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On-line near-infrared spectroscopy optimizing and monitoring biotransformation process of γ-aminobutyric acid 被引量:2
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作者 Guoyu Ding yuanyuan hou +3 位作者 Jiamin Peng Yunbing Shen Min Jiang Gang Bai 《Journal of Pharmaceutical Analysis》 SCIE CAS 2016年第3期171-178,共8页
Near-infrared spectroscopy (NIRS) with its fast and nondestructive advantages can be qualified for the real-time quantitative analysis. This paper demonstrates that NIRS combined with partial least squares (PLS) r... Near-infrared spectroscopy (NIRS) with its fast and nondestructive advantages can be qualified for the real-time quantitative analysis. This paper demonstrates that NIRS combined with partial least squares (PLS) regression can be used as a rapid analytical method to simultaneously quantify L-glutamic acid (L- GIu) and γ-aminobutyric acid (GABA) in a biotransformation process and to guide the optimization of production conditions when the merits of NIRS are combined with response surface methodology. The high performance liquid chromatography (HPLC) reference analysis was performed by the o-phthaldialdehyde pre-column derivatization. NIRS measurements of two batches of 141 samples were firstly analyzed by PLS with several spectral pre-processing methods. Compared with those of the HPLC reference analysis, the resulting determination coefficients (R2), root mean square error of prediction (RMSEP) and residual predictive deviation (RPD) of the external validation for the L-GIu concentration were 99.5%, 1.62 g/L, and 11.3, respectively. For the GABA concentration, R2, RMSEP, and RPD were 99.8%, 4.00 g/L, and 16.4, respectively. This NIRS model was then used to optimize the biotransformation process through a Box- Behnken experimental design. Under the optimal conditions without pH adjustment, 200 gjL L-GIu could be catalyzed by 7148 U/L glutamate decarboxylase (GAD) to GABA, reaching 99% conversion at the fifth hour. NIRS analysis provided timely information on the conversion from L-GIu to GABA. The results suggest that the NIRS model can not only be used for the routine profiling of enzymatic conversion, providing a simple and effective method of monitoring the biotransformation process of GABA, but also be considered to be an optimal tool to guide the optimization of production conditions. 展开更多
关键词 Near-intrared spectroscopy L-glutamic acid γ-aminobutyric acid Box-Behnken design Glutamate decarboxylase
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Förster resonance energy transfer reveals phillygenin and swertiamarin concurrently target AKT on different binding domains to increase the anti-inflammatory effect
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作者 Xiaoyao Ma Jinling Zhang +5 位作者 Ge Fang He Gao Jie Gao Li Fu yuanyuan hou Gang Bai 《Chinese Chemical Letters》 SCIE CAS CSCD 2024年第5期207-212,共6页
The clinical benefit of combination therapy is significant,but it is not easy to define the mechanism of complexity and diversity.Previous studies illustrate that phillygenin(Phi)binds in the allosteric inhibit pocket... The clinical benefit of combination therapy is significant,but it is not easy to define the mechanism of complexity and diversity.Previous studies illustrate that phillygenin(Phi)binds in the allosteric inhibit pocket of protein kinase B(AKT),and swertiamarin(Swe)acts on the pleckstrin homology(PH)domain of AKT.However,the combined synergistic effect of relieving the inflammatory response has yet to be elucidated.Based on high sensitivity,specificity and fast-responsibility fluorescent sensors,the Förster resonance energy transfer(FRET)technique offers a route to provide clear insights into physiological and pathological processes.In the study,molecular docking,the fluorescent probes of Phi and Swe for FRET were designed and synthesized.FRET analysis shown that Swe and Phi concurrently acted on the PH domain and allosterically inhibited pocket of AKT,respectively.The combination of Swe and Phi significantly increased the heat stability of AKT and decreased protease-induced degeneration.In lipopolysaccharides(LPS)-induced mice and cells,the combination arrested AKT activation,nuclear factor kappa-B(NF-κB)phosphorylation,and the expression of tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-8.In conclusion,FRET revealed Phi and Swe concurrently targeted AKT on different domains and the combination of Phi and Swe enhanced the anti-inflammatory effect. 展开更多
关键词 FRET SWERTIAMARIN Phillygenin AKT ANTI-INFLAMMATION Combinatorial drug
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Revealing drug targets with multimodal bioorthogonal AMPD probes through visual metabolic labeling
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作者 Fukui Shen Yuqing Zhang +5 位作者 Guoqing Luan Kaixue Zhang Zhenzhen Wang Yunhao Luo yuanyuan hou Gang Bai 《Chinese Chemical Letters》 SCIE CAS CSCD 2024年第12期405-410,共6页
Multimodal bioorthogonal small molecule probes play a pivotal role in drug-focused biomedical research.However,existing drug tracking and imaging techniques face obstacles in living organisms,hindering precise drug lo... Multimodal bioorthogonal small molecule probes play a pivotal role in drug-focused biomedical research.However,existing drug tracking and imaging techniques face obstacles in living organisms,hindering precise drug localization and target protein capture.Herein,we introduced a multimodal probe named 1-(azidomethyl)pyrene-4,5–dione(AMPD).The probe incorporates adjacent dione structures at the pyrene core.AMPD selectively interacts with oxygen-rich alkene-labeled drug molecules under ice-blue LED light exposure,producing specific fluorescence emission and enabling in vivo tracking and flow cytometry sorting.A methyl azide group was also introduced at the pyrene core to help efficiently enrich target proteins via click chemistry with alkyne-functionalized beads.AMPD demonstrates exceptional biocompatibility,rendering it highly suitable for visual photo-triggered tracking studies.Combined with metabolic labeling using an oxygen-rich alkene-tagged drug molecule probe,AMPD is effective for live animal,tissue,cellular,and in-gel imaging,as well as target protein identification through magnetic capture.With its versatile capabilities,AMPD enhances our comprehension of drug-target interactions at the in vivo level and expedites the process of drug discovery. 展开更多
关键词 Multimodal bioorthogonal probe Bioorthogonal reactions Photoclick IN-SITU Drug tracking
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Qingfei Xiaoyan Wan,a traditional Chinese medicine formula, ameliorates Pseudomonas aeruginosa–induced acute lung inflammation by regulation of PI3K/AKT and Ras/MAPK pathways 被引量:19
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作者 yuanyuan hou Yan Nie +5 位作者 Binfeng Cheng Jin Tao Xiaoyao Ma Min Jiang Jie Gao Gang Bai 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2016年第3期212-221,共10页
Gram-negative pathogen–induced nosocomial infections and resistance are a most serious menace to global public health. Qingfei Xiaoyan Wan(QF), a traditional Chinese medicine(TCM)formula, has been used clinically in ... Gram-negative pathogen–induced nosocomial infections and resistance are a most serious menace to global public health. Qingfei Xiaoyan Wan(QF), a traditional Chinese medicine(TCM)formula, has been used clinically in China for the treatment of upper respiratory tract infections, acute or chronic bronchitis and pulmonary infection. In this study, the effects of QF on Pseudomonas aeruginosa–induced acute pneumonia in mice were evaluated. The mechanisms by which four typical antiinflammatory ingredients from QF, arctigenin(ATG), cholic acid(CLA), chlorogenic acid(CGA) and sinapic acid(SPA), regulate anti-inflammatory signaling pathways and related targets were investigated using molecular biology and molecular docking techniques. The results showed that pretreatment with QF significantly inhibits the release of cytokines(TNF-α and IL-6) and chemokines(IL-8 and RANTES),reduces leukocytes recruitment into inflamed tissues and ameliorates pulmonary edema and necrosis. In addition, ATG was identified as the primary anti-inflammatory agent with action on the PI3K/AKT and Ras/MAPK pathways. CLA and CGA enhanced the actions of ATG and exhibited synergistic NF-κB inactivation effects possibly via the Ras/MAPK signaling pathway. Moreover, CLA is speculated to target FGFR and MEK firstly. Overall, QF regulated the PI3K/AKT and Ras/MAPK pathways to inhibit pathogenic bacterial infections effectively. 展开更多
关键词 ANTI-INFLAMMATORY Network PHARMACOLOGY PATHOGENIC bacterial infection PI3K/AKT PATHWAY Ras/MAPK PATHWAY Lung Mouse
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Screening and evaluation of antioxidants from lees by micro-injector systems combined with a fluorescent probe,N-borylbenzyloxycarbonyl-3,7-dihydroxyphenoxazine,in living Drosophila 被引量:2
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作者 Guangcui Chu Dandan Cheng +6 位作者 Wenjuan Liu Xuefeng Wang Xiaotao hou yuanyuan hou Hongjun Wei Jiagang Deng Gang Bai 《Chinese Chemical Letters》 SCIE CAS CSCD 2018年第10期1521-1527,共7页
Over the past few decades, the determination of antioxidant activity by chemical probe has been widely reported, but in vivo evaluation via model organisms of Drosophila melanogaster and rapid discovery system has not... Over the past few decades, the determination of antioxidant activity by chemical probe has been widely reported, but in vivo evaluation via model organisms of Drosophila melanogaster and rapid discovery system has not been studied adequately. In this study, we determined the antioxidant activity of lees and demonstrated the ability of compounds in lees to scavenge H_2O_2 in vitro and in vivo by different chemical probes. Lees increased the ability of Drosophila against oxidative stress and antioxidant enzyme activity in vivo. Five ingredients of organic acids and flavones in lees extract that rapidly scavenged H_2O_2 were revealed by a post-column-derived HPLC-UV-FLD system based on 4-hydroxyphenylacetic acid(PHPAA)chemiluminescence. Additionally, another fluorescent probe,N-borylbenzyloxycarbonyl-3,7-dihydroxyphenoxazine(NBCD), was selected to evaluate the reactive oxygen species(ROS) scavenging capacity of lees in living Drosophila melanogaster using a microfluidic injection test coupled with microscopic imaging analysis, and similar effects were observed in flies when they were treated with tartaric acid and caffeic acid. The results demonstrated that the novel integrated system was suitable for screening and evaluating antioxidant ingredients from natural products. 展开更多
关键词 LEES Antioxidant MICROINJECTION HPLC-UV-FLD NBCD PHPAA
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Chemical proteomics reveals ligustilide targets SMAD3,inhibiting collagen synthesis in aortic endothelial cells 被引量:1
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作者 Wei Lei Fukui Shen +5 位作者 Nianwei Chang Lin Niu yuanyuan hou Boli Zhang Min Jiang Gang Bai 《Chinese Chemical Letters》 SCIE CAS CSCD 2021年第1期190-193,共4页
Atherosclerosis is a persistent inflammatory state,while vascular endothelial fibrosis is one of the primary causes of atherosclerosis development.Although ligustilide(Lig) was shown to exert obvious antiatherogenic e... Atherosclerosis is a persistent inflammatory state,while vascular endothelial fibrosis is one of the primary causes of atherosclerosis development.Although ligustilide(Lig) was shown to exert obvious antiatherogenic effects in previous studies,its precise mechanism has not been deeply discussed.In this paper,we designed a Lig-derived photoaffinity labelling(PAL) probe to identify potential therapeutic targets of Lig via chemical proteomics approach.Mothers against decapentaplegic homologue 3(SMAD3),a signal transmitter of transforming growth factor-β(TGF-β) which promotes the development of vascular fibrosis,was identified as a potential target of Lig.Lig suppressed the phosphorylation and nuclear translocation of SMAD3 by blocking the interaction between SMAD3 and TGF-β receptor 1,thereby inhibiting the collagen synthesis process.Hence,developing a novel SMAD3 inhibitor may present a promising therapeutic option for preventing vascular fibrosis. 展开更多
关键词 LIGUSTILIDE SMAD3 Collagen synthesis Chemical proteomics Photoaffinity labelling
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20(S)-Protopanaxatriol promotes the binding of P53 and DNA to regulate the antitumor network via multiomic analysis 被引量:1
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作者 Zhihua Wang Wenbo Wu +10 位作者 Xiangchen Guan Shuang Guo Chaowen Li Ruixue Niu Jie Gao Min Jiang Liping Bai Elaine Laihan Leung yuanyuan hou Zhihong Jiang Gang Bai 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2020年第6期1020-1035,共16页
Although the tumor suppressor P53 is known to regulate a broad network of signaling pathways,it is still unclear how certain drugs influence these P53 signaling netw orks.Here,we used a comprehensive singlecell multio... Although the tumor suppressor P53 is known to regulate a broad network of signaling pathways,it is still unclear how certain drugs influence these P53 signaling netw orks.Here,we used a comprehensive singlecell multiomics view of the effects of ginsenosides on cancer cells.Transcriptome and proteome profiling revealed that the antitumor activity of ginsenosides is closely as sociated with P53 protein.A miRNA-proteome interaction network revealed that P53 controlled the transcription of at least 38 proteins,and proteomemetabolome profiling analysis revealed that P53 regulated proteins involved in nucleotide metabolism,amino acid metabolism and"Warburg effect".The results of integrative multiomics analysis revealed P53 protein as a potential key target that influences the anti-tumor activity of ginsenosides.Furthermore,by applying affinity mass spectrometry(MS)screening and surface plasmon resonance fragment library screening,we confirmed that 20(S)-protopanaxatriol directly targeted adj acent regions of the P53 DNA-binding pocket and promoted the stability of P53-DNA interactions,which further induced a series of omics changes. 展开更多
关键词 Multiomics analysis P53 20(S)-Protopanaxatriol DNA binding Ginsenosides anti-tumor network
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Chemical proteomics combined with metabonomics reveals berberine targets NDUFV1 of complex Ⅰ in the respiratory chain to regulate energy metabolism
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作者 Xiaoyao Ma Yiman Han +4 位作者 Kaixin Liu Yongping Bai He Gao yuanyuan hou Gang Bai 《Chinese Chemical Letters》 SCIE CAS CSCD 2023年第3期419-423,共5页
Berberine(BBR) is the primary alkaloid compound of the heat-clearing traditional Chinese medicine Huanglian(Coptis chinensis) and exerts regulatory effects on energy metabolism. However, the specific targets and molec... Berberine(BBR) is the primary alkaloid compound of the heat-clearing traditional Chinese medicine Huanglian(Coptis chinensis) and exerts regulatory effects on energy metabolism. However, the specific targets and molecular mechanisms are not clear. In this paper, the BBR-affected energy metabolism pathway was screened by nontargeted metabolomics, and a BBR-derived photoaffinity labeled(PAL) probe was designed to identify potential targets via a chemical proteomics approach. NDUFV1, a subunit of complex Ⅰ on mitochondria, was identified as a potential target of BBR. In the respiratory chain, BBR suppressed the activity of complex Ⅰ, reduced the electrochemical potential in the mitochondrial intermembrane and inhibited the generation of ATP and heat via competitive binding with NDUFV1. The results illustrated the underlying mechanism of BBR in the downregulation of energy metabolism. 展开更多
关键词 BERBERINE Photoaffinity labeled Chemical proteomics NDUFV1 ComplexⅠ Energy metabolism
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A temperature-regulated bioorthogonal reaction to target lysine:Hemiacetal pharmacophore in genipin irreversibly binds with UCP2,inhibiting mitochondrial thermogenesis
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作者 Fukui Shen Wen Yang +4 位作者 Kaixue Zhang Yanting Jiao Jing Cui yuanyuan hou Gang Bai 《Chinese Chemical Letters》 SCIE CAS CSCD 2023年第10期191-196,共6页
Mitochondria are essential for eukaryotic life as powerhouses for energy metabolism. Excessive mitochondrial hyperthermia and reactive oxygen species(ROS) production have been associated with aging, cancer,neurodegene... Mitochondria are essential for eukaryotic life as powerhouses for energy metabolism. Excessive mitochondrial hyperthermia and reactive oxygen species(ROS) production have been associated with aging, cancer,neurodegenerative diseases, and other disorders. Uncoupling protein 2(UCP2) is the effector responsible for regulating cellular thermogenesis and ROS production via dissipating protons in an electrochemical gradient. A UCP2 inhibitor named genipin(GNP) is being researched for its effect on mitochondrial temperature, but little is known about its mechanisms. This study developed several molecular probes to explore the interactions between GNP and UCP2. The result indicated that the hemiacetal structure in GNP could selectively react with the ?-amine of lysine on the UCP2 proton leakage channel through ringopening condensation at the mitochondrial, cellular, and animal levels. A notable feature of the reaction is its temperature sensitivity and ability to conjugate with UCP2 at high fever as lysine-specific covalent inhibitors that prevent mitochondrial thermogenesis. The result not only clarifies the existence of an antipyretic properties of GNP via its irreversible coupling to UCP2, but also reveals a bioorthogonal reaction of hemiacetal iridoid aglycone for selectively binding with the ?-amine of lysine on proteins. 展开更多
关键词 Bioorthogonal reaction Mitochondria GENIPIN UCP2 Irreversible binding
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Labor Inputs and Productivity in Chinese Industries:2000-2018
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作者 Menggen Chen yuanyuan hou 《China Finance and Economic Review》 2022年第1期24-47,共24页
Under the framework of growth accounting,this paper introduces four heterogeneity characteristics of labor,namely,educational level,age,gender and industry,constructs a cross classification matrix of employment,labor ... Under the framework of growth accounting,this paper introduces four heterogeneity characteristics of labor,namely,educational level,age,gender and industry,constructs a cross classification matrix of employment,labor compensation and working hours,and calculates the labor input(volume)of the whole country and of 19 industries during 2000-2018.Then it decomposes the volume into quantity and quality parts to analyze the total amount of labor input and the performance of industry labor input.The results are as follows.First,during the research period,the annual growth rate of labor input was 2.5%,and 78.8%of that came from the growth of labor input quality.The growth of labor input was mainly resulted from the improvement of educational level and the optimization of industrial structure.Second,in 2018,the proportions of labor input of the primary,secondary and tertiary sectors were 13.76%,31.06%and 55.18%respectively,and the transfer speed of labor input to the secondary and tertiary sectors was higher than that of the quantity structure;the labor input volume in the new economy and related industries in the tertiary sector has been greatly increased.Third,the index method-based labor productivity(ILP)of some producer service and consumer service industries was relatively low,and the growth of total industry output mainly attributed to the increase of labor input and the expansion of industrial scale.The improvement of labor input quality has become the key to the growth of labor input in China,and the improvement of educational level is the core power to improve the labor input quality. 展开更多
关键词 labor input volume labor input quality labor productivity total employment working hours
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