64 research outputs found
Novel discrete fracture networks model for multiphase flow in coal
Acknowledgments This research was funded by the National Natural Science Foundation of China (Grants 41830427, 41922016, and 42130806) and the China Scholarship Council (202006400048).Peer reviewedPostprin
Variation of adsorption effects in coals with different particle sizes induced by differences in microscopic adhesion
Acknowledgements This research was funded by the National Natural Science Foundation of China (grant nos. 41830427, 42130806 and 41922016), the Fundamental Research Funds for Central Universities (grant no. 2-9-2021-067) and the 2021 Graduate Innovation Fund Project of China University of Geosciences, Beijing (grant no. ZD2021YC035). We are very grateful to the reviewers and editors for their valuable comments and suggestionsPeer reviewedPostprin
Effects of natural micro-fracture morphology, temperature and pressure on fluid flow in coals through fractal theory combined with lattice Boltzmann method
Acknowledgements: This research was funded by the National Natural Science Foundation of China (grant nos. 343 41830427, 41922016 and 41772160) and the Fundamental Research Funds for Central Universities (grant no. 2652019255). The authors also want to thank the Royal Society Edinburgh and NSFC to support their collaborations.Peer reviewedPostprin
Atomic force microscopy investigation of nano-scale roughness and wettability in middle to high rank coals, with samples from Qinshui Basin, China
Acknowledgements This research was funded by the National Natural Science Fund (grant nos. 41830427, 42130806 and 41922016), the Fundamental Research Funds for Central Universities (grant no. 2652018002), and financial support from China Scholarship Council ((No.202006400048).Peer reviewedPostprin
Nano-CT measurement of pore-fracture evolution and diffusion transport induced by fracturing in medium-high rank coal
Acknowledgements This research was funded by the National Natural Science Foundation of China (grant nos. 42130806, 41830427 and 41922016), 2021 Graduate Innovation Fund Project of China University of Geosciences, Beijing (grant no. ZD2021YC035) and the Fundamental Research Funds for Central Universities (grant no. 2-9-2021-067). We are very grateful to the reviewers and editors for their valuable comments and suggestions.Peer reviewedPostprin
Interference mechanism in coalbed methane wells and impacts on infill adjustment for existing well patterns
This research was funded by the National Natural Science Foundation of China (grant nos. 41830427, 42130806 and 41922016), 2021 Graduate Innovation Fund Project of China University of Geosciences, Beijing (grant no. ZD2021YC035) and the Fundamental Research Funds for Central Universities, China (grant no. 2-9-2021-067). We are very grateful to the reviewers and editors for their valuable comments and suggestions.Peer reviewedPublisher PD
Hydrodynamic and Geostress Controls on CBM Enrichment in the Anze Block, Southern Qinshui Basin, North China
Acknowledgments This research was funded by the National Natural Science Foundation of China (grant nos. 42130806, 41830427, 41922016, 41772160, and 42102227).Peer reviewedPublisher PD
Structure-function relationship of uridine diphosphate glucuronosyltransferases (UGTs)
PURPOSE
Uridine diphosphate glucuronosyltransferases (UGTs) are Phase II conjugation enzymes that are critical for vertebrate detoxication. They catalyze the glucuronidation biotransformations of numerous endo- and xenobiotics to facilitate their clearance and elimination and are important for hormonal regulation. Glucuronidation-related disorders include congenital syndromes, excessive chemical toxicities, adverse drug reactions, and dysregulated hormonal status. Since the 1980s it has been known that UGT proteins can be expressed but not fully active, yet little is known about how the UGT protein structure regulates its activity and function, because of the lack of a complete structure. We hypothesized that translational and post-translational mechanisms may play a role in regulating the activity and function of human UGTs. Aim 1 and 2 focused on UGT isoform 1A6, one of the most important isoforms in endo- and xenobiotic metabolism. Aim 3 studied the co-expression of major human hepatic UGT isoforms to gain an insight on their co-regulation in vivo.
METHODS
N-glycosylation variants of human UGT1A6 were established to study the influence of N-glycosylation on their expression, activity, cellular function and localization. HEK293 expressed UGT1A6-(His)6 and Sf9-insect expressed soluble UGT1A6 were purified and their activity and latency were characterized. The co-expression between 7 UGTs was investigated based on a western blot database collected from healthy liver donors, aged fetal (20 weeks) – 87 years.
GENERAL CONCLUSIONS
N-glycosylation is an important regulator of human UGT1A6 in expression, activity, and cellular function. Different forms of N-glycosylation were observed for UGT1A6 between HEK293 cells and human liver microsomes, showing a caveat of using recombinant cell lines to study UGT structure/function. Sf9-insect expressed soluble UGT1A6 is a good candidate for structure analysis due to sufficient yield and activity after purification. The influence of membranes on UGTs may be different from traditional beliefs as the data suggested alamethicin and Brij 58 can directly activate the enzyme. Lastly, expression of major human hepatic UGTs was significantly correlated and correlations were affected by age. The UGTs may be co-regulated in the human liver so single-isoform systems may have limitations on reflecting UGT activity in vivo.Pharmaceutical Sciences, Faculty ofGraduat
Revisiting the Latency of Uridine Diphosphate-Glucuronosyltransferases (UGTs)—How Does the Endoplasmic Reticulum Membrane Influence Their Function?
Uridine diphosphate-glucuronosyltransferases (UGTs) are phase 2 conjugation enzymes mainly located in the endoplasmic reticulum (ER) of the liver and many other tissues, and can be recovered in artificial ER membrane preparations (microsomes). They catalyze glucuronidation reactions in various aglycone substrates, contributing significantly to the body’s chemical defense mechanism. There has been controversy over the last 50 years in the UGT field with respect to the explanation for the phenomenon of latency: full UGT activity revealed by chemical or physical disruption of the microsomal membrane. Because latency can lead to inaccurate measurements of UGT activity in vitro, and subsequent underprediction of drug clearance in vivo, it is important to understand the mechanisms behind this phenomenon. Three major hypotheses have been advanced to explain UGT latency: compartmentation, conformation, and adenine nucleotide inhibition. In this review, we discuss the evidence behind each hypothesis in depth, and suggest some additional studies that may reveal more information on this intriguing phenomenon
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