High-efficiently utilizing micro-nano ozone bubbles to enhance electro-peroxone process for rapid removal of trace pharmaceutical contaminants from hospital wastewater.

The electro-peroxone (EP) process encounters two inherent challenges in wastewater treatment: sluggish O2/O3 transfer and substantial ozone waste. To overcome these limitations, we introduced micro-nano bubbles (MNBs) aeration to enhance O2/O3 dissolution and diffusion, ultimately aiming to improve the removal of trace pharmaceutical contaminants from hospital wastewater. In the MNBs aeration system, the ozone transfer coefficient ranging from 0.536 to 0.265 min-1, significantly surpassing that of conventional aeration (0.220 to 0.090 min-1) by approximately 2 to 4.5 times. Consequently, the EP process under MNBs aeration significantly enhanced ozone-resistant ibuprofen (IBU) removal, achieving a removal rate of 98.4 ± 1.5 %, far exceeding the 47.3 ± 4.7 % observed with conventional aeration. This significant improvement was attributed to the heightened production of hydroxyl radicals (•OH), reaching 0.97 × 10-9 M s, compared to only 0.28 × 10-9 M s in conventional aeration. The mechanism behind the enhanced •OH production in the MNBs-EP process relied primarily on two factors: improved O2/O3 dissolution due to high internal pressure/large surface and enhanced O3/H2O2 activation from high collapse energy. These factors together contributed to the robust oxidation capability of the MNBs-EP system. As a result, over 97 % removal efficiency was achieved for five representative pharmaceutical pollutants (sulfamethoxazole, ribavirin, norfloxacin, tetracycline and ampicillin) in just 1 min. Furthermore, when applied to real hospital wastewater, the MNBs-O3-E treatment system reduced all 15 detected trace pharmaceutical compounds to below 10 ng L-1 and achieved 14 types of pollutants with removal rates of over 85 % within 15 min, resulting in an ultrahigh total removal rate of 98.6 %, from an initial total concentration of 2108 ng L-1 to less than 30 ng L-1. Thus, micro-nano aeration endowed the EP process as a promising advanced oxidation system for rapid and highly-effective removal of trace pharmaceutical contaminants from hospital wastewater.

Feedback of chain elongation microorganisms on iron-based conductive materials: Enhanced microbial functions and biotoxicity adaptation mechanisms.

Despite the increased research efforts aimed at understanding iron-based conductive materials (CMs) for facilitating chain elongation (CE) to produce medium chain fatty acids (MCFAs), the impact of these materials on microbial community functions and the adaptation mechanisms to their biotoxicity remain unclear. This study found that the supply of zero-valent iron (ZVI) and magnetite enhanced the MCFAs carbon-flow distribution by 26 % and 52 %, respectively. Metagenomic analysis revealed the upregulation of fatty acid metabolism, pyruvate metabolism and ABC transporters with ZVI and magnetite. The predominant functional microorganisms were Massilibacterium and Tidjanibacter with ZVI, and were Petrimonas and Candidatus_Microthrix with magnetite. Furthermore, it was demonstrated that CE microorganisms respond and adapt to the biotoxicity of iron-based CMs by adjusting Two-component system and Quorum sensing for the first time. In summary, this study provided a new deep-insight on the feedback mechanisms of CE microorganisms on iron-based CMs.

Purinergic P2X7 receptor involves in anti-retinal photodamage effects of berberine.

Berberine (BBR) is a Chinese herb with antioxidant and anti-inflammatory properties. In a previous study, we found that BBR had a protective effect against light-induced retinal degeneration in BALB/c mice. The purinergic P2X7 receptor (P2X7R) plays a key role in retinal degeneration via inducing oxidative stress, inflammatory changes, and cell death. The aim of this study was to investigate whether BBR can induce protective effects in light damage experiments and whether P2X7R can get involved in these effects. C57BL/6 J mice and P2X7 knockout (KO) mice on the C57BL/6 J background were used. We found that BBR preserved the outer nuclear layer (ONL) thickness and retinal ganglion cells following light stimulation. Furthermore, BBR significantly suppressed photoreceptor apoptosis, pro-apoptotic c-fos expression, pro-inflammatory responses of Mϋller cells, and inflammatory factors (TNF-α, IL-1ß). In addition, protein levels of P2X7R were downregulated in BBR-treated mice. Double immunofluorescence showed that BBR reduced overexpression of P2X7R in retinal ganglion cells and Mϋller cells. Furthermore, BBR combined with the P2X7R agonist BzATP blocked the effects of BBR on retinal morphology and photoreceptor apoptosis. However, in P2X7 KO mice, BBR had an additive effect resulting in thicker ONL and more photoreceptors. The data suggest that the P2X7 receptor is involved in retinal light damage, and BBR inhibits this process by reducing histological impairment, cell death, and inflammatory responses.

Urinary microalbumin/creatinine ratio is a predictor of the occurrence and severity of leukoaraiosis.

OBJECTIVE: To investigate the correlation between the urinary microalbumin/creatinine ratio (UACR) and the occurrence and severity of leukoaraiosis. METHODS: A total of 323 patients were retrospectively recruited. Demographic, clinical, and laboratory data were collected at the time of admission, and the UACR was calculated based on the levels of urinary microalbumin and creatinine. All patients showed improvement in cranial magnetic resonance imaging (MRI) examination. The subjects were divided into leukoaraiosis and non-leukoaraiosis groups according to the results of the cranial MRI examination. According to the Fazekas standard score, the patients in the leukoaraiosis group were divided into the mild leukoaraiosis group: Fazekas (1-2 points), moderate leukoaraiosis group: Fazekas (3-4points); and severe leukoaraiosis group: Fazekas (5-6 points). RESULTS: A regression analysis was performed to adjust for confounding factors. (1) Compared with the non-leukoaraiosis group, UACR level was higher in the leukoaraiosis group at admission, and the difference between the groups was statistically significant (p < 0.05). (2) In the multivariate logistic regression analysis, UACR was correlated with the occurrence of leukoaraiosis, which may be an independent risk factor. (3) The UACR levels increased gradually in the mild, moderate and severe leukoaraiosis groups, and the difference was statistically significant (p< 0.05). (4) In the ordered multi-category logistic regression analysis, UACR was correlated with the severity of leukoaraiosis, which may be an independent risk factor. CONCLUSION: UACR is associated with the occurrence and severity of leukoaraiosis, and may be an independent risk factor.

MG53 alleviates hypoxia/reoxygenation-induced cardiomyocyte injury by succinylation and ubiquitination modification.

BACKGROUND: Mitsugumin 53 (MG53) is a membrane repair factor that is associated with acute myocardial infarction. This study aimed to investigate the effects of MG53 on cardiomyocyte injury and the posttranslational modification of MG53. METHODS: Cardiomyocyte injury was evaluated by enzyme-linked immunosorbent assay and flow cytometry. The succinylation and ubiquitination levels of MG53 were examined by immunoprecipitation (IP) and western blot. The relationship between MG53 and KAT3B or SIRT7 was assessed by co-IP and immunofluorescence. RESULTS: The results showed that overexpression of MG53 inhibited inflammation response and apoptosis of cardiomyocytes induced by hypoxia/reoxygenation (H/R). Succinylation and protein levels of MG53 were downregulated in H/R-induced cells, which was inhibited by SIRT7 and promoted by KAT3B. SIRT7 aggravated and KAT3B alleviated MG53-mediated cardiomyocyte injury. Moreover, MG53 was succinylated and ubiquitinated at K130. CONCLUSION: SIRT7 inhibited/KAT3B promoted succinylation of MG53 at K130 sites, which suppressed ubiquitination of MG53 and upregulated its protein levels, thereby alleviating H/R-induced cardiomyocyte injury. The findings suggested that MG53 may be a potential therapy for myocardial infarction.

High-efficiency mode-locked erbium-doped ZBLAN fiber laser around 2.8 µm by directly depositing Bi2S3 particles onto a cavity mirror.

Mid-infrared (MIR) pulsed lasers near a 3 µm waveband show great potential for the high absorption of water molecules and many important gas molecules. A passively Q-switched mode-locked (QSML) E r 3+-doped fluoride fiber laser with a low laser threshold and high slope efficiency around a 2.8 µm waveband is reported. The improvement is achieved by depositing bismuth sulfide (B i 2 S 3) particles onto the cavity mirror directly as a saturable absorber and using the cleaved end of the fluoride fiber as output directly. -QSML pulses begin to appear with the pump power of 280 mW. The repetition rate of the QSML pulses reaches a maximum of 33.59 kHz with the pump power of 540 mW. When the pump power is further increased, the output of the fiber laser switches from the QSML to the continuous-wave mode-locked operation with the repetition rate of 28.64 MHz and the slope efficiency of 12.2%. The results indicate that B i 2 S 3 is a promising modulator for the pulsed lasers near a 3 µm waveband, which paves the way for further development of various applications in MIR wavebands, including material processing, MIR frequency combs, and modern healthcare.

Tailoring the p-Band Center of NS Pair for Accelerating High-Performance Lithium-Oxygen Battery.

The local coordination environment of catalytical moieties directly determines the performance of electrochemical energy storage and conversion devices, such as Li-O2 batteries (LOBs) cathode. However, understanding how the coordinative structure affects the performance, especially for non-metal system, is still insufficient. Herein, a strategy that introduces S-anion to tailor the electronic structure of nitrogen-carbon catalyst (SNC) is proposed to improve the LOBs performance. This study unveils that the introduced S-anion effectively manipulates the p-band center of pyridinic-N moiety, substantially reducing the battery overpotential by accelerating the generation and decomposition of intermediate products Li1-3 O4 . The lower adsorption energy of discharging product Li2 O2 on NS pair accounts for the long-term cyclic stability by exposing the high active area under operation condition. This work demonstrates an encouraging strategy to enhance LOBs performance by modulating the p-band center on non-metal active sites.

Visual ratiometric optical thermometer with high sensitivity and excellent signal discriminability based on LiScSiO4:Ce3+, Tb3+ thermochromic phosphor.

Developing optical thermometer phosphors with high sensitivity, high signal discriminability and strong fluorescence intensity is ongoing. A dual-emitting thermochromic phosphor, LiScSiO4:Ce3+, Tb3+, was successfully synthesized via solid-state reaction method. The crystal structure, electronic structure, luminescent performance and thermal luminescence behaviors as well as the luminescence mechanism of LiScSiO4:Ce3+, Tb3+ were systematically investigated. Due to the energy transfer and different thermoluminescence behaviors between Ce3+ and Tb3+, high relative sensitivity (2.2 % K-1@473 K), excellent signal discriminability (5747 cm-1), outstanding temperature resolution (0.067 K) and good repeatability, as well as efficient emission at high temperatures were achieved based on the fluorescence intensity ratio of Ce3+ and Tb3+, indicating its potential in ratiometric optical thermometer. Moreover, the excellent visualizing thermochromic enable LiScSiO4:Ce3+, Tb3+ to be used as safety sign in variable temperature environment to monitor temperature distribution.

Unsaturated Fatty Acid Liposomes Selectively Regulate Glutathione Peroxidase 4 to Exacerbate Lipid Peroxidation as an Adaptable Liposome Platform for Anti-Tumor Therapy.

Regulating non-apoptotic cell death of cancer cells provides a promising strategy to overcome apoptosis resistance during cancer treatment. Lipids are essential components to exacerbate several non-apoptotic cell death pathways. In the present study, unsaturated fatty acid (UFA) liposomes prepared with linoleic acid, oleic acid, or α-linolenic acid have the potential to affect lipid metabolism. Notably, UFA liposomes markedly increased cellular reactive oxygen species (ROS) and down-regulated the expression of glutathione peroxidase 4 (GPX4) in tumor cells, resulting in lipid peroxidation, which in turn caused rapid membrane rupture and induced non-apoptotic cell death of tumor cells. Concomitantly, UFA liposomes induced ROS-mediated tumor-associated macrophages toward a tumoricidal phenotype to reverse the immunosuppressive tumor microenvironment. Consequently, UFA liposomes substantially inhibited tumor growth in a melanoma model by promoting lipid peroxidation, inducing non-apoptotic cell death of tumor cells, and increasing infiltration of anti-tumor immune cells at tumor sites. Therefore, UFA liposomes regulate GXP4 to exacerbate lipid peroxidation and provide a versatile liposome platform for enhancing anti-tumor therapy which could be readily extended to the delivery of anticancer agents.

Design of a nitridoalumosilicate red phosphor synthesized under mild conditions.

Developing nitridosilicate red phosphors under mild synthesis conditions is important for regulating the emission quality of white light-emitting diodes (WLEDs). Based on the thermodynamic theory and crystal structure chemistry for the synthesis of nitridosilicates, the Gibbs free energy variation of a hybrid system can be made more negative by reducing the proportion of Si3N4 and increasing the proportion of M2N3 and AlN, enabling the formation of new nitridosilicates under mild conditions. Therefore, a general chemical formula MxSiyAlzNk was proposed for the design of nitridosilicate red phosphors prepared under mild conditions, where M is an alkaline earth metal ion; x > y; z ≥ y; 1 ≤ y ≤ 3; x + 2y = 3n + 3; k - z = 2n + 2; and n is a positive integer. Therefore, in this study, we successfully synthesized the nitridoalumosilicate red phosphor Ca4SiAl3N7:Eu2+ at normal pressure and lower temperature (1350 °C). Under excitation with 460 nm blue light, the Ca4SiAl3N7:Eu2+ phosphor efficiently emits red light at 645 nm and exhibits excellent thermal stability. The crystal structure and luminescence properties of Ca4SiAl3N7:Eu2+ were investigated in detail. The results indicate that Ca4SiAl3N7:Eu2+ exhibits strong potential for use in WLEDs. The design of nitridoalumosilicate red phosphors synthesized under mild conditions based on Gibbs free energy variation provides a new idea for the development of new nitride phosphors.

Individualized positive end-expiratory pressure with and without recruitment maneuvers in obese patients during bariatric surgery.

This study aimed to determine whether regular recruitment maneuvers (RMs) are essential for obese patients (OPs) undergoing elective laparoscopic bariatric surgery (LBS) during intraoperative ventilation with individualized positive end-expiratory pressure (PEEP). Patients were randomly assigned to two arms: the RM + PEEP-EIT arm consisted of individualized PEEP titrated by electrical impedance tomography (EIT) with two regular RMs and the PEEP-EIT arm consisted of individualized PEEP titrated by EIT without additional RMs. For these two arms together, EIT-guided PEEP varied among individuals. The partial pressure of oxygen in arterial blood to fractional inspired oxygen (PaO2 /FiO2 ) ratio in the RM + PEEP-EIT arm was higher than that in the PEEP-EIT arm at 1 h after pneumoperitoneum (p = 0.024) and at the end of surgery (p = 0.035). There was no great difference in the PaO2 /FiO2 ratio between these two arms when measured 5 min prior to postanesthesia care unit (PACU) departure and on postoperative day 1. Compared with the PEEP-EIT arm, patients in the RM + PEEP-EIT arm had significantly higher intraoperative dynamic respiratory system compliance (p < 0.001) but consumed more vasopressors (p = 0.036). Postoperative pulmonary complications occurred in 1 of 29 patients in the RM + PEEP-EIT arm compared with 2 of 31 patients in the PEEP-EIT arm. Regular lung RMs can improve intraoperative oxygenation and respiratory system compliance among OPs undergoing LBS with EIT-guided individual PEEP. However, the improvement might disappear before leaving the PACU, and regular RMs resulted in more vasopressor consumption.

2†µm sub-GHz harmonic mode-locked soliton generation based on a Bi2S3 saturable absorber.

Saturable absorber (SA) based harmonic mode-locking (HML) techniques at 2 µm waveband are much less reported than those at 1.5 µm waveband, the maximum repetition rate of the harmonic pulse generated by such techniques at 2 µm waveband is also much lower than those generated at 1.5 µm waveband. In this paper, the 39th harmonic with the repetition rate of 908.6 MHz is realized in a Bi2S3-based thulium-doped fiber laser. The fundamental mode-locked pulse has a central wavelength of 1954.2 nm and a 3-dB bandwidth of 5.1 nm. The repetition rate is 23.27 MHz and the pulse width is 902 fs. The characteristics of the material and harmonic mode-locked pulse are investigated. To the best of our knowledge, this is the highest and the closest resonance frequency to GHz among the reported SA-based harmonic mode-locked fiber lasers operating at 2 µm waveband.

Full-visible-spectrum lighting realized by a novel Eu2+-doped nitride-based cyan-emitting phosphor.

Cyan phosphors have attracted considerable attention in recent years as an indispensable component for realizing full-spectrum lighting. In this study, a novel nitride-based cyan-emitting phosphor Ca2BN2Cl:Eu2+ was successfully prepared. Its crystal structure refined by the Rietveld refinement reveals that Ca2BN2Cl is formed by a tight host lattice and the edge-sharing Ca(N,Cl)4 tetrahedrons along with multiple crystallographic Ca sites for Eu2+ ions to occupy, which corresponds to its broad emission band. Under the near ultraviolet (NUV) light excitation, Ca2BN2Cl:Eu2+ emits a broad-band cyan light and its full width at half-maximum (FWHM) can reach 121 nm, which effectively compensates the "cyan cavity". The time-resolved photoluminescence (TRPL) spectra of Ca2BN2Cl:Eu2+ were investigated to expose the energy transfer between the multiple luminescent centers. Furthermore, the temperature-dependent spectra of Ca2BN2Cl:Eu2+ were measured to evaluate its thermal stability. All of the discussion and results reveal that Ca2BN2Cl:Eu2+ is a promising cyan phosphor for use in white light-emitting diodes to realize full-spectrum lighting.

ATP and Adenosine in the Retina and Retinal Diseases.

Extracellular ATP and its ultimate degradation product adenosine are potent extracellular signaling molecules that elicit a variety of pathophysiological pathways in retina through the activation of P2 and P1 purinoceptors, respectively. Excessive build-up of extracellular ATP accelerates pathologic responses in retinal diseases, whereas accumulation of adenosine protects retinal cells against degeneration or inflammation. This mini-review focuses on the roles of ATP and adenosine in three types of blinding diseases including age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR). Several agonists and antagonists of ATP receptors and adenosine receptors (ARs) have been developed for the potential treatment of glaucoma, DR and AMD: antagonists of P2X7 receptor (P2X7R) (BBG, MRS2540) prevent ATP-induced neuronal apoptosis in glaucoma, DR, and AMD; A1 receptor (A1R) agonists (INO-8875) lower intraocular pressure in glaucoma; A2A receptor (A2AR) agonists (CGS21680) or antagonists (SCH58261, ZM241385) reduce neuroinflammation in glaucoma, DR, and AMD; A3 receptor (A3R) agonists (2-Cl-lB-MECA, MRS3558) protect retinal ganglion cells (RGCs) from apoptosis in glaucoma.

Carbon monoxide poisoning: a prediction model using meteorological factors and air pollutant.

BACKGROUND: While the influence of meteorology on carbon monoxide (CO) poisoning has been reported, few data are available on the association between air pollutants and the prediction of CO poisoning. Our objective is to explore meteorological and pollutant patterns associated with CO poisoning and to establish a predictive model. RESULTS: CO poisoning was found to be significantly associated with meteorological and pollutant patterns: low temperatures, low wind speeds, low air concentrations of sulfur dioxide (SO2) and ozone (O38h), and high daily temperature changes and ambient CO (r absolute value range: 0.079 to 0.232, all P values < 0.01). Based on the above factors, a predictive model was established: "logitPj = aj - 0.193 * temperature - 0.228 * wind speed + 0.221 * 24 h temperature change + 1.25 * CO - 0.0176 * SO2 + 0.0008 *O38h; j = 1, 2, 3, 4; a1 = -4.12, a2 = -2.93, a3 = -1.98, a4 = -0.92." The proposed prediction model based on combined factors showed better predictive capacity than a model using only meteorological factors as a predictor. CONCLUSION: Low temperatures, wind speed, and SO2 and high daily temperature changes, O38h, and CO are related to CO poisoning. Using both meteorological and pollutant factors as predictors could help facilitate the prevention of CO poisoning.

Constructing an experiential education model in undergraduate radiology education by the utilization of the picture archiving and communication system (PACS).

BACKGROUND: Medical education in China is in a transitional period, from passive learning models to experiential education. We modified an experiential education method for radiology education. The aim of this study is to evaluate the effect of this method on undergraduate radiology education. METHOD: With the help of the picture archiving and communication system (PACS) and RadiAnt DICOM Viewer, we modified an experiential education method that simulates similar working conditions for undergraduate medical students to formulate radiology diagnosis similar to clinical radiologists. A total of 101 students were allocated into either the experiential education group or the control group. The final examination scores and a 5-point Likert scale self-assessment questionnaire of radiologic skills were collected from all the students as an objective assessment and a subjective assessment respectively. A questionnaire was also used to assess the satisfaction with the experiential model in the experiential education group. Mann-Whitney U test was used to compare the ranked data, and t-tests were used to compare the numeric data. RESULTS: The experiential education group demonstrated significantly higher scores (7.4 ± 1.3) compared to the control group (6.7 ± 1.5, p < 0.05) in the question type "description and diagnosis". The self-assessment questionnaire indicated that the experiential education was related to increased familiarity with the diagnosis thinking principle and the sequences and reconstruction methods of computer tomography (CT) imaging, which also strengthen participants' self-confidence to perform future clinical work (p < 0.05). The self-assessment questionnaire in the experiential education group showed that the majority of students were satisfied with the organization (82.5%), interactivity (85%) and quality (85%) of the learning activity. Most students found this model of learning to be helpful for studying radiology (85%) and for understanding anatomy (90%). CONCLUSION: Compared with the traditional radiology education approach, the experiential education method showed greater efficacy in improving students' analysis and diagnostic skills and their self-confidence.

Expression of recombinant human acetylcholinesterase and its application in screening its inhibitors.

This study is designed to obtain recombinant human acetylcholinesterase (rhAChE) and apply it in screening acetylcholinesterase inhibitors. The rhAChE was overexpressed in HEK293 cells transfected by plasmid of pCMV-AChE with the cationic liposome and rhAChE was found to be secreted into cell culture medium. AChE activity was assayed according to modified Ellman method to obtain kinetic parameters. IC so50 values for donepezil compounds of rhAChE were calculated to determine their activities of inhibition. The results showed that Km value was 151.9 micromol.L-1 donepezil inhibited rhAChE in a mixed competitive-noncompetitive way (Ki= 16.03 nmol.L-1, Ki = 18.36 nmol.L-1) and that most new compounds tested exhibited high activities of inhibition on rhAChE. The study suggests that rhAChE is available to be applied in screening AChE inhibitors in vitro.

Effects of chromium-loaded chitosan nanoparticles on growth, blood metabolites, immune traits and tissue chromium in finishing pigs.

Effects of chromium-loaded chitosan nanoparticles (Cr-CNP) on growth performance, blood metabolites, immune traits, and tissue chromium in finishing pigs were investigated. A total of 160 crossbred barrows (66.06 ± 1.01 kg initial weight) were randomly divided into four groups, each group with four pens, ten pigs per pen. Pigs were fed on the same basal diet supplemented with 0 (the control), 100, 200, and 400 µg/kg Cr from Cr-CNP. All pigs were given free access to feed and water. Eight pigs from each treatment were selected to collect blood and tissue samples after 35 days on trial for analysis of blood metabolites and immune traits and tissue chromium. The results of feeding trial showed that there were no significant difference in growth performance between control and Cr-CNP-treated groups. The supplementation of Cr-CNP decreased serum glucose (P < 0.001) in a linear and quadratic manner. Serum immunoglobulins A and M were linearly increased in Cr-CNP-treated groups (P < 0.001), and serum complement 4 in Cr-CNP-treated groups was also linearly increased (P < 0.05). Cr-CNP supplementation linearly increased the chromium content in the blood, longissimus muscle, heart, liver, kidney, and pancreas (P < 0.001). These results suggested that dietary supplementation of Cr as Cr-CNP affects serum glucose, influences immune status, and increases the tissue chromium content of blood, muscle, and selected organs in finishing pigs.

PXR-mediated transcriptional activation of CYP3A4 by cryptotanshinone and tanshinone IIA.

Danshen (Radix Salvia miltiorrhiza) is a famous Traditional Chinese Medicine used widely for the treatment of coronary heart disease and cerebrovascular disease. Diterpenoid tanshinones including tanshinone I, tanshinone IIA and cryptotanshinone are the major bioactive components from Danshen herb. Previous reports have demonstrated that Danshen extracts could induce the expression of CYP3A in rodents, however, the constituents responsible for Danshen-mediated CYP3A induction and the underlying molecular mechanisms remain unknown. The discovery of a family of nuclear receptors such as pregnane X receptor (PXR), constitutive androstane receptor (CAR) and glucocorticoid receptor (GR) gives insight into the molecular explanation of CYP3A induction by xenobiotics. In the present study, interactions between Danshen constituents and human PXR were evaluated using a reporter gene assay. Our observations showed that Danshen ethanol extract could activate human PXR and induce the CYP3A4 reporter construct in HepG2 cells. Tanshinone IIA and cryptotanshinone were identified as efficacious PXR agonists, and cryptotanshinone activated the CYP3A4 promoter more strongly than tanshinone IIA. Furthermore, CAR and GR were also involved in the induction of CYP3A4 expression by tanshinones, though their roles seemed not as important as PXR. Treatment of LS174T cells with cryptotanshinone or tanshinone IIA resulted in a significant increase of CYP3A4 mRNA, which was consistent with the results from the reporter gene assay. Collectively, activation of PXR and the resultant CYP3A4 induction mediated by cryptotanshinone and tanshinone IIA provide a molecular mechanism for previously observed CYP3A induction by Danshen extracts, and our findings also suggest that caution should be taken when Danshen products are used in combination with therapeutic drugs metabolized by CYP3A4.

[Coexpression of PXRLBD with SRC88 and construction of equilibrium dialysis model of screening PXR ligands].

The aim of this study was to obtain the soluble protein of human pregnane X receptor ligand binding domain (PXRLBD) through the coexpression of PXRLBD and 88 amino acids of steroid receptor coactivator-1 (SRC88) and apply the protein to constructing a new model of screening PXR ligands. Expression plasmid of pETDuet-1-SRC88-PXRLBD was constructed and transformed into Escherichia coli Rosetta (DE3) to coexpress PXRLBD and SRC88 via induction by IPTG at low temperature. Then an equilibrium dialysis model was constructed to study the interaction between PXRLBD and drugs including clotrimazole and dexamethasone, using HPLC as the analysis method. The results showed that the soluble protein of PXRLBD was obtained and the HPLC data indicated that clotrimazole bound to PXRLBD, while dexamethasone did not bind to PXRLBD, which indicated the successful establishment of a new method for studying the interaction between PXR and drugs. The new method may be useful in the screening of PXR ligands in vitro.