of l-malic acid, and the kinetics of PMLA acid hydrolysis was modeled to simulate the whole degradation process. The present work
paved the road to produce this multifunctional biomaterial (PMLA) at industrial scale and promised one alternative method
to produce l-malic acid in the future. 相似文献
68.
Dai Sik Ko Junho Kang Hye Jin Heo Eun Kyoung Kim Kihun Kim Jin Mo Kang YunJae Jung Seung Eun Baek Yun Hak Kim 《International journal of biological sciences》2022,18(13):5154
Vascular smooth muscle cell (VSMC) proliferation is a hallmark of neointimal hyperplasia (NIH) in atherosclerosis and restenosis post-balloon angioplasty and stent insertion. Although numerous cytotoxic and cytostatic therapeutics have been developed to reduce NIH, it is improbable that a multifactorial disease can be successfully treated by focusing on a preconceived hypothesis. We, therefore, aimed to identify key molecules involved in NIH via a hypothesis-free approach. We analyzed four datasets (, GSE28829, GSE43292, and GSE100927), evaluated differentially expressed genes (DEGs) in wire-injured femoral arteries of mice, and determined their association with VSMC proliferation in vitro. Moreover, we performed RNA sequencing on platelet-derived growth factor (PDGF)-stimulated human VSMCs (hVSMCs) post-phosphoenolpyruvate carboxykinase 2 (PCK2) knockdown and investigated pathways associated with PCK2. Finally, we assessed NIH formation in Pck2 knockout (KO) mice by wire injury and identified PCK2 expression in human femoral artery atheroma. Among six DEGs, only PCK2 and RGS1 showed identical expression patterns between wire-injured femoral arteries of mice and gene expression datasets. PDGF-induced VSMC proliferation was attenuated when hVSMCs were transfected with PCK2 siRNA. RNA sequencing of PCK2 siRNA-treated hVSMCs revealed the involvement of the Akt-FoxO-PCK2 pathway in VSMC proliferation via Akt2, Akt3, FoxO1, and FoxO3. Additionally, NIH was attenuated in the wire-injured femoral artery of Pck2-KO mice and PCK2 was expressed in human femoral atheroma. PCK2 regulates VSMC proliferation in response to vascular injury via the Akt-FoxO-PCK2 pathway. Targeting PCK2, a downstream signaling mediator of VSMC proliferation, may be a novel therapeutic approach to modulate VSMC proliferation in atherosclerosis. GSE120521相似文献
69.
Yun‐Zhen Xu Ni‐Ni Guo Zong‐Ming Zheng Xian‐Jin Ou Hong‐Juan Liu De‐Hua Liu 《Biotechnology and bioengineering》2009,104(5):965-972
Klebsiella pneumoniae HR526, a new isolated 1,3‐propanediol (1,3‐PD) producer, exhibited great productivity. However, the accumulation of lactate in the late‐exponential phase remained an obstacle of 1,3‐PD industrial scale production. Hereby, mutants lacking D ‐lactate pathway were constructed by knocking out the ldhA gene encoding fermentative D ‐lactate dehydrogenase (LDH) of HR526. The mutant K. pneumoniae LDH526 with the lowest LDH activity was studied in aerobic fed‐batch fermentation. In experiments using pure glycerol as feedstock, the 1,3‐PD concentrations, conversion, and productivity increased from 95.39 g L?1, 0.48 and 1.98 g L?1 h?1 to 102. 06 g L?1, 0.52 mol mol?1 and 2.13 g L?1 h?1, respectively. The diol (1,3‐PD and 2,3‐butanediol) conversion increased from 0.55 mol mol?1 to a maximum of 0.65 mol mol?1. Lactate would not accumulate until 1,3‐PD exceeded 84 g L?1, and the final lactate concentration decreased dramatically from more than 40 g L?1 to <3 g L?1. Enzymic measurements showed LDH activity decreased by 89–98% during fed‐batch fermentation, and other related enzyme activities were not affected. NADH/NAD+ enhanced more than 50% in the late‐exponential phase as the D ‐lactate pathway was cut off, which might be the main reason for the change of final metabolites concentrations. The ability to utilize crude glycerol from biodiesel process and great genetic stability demonstrated that K. pnemoniae LDH526 was valuable for 1,3‐PD industrial production. Biotechnol. Bioeng. 2009; 104: 965–972. © 2009 Wiley Periodicals, Inc. 相似文献
70.
肝癌先天性多表达多药耐药基因,严重影响肝癌的化疗效果,筛选肝癌细胞中的耐药基因,研究其耐药机制有助于提高肝癌化疗效果,提高肝癌的治愈率。首先构建肝癌细胞逆转录病毒的cDNA文库,感染成纤维细胞,使得逆转录病毒基因整合进细胞,加药筛选,存活细胞中的基因再次包装成病毒,用于下一轮筛选。采用循环包装回收(Cyclical packaging rescue,CPR)技术进行肝癌细胞耐药基因的筛选即是通过病毒包装将基因从细胞中钓取出来,相比于常规筛选方法,仅通过一轮筛选可能会出现很多假阳性基因,采用CPR技术则是通过多轮筛选,很大程度减少了假阳性细胞的出现。通过该方法经过四轮筛选获得核糖体蛋白S11(RPS11)、核糖体蛋白L6(RPL6)、核糖体蛋白L11(RPL11)、核糖体蛋白L24(RPL24)等几种基因,经初步检测,增加了细胞的耐药性。 相似文献