•Rainfallwas obtained fromTRMMdata for the period 1999–2008.•We model runoff and Water balance in the Tiaoxi catchment.•The gauge-adjusted TRMM 3B42 data can be a valuable tool for hydrologic ...modeling.
Spatial rainfall data is an essential input to Distributed Hydrological Models (DHM), and a significant contributor to hydrological model uncertainty. Model uncertainty is higher when rain gauges are sparse, as is often the case in practice. Currently, satellite-based precipitation products increasingly provide an alternative means to ground-based rainfall estimates, in which case a rigorous product assessment is required before implementation. Accordingly, the twofold objective of this work paper was the real-world assessment of both (a) the Tropical Rainfall Measuring Mission (TRMM) rainfall product using gauge data, and (b) the TRMM product’s role in forcing data for hydrologic simulations in the area of the Tiaoxi catchment (Taihu lake basin, China). The TRMM rainfall products used in this study are the Version-7 real-time 3B42RT and the post-real-time 3B42. It was found that the TRMM rainfall data showed a superior performance at the monthly and annual scales, fitting well with surface observation-based frequency rainfall distributions. The Nash-Sutcliffe Coefficient of Efficiency (NSCE) and the relative bias ratio (BIAS) were used to evaluate hydrologic model performance. The satisfactory performance of the monthly runoff simulations in the Tiaoxi study supports the view that the implementation of real-time 3B42RT allows considerable room for improvement. At the same time, post-real-time 3B42 can be a valuable tool of hydrologic modeling, water balance analysis, and basin water resource management, especially in developing countries or at remote locations in which rainfall gauges are scarce.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
2.
A message from the Co-Editor-in-Chief Ding, Xinxin
Acta pharmaceutica Sinica. B,
June 2021, 2021-06-00, 20210601, 2021-06-01, Volume:
11, Issue:
6
Journal Article
Peer reviewed
Open access
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Reticulon (Rtn) proteins shape tubular domains of the endoplasmic reticulum (ER), and in some cases are autophagy receptors for selective ER turnover. We have found that maize Rtn1 and Rtn2 control ...ER homeostasis and autophagic flux in endosperm aleurone cells, where the ER accumulates lipid droplets and synthesizes storage protein accretions metabolized during germination. Maize Rtn1 and Rtn2 are expressed in the endosperm, localize to the ER, and re-model ER architecture in a dose-dependent manner. Rtn1 and Rtn2 interact with Atg8a using four Atg8-interacting motifs (AIMs) located at the C-terminus, cytoplasmic loop, and within the transmembrane segments. Binding between Rtn2 and Atg8 is elevated upon ER stress. Maize
mutants display increased autophagy and up-regulation of an ER stress-responsive chaperone. We propose that maize Rtn1 and Rtn2 act as receptors for autophagy-mediated ER turnover, and thus are critical for ER homeostasis and suppression of ER stress.
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The cytochrome P450 enzymes (P450s or CYPs) are a class of heme-containing monooxygenases responsible for the oxidative metabolism of a wide range of endogenous substances and foreign ...chemicals. Deciphering the physiological functions of CYPs and their relevance to human diseases requires reliable tools for sensing target enzyme in complex biological systems. Over the past few decades, great efforts have been made to develop isoform-specific probe substrates for human CYP(s) and use them in both basic researches and translational applications. The growing database of the ligands and 3D-structures of human CYPs strongly facilitates the design and development of CYP probe substrates with improved specificity. Herein, we summarize the recent progress in the development and applications of molecular probes for human CYPs. The structural and catalytic features of human CYPs, as well as the design principles and strategies used in the development of CYP probe substrates, have been well summarized. Two comprehensive lists of molecular probes for various human CYP enzymes, including non-optical and optical probe substrates, along with their structural information and kinetic parameters, are presented. Finally, the current challenges and future perspectives in this field are proposed and highlighted. The information and knowledge presented here provides practical tools for sensing CYP activities in complex biological systems, exploring the relevance of CYPs to human diseases, as well as screening and characterizing of CYP modulators.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Oral administration is the most commonly used route for drug treatment.Intestinal cytochrome P450(CYP)-mediated metabolism can eliminate a large proportion of some orally administered drugs before ...they reach systemic circulation,while leaving the passage of other drugs unimpeded.A better understanding of the ability of intestinal P450 enzymes to metabolize various clinical drugs in both humans and preclinical animal species,including the identification of the CYP enzymes expressed,their regulation,and the relative importance of intestinal metabolism compared to hepatic metabolism,is important for improving bioavailability of current drugs and new drugs in development.Here,we briefly review the expression of drug-metabolizing P450 enzymes in the small intestine of humans and several preclinical animal species,and provide an update of the various factors or events that regulate intestinal P450 expression,including a cross talk between the liver and the intestine.We further compare various clinical and preclinical approaches for assessing the impact of intestinal drug metabolism on bioavailability,and discuss the utility of the intestinal epithelium–specific NADPH-cytochrome P450 reductasenull(IECN) mouse as a useful model for studying in vivo roles of intestinal P450 in the disposition of orally administered drugs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Drug discovery and development involve the utilization of in vitro and in vivo experimental models. Different models, ranging from test tube experiments to cell cultures, animals, healthy human ...subjects, and even small numbers of patients that are involved in clinical trials, are used at different stages of drug discovery and development for determination of efficacy and safety. The proper selection and applications of correct models, as well as appropriate data interpretation, are critically important in decision making and successful advancement of drug candidates. In this review, we discuss strategies in the applications of both in vitro and in vivo experimental models of drug metabolism and disposition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The optimization of mix proportions based on the targeted fresh and hardened performances of self-compacting concrete (SCC) is a foundation for its transition from laboratory research to industrial ...production. In this paper, the mix proportions of various SCC mixtures were designed by the absolute volume method with changes in the content of river sand and manufactured sand, the content of fly ash and granulated ground blast furnace slag (GGBS) and the maximum particle sizes of coarse aggregates. This experimental study was carried out to verify the workability, density and cubic compressive strength of SCC. The results show that SCC demonstrated good performance with appropriate mix proportions of manufactured sand and river sand. A hybrid effect of fly ash and GGBS appeared on the fresh performance of SCC with a constant strength, and the coarse aggregate with a smaller maximum particle size was beneficial to the workability but detrimental to the compressive strength of SCC. Finally, the optimization of the mix proportion of SCC was evaluated by grey relational analysis, in which the weight of the indicators was determined by the entropy method to improve the evaluation credibility. As a result, the optimal mix proportions of SCC were selected.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
While large language models (LLMs) such as ChatGPT and Google Bard have shown significant promise in various fields, their broader impact on enhancing patient health care access and quality, ...particularly in specialized domains such as oral health, requires comprehensive evaluation.
This study aims to assess the effectiveness of Google Bard, ChatGPT-3.5, and ChatGPT-4 in offering recommendations for common oral health issues, benchmarked against responses from human dental experts.
This comparative analysis used 40 questions derived from patient surveys on prevalent oral diseases, which were executed in a simulated clinical environment. Responses, obtained from both human experts and LLMs, were subject to a blinded evaluation process by experienced dentists and lay users, focusing on readability, appropriateness, harmlessness, comprehensiveness, intent capture, and helpfulness. Additionally, the stability of artificial intelligence responses was also assessed by submitting each question 3 times under consistent conditions.
Google Bard excelled in readability but lagged in appropriateness when compared to human experts (mean 8.51, SD 0.37 vs mean 9.60, SD 0.33; P=.03). ChatGPT-3.5 and ChatGPT-4, however, performed comparably with human experts in terms of appropriateness (mean 8.96, SD 0.35 and mean 9.34, SD 0.47, respectively), with ChatGPT-4 demonstrating the highest stability and reliability. Furthermore, all 3 LLMs received superior harmlessness scores comparable to human experts, with lay users finding minimal differences in helpfulness and intent capture between the artificial intelligence models and human responses.
LLMs, particularly ChatGPT-4, show potential in oral health care, providing patient-centric information for enhancing patient education and clinical care. The observed performance variations underscore the need for ongoing refinement and ethical considerations in health care settings. Future research focuses on developing strategies for the safe integration of LLMs in health care settings.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
This paper studies the effect of high-strength steel fiber reinforced concrete (SFRC) on the axial compression behavior of rectangular-sectional SFRC-filled steel tube columns. The purpose is to ...improve the integrated bearing capacity of these composite columns. Nine rectangular-sectional SFRC-filled steel tube columns and one normal concrete-filled steel tube column were designed and tested under axial loading to failure. The compressive strength of concrete, the volume fraction of steel fiber, the type of internal longitudinal stiffener and the spacing of circular holes in perfobond rib were considered as the main parameters. The failure modes, axial load-deformation curves, energy dissipation capacity, axial bearing capacity, and ductility index are presented. The results identified that steel fiber delayed the local buckling of steel tube and increased the ductility and energy dissipation capacity of the columns when the volume fraction of steel fiber was not less than 0.8%. The longitudinal internal stiffening ribs and their type changed the failure modes of the local buckling of steel tube, and perfobond ribs increased the ductility and energy dissipation capacity to some degree. The compressive strength of SFRC failed to change the failure modes, but had a significant impact on the energy dissipation capacity, bearing capacity, and ductility. The predictive formulas for the bearing capacity and ductility index of rectangular-sectional SFRC-filled steel tube columns are proposed to be used in engineering practice.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Pyrrolizidine alkaloids (PAs) are common phytotoxins with both hepatotoxicity and pneumotoxicity. Hepatic cytochrome P450 enzymes are known to bioactivate PAs into reactive metabolites, which can ...interact with proteins to form pyrrole-protein adducts and cause intrahepatic cytotoxicity. However, the metabolic and initiation biochemical mechanisms underlying PA-induced pneumotoxicity remain unclear. To investigate the in vivo metabolism basis for PA-induced lung injury, this study used mice with conditional deletion of the cytochrome P450 reductase (
Cpr
) gene and resultant tissue-selective ablation of microsomal P450 enzyme activities. After oral exposure to monocrotaline (MCT), a pneumotoxic PA widely used to establish animal lung injury models, liver-specific
Cpr
-null (LCN) mice, but not extrahepatic
Cpr
-low (xh-CL) mice, had significantly lower level of pyrrole-protein adducts in the serum, liver and lungs compared with wild-type (WT) mice. While MCT-exposed LCN mice had significantly higher blood concentration of intact MCT, compared to MCT-exposed WT or xh-CL mice. Consistent with the MCT in vivo bioactivation data, MCT-induced lung injury, represented by vasculature damage, in WT and xh-CL mice but not LCN mice. Furthermore, reactive metabolites of MCT were confirmed to exist in the blood efflux from the hepatic veins of MCT-exposed rats. Our results provide the first mode-of-action evidence that hepatic P450s are essential for the bioactivation of MCT, and blood circulating reactive metabolites of MCT to the lung causes pneumotoxicity. Collectively, this study presents the scientific basis for the application of MCT in animal lung injury models, and more importantly, warrants public awareness and further investigations of lung diseases associated with exposure to not only MCT but also different PAs.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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