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Nowadays, considerable efforts have been extensively devoted to explore a general strategy for improving the color uniformity and thermal stability of phosphors, which is vital for its applications in health and comfort lighting.

Intra-oceanic subduction is a fundamental process on Earth, the study of which can improve the understanding of plate tectonic processes and the history of continental growth. Here, we report on newly recognized trondhjemite in the north of Diyanmiao ophiolite belt in North China. The trondhjemite was found along the Erenhot-Hegenshan suture zone. U-Pb zircon dating revealed that the trondhjemite crystallized at 309 ± 2.1 Ma. The trondhjemite had a high amount of SiO2 (68.94–76.45 wt %), Al2O3 (13.37–15.90 wt %), and Sr (232–601 ppm); and a low amount of K2O (1.57–2.70 wt %), Y (6.91–9.39 ppm), Ni (1.10–4.19 ppm), and Cr (1.55–13.50 ppm). The Na2O/K2O ratios were 1.90–4.37. There was a lack of negative Eu anomalies. It was relatively enriched in large-ion lithophile elements (LILEs) such as Rb, Ba, K, and Sr; was depleted in high-field-strength elements (HFSEs) such as Nb, Ta, Ti, and P; and had low total rare-earth element (REE) contents (27.73–49.63 ppm) with distinct REE fractionation (chondrite-normalized (La/Yb)N of 5.76–10.52), which was similar to adakitic rocks formed by partial melting of subducted oceanic crust. The trondhjemite, together with Diyanmiao ophiolite (335.6 Ma), may have formed during the stages of intra-oceanic subduction, suggesting that in the Early Carboniferous–Late Carboniferous, the southern Paleo-Asian Ocean was in its subduction stage.

Rivaroxaban, an oral anticoagulant, undergoes the metabolism mediated by human cytochrome P450 (CYP). The present study is to quantitatively analyze and compare the contributions of multiple CYPs in the metabolism of rivaroxaban to provide new information for medication safety. The metabolic stability of rivaroxaban in the presence of human liver microsomes (HLMs) and recombinant CYPs was systematically evaluated to estimate the participation of various CYP isoforms. Furthermore, the catalytic efficiency of CYP isoforms was compared via metabolic kinetic studies of rivaroxaban with recombinant CYP isoenzymes, as well as via CYP-specific inhibitory studies. Additionally, docking simulations were used to illustrate molecular interactions. Multiple CYP isoforms were involved in the hydroxylation of rivaroxaban, with decreasing catalytic rates as follows: CYP2J2 > 3A4 > 2D6 > 4F3 > 1A1 > 3A5 > 3A7 > 2A6 > 2E1 > 2C9 > 2C19. Among the CYPs, 2J2, 3A4, 2D6, and 4F3 were the four major isoforms responsible for rivaroxaban metabolism. Notably, the intrinsic clearance of rivaroxaban catalyzed by CYP2J2 was nearly 39-, 64-, and 100-fold that catalyzed by CYP3A4, 2D6, and 4F3, respectively. In addition, rivaroxaban hydroxylation was inhibited by 41.1% in the presence of the CYP2J2-specific inhibitor danazol, which was comparable to the inhibition rate of 43.3% by the CYP3A-specific inhibitor ketoconazole in mixed HLMs. Furthermore, molecular simulations showed that rivaroxaban is principally bound to CYP2J2 by π-alkyl bonds, carbon-hydrogen bonds, and alkyl interactions. CYP2J2 dominated the hydroxylation of rivaroxaban, which may provide new insight into clinical drug interactions involving rivaroxaban.

English teaching plays an extremely important role in college education. It can not just improve students’ English level, but also help students adapt to the increasingly open and complex society. Besides, it is an important foundation for students to further go to the world and integrate in the world development trend. Although English teaching has received attention of various colleges and universities, there are still many problems in college English teaching, and the teaching effect is not obvious. To make teaching conform to the rapid development of the new education environment and make teaching practice more fitted with the standard of modern education, teaching mode reform for college English is imperative. Based on the teaching idea of “assessment for learning”, the teaching management system was designed in this study, including three steps: teaching intelligence system, assessment and test system, and information feedback system. Meanwhile, interactive teaching approach was combined to plan the interactive teaching process of college English course, including the process of proposing and solving questions, independent thinking and cooperative learning module, and leaning achievement exchange activity. In the end, assessment-for-learning teaching mode was used to collect the data of four dimensions (degree of learning engagement, completion degree of English learning content, degree of English learning interaction, and English learning effect) and the learning performance evaluation system supported by big data was established. The experimental results show that the teaching mode in this study could effectively improve students’ learning performance and enhance their actual English application ability.

UDP-glucuronosyltransferases (UGTs) and β-glucuronidase (GUS) catalyze entirely distinct metabolism reactions. UGTs are responsible for the glucuronidation of a variety of drugs, endogenous and environmental chemicals, whereas GUS hydrolyzes glucuronides and liberates the parent substrates. Information on the overlap of ligand selectivity between UGT and GUS is essential for exploring the pharmacological or toxicological effects of the inhibitors of these two metabolic enzymes. This study is conducted to test whether UGTs and GUS share common ligands, by investigating the inhibitory effects towards E. coli GUS by a series of UGT typical substrates and inhibitors. Results showed that three typical ligands of UGTs, including two specific substrates (estradiol and trifluoperazine, E2 and TFP) and one selective inhibitor (magnolol, Mag), can inhibit the activity of GUS. Kinetic assays indicated that all the three UGT specific chemicals displayed competitive inhibition, with Ki values of 31.4 (E2), 56.9 (TFP), and 16.6 μM (Mag). Docking studies further revealed that the three chemicals can enter the active sites of GUS by forming contacts with residues Glu-413, Trp-549, Asp-163, Tyr-472, Arg-562, or bound water. Our study indicates that ligand selectivity overlaps between UGTs and GUS, and some chemicals can act as co-inhibitors of these two metabolic enzymes. The pharmacological or toxicological effects of those co-inhibitors require further investigations.

The 2019 novel coronavirus (SARS-CoV-2) has spread rapidly worldwide and was declared a pandemic by the WHO in March 2020. The evolution of SARS-CoV-2, either in its natural reservoir or in the human population, is still unclear, but this knowledge is essential for effective prevention and control. We propose a new framework to systematically identify recombination events, excluding those due to noise and convergent evolution. We found that several recombination events occurred for SARS-CoV-2 before its transfer to humans, including a more recent recombination event in the receptor-binding domain. We also constructed a probabilistic mutation network to explore the diversity and evolution of SARS-CoV-2 after human infection. Clustering results show that the novel coronavirus has diverged into several clusters that cocirculate over time in various regions and that several mutations across the genome are fixed during transmission throughout the human population, including D614G in the S gene and two accompanied mutations in ORF1ab. Together, these findings suggest that SARS-CoV-2 experienced a complicated evolution process in the natural environment and point to its continuous adaptation to humans. The new framework proposed in this study can help our understanding of and response to other emerging pathogens.

Aiming at the problem that the sensorless surface-mounted permanent magnet synchronous motor has a certain failure rate and poor low-speed control performance, an improved sensorless rotor initial position detection and low-speed position tracking method is proposed. First of all, the pulsating high-frequency voltage is injected into the estimated coordinate system, and the relationship between current response and position error is obtained through the principle of flux linkage cross-coupling. The composite phase-locked loop rotor position observer is established by optimizing the filter and performing phase compensation of the modulation signal. Then, combined with pulse voltage vector injection, the conditions for determining the rotor polarity are given. This observer can accurately detect and track the rotor position from start to low speed in sensorle ss control. Finally, build a test platform for oil pump experiments, the experimental results verify that the method can realize the closed-loop start of the surface-mounted permanent magnet synchronous motor with large torque at rest, which improves the efficiency and robustness of low-speed operation.

Background The novel COVID-19 disease has spread worldwide, resulting in a new pandemic. The Chinese government implemented strong intervention measures in the early stage of the epidemic, including strict travel bans and social distancing policies. Prioritizing the analysis of different contributing factors to outbreak outcomes is important for the precise prevention and control of infectious diseases. We proposed a novel framework for resolving this issue and applied it to data from China. Objective This study aimed to systematically identify national-level and city-level contributing factors to the control of COVID-19 in China. Methods Daily COVID-19 case data and related multidimensional data, including travel-related, medical, socioeconomic, environmental, and influenza-like illness factors, from 343 cities in China were collected. A correlation analysis and interpretable machine learning algorithm were used to evaluate the quantitative contribution of factors to new cases and COVID-19 growth rates during the epidemic period (ie, January 17 to February 29, 2020). Results Many factors correlated with the spread of COVID-19 in China. Travel-related population movement was the main contributing factor for new cases and COVID-19 growth rates in China, and its contributions were as high as 77% and 41%, respectively. There was a clear lag effect for travel-related factors (previous vs current week: new cases, 45% vs 32%; COVID-19 growth rates, 21% vs 20%). Travel from non-Wuhan regions was the single factor with the most significant impact on COVID-19 growth rates (contribution: new cases, 12%; COVID-19 growth rate, 26%), and its contribution could not be ignored. City flow, a measure of outbreak control strength, contributed 16% and 7% to new cases and COVID-19 growth rates, respectively. Socioeconomic factors also played important roles in COVID-19 growth rates in China (contribution, 28%). Other factors, including medical, environmental, and influenza-like illness factors, also contributed to new cases and COVID-19 growth rates in China. Based on our analysis of individual cities, compared to Beijing, population flow from Wuhan and internal flow within Wenzhou were driving factors for increasing the number of new cases in Wenzhou. For Chongqing, the main contributing factor for new cases was population flow from Hubei, beyond Wuhan. The high COVID-19 growth rates in Wenzhou were driven by population-related factors. Conclusions Many factors contributed to the COVID-19 outbreak outcomes in China. The differential effects of various factors, including specific city-level factors, emphasize the importance of precise, targeted strategies for controlling the COVID-19 outbreak and future infectious disease outbreaks.

Aim Rivaroxaban, an oral anticoagulant, undergoes the metabolism mediated by human cytochrome P450 (CYP). The present study is to quantitatively analyze and compare the contributions of multiple CYPs in the metabolism of rivaroxaban to provide new information for medication safety. Methods The metabolic stability of rivaroxaban in the presence of human liver microsomes (HLMs) and recombinant CYPs was systematically evaluated to estimate the participation of various CYP isoforms. Furthermore, the catalytic efficiency of CYP isoforms was compared via metabolic kinetic studies of rivaroxaban with recombinant CYP isoenzymes, as well as via CYP-specific inhibitory studies. Additionally, docking simulations were used to illustrate molecular interactions. Results Multiple CYP isoforms were involved in the hydroxylation of rivaroxaban, with decreasing catalytic rates as follows: CYP2J2 > 3A4 > 2D6 > 4F3 > 1A1 > 3A5 > 3A7 > 2A6 > 2E1 > 2C9 > 2C19. Among the CYPs, 2J2, 3A4, 2D6 and 4F3 were the four major isoforms responsible for rivaroxaban metabolism. Notably, the intrinsic clearance of rivaroxaban catalyzed by CYP2J2 was nearly 39-, 64- and 100-fold that catalyzed by CYP3A4, 2D6 and 4F3, respectively. In addition, rivaroxaban hydroxylation was inhibited by 41.1% in the presence of the CYP2J2-specific inhibitor danazol, which was comparable to the inhibition rate of 43.3% by the CYP3A-specific inhibitor ketoconazole in mixed HLMs. Furthermore, molecular simulations showed that rivaroxaban principally bound to CYP2J2 by π-alkyl bonds, carbon-hydrogen bonds and alkyl interactions. Conclusion CYP2J2 dominated the hydroxylation of rivaroxaban, which may provide new insight into clinical drug interactions involving rivaroxaban.

BACKGROUND The novel COVID-19 disease has spread worldwide, resulting in a new pandemic. The Chinese government implemented strong intervention measures in the early stage of the epidemic, including strict travel bans and social distancing policies. Prioritizing the analysis of different contributing factors to outbreak outcomes is important for the precise prevention and control of infectious diseases. We proposed a novel framework for resolving this issue and applied it to data from China. OBJECTIVE This study aimed to systematically identify national-level and city-level contributing factors to the control of COVID-19 in China. METHODS Daily COVID-19 case data and related multidimensional data, including travel-related, medical, socioeconomic, environmental, and influenza-like illness factors, from 343 cities in China were collected. A correlation analysis and interpretable machine learning algorithm were used to evaluate the quantitative contribution of factors to new cases and COVID-19 growth rates during the epidemic period (ie, January 17 to February 29, 2020). RESULTS Many factors correlated with the spread of COVID-19 in China. Travel-related population movement was the main contributing factor for new cases and COVID-19 growth rates in China, and its contributions were as high as 77% and 41%, respectively. There was a clear lag effect for travel-related factors (previous vs current week: new cases, 45% vs 32%; COVID-19 growth rates, 21% vs 20%). Travel from non-Wuhan regions was the single factor with the most significant impact on COVID-19 growth rates (contribution: new cases, 12%; COVID-19 growth rate, 26%), and its contribution could not be ignored. City flow, a measure of outbreak control strength, contributed 16% and 7% to new cases and COVID-19 growth rates, respectively. Socioeconomic factors also played important roles in COVID-19 growth rates in China (contribution, 28%). Other factors, including medical, environmental, and influenza-like illness factors, also contributed to new cases and COVID-19 growth rates in China. Based on our analysis of individual cities, compared to Beijing, population flow from Wuhan and internal flow within Wenzhou were driving factors for increasing the number of new cases in Wenzhou. For Chongqing, the main contributing factor for new cases was population flow from Hubei, beyond Wuhan. The high COVID-19 growth rates in Wenzhou were driven by population-related factors. CONCLUSIONS Many factors contributed to the COVID-19 outbreak outcomes in China. The differential effects of various factors, including specific city-level factors, emphasize the importance of precise, targeted strategies for controlling the COVID-19 outbreak and future infectious disease outbreaks.

UDP-glucuronosyltransferases (UGTs) and β-glucuronidase (GUS) catalyze entirely distinct metabolism reactions. UGTs are responsible for the glucuronidation of a variety of drugs, endogenous and environmental chemicals, whereas GUS hydrolyzes glucuronides and liberates the parent substrates. Information on the overlap of ligand selectivity between UGT and GUS is essential for exploring the pharmacological or toxicological effects of the inhibitors of these two metabolic enzymes. This study is conducted to test whether UGTs and GUS share common ligands, by investigating the inhibitory effects towards

Microemulsions are promising drug delivery systems for the oral administration of poorly water-soluble drugs. However, the evolution of microemulsions in the gastrointestinal tract is still poorly characterized, especially the structural change of microemulsions under the effect of lipase and mucus. To better understand the fate of microemulsions in the gastrointestinal tract, we applied small-angle X-ray scattering (SAXS) and fluorescence resonance energy transfer (FRET) to monitor the structural change of microemulsions under the effect of lipolysis and mucus. First, the effect of lipolysis on microemulsions was studied by SAXS, which found the generation of liquid crystalline phases. Meanwhile, FRET spectra indicated micelles with smaller particle sizes were generated during lipolysis, which could be affected by CaCl2, bile salts and lecithin. Then, the effect of mucus on the structural change of lipolysed microemulsions was studied. The results of SAXS and FRET indicated that the liquid crystalline phases disappeared, and more micelles were generated. In summary, we studied the structural change of microemulsions in simulated gastrointestinal conditions by SAXS and FRET, and successfully monitored the appearance and disappearance of the liquid crystalline phases and micelles., Graphical abstract Small-angle X-ray scattering (SAXS) and fluorescence resonance energy transfer (FRET) methods were applied to monitor the structural change of microemulsions under the effect of lipolysis and mucus in this work. We found that liquid crystalline phases and micelles were appeared under lipolysis, and liquid crystalline phases were disappeared in mucus.fx1

The recently discovered Diyanmiao ophiolite in the eastern part of the Erenhot-Hegenshan ophiolite belt forms part of the southeastern domain of the Central Asian Orogenic Belt (CAOB). The ophiolite suite is composed of the northern Baiyinbulage ophiolite and the southern Naolaiketu ophiolite, each extending for nearly 100 km, and a width of around 6 km. The suite preserves a well-exposed and a nearly-complete ophiolite stratigraphy, and includes, from bottom to top, harzburgite, bedded gabbro, isotropic gabbros, anorthosite, spilite, pillow basalt, keratophyre, baschtauite, with overlying chert, and plagiogranite veins locally intruding the pillow basalt and gabbro. The pillow basalts possess the geochemical characteristics of Hahajima island arc tholeiite (IAT), indicating that the Diyanmiao ophiolite formed in the incipient arc setting of the supra-subduction zone. LA-ICP-MS U-Pb dating of zircon grains from three gabbro samples yield ages of 361 ± 13 Ma, 356.7 ± 3.8 Ma and 340 ± 14 Ma, indicating an early-Carboniferous age for the Diyanmiao ophiolite. We suggest that the intra-oceanic subduction initiation of the Erenhot-Hegenshan paleo-ocean during the Early Carboniferous resulted in the formation of an incipient arc oceanic crust, and that the Diyanmiao ophiolite represents an important north-dipping subduction event of the paleo Asian oceanic crust beneath the southern margin of the Siberian Plate after Early Carboniferous and Early Permian. Our study provides further insights into the evolution of the Paleo-Asian Ocean and eventual construction of CAOB, the globe's largest Phanerozoic orogen.

A series of single-component CaAlSiN 3 : Ce 3+ , Eu 2+ phosphors with dual emission colors (yellow and red) were successfully prepared via a direct-nitriding method to achieve spectral tuning and broadening of CaAlSiN 3 : Eu 2+ red phosphor. Crystal structure, morphology, photoluminescence properties and energy transfer mechanism were thoroughly investigated. The particular plate-like morphology of CaAlSiN 3 : Ce 3+ , Eu 2+ phosphor was obtained due to the lattice distortion and preferential orientation growth of host lattice originated from the introduction of Ce 3+ into CaAlSiN 3 . More interestingly, the luminescent intensity of red emission peak was enhanced through an energy transfer process between Ce 3+ and Eu 2+ ions. Under excitation of 460 nm, CaAlSiN 3 : 0.02Ce 3+ , 0.001Eu 2+ phosphor exhibited intense and broad emission peaks centered at 580 nm (yellow) and 618 nm (closely near to the red isochromatic region around 615 nm). Furthermore, the energy transfer mechanism from Ce 3+ to Eu 2+ ion was determined to be electric dipole-dipole interaction and the energy transfer efficiency was 94%. The CaAlSiN 3 : Ce 3+ , Eu 2+ phosphors showed super broad excitation spectra from 270 to 500 nm, high external quantum efficiency (74%) and small thermal quenching. Evidently, CaAlSiN 3 : Ce 3+ , Eu 2+ samples may be potential candidates of red phosphor for improving optical performance of illumination-grade light sources.

Phthalate esters (PAEs) have been extensively used in industry as plasticizers and there remains concerns about their safety. The present study aimed to determine the inhibition of phthalate esters (PAEs) on the activity of the phase II drug-metabolizing enzymes UDP-glucuronosyltransferases (UGTs). In vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone was used to investigate the inhibition potentials of PAEs towards various s UGTs. PAEs exhibited no significant inhibition of UGT1A1, UGT1A3, UGT1A8, UGT1A10, UGT2B15, and UGT2B17, and limited inhibition of UGT1A6, UGT1A7 and UGT2B4. However, UGT1A9 was strongly inhibited by PAEs. In silico docking demonstrated a significant contribution of hydrogen bonds and hydrophobic interactions contributing to the inhibition of UGT by PAEs. The Ki values were 15.5, 52.3, 23.6, 12.2, 5.61, 2.79, 1.07, 22.8, 0.84, 73.7, 4.51, 1.74, 0.58, 6.79, 4.93, 6.73, and 7.23 μM for BBOP-UGT1A6, BBZP-UGT1A6, BBOP-UGT1A7, BBZP-UGT1A7, DiPP-UGT1A9, DiBP-UGT1A9, DCHP-UGT1A9, DBP-UGT1A9, BBZP-UGT1A9, BBOP-UGT1A9, DMEP-UGT1A9, DPP-UGT1A9, DHP-UGT1A9, DiBP-UGT2B4, DBP-UGT2B4, DAP-UGT2B4, and BBZP-UGT2B4, respectively. In conclusion, exposure to PAEs might influence the metabolic elimination of endogenous compounds and xenobiotics through inhibiting UGTs.

A high performance liquid chromatography (HPLC) monolithic column was prepared by redox polymerization of styrene, dipentaerythritol hexaacrylate (DPHA) and ethylene glycol dimethacrylate (EDMA) in a porogen system of n-propanol/PEG400. The monolith was characterized by scanning electron microscopy (SEM), mercury intrusion porosimetry (MIP) and the results indicated that the monolith had a stable and homogeneous structure. The porosity of the monolithic column was 75.86% and average pore diameter was 2.1 µm. Several alkylbenzenes and anilines were used to evaluate the column performance in terms of hydrophobicity. Then the column was applied to separate small molecules including phytosterol and BSA tryptic digest. Finally, five standard proteins, egg white and plasma were separated respectively and high separation capacity of protein was obtained.

An efficient glucosylation of alcoholic hydroxyls in the structures of protostane triterpenoids catalyzed by fungus has been developed. Four protostanes 1–4 as the substrates have been transformed by Syncephalastrum racemosum AS 3.264 and generated corresponding 11-OH glucosylation derivatives. The regioselective characteristics were also identified by various highly oxygenated protostane substrates. The time-courses displayed the highest yields of 1a, 3a, and 4a at > 50%, and 1a had the highest yield of 72%. All of the protostane analogues displayed hCE-2 inhibitory effects in an in vitro bioassay. This report describes a rare biocatalytic alcoholic hydroxyl glucosylation with considerable yield and regioselective characteristics.

PFASs are highly persistent in both natural and living environment, and pose a significant risk for wildlife and human beings. The present study was carried out to determine the inhibitory behaviours of fourteen PFASs on metabolic activity of two major isoforms of carboxylesterases (CES). The probe substrates 2-(2-benzoyl-3-methoxyphenyl) benzothiazole (BMBT) for CES1 and fluorescein diacetate (FD) for CES2 were utilized to determine the inhibitory potentials of PFASs on CES in vitro. The results demonstrated that perfluorododecanoic acid (PFDoA), perfluorotetradecanoic acid (PFTA) and perfluorooctadecanoic acid (PFOcDA) strongly inhibited CES1 and CES2. The half inhibition concentration (IC50) value of PFDoA, PFTA and PFOcDA for CES1 inhibition was 10.6 μM, 13.4 μM and 12.6 μM, respectively. The IC50 for the inhibition of PFDoA, PFTA and PFOcDA towards CES2 were calculated to be 9.56 μM, 17.2 μM and 8.73 μM, respectively. PFDoA, PFTA and PFOcDA exhibited noncompetitive inhibition towards both CES1 and CES2. The inhibition kinetics parameters (Ki) were 27.7 μM, 26.9 μM, 11.9 μM, 4.04 μM, 29.1 μM, 27.4 μM for PFDoA-CES1, PFTA-CES1, PFOcDA-CES1, PFDoA-CES2, PFTA-CES2, PFOcDA-CES2, respectively. In vitro-in vivo extrapolation (IVIVE) predicted that when the plasma concentrations of PFDoA, PFTA and PFOcDA were greater than 2.77 μM, 2.69 μM and 1.19 μM, respectively, it might interfere with the metabolic reaction catalyzed by CES1 in vivo; when the plasma concentrations of PFDoA, PFTA and PFOcDA were greater than 0.40 μM, 2.91 μM, 2.74 μM, it might interfere with the metabolic reaction catalyzed by CES2 in vivo. Molecular docking was used to explore the interactions between PFASs and CES. In conclusion, PFASs were found to cause inhibitory effects on CES in vitro, and this finding would provide an important experimental basis for further in vivo testing of PFASs focused on CES inhibition endpoints.

Horseradish peroxidase (HRP) and laccase are well known oxidases, which have been widely applied for the biosynthesis of organic compounds. In the present work, flavone analogues as an important type of bioactive natural product could be oxidized by HRP or laccase, which afforded dimeric and oxidative flavones. All of the flavone analogues usually possessing phenolic groups could be transformed using HRP. However, only flavonols, isoflavones and chalcones with phenolic groups and dihydroxylflavones were effective substrates of laccase. The radical reaction mechanism with the B-ring of flavone analogues as the radical reaction trigger was proposed for the oxidation of flavones. In silico molecular docking analyses for assaying the interaction between flavone analogues and oxidases indicated that the phenolic groups at the B rings of flavones docked into the HEME active pocket of HRP well. Kinetic behaviors of the oxidation for various flavone analogues mediated by HRP or laccase displayed Hill and substrate inhibition kinetic models. Therefore, in the present work, the oxidation of various flavone analogues mediated by HRP or laccase has been successfully characterized, which would be helpful for the preparation of flavone derivatives.

Cytochrome P450 2J2 (CYP2J2), a key enzyme responsible for oxidative metabolism of various xenobiotics and endogenous compounds, participates in a diverse array of physiological and pathological processes in humans. Its biological role in tumorigenesis and cancer diagnosis remains poorly understood, owing to the lack of molecular tools suitable for real-time monitoring CYP2J2 in complex biological systems. Using molecular design principles we were able to modify the distance between the catalytic unit and metabolic recognition moiety, allowing us to develop a CYP2J2 selective fluorescent probe using a near-infrared fluorophore (E)-2-(2-(6-hydroxy-2, 3-dihydro-1H-xanthen-4-yl)vinyl)-3,3- dimethyl-1-propyl-3H-indol-1-ium iodide (HXPI). To improve the reactivity and isoform specificity, a self-immolative linker was introduced to the HXPI derivatives in order to better fit the narrow substrate channel of CYP2J2, the modification effectively shortened the spatial distance between the metabolic moiety (O-alkyl group) and catalytic center of CYP2J2. After screening a panel of O-alkylated HXPI derivatives, BnXPI displayed the best combination of specificity, sensitivity and applicability for detecting CYP2J2 in vitro and in vivo. Upon O-demethylation by CYP2J2, a self-immolative reaction occurred spontaneously via 1,6-elimination of p-hydroxybenzyl resulting in the release of HXPI. Allowing BnXPI to be successfully used to monitor CYP2J2 activity in real-time for various living systems including cells, tumor tissues, and tumor-bearing animals. In summary, our practical strategy could help the development of a highly specific and broadly applicable tool for monitoring CYP2J2, which offers great promise for exploring the biological functions of CYP2J2 in tumorigenesis.

Melatonin (Mel) as an endogenous hormone, has been widely used in clinic for multiple therapeutic purposes. Further, the natural anthraquinones were widespread in various plants including herbs, foods, and some flavoring agents. The present work aims to evaluate the metabolic disorder of Mel caused by various common herbs and further identify their underlying mechanism. More importantly, the relationships between inhibitory activity and their structures were also investigated. Our results demonstrate that some herbs containing anthraquinone derivatives exhibited strong inhibition on Mel metabolism. Additionally, five anthraquinones from R. palmatum could inhibit phase I and II metabolism of Mel with a mixed inhibition kinetic model based on the mechanism of inhibiting human CYP1A1, 1A2, and SULT1A1. At last, the influence of R. palmatum and its five major components on the Mel metabolism were verified in human primary hepatocytes. In conclusion, our studies elucidated that herbs or foods containing abundant anthraquinones such as R. palmatum will cause a metabolic disorder of Mel, and should be avoided to combined application with Mel in clinic.

A nanodiamond-based composite monolithic column was fabricated by redox initiation for high performance liquid chromatography (HPLC). The functionalized nanodiamond was modified via Fenton Reagent and 3-methacryl oxypropyltrimethoxysilane (KH-570). After being optimized conditions, composite monolithic columns were prepared with functionalized ND (f-ND) as functional monomer, dipentaerythritol hexaacrylate and ethylene dimethacrylate as crosslinking agents, dodecanol and 1-propanol as co-porogens, dibenzoyl peroxide and N,N-dimethyl aniline as initiators. Characterizations of the resulting nanocomposite, including fourier transform infrared spectra, scanning electron microscopy images, thermal gravimetric analysis, mercury intrusion porosimetry and nitrogen adsorption–desorption isotherm were all carried out in detail. Bigger specific surface area, better mechanical stability, thermostability property and orderliness skeleton structure with flow-through channels and macroporous of the composite monolithic column was exhibited than those columns without f-ND added. At last, the nanodiamond-based composite monolithic column was used to separate a series of small molecules including acidic, alkaline and neutral compounds with good resolution and reproducibility in HPLC.

A series of SryCa1−x−yAlSiN3:xEu2+ (x = 0–0.01, y = 0–0.8) phosphors have been successfully prepared by solid state reaction under atmospheric pressure. All the phosphors exhibit orthorhombic crystal structure similar with CaAlSiN3 structure. It is found that the emission bands for all Ca1−xAlSiN3:xEu2+ phosphors are centered at ~650 nm and fluorescence quenching has been observed along with the increase of Eu2+ concentration in host materials. Through substitution of Ca2+ by Sr2+, an expected red emission peak (625 nm) and enhanced luminescent intensity can be achieved. The obtained Sr0.8Ca0.192AlSiN3:0.008Eu2+ phosphor was further used as efficient red component to fabricate white light emitting diodes (LEDs). Under the optimized condition of LED packaging, the white LEDs own the excellent optical properties with luminous efficiency of 90.6 lm/W and an ideal color rendering index (Ra = 82). Furthermore, the color correlated temperature of white LEDs can be simply adjusted through changing the red phosphor concentration and dispensing package saves time.

Horseradish peroxidase (HRP) was used to effectively catalyze the dimerization of coumarins. On the basis of screening and preparative transformation, the catalytic ability of HRP to dimerize various coumarins was investigated. Coumarins that only had one substituted phenolic hydroxyl group could be selectively transformed into novel bicoumarins, while coumarins that had two or more hydroxyls could be transformed into multiple bicoumarins. Eight bicoumarins were obtained and identified by spectroscopic analysis. Among them, bicoumarins 1b, 2a, 2b, 3a and 3b are reported here for the first time. The interactions between the different types of coumarins and HRP were also investigated by in silico docking analysis. Using the transformed products as standard substances, kinetic analyses of the catalytic reactions were carried out. The optimized reaction conditions for the dimerization of coumarins catalyzed by HRP were 1 g L−1 HRP, 0.66 M H2O2, pH 3, 25 °C, and 15 min of incubation time. The yields of the bicoumarins ranged from 10 to 40%, especially for bicoumarin 1a, which was obtained in approximately 35% yield. In an in vitro bioassay, several novel bicoumarins displayed potential α-glucosidase inhibitory activities, which can be further used to develop antidiabetic agents.

Metal (Au or Pt)-modified CeO2 materials with excellent redox ability for the oxidation of CO to CO2 were prepared by a redox precipitation method to investigate the role of surface oxygen vacancies. It was found that most of the Au or Pt was encapsulated by CeO2. Both Au and Pt can effectively improve the reducibility of CeO2 to form more oxygen vacancies at lower temperatures. The surface oxygen vacancies were thoroughly studied by UV-Vis spectroscopy, CO adsorption FTIR, H2-TPR and CO pulse oxidation techniques. During the reaction cycle of CO oxidation, the oxygen vacancies were affected by the modified metals but played different roles in the performance of CO oxidation. There were more oxygen vacancies on Pt-CeO2, which facilitated the formation of more carbonates. A certain amount (4.2%) of oxygen vacancies was necessary to improve the CO oxidation on this material. Comparatively, the rather fewer oxygen vacancies and the lower adsorption strength of carbonates did not affect the final elimination efficiency of CO on Au-CeO2.

Bufadienolides are a major class of bioactive compounds derived from amphibian skin secretion. Recent studies demonstrate that bufadienolides have a promising role in targeted cancer chemotherapy. However, extensive metabolism and inactivation strongly restrict the clinical applications of bufadienolides. This study aimed to systematically characterize the sulfation of six representative bufadienolides (including bufalin, resibufogenin, cinobufagin, bufotalin, telocinobufagin and deacetylcinobufagin) in amphibian skin secretion and to provide insight into the structure–sulfation relationship by experimentation and molecular docking analysis with series of bufadienolides and derivatives. For all the six representative bufadienolides, one corresponding monosulfate was detected in the incubation mixtures. The sulfates were accurately identified as bufadienolides 3-O-sulfates by NMR and HPLC-MSn techniques. Reaction phenotyping studies using human recombinant sulfotransferase (SULT) and liver S9 demonstrated that SULT2A1 mediated the formation of bufadienolide 3-O-sulfate with a high specific selectivity. Further kinetic evaluation demonstrated that deacetylcinobufagin could be used as a preferred probe of SULT2A1. The regio- and stereo-selective sulfation properties of SULT2A1 and the structural variation effects of bufadienolides were investigated by docking analysis, which revealed the significance of appropriate molecule orientation and hydrophobic interactions of motifs with SULT2A1 His99 residues. Additionally, significant differences between humans and animal species were observed in the sulfation of bufalin and resibufogenin. This study provided important data for elucidating the mechanisms of bufadienolide sulfation and leads to a better understanding of the bufadienolide–SULT interaction which can be further used in preclinical development and rational use of bufadienolides.

Phyllodium pulchellum(P. pulchellum) is a folk medicine with a significant number of bioactivities. The aim of this study was to investigate the effects displayed by alkaloids fractions, isolated from the roots ofP. pulchellum, on neurotransmitters monoamine levels and on monoamine oxidase (MAO) activity. Six alkaloids, which had indolealkylamine orβ-carboline skeleton, were obtained by chromatographic technologies and identified by spectroscopic methods such as NMR and MS. After treatment with alkaloids ofP. pulchellum, the reduction of DA levels (54.55%) and 5-HT levels (35.01%) in rat brain was observed by HPLC-FLD. The effect of alkaloids on the monoamines metabolism was mainly related to MAO inhibition, characterized by IC50values of37.35±6.41and126.53±5.39 μg/mL for MAO-A and MAO-B, respectively. The acute toxicity indicated thatP. pulchellumextract was nontoxic.

A series of Eu2+ activated Ca10(PO4)6Cl2 phosphors (ClAp: Eu2+) with enhanced blue emission have been prepared by the deposition precipitation (DP) process. The XRD patterns indicate that Eu2+ ions are incorporated into Ca10(PO4)6Cl2 lattice during the DP process. The ClAp: xEu2+-DP phosphor exhibits an super broad excitation band of 250 nm–420 nm consisting of three distinct peaks at 276 nm, 343 nm and 365 nm, ascribed to the 4f6 → 4f75 d1 transition of Eu2+ ions in 4f and 6 h sites. Under 350 nm excitation, ClAp: xEu2+-DP phosphors show the intense blue emission at 453 nm and the maximum intensity is obtained when x = 0.3. Notably, an enhanced blue emission intensity of ~2.1 times can be found for ClAp:0.3Eu2+-DP phosphor compared with the sample prepared by traditional solid state reaction (SSR) method. Further, the EDX elemental mapping of the phosphor demonstrates that DP process can effectively promote the uniform distribution of Eu2+ ions on the surface of ClAp crystal and avoid the aggregating problem of activators in SSR method, which can greatly improves the photoluminescence property. It can be concluded from HRTEM images and decay curves that ClAp:0.3Eu2+-DP phosphor exhibits characteristic lattice fringes similar to those of ClAp:0.3Eu2+-SSR phosphor, but a longer average decay lifetime (392 ns). In addition, the presence of trivalent europium ions on the surface of ClAp: 0.3Eu2+-SSR and ClAp: 0.3Eu2+-DP phosphors can be identified by XPS analysis. All the results reveal that DP process is an efficient way to prepare highly dispersed Eu2+ activators in Ca10(PO4)6Cl2 host and the ClAp: Eu2+-DP phosphors can be the promising candidate for blue emission in white LEDs.

Subduction of oceanic lithosphere is the primary driver of plate tectonics on Earth. However, one of the least understood aspects of plate tectonics is how subduction zones initiate, due to the lack of recognition of subduction initiation records in many ophiolites. Here we report a newly recognized complete magmatic record including Early Carboniferous fore-arc basalts (FABs), transitional lavas and boninites in the Diyanmiao ophiolite zone in central Inner Mongolia, North China. The stratigraphy and chemo-temporal relations of the suite are identical to those of the Izu–Bonin–Mariana (IBM) forearc as well as the ophiolite suites associated with subduction initiation such as Semail in Oman. In the Diyanmiao suite, the FABs are exposed over a large area, overlying gabbroic rocks of the ophiolite, and underlain by transitional lavas and boninites from bottom to top. Zircon U–Pb geochronology of the FABs shows a mean age of 335.6 ± 2.6 Ma. The Diyanmiao FABs are mainly aphyric, with variolitic groundmass texture, and pillow structure. The boninites (∼328 Ma) are strongly porphyritic with skeletal olivine crystal, clinopyroxene and orthopyroxene phenocrysts. The major and trace element and Sr–Nd isotopic characteristics of FABs, transitional lavas and boninites in the Diyanmiao ophiolite are comparable to those of corresponding rocks in the IBM forearc. The FABs display compositions similar to those of the most depleted mid-ocean ridge basalts (MORB), but with lower Ti/V ratios, suggesting slightly higher concentrations of fluid-soluble elements than MORB. The Diyanmiao transitional lavas have transitional compositions between FABs and boninites, and have higher large ion lithophile elements (LILEs) and lower high field strength elements (HFSEs) than FABs. The boninites are characterized by significant depletion of Ti, heavy rare earth element (HREE), and HFSE and are more LILE-enriched. This volcanic sequence is akin to that in the Mariana forearc, suggesting that the Diyanmiao FABs might record initial volcanism associated with subduction initiation in the southeastern Paleo-Asian Ocean during Early Carboniferous (∼335.6 Ma). We infer that the primary magmas of the Diyanmiao FABs were generated by partial melting of upwelling mantle associated with decompression during forearc spreading with little or no slab input. Progressive subduction of the Paleo-Asian oceanic slab (ca. 328 Ma), and flushing by slab-derived hydrous fluids resulted in melting of the more depleted, residual mantle at (probably) shallower levels generating the boninites.

Europium(ii)-doped phosphate cyan@red-emitting phosphors with highly dispersed luminescence centers were developed for the first time by using the deposition-precipitation method. Amazingly, when excited by near-ultraviolet light, the single phosphor generated warm white light with an adjustable correlated colour temperature (4000-2500 K) and high colour-rendering index (Ra ∼ 90).

Background Carboxylesterases (CEs) belong to the serine hydrolase family, and are in charge of hydrolyzing chemicals with carboxylic acid ester and amide functional groups via Ser-His-Glu. Uncaria rhynchophylla (Miq.) Miq. ex Havil. is a famous traditional Chinese medicine used in managing hyperpyrexia, epilepsy, preeclampsia, and hypertension in China. Hypothesis/purpose To discover the potential natural human carboxylesterase 2 (hCE 2) inhibitors from U. rhynchophylla. Methods Compounds were obtained from the hooks of U. rhynchophylla by silica gel and preparative HPLC. Their structures were elucidated by using HRESIMS, 1D and 2D NMR spectra. Their inhibitory activeties and inhibition kinetics against hCE 2 were assayed by the fluorescent probe, and potential mechanisms were also investigated by molecular docking. Results Twenty-three compounds, including a new phenolic acid uncariarhyine A (1), eight known triterpenoids (2–9), and ten known aromatic derivatives (10, 13–16, and 19–23), were isolated from U. rhynchophylla. Compounds 1–5, 7, 9, and 15 showed significant inhibitory activities against hCE 2 with IC50 values from 4.01 ± 0.61 µM to 18.60 ± 0.21 µM, and their inhibition kinetic analysis results revealed that compounds 1, 5, 9, and 15 were non-competitive; compounds 3 and 4 were mixed-type, and compounds 2 and 7 were uncompetitive. Molecular docking studies indicated inhibition mechanisms of compounds 1–5, 7, 9, and 15 against hCE 2. Conclusion Our present findings highlight potential natural hCE 2 inhibitors from U. rhynchophylla.