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Jia Jin Xiaoqing Ye Derrick Boateng Kaili Dai Fei Ye Pengfei Du Han Yu 《Bioorganic & medicinal chemistry letters》2019,29(16):2358-2363
Protein tyrosine phosphatase 1B (PTP1B) plays an important role in the negative regulation of insulin and leptin signaling. The development of small molecular inhibitors targeting PTP1B has been validated as a potential therapeutic strategy for Type 2 diabetes (T2D). In this work, we have identified a series of compounds containing dihydropyridine thione and particular chiral structure as novel PTP1B inhibitors. Among those, compound 4b showed moderate activity with IC50 value of 3.33 μM and meanwhile with good selectivity (>30-fold) against TCPTP. The further MOA study of PTP1B demonstrated that compounds 4b is a substrate-competitive inhibitor. The binding mode analysis suggested that compound 4b simultaneously occupies the active site and the second phosphotyrosine (pTyr) binding site of PTP1B. Furthermore, the cell viability assay of compound 4b showed tolerable cytotoxicity in L02 cells, thus 4b may be prospectively used to further in vivo study. 相似文献
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Yuan‐Yuan Li Lei Guo Hui Li Jian Li Feng Dong Zi‐Yun Yi Ying‐Chun Ouyang Yi Hou Zhen‐Bo Wang Qing‐Yuan Sun Sheng‐Sheng Lu Zhiming Han 《Molecular reproduction and development》2019,86(9):1189-1198
NEK5, a member of never in mitosis‐gene A‐related protein kinase, is involved in the regulation of centrosome integrity and centrosome cohesion at mitosis in somatic cells. In this study, we investigated the expression and function of NEK5 during mouse oocyte maturation and preimplantation embryonic development. The results showed that NEK5 was expressed from germinal vesicle (GV) to metaphase II (MII) stages during oocyte maturation with the highest level of expression at the GV stage. It was shown that NEK5 localized in the cytoplasm of oocytes at GV stage, concentrated around chromosomes at germinal vesicle breakdown (GVBD) stage, and localized to the entire spindle at prometaphase I, MI and MII stages. The small interfering RNA‐mediated depletion of Nek5 significantly increased the phosphorylation level of cyclin‐dependent kinase 1 in oocytes, resulting in a decrease of maturation‐promoting factor activity, and severely impaired GVBD. The failure of meiotic resumption caused by Nek5 depletion could be rescued by the depletion of Wee1B. We found that Nek5 depletion did not affect CDC25B translocation into the GV. We also found that NEK5 was expressed from 1‐cell to blastocyst stages with the highest expression at the blastocyst stage, and Nek5 depletion severely impaired preimplantation embryonic development. This study demonstrated for the first time that NEK5 plays important roles during meiotic G2/M transition and preimplantation embryonic development. 相似文献
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Chunyan Zheng Fang Ouyang Xianghui Liu Junhua Ma Fenghua Zhao Zhu Ouyang Feng Ge 《Ecology and evolution》2019,9(19):11367-11378
Groundwater and nitrogen fertilizer overuse severely threatens crop productions; thus, current ecological agriculture requires low irrigation and nitrogen fertilizer inputs. The effects of combined reduced irrigation and nitrogen fertilizer addition on soil organism (e.g., mite) community and biodiversity remain poorly understood. We analyzed soil mite community composition, wheat grain yield, and soil characteristics in a 10‐year manipulation experiment with two levels of irrigation (reduced and conventional irrigation) and five nitrogen fertilizer levels (0, 70, 140, 210, and 280 kg N/ha). Reduced irrigation (20% reduction, from 280 to 220 mm) and nitrogen fertilizer (25% reduction, from 280 to 210 kg N/ha) addition did not significantly influence soil mite community and wheat yield. The relative abundances of fungivores and predators showed negative quadratic relationships with wheat yield, while that of plant parasites showed a positive relationship. The relationships between soil mite trophic groups and wheat yield revealed that we can evaluate the impacts of reduced irrigation and nitrogen fertilizer addition from the perspective of soil fauna. Soil mite community composition was altered by soil abiotic factors prior to reduced irrigation and nitrogen fertilizer addition. Overall, moderate reductions of irrigation and nitrogen fertilizer may not threaten to soil mite community and diversity or decrease crop production; in contrast, such reductions will benefit mite community development and the sustainable agriculture. 相似文献
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Zhenling Ma Xueli Zhao Mingjiao Deng Zhengjie Huang Jing Wang Yi Wu Dan Cui Yingfu Liu Rushi Liu Gaoliang Ouyang 《Cell reports》2019,26(6):1533-1543.e4
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Wang Jun Liu Fangchao Li Jianxin Huang Keyong Yang Xueli Chen Jichun Liu Xiaoqing Cao Jie Chen Shufeng Shen Chong Yu Ling Lu Fanghong Wu Xianping Zhao Liancheng Li Ying Hu Dongsheng Huang Jianfeng Gu Dongfeng Lu Xiangfeng 《中国科学:生命科学英文版》2022,65(1):119-128
Science China Life Sciences - Evidence about the response patterns of fruit and vegetable consumption with the risk of cardiovascular disease (CVD) and all-cause mortality was inconsistent. These... 相似文献
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Multichannel automated chamber system for continuous monitoring of CO2 exchange between the agro-ecosystem or soil and the atmosphere 总被引:1,自引:0,他引:1
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A multichannel automated chamber system was developed for continuous monitoring of CO2 exchange at multiple points between agro-ecosystem or soil and atmosphere. This system consisted of an automated chamber subsystem with a CO2 concentration analyzer and a data logging subsystem. Both subsystems were under the control of a programmable logic controller (PLC). The automated chamber subsystem contained 18 chambers (50 cm × 50 cm × 50 cm) and a compressor. The chamber lids were closed and can be automatically opened. During measurement, one of the 18 chambers was kept closed for three minutes for measuring and the other chambers were kept open to maintain the natural soil conditions to the maximum extent. Environmental variables were simultaneously measured using sensors and recorded by the data logger. The reliability of the multichannel automated chamber system was tested and the results showed that the turbulence of the fans had no significant effect on the CO2 exchange. The changes in the air and the temperature of soil and soil moisture inside the chambers, caused by the enclosure of the chambers, were not significant. The net ecosystem CO2 exchange for the wheat ecosystem was ?2.35 μmol·m?2·s>?1 and the soil respiration was 3.87 μmol·m?2·s>?1 in the wheat field, and 6.61 μmol·m?2·s>?1 in the apple orchard. 相似文献