ABSTRACT
During the COVID-19 pandemic, strict stay-at-home orders have been implemented in many Chinese universities in virus-hit regions. While changes in electricity consumption in the residential sector caused by COVID-19 have been thoroughly analysed, there is a lack of insight into the impact of the stay-at-home order on electricity consumption in university dormitory buildings. Based on questionnaire survey results, this study adopted the statistical Kaplan-Meier survival analysis to analyse the energy-use behaviours of university students in dormitories during the COVID-19 pandemic. The electricity load profiles of the dormitory buildings before and during the implementation of the stay-at-home order were generated and compared to quantitatively analyse the influence of COVID-19 pandemic on the energy-use behaviours of university students, and the proposed load forecasting method was validated by comparing the forecasting results with monitoring data on electricity consumption. The results showed that: 1) during the implementation of the stay-at-home order, electricity consumption in the university dormitory buildings increased by 41.05%; 2) due to the increased use of illuminating lamps, laptops, and public direct drinking machines, the daily electricity consumption increased most significantly from 13:00 to 18:00, with an increase rate of 97.15%; and 3) the morning peak shifted backward and the evening peak shifted forward, demonstrating the effect of implementing the stay-at-home order on reshaping load profiles.
ABSTRACT
P-glycoprotein (P-gp, MDR1) is expressed at the blood-brain barrier (BBB) and restricts penetration of its substrates into the central nervous system (CNS). In vitro MDR1 assays are frequently used to predict the in vivo relevance of MDR1-mediated efflux at the BBB. It has been well established that drug candidates with high MDR1 efflux ratios (ERs) display poor CNS penetration. Following a comparison of MDR1 transporter function between the MDR1-MDCKI cell line from National Institutes of Health (NIH) and our internal MDR1-MDCKII cell line, the former was found to provide better predictions of in vivo brain penetration than our in-house MDR1-MDCKII cell line. In particular, the NIH MDR1 assay has an improved sensitivity to differentiate the compounds with ERs of <3 in our internal cell line and is able to reduce the risk of false negatives. A better correlation between NIH MDR1 ERs and brain penetration in rat and non-human primate (NHP) was demonstrated. Additionally, a comparison of brain penetration time course of MDR1 substrates and an MDR1 non-substrate in NHP demonstrated that MDR1 interaction can delay the time to equilibrium of drug concentration in the brain with plasma. It is recommended to select highly permeable compounds without MDR1 interaction for rapid brain penetration to produce the maximal pharmacological effect in the CNS with a quicker onset.
Subject(s)
Blood-Brain Barrier/metabolism , Brain/metabolism , Pharmaceutical Preparations/metabolism , ATP Binding Cassette Transporter, Subfamily B/metabolism , Animals , Dogs , Drug Evaluation, Preclinical/methods , Humans , Macaca fascicularis , Madin Darby Canine Kidney Cells , Male , Rats , Rats, Sprague-Dawley , Species Specificity , Time Factors , Tissue DistributionABSTRACT
Supplying immunostimulants to aquatic feed has been an effective way to enhance the health of aquatic animals and substitute for antibiotics. In the present study, the potential effects of Astragalus polysaccharides (APS) were evaluated in turbot, Scophthalmus maximus. Two levels of APS (50 and 150 mg/kg) were added to the basal diet (CON) and a 63-day growth trial (initial weight 10.13 ± 0.04 g) was conducted. As the results showed, significant improvement on growth performance in the APS groups were observed. In addition, dietary 150 mg/kg APS significantly increased the total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX) and lysozyme activities in liver. Meanwhile, APS diets induced the mRNA expression of toll-like receptors (TLRs) such as tlr5α, tlr5ß, tlr8 and tlr21, while reduced the expression of tlr3 and tlr22. The expression of inflammatory genes myeloid differentiation factor 88 and nuclear factor kappa b p65 and pro-inflammatory cytokines tumor necrosis factor-α and interleukin-1ß were up-regulated in APS groups while the expression of anti-inflammatory cytokine transforming growth factor beta was inhibited. Taken together, the present study indicated that Astragalus polysaccharides could remarkably enhance the growth performance, antioxidant activity and maintain an active immune response in turbot.
Subject(s)
Astragalus Plant/chemistry , Dietary Carbohydrates/administration & dosage , Flatfishes/growth & development , Flatfishes/immunology , Polysaccharides/administration & dosage , Animals , Antioxidants/metabolism , Body Weight , Dietary Supplements , Flatfishes/physiology , Inflammation , Liver/immunology , Muramidase/metabolism , Signal Transduction/immunologyABSTRACT
The fast removal of dyes from aqueous solution and the recycling of adsorbents are currently popular topics in the study of adsorbents. Fe3O4 magnetic nanoparticles (MNPs) are usually applied in the preparation of composite adsorbents as magnetic carriers. Therefore, it is significant if single Fe3O4 MNPs can quickly remove dyes from aqueous solution with good cycling stability. Here, we report the preparation of Fe3O4 MNPs through an improved co-precipitation method, which has the inherent advantage of fast, inexpensive and without requiring the protection of nitrogen or an inert gas. The as-prepared Fe3O4 MNPs were used as an adsorbent to remove of methylene blue (MB) under alkaline condition, and then they were characterized by different measurements. The adsorption process was studied by various parameters, such as solution pH, initial MB concentration and contact time. The adsorption of MB over Fe3O4 MNPs reached equilibrium in 5 min, and it was observed to obey the pseudo-second-order kinetics model and Langmuir isotherm with a maximum adsorption capacity of 45.43 mg/g at pH = 12 and T = 298 K. Furthermore, two simple methods for desorption and chemical oxidation were used to the regenerate Fe3O4, and it turned out that Fe3O4 magnetic nanoparticles were able to maintain a high adsorption capacity (36 mg/g for desorption and 36.9 mg/g for chemical oxidation, respectively) after 4 circulations.
ABSTRACT
Adsorption is an effective means to remove organic pollutant. However, it is challenging to prepare the adsorbents with high adsorption capacities and their regeneration. Herein, Co/Cr-codoped ZnO nanoparticles (NPs) with superb adsorption for dyes and antibiotics have been successfully synthesized by a mild solvothermal method. At the optimal Co:Cr:Zn doping moral ratio of 4:6:100, the maximum adsorption capacities of methyl orange (MO) and tetracycline hydrochloride (TC-HCl) on Co/Cr-codoped ZnO NPs is 1057.90â¯mgâ¯g-1 and 874.46â¯mgâ¯g-1, respectively. The adsorption process of the sample over MO and TC-HCl both agreed well with the pseudo-second-order kinetic model and Langmuir isotherm model. Adsorption thermodynamics proved that the adsorption of MO and TC-HCl on Co/Cr-codoped ZnO NPs was a spontaneous and endothermic process. The mechanism shows that the surface of Co/Cr-codoped ZnO NPs have more positive charges, larger specific surface area and more crystal defects due to Co3+ and Cr3+ substitutes Zn2+ in ZnO lattice, improving their adsorption property. In addition, Co/Cr-codoped ZnO NPs have also excellent adsorption capacity for Direct Red, Congo Red, Evans Blue and Methyl Blue. More importantly, the regeneration of adsorbents was studied to achieve the reuse of materials, and avoid secondary pollution. Co/Cr-codoped ZnO NPs will be a promising choice for wastewater treatment owing to its excellent adsorption capacity and relatively low cost.
ABSTRACT
Typically, concentration-response curves are based upon nominal inducer concentrations for in-vitro-to-in-vivo extrapolation of CYP3A4 induction. The limitation of this practice is that it assumes the hepatocyte culture model is a static system. We assessed whether correcting for: 1) changes in perpetrator concentration in the induction medium during the incubation period, 2) perpetrator binding to proteins in the induction medium, and 3) nonspecific binding of perpetrator can improve the accuracy of CYP3A4 induction predictions. Of the seven compounds used in this evaluation, significant parent loss and nonspecific binding were observed for rifampicin (29.3-38.3%), pioglitazone (64.3-78.6%), and rosiglitazone (57.1-75.5%). As a result, the free measured EC50 values (EC50u) of pioglitazone, rosiglitazone, and rifampicin were significantly lower than the nominal EC50 values. In general, the accuracy of the induction predictions, using multiple static models, improved when corrections were made for measured medium concentrations, medium protein binding, and nonspecific binding of the perpetrator, as evidenced by 18-29% reductions in the root mean square error. The relative induction score model performed better than the basic static and mechanistic static models, resulting in lower prediction error and no false-positive or false-negative predictions. However, even when the EC50u value was used, the induction prediction for bosentan, which is a substrate of organic anion transporter proteins, was overpredicted by approximately 2-fold. Accounting for the ratio of unbound intracellular concentrations to unbound medium concentrations (Kpuu,in vitro) (0.5-7.5) and the predicted multiple-dose Kpuu,in vivo (0.6) for bosentan resulted in induction predictions within 35% of the observed interaction.
Subject(s)
Cytochrome P-450 CYP3A Inducers/pharmacology , Cytochrome P-450 CYP3A/biosynthesis , Hepatocytes/drug effects , Hepatocytes/enzymology , Cryopreservation , Cytochrome P-450 CYP3A/metabolism , Cytochrome P-450 CYP3A Inducers/pharmacokinetics , Dose-Response Relationship, Drug , Drug Interactions , Enzyme Induction/drug effects , Hepatocytes/cytology , Hepatocytes/metabolism , Humans , Kinetics , Pioglitazone , Rifampin/pharmacokinetics , Rifampin/pharmacology , Rosiglitazone , Thiazolidinediones/pharmacokinetics , Thiazolidinediones/pharmacologyABSTRACT
Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a re-emerging environmental contaminant that has been frequently detected at sub-ppb (<µg/L) concentrations in natural waters. The objective of this study was to evaluate effects of TDCIPP on growth in initial generation (F0) zebrafish after chronic exposure to environmentally relevant concentrations, and to examine possible parental transfer of TDCIPP and transgenerational effects on growth of first generation (F1) larvae. When zebrafish (1-month old) were exposed to 580 or 7500 ng TDCIPP/L for 240 days, bioconcentration resulted in significantly less growth as measured by body length, body mass, brain-somatic index (BSI) and hepatic-somatic index (HSI) in F0 females but not F0 males. These effects were possibly due to down-regulation of expression of genes along the growth hormone/insulin-like growth factor (GH/IGF) axis. Furthermore, residues of TDCIPP were detected in F1 eggs after exposure of parents, which resulted in less survival, body length and heart rate in F1 individuals. Down-regulation of genes in the GH/IGF axis (e.g., gh, igf1) might be responsible for transgenerational toxicity. This study provides the first known evidence that exposure of zebrafish to environmentally relevant concentrations of TDCIPP during development can inhibit growth of offspring, which were not exposed directly to TDCIPP.
Subject(s)
Flame Retardants/toxicity , Organophosphorus Compounds/toxicity , Water Pollutants, Chemical/toxicity , Zebrafish/physiology , Animals , Down-Regulation , Female , Flame Retardants/metabolism , Larva/drug effects , Liver/metabolism , Male , Organophosphates/metabolism , Organophosphorus Compounds/metabolism , Water Pollutants, Chemical/metabolism , Zebrafish/growth & development , Zebrafish/metabolismABSTRACT
PURPOSE: Thalidomide, originally developed as a sedative, was subsequently identified to have antiangiogenic properties. Lenalidomide is an antiangiogenic and immunomodulatory agent that has been utilized in the treatment of patients with brain tumors. We studied the pharmacokinetics and cerebrospinal fluid (CSF) penetration of thalidomide and lenalidomide in a nonhuman primate model. METHODS: A dose of 50 mg of thalidomide or 20 mg of lenalidomide was administered once orally to each of three rhesus monkeys. Plasma and CSF samples were obtained at specified intervals, and the thalidomide or lenalidomide concentrations were determined by high-performance liquid chromatography with tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods. CSF penetration was calculated as area under the concentration-time curve (AUC) CSF/AUC plasma. RESULTS: For thalidomide, the median apparent clearance (Cl/F) was 2.9 mL/min/kg, the median plasma AUC was 80 µM h, and the median terminal half-life (t(½)) was 13.3 h. For lenalidomide, the median Cl/F was 8.7 mL/min/kg, the median AUC was 9 µM h, and the median t(½) was 5.6 h. Thalidomide was detected in the CSF of all animals, with a median penetration of 42%. Lenalidomide was detected in the CSF of 2 of 3 animals, with a CSF penetration of 11% in each. CONCLUSION: Thalidomide and lenalidomide penetrate into the CSF after oral administration of clinically relevant doses. Plasma exposure to lenalidomide was similar in our model to that observed in studies involving children who have brain tumors. These results support further development of lenalidomide for the treatment of central nervous system malignancies.
Subject(s)
Thalidomide/analogs & derivatives , Thalidomide/blood , Thalidomide/cerebrospinal fluid , Animals , Antineoplastic Agents/blood , Antineoplastic Agents/cerebrospinal fluid , Antineoplastic Agents/pharmacokinetics , Chromatography, High Pressure Liquid/methods , Lenalidomide , Macaca mulatta , Male , Thalidomide/pharmacokineticsABSTRACT
Because the prevailing form of hormone replacement therapy is associated with the development of cancer in breast and endometrial tissues, alternatives are needed for the management of menopausal symptoms. Formulations of Trifolium pratense L. (red clover) are being used to alleviate menopause-associated hot flashes but have shown mixed results in clinical trials. The strobiles of Humulus lupulusL. (hops) have been reported to contain the prenylflavanone, 8-prenylnaringenin (8-PN), as the most estrogenic constituent, and this was confirmed using an estrogen receptor ligand screening assay utilizing ultrafiltration mass spectrometry. Extracts of hops and red clover and their individual constituents including 8-PN, 6-prenylnaringenin (6-PN), isoxanthohumol (IX), and xanthohumol (XN) from hops and daidzein, formononetin, biochanin A, and genistein from red clover were compared using a variety of in vitro estrogenic assays. The IC50 values for the estrogen receptor alpha and beta binding assays were 15 and 27 microg/mL, respectively, for hops and 18.0 and 2.0 microg/mL, respectively, for the red clover extract. Both of the extracts, genistein, and 8-PN activated the estrogen response element (ERE) in Ishikawa cells while the extracts, biochanin A, genistein, and 8-PN, significantly induced ERE-luciferase expression in MCF-7 cells. Hop and red clover extracts as well as 8-PN up-regulated progesterone receptor (PR) mRNA in the Ishikawa cell line. In the MCF-7 cell line, PR mRNA was significantly up-regulated by the extracts, biochanin A, genistein, 8-PN, and IX. The two extracts had EC50 values of 1.1 and 1.9 microg/mL, respectively, in the alkaline phosphatase induction assay. On the basis of these data, hops and red clover could be attractive for the development as herbal dietary supplements to alleviate menopause-associated symptoms.
Subject(s)
Humulus/chemistry , Phytoestrogens/pharmacology , Trifolium/chemistry , Alkaline Phosphatase/biosynthesis , Cell Line, Tumor , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/metabolism , Estrogens , Gene Expression/drug effects , Humans , Luciferases/genetics , Phytoestrogens/isolation & purification , Phytoestrogens/metabolism , Receptors, Progesterone/genetics , Response Elements/drug effects , Response Elements/genetics , TransfectionABSTRACT
Although hormone replacement therapy (HRT) is used by post-menopausal women for the relief of menopausal symptoms and the potential reduction of osteoporosis, HRT also increases their risk of Alzheimer's disease, stroke, breast cancer, and endometrial cancer. Since the majority of these effects are associated primarily with estrogen binding to only one of the estrogen receptors (ER), new assays are needed that can more efficiently evaluate ER-binding and identify ligands selective for ER-alpha and ER-beta. High performance liquid chromatography-tandem mass spectrometry (LC-MS-MS) was combined with ultrafiltration as a new method to investigate the relative binding of compounds to the ERs and to evaluate the structures of these estrogens. Mixtures of estradiol and six equine estrogens, including equilin, equilenin, 8,9-dehydroestrone, and their 17beta-hydroxyl derivatives, were assayed simultaneously to determine their relative binding to human ER-alpha and ER-beta. Estrogens containing a 17beta-OH group were found to have higher relative affinities for the estrogen receptors than their ketone analogs. In addition, 17beta-EN showed selectivity for binding to ER-beta over ER-alpha. The results were compared to the IC50 values obtained by using a conventional radiolabled estradiol competitive binding assay. Finally, the utility of negative ion electrospray tandem mass spectrometry for the unambiguous identification of these estrogen isomers was investigated. Several characteristic recyclization pathways during tandem mass spectrometry were identified, which might be useful for distinguishing related estrogens.
Subject(s)
Estrogens/chemistry , Estrogens/metabolism , Receptors, Estrogen/metabolism , Spectrometry, Mass, Electrospray Ionization/methods , Animals , Estrogens/analysis , Horses , Humans , Molecular Structure , Receptors, Estrogen/chemistry , UltrafiltrationABSTRACT
Ginkgo biloba (ginkgo) is one of most frequently used botanical dietary supplements. The bioactive constituents include the terpenoid lactones consisting of bilobalide and the ginkgolides A, B, C and J. A new assay based on high-performance liquid chromatography/electrospray tandem mass spectrometry (LC/MS/MS) was developed for the measurement of the terpenoid lactones in ginkgo products such as leaf powder and extracts. Initially, the MS/MS fragmentation pathways of ginkgolides were investigated to identify abundant fragment ions that might be useful for the sensitive and selective detection of ginkgolides and bilobalide during LC/MS/MS. Then, sample preparation and clean-up procedures were streamlined to maximize throughput by taking advantage of the selectivity of LC/MS/MS detection. Analyte recoveries exceeded 90%, the intra-assay and inter-assay relative standard deviations were <5%, the relative error was <8% and the limits of detection and quantification were 3.6-120 and 11-350 fmol, depending on the analyte that was injected on to the LC column. Therefore, this LC/MS/MS assay facilitated the rapid quantitative analysis of ginkgolides A, B, C and J and bilobalide in ginkgo dietary supplements with excellent recovery, reproducibity, accuracy and sensitivity.
Subject(s)
Dietary Supplements/analysis , Ginkgo biloba/chemistry , Lactones/analysis , Lactones/chemistry , Terpenes/analysis , Terpenes/chemistry , Chromatography, Liquid , Lactones/isolation & purification , Plant Extracts/analysis , Plant Extracts/chemistry , Plants, Medicinal/chemistry , Sensitivity and Specificity , Spectrometry, Mass, Electrospray Ionization , Terpenes/isolation & purificationABSTRACT
Previously, we have presented a method for quantifying beta-carotene bioavailability based on analysis in serum, following administration of (13)C-labeled beta-carotene. Because stool samples can be collected noninvasively, we have now extended the method to measure the bioavailability based on measurements in feces. An extraction method was developed to enable measurement of concentrations and degree of isotopic enrichment of retinol, retinyl palmitate and carotenoids in feces. Relative bioavailability of beta-carotene from pumpkin (n = 6) was found to be 1.8 times (interval, 0.6, 5.5) greater than that from spinach (n = 8), based on data from feces compared with 1.7 times (interval, 0.9, 3.1) based on data from serum.
Subject(s)
Carotenoids/analysis , Feces/chemistry , beta Carotene/pharmacokinetics , Biological Availability , Carbon Isotopes , Carotenoids/blood , Child , Female , Humans , Indonesia , Male , Vitamin A/analysis , Vitamin A/blood , beta Carotene/analysis , beta Carotene/bloodABSTRACT
Caffeic acid derivatives occurring in black cohosh [Cimicifuga racemosa (L.) Nutt., Actaea racemosa (Ranunculaceae)], some of which may have pharmacological activity, were analyzed using high-performance liquid chromatography (HPLC) electrospray ionization tandem mass spectrometry (ESI-MS/MS) with the aim of developing a methodology for their rapid identification in a complex plant matrix. Based on these studies, structurally characteristic product ions and neutral molecule losses were identified, which were then used during LC/MS/MS with product ion scanning, precursor scanning and constant neutral loss scanning to detect caffeic acid derivatives in a crude extract of black cohosh. Several caffeic acid derivatives were detected, and the identification of six of them were confirmed by comparison with authentic standards including caffeic acid, ferulic acid, isoferulic acid, fukinolic acid, cimicifugic acid A, and cimicifugic acid B. Four other compounds were detected that appeared to be caffeic acid derivatives based on LC/MS/MS retention times, molecular weights, and fragmentation patterns during MS/MS. Since standards were unavailable for these four compounds, they were tentatively identified using LC/MS/MS as cimicifugic acid E, cimicifugic acid F, dehydrocimicifugic acid A, and dehydrocimicifugic acid B. Dehydrocimicifugic acid A and dehydrocimicifugic acid B have not been reported previously to be constituents of black cohosh.
Subject(s)
Caffeic Acids/chemistry , Cimicifuga/chemistry , Chromatography, High Pressure Liquid , Chromatography, Liquid , Plant Extracts/analysis , Spectrometry, Mass, Electrospray IonizationABSTRACT
Analysis of two commercial extracts of Andrographis paniculata using high-performance liquid chromatography (HPLC) with photodiode array absorbance detection showed the presence of several unexpected compounds, which were isolated and identified as methyl, ethyl, and propyl esters of p-hydroxybenzoic acid by using high-resolution mass spectrometry and nuclear magnetic resonance. Quantitative analysis using HPLC revealed the presence of 0.22% p-hydroxybenzoic acid methyl ester (methlyparaben) in one commercial extract, and both 0.11% p-hydroxybenzoic acid ethyl ester (ethylparaben) and 0.20% p-hydroxybenzoic acid propyl ester (propylparaben) in a second commercial extract of A. paniculata. Analyses of additional commercial products of A. paniculata in tablet form purchased from Chicago pharmacies also showed the presence of methyl- and ethylparabens. To determine whether these compounds were natural chemical constituents of the plant, pharmacopoeial reference A. paniculata plant powder as well as samples of authenticated A. paniculata plant materials collected from Indonesia, Hong Kong, and mainland China were obtained and analyzed by HPLC-tandem mass spectrometry (LC-MS-MS). LC-MS-MS analyses confirmed the presence of trace concentrations (<0.0008% w/w) of p-hydroxybenzoic acid methyl ester but no p-hydroxybenzoic acid ethyl or propyl esters in these plant samples. The limits of detection of the LC-MS-MS assay for these compounds were 5 pg on-column and 5 ppb in the plant material. The levels of these p-hydroxybenzoic acid esters measured in the commercial products of A. paniculata suggest that they were introduced inadvertently during processing or as artificial additives.
Subject(s)
Andrographis/chemistry , Parabens/analysis , Plant Extracts/chemistry , Plant Preparations/chemistry , Chromatography, High Pressure Liquid , Drug Contamination , Magnetic Resonance Spectroscopy , Mass Spectrometry , Quality ControlABSTRACT
In response to concerns that commercial dietary supplements containing Ginkgo biloba (ginkgo) and Echinacea purpurea, Echinacea angustifolia, or Echinacea pallida (echinacea) might be contaminated with colchicine, a highly selective and sensitive assay was developed for colchicine that is based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS-MS). The method utilizes reversed-phase HPLC separation of compounds in a methanolic extract of the dietary supplement or botanical sample followed by positive ion electrospray ionization with collision-induced dissociation and multiple reaction monitoring of three characteristic fragmentation pathways of the protonated molecule of colchicine, m/z 400 --> 358, 400 --> 326, and 400 --> 310. The minimal detectable concentration of colchicine using this assay was 10 pg on-column, which is equivalent to 20 ppb colchicine in a 0.5 g ginkgo leaf sample. The method was validated by analyzing 0.5 g samples spiked with colchicine and determining the recovery. A total of 26 commercial ginkgo and echinacea dietary supplements were purchased from pharmacies in Chicago, IL, and analyzed for colchicine. In contrast to a recent report, no colchicine was detected in any of the samples. In addition, authenticated ginkgo leaves were collected, assayed, and found to contain no colchicine, which is consistent with the botanical literature. On the basis of the results obtained using this new LC-MS-MS assay, which is more sensitive and more selective than previously published methods for colchicine, we find no cause for concern regarding colchicine contamination of ginkgo or echinacea dietary supplements.