Effects of flavonoids derived from Taxus yunnanensis on p-glycoprotein and cytochrome P450 3A4

AbstractThe intestinal uptake of paclitaxel is hampered by trans-membrane efflux transporters such as P-glycoprotein (P-gp), and paclitaxel is mainly metabolized by cytochrome P450 3A4 (CYP3A4) presented in the liver. Our previous results demonstrated that flavonoids extracted from Taxus yunnanensis could improve the oral absorption of paclitaxel. The current study was purposed to investigate the effects of the flavonoid extracts on P-gp and CYP3A4 in vitro. The expression and activity of P-gp were detected by western blotting and intracellular rhodamine 123 accumulation assay in Caco-2 cells treated with the flavonoids extract. The expression of CYP3A4 was investigated by western blotting in mouse primary hepatocytes and the activity of CYP3A4 was detected by LC-MS/MS method using rat liver microsomes. Our results showed that the flavonoid extracts from T. yunnanensis could inhibit P-gp activity and concurrently decrease the expression and activity of CYP3A4. In conclusion, activity of P-gp and CYP3A4 could be inhibited by flavonoids extracted from T. yunnanensis which might be potential candidates for development of oral formulation of paclitaxel

High visibility on-chip quantum interference of single surface plasmons

Quantum photonic integrated circuits (QPICs) based on dielectric waveguides have been widely used in linear optical quantum computation. Recently, surface plasmons have been introduced to this application because they can confine and manipulate light beyond the diffraction limit. In this study, the on-chip quantum interference of two single surface plasmons was achieved using dielectric-loaded surface-plasmon-polariton waveguides. The high visibility (greater than 90%) proves the bosonic nature of single plasmons and emphasizes the feasibility of achieving basic quantum logic gates for linear optical quantum computation. The effect of intrinsic losses in plasmonic waveguides with regard to quantum information processing is also discussed. Although the influence of this effect was negligible in the current experiment, our studies reveal that such losses can dramatically reduce quantum interference visibility in certain cases; thus, quantum coherence must be carefully considered when designing QPIC devices.Comment: 6 pages, 4 figure

Global Proteomic Analysis of Lysine Malonylation in Toxoplasma gondii

Lysine malonylation (Kmal) is a new post-translational modification (PTM), which has been reported in several prokaryotic and eukaryotic species. Although Kmal can regulate many and diverse biological processes in various organisms, knowledge about this important PTM in the apicomplexan parasite Toxoplasma gondii is limited. In this study, we performed the first global profiling of malonylated proteins in T. gondii tachyzoites using affinity enrichment and Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Three experiments performed in tandem revealed 294, 345, 352 Kmal sites on 203, 236, 230 malonylated proteins, respectively. Computational analysis showed the identified malonylated proteins to be localized in various subcellular compartments and involved in many cellular functions, particularly mitochondrial function. Additionally, one conserved Kmal motif with a strong bias for cysteine was detected. Taken together, these findings provide the first report of Kmal profile in T. gondii and should be an important resource for studying the physiological roles of Kmal in this parasite

Transformation of hexagonal Lu to cubic LuH2+x_{2+x} single-crystalline films

With the recent report of near ambient superconductivity at room temperature in the N-doped lutetium hydride (Lu-H-N) system, the understanding of cubic Lu-H compounds has attracted worldwide attention. Generally, compared to polycrystal structures with non-negligible impurities, the single-crystalline form of materials with high purity can provide an opportunity to show their hidden properties. However, the experimental synthesis of single-crystalline cubic Lu-H compounds has not been reported thus far. Here, we developed an easy way to synthesize highly pure LuH$_{2+x}$ single-crystalline films by the post-annealing of Lu single-crystalline films (purity of 99.99%) in the H$_2$ atmosphere. The crystal and electronic structures of films were characterized by X-ray diffraction, Raman spectroscopy, and electrical transport. Interestingly, Lu films are silver-white and metallic, whereas their transformed LuH$_{2+x}$ films become purple-red and insulating, indicating the formation of an unreported electronic state of Lu-H compounds possibly. Our work provides a novel route to synthesize and explore more single-crystalline Lu-H compounds

Preparation and PEGylation of recombinant human interferon lambda3

The purpose of this study was to express recombinant human interferon lambda3 (rhIFN-λ3) in Escherichia coli, and prepare PEGylated recombinant human interferon lambda3 (PEG-rhIFN-λ3). The rhIFN-λ3 gene was inserted into pThioHisA vector after codon optimization and transformed into E. coli top10 strain, and then it was induced with isopropyl-β-D-thio-galactoside (IPTG). The recombinant protein was subjected to mPEG-ButyrALD modification after dialysis, renaturation and chromatographic purification. Subsequently, the modified product was preliminary isolated and purified for determining its activity. Results show that the recombinant protein was expressed in the form of inclusion bodies. After ion exchange, molecular sieve and other column chromatography purification, the purity of the purified rhIFN-λ3 was as high as 90% and the purity of the mono-PEGylated rhIFN-λ3 after cation-exchange chromatography was as high as 86%. The 50% effective concentration (EC50) of rhIFN-λ3 in WISH cells against vesicular stomatitis virus (VSV) was 8.43 ng/mL, while the EC50 of mono-PEGylated rhIFN-λ3 was 49.19 ng/mL, which reserved 17.14% of the in vitro activity and supported further studies of this new type of investigational interferon. Further study is needed to better understand the in vivo immunogenicity, antigenicity, stability and antiviral activity of PEG-rhIFN-λ3.Keywords: Recombinant human interferon lambda3, prokaryotic expression, purification, mPEG-ButyrALD, antiviral activity

Seroprevalence of Toxoplasma gondii infection in pet dogs in Kunming, Southwest China

BACKGROUND: Toxoplasmosis is a zoonotic parasitic disease caused by the protozoan Toxoplasma gondii, which infects almost all warm-blooded animals, including humans, with a worldwide distribution. However, little is known of T. gondii seroprevalence in pet dogs in Kunming, the capital of Yunnan Province, southwest China. The objective of this investigation was to estimate the seroprevalence of T. gondii infection in pet dogs in this area. METHODS: A total of 611 serum samples were collected from 7 pet hospitals in Kunming, and assayed for T. gondii antibodies by the indirect haemagglutination (IHA) using a commercially-marked kit. RESULTS: 132 (21.6%) pet dogs were positive for T. gondii antibodies, and the seroprevalence ranged from 17.3% to 34.7% among different sampling regions, the difference was statistically significant (P < 0.05). The T. gondii seroprevalence in female and male dogs were 20.8% and 22.4%, respectively, the difference was not statistically significant (P > 0.05). The seroprevalence ranged from 17.5% to 23.6% among different age groups, but the difference was not statistically significant (P > 0.05), and there were no interactions in statistics (P > 0.05) between gender and age of pet dogs in the region. CONCLUSIONS: The findings of the present survey indicate high T. gondii seroprevalance in pet dogs in Kunming, southwest China, posing significant public health concern. It is necessary to enhance integrated strategies and measures to prevent and control T. gondii infection in pet dogs in this area

Carbapenemase-Producing Escherichia coli among Humans and Backyard Animals

Background: The rapidly increasing dissemination of carbapenem-resistant Enterobacteriaceae (CRE) in both humans and animals poses a global threat to public health. However, the transmission of CRE between humans and animals has not yet been well studied. Objectives: We investigated the prevalence, risk factors, and drivers of CRE transmission between humans and their backyard animals in rural China. Methods: We conducted a comprehensive sampling strategy in 12 villages in Shandong, China. Using the household [residents and their backyard animals (farm and companion animals)] as a single surveillance unit, we assessed the prevalence of CRE at the household level and examined the factors associated with CRE carriage through a detailed questionnaire. Genetic relationships among human- and animal-derived CRE were assessed using whole-genome sequencing–based molecular methods. Results: A total of 88 New Delhi metallo-β-lactamases –type carbapenem-resistant Escherichia coli (NDM-EC), including 17 from humans, 44 from pigs, 12 from chickens, 1 from cattle, and 2 from dogs, were isolated from 65 of the 746 households examined. The remaining 12 NDM-EC were from flies in the immediate backyard environment. The NDM-EC colonization in households was significantly associated with a) the number of species of backyard animals raised/kept in the same household, and b) the use of human and/or animal feces as fertilizer. Discriminant analysis of principal components (DAPC) revealed that a large proportion of the core genomes of the NDM-EC belonged to strains from hosts other than their own, and several human isolates shared closely related core single-nucleotide polymorphisms and blaNDM genetic contexts with isolates from backyard animals. Conclusions: To our knowledge, we are the first to report evidence of direct transmission of NDM-EC between humans and animals. Given the rise of NDM-EC in community and hospital infections, combating NDM-EC transmission in backyard farm systems is needed. https://doi.org/10.1289/EHP525

Tris(2-hydroxy­ethyl)ammonium 1,3-benzo­thia­zole-2-thiol­ate

In the title compound, C6H16NO3 +·C7H4NS2 −, the cations and anions are connected by O—H⋯N and O—H⋯S hydrogen bonding. Weak C—H⋯O hydrogen bonding between adjacent cations helps to stabilize the crystal structure

Transitional care for patients with chronic obstructive pulmonary disease

AbstractObjectivesTo observe the effects of transitional care on the quality of life of chronic obstructive pulmonary disease (COPD) patients.MethodsA total of 114 COPD patients were recruited from the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China and divided equally into an intervention group and control group. Following discharge, patients from the intervention group recieved three-months intervention in addition to regular nursing care, while control group patients received regular nursing care only. Patients' quality of life was measured using the St. George's respiratory questionnaire (SGRQ), the 12-item General Health Questionnaire (GHQ-12) and body mass index (BMI).ResultsThe symptoms section score, the activity section score, the impacts section score, the total score and the rate of mental disorders were significantly changed after the intervention while there was no statistical difference in BMI between groups.ConclusionsTransitional care can improve health-related quality of life in COPD patients who have recently suffered an exacerbation