Understanding the influence of natural organic matter (NOM) on synthetic organic contaminant (SOC) adsorption by carbon nanotubes (CNTs) is important for assessing the environmental implications of ...accidental CNT release and spill to natural waters, and their potential use as adsorbents in engineered systems. In this study, adsorption of two SOCs by three single-walled carbon nanotubes (SWNTs), one multi-walled carbon nanotube (MWNT), a microporous activated carbon fiber (ACF) i.e., ACF10 and a bimodal porous granular activated carbon (GAC) i.e., HD4000 was compared in the presence and absence of NOM. The NOM effect was found to depend strongly on the pore size distribution of carbons. Minimal NOM effect occurred on the macroporous MWNT, whereas severe NOM effects were observed on the microporous HD4000 and ACF10. Although the single-solute adsorption capacities of the SWNTs were much lower than those of HD4000, in the presence of NOM the SWNTs exhibited adsorption capacities similar to those of HD4000. Therefore, if released into natural waters, SWNTs can behave like an activated carbon, and will be able to adsorb, carry, and transfer SOCs to other systems. However, from an engineering application perspective, CNTs did not exhibit a major advantage, in terms of adsorption capacities, over the GAC and ACF. The NOM effect was also found to depend on molecular properties of SOCs. NOM competition was more severe on the adsorption of 2-phenylphenol, a nonplanar and hydrophilic SOC, than phenanthrene, a planar and hydrophobic SOC, tested in this study. In terms of surface chemistry, both adsorption affinity to SOCs and NOM effect on SOC adsorption were enhanced with increasing hydrophobicity of the SWNTs.
A highly feasible and reliable ultra‐high performance liquid chromatography tandem mass spectrometry method was presented for therapeutic drug monitoring of five anti‐schizophrenic drugs ...(amisulpride, olanzapine, aripiprazole, paliperidone and ziprasidone) simultaneously. To meet the requirements of practical clinical usage (easy handling, high throughput and cost effectiveness), the pretreatment process was simplified (only including protein precipitation and mobile phase dilution steps) and the UPLC separation cycle was set within 6 min. The whole methodology was carefully validated according to the latest international guidelines showing the excellent selectivity, accuracy, precision, applicability and stability. After a 10 month clinical application, a retrospective analysis of 253 positive samples was carried out to investigate conformance with the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie therapeutic reference range for Chinese patients. The results suggested good consistency for olanzapine, aripiprazole, paliperidone and ziprasidone, while for amisulpride, the plasma concentration level (445.2 ± 231.5 ng/mL) was relatively higher than the recommended range (100–320 ng/mL). We supposed that such phenomenon indicated the necessity of reconstructing a Chinese‐specific therapeutic reference range for amisulpride treatment, which would be helpful to improve medication efficiency and safety for Chinese patients.
Sex hormones, including androgens, estrogens, and progestogens, are important biomarkers for various diseases. Quantification of sex hormones is typically conducted by LC-MS/MS. At present, most ...methods require liquid-liquid extraction or solid phase extraction for sample preparation. However, these pretreatments are prone to compromise LC-MS/MS throughput. To improve on the current standard practices, we investigated cold-induced phase separation for sex hormone extraction. After protein precipitation with acetonitrile and adjusting the solution constitution with water, samples were stored at −30°C for 10 min to generate two distinct phases: an acetonitrile-rich layer on top of a water-rich layer. During this process, the hydrophobic sex hormones spontaneously separate into the upper layer. This simple and reliable cold-induced phase separation-based LC-MS/MS methodology was used here to simultaneously detect estrone, estradiol, estriol, testosterone, androstenedione, dehydroepiandrosterone, progesterone, and 17-hydroxyprogesterone in serum. Validation of this method indicated satisfactory performance, including acceptable linearity, accuracy, precision, and tractability. Compared with the mainstream liquid-liquid extraction-based method, this new method exhibits significant progress in throughput, which shortens the time cost of sample preparation from 90 to 40 min. We propose that this method can be an excellent alternative for sex hormone analysis in routine clinical laboratories.
This study set out to examine the implementation of a video blog (vlog) project in an English for Specific Purposes (ESP) course that aimed to increase students' opportunities to use the target ...language. Specifically, it explored students' perceptions towards vlogs and analysed the advantages and disadvantages of vlogs as identified by the students. Data sources included an attitude survey, an open‐ended questionnaire, student interviews, written peer feedback, video clips in vlogs and reflective journals. The results indicated that firstly, the students favourably perceived the vlog project because vlogs not only helped them organise and reflect on their learning products, but also allowed them to archive their learning processes. Second, they reported a number of advantages associated with vlogging, such as visual representation, relief from time constraints, self‐evaluation, professional development, wider audience, peer learning and technical capability. Third, in the opinion of the students, the challenges compromising the effectiveness of the vlog project involved technical difficulties, affective interferences, weak linkage to real‐time communication and time issues. In light of these findings, the researcher proposes two pedagogical implications for ESP instructional practices.
In this study, a Taguchi-based optimization method is proposed to search the coil parameters used for low-power wireless charging that will maximize the transmission efficiency. The coils were then ...implemented to charge a battery with a nominal voltage of 3.7 V and a rated capacity of 760 mAh, and it was found that the coil transmission efficiency increased by 3.7% compared to adopting the coil parameters obtained by using a genetic algorithm. Moreover, a 5-watt wireless charging system integrated with the Taguchi-based coils was built to charge a battery with a nominal voltage of 3.7 V and a rated capacity of 2200 mAh. The results showed that the coil transmission efficiency was higher than that of a commercial charger, but the dimension of the coil was larger than that of the commercial charger. Nevertheless, the air gap between transmitter and receiver coils was larger than that in the charger, and the charge time required for a 2200 mAh battery to reach a full charge was shorter than that required for the commercial charger. Although outcomes are still far from being satisfactory in the transmission efficiency, the proposed approach can greatly reduce computation cost in designing coils used for wireless charging.
Chronic eosinophilic pneumonia (CEP) is rare and an idiopathic disorder. The disease has been associated with drugs, infection, or irradiation, and its relationship with asthma remains unclear.
We ...reported a case of a 49-year-old female patient after trastuzumab and radiation therapy for breast cancer. Two months after radiation treatment, the patient complained of productive cough, progressive breathlessness, occasional wheezing, and left pectoralgia.
Computed tomography (CT) scan revealed infiltrates in lungs. Without evidence of infection, marked increased eosinophils in a transbronchial biopsy performed from the left upper lobe confirmed the diagnosis of CEP after trastuzumab and radiation therapy.
The patient was started with oral prednisone at 0.5 mg/kg/day.
A CT scan of the chest obtained 2 weeks after steroid treatment showed diminishment of the lesions, and at the 6-month follow-up, the patient had no complaints of discomfort with no relapse of pulmonary lesions.
Physicians should consider CEP as a diagnosis in patients who have had previous exposure to trastuzumab and radiation therapy, especially with a history of asthma. Timely diagnosis and treatment may benefit these patients.
•Hydroxytyrosol was selectively purified by zirconia through cis-diol recognition mechanism.•The whole pretreatment could be completed within 10 min.•Method LOD could reach 1 ng/mL, 0.5 μg/kg and ...0.1 ng/mL in wine, oil and plasma.
Hydroxytyrosol (HT) possesses significant biological activity. However, the methodologies for its quantification always suffered from low sensitivity, intricate treatment and high sample consumption. Here, we presented the very first attempt for specific extraction of HT through cis-diol recognition mechanism. By using easily prepared zirconia as dispersive solid phase extraction medium, HT from small amount of wine (10 μL), oil (20 mg) and plasma (100 μL) was efficiently purified within ten minutes. Coupled with LC-MS/MS analysis, the method limit of detection (LOD) could reach 1 ng/mL in wine, 0.5 μg/kg in oil and 0.1 ng/mL in plasma. Profited by this superior method, HT analysis was successfully performed in diverse wine and oil products as well as human plasma samples after intake of extra virgin olive oil. In addition, we further confirmed the endogenous HT was undetectable from routine human plasma even after upgrading the detection sensitivity through post isonicotinoyl chloride derivatization.
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•The method is single-batched and prevents complex pretreatments.•Only 100 μL serum is needed for sex hormone profiling.•The method is evaluated with SRMs and exhibits excellent ...consistency.•The method is systematically validated according to FDA and CLSI C62-A guidelines.•The methodology is applied to conduct the re-examination of sex hormone regulation for male coronary atherosclerosis.
Comprehensive serum sex hormone profiling is essential for monitoring the occurrence and development of many related diseases. However, the current methods for multi-class sex hormone detection were always lack of Standard Reference Material (SRM) certification and suffered from large sample consumption. For improvement, we developed a new liquid chromatography-tandem mass spectrometry (LC–MS/MS) method focused on SRM certification and minimization of serum consumption for simultaneous quantification of seven mainstream serum sex hormones including estrogens (estrone E1, estradiol E2 and estriol E3), androgens (testosterone T, androstenedione AD, dehydroepiandrosterone DHEA) and progestogens (progesterone P).
To achieve one-batch analysis, a straightforward strategy was designed and carefully optimized. Schematically, serum was firstly spiked with isotope-labeled internal standards. Then, liquid-liquid extraction was performed with methyl tert-butyl ether. After drying under nitrogen, dansyl chloride was introduced for derivatization. Finally, the mixture was submitted to LC–MS/MS for quantification.
The limit of quantification was 0.005 ng/mL for E1, E2 and E3, 0.01 ng/mL for T, P and AD, 0.25 ng/mL for DHEA. Inter- and intra-assay CVs were less than 11.8%. The selectivity was proved satisfactory by interference spiking tests. With systematical SRM validation, the mean bias of −5.4 to 4.7% was observed, which indicated excellent method reliability. We found significant positive bias in chemiluminescence immunoassay (CLIA) detection comparing with current method, which promoted us to reconsider our previous results on sex hormone regulation in male patients with coronary atherosclerotic disease. After redetecting the related samples, modified and improved conclusions were proposed.
A LC–MS/MS method for multi-class serum sex hormone profiling was developed with SRM certification and minimized serum consumption. Taking advantages of such reliable method, the previous CLIA-based research findings on sex hormone regulation in male patients with coronary atherosclerosis were modified and improved after redetecting the same sample-pool.
Abstract
Background
N
6-Methyladenosine (m6A) is the most common RNA modification and regulates RNA splicing, translation, translocation, and stability. Aberrant expression of m6A has been reported ...in various types of human cancers. m6A RNA modification is dynamically and reversibly mediated by different regulators, including methyltransferase, demethylases, and m6A binding proteins. However, the role of m6A RNA methylation regulators in thyroid cancer remains unknown. The aim of this study is to investigate the effect of the 13 main m6A RNA modification regulators in thyroid carcinoma.
Methods
We obtained clinical data and RNA sequencing data of 13 m6A RNA methylation regulators from The Cancer Genome Atlas (TCGA) THCA database. We performed consensus clustering to identify the clinical relevance of m6A RNA methylation regulators in thyroid carcinoma. Then we used LASSO Cox regression analysis to generate a prognostic signature based on m6A RNA modification regulator expression. Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Gene Set Enrichment Analyses were performed to explore differential cellular processes and signaling pathways between the two groups based on risk signature.
Results
We found that most of the m6A RNA modification regulators are down-regulated in 450 patients with thyroid carcinoma. We derived a three m6A RNA modification regulator genes-based risk signature (FTO, RBM15 and KIAA1429), that is an independent prognostic biomarker in patients with thyroid carcinoma. Moreover, we found that this risk signature could better predict outcome in male than female. Functional research in vitro demonstrated that the m6A RNA methylation regulators involved in the model acted significant role in the proliferation and migration of thyroid cancer cells.
Conclusions
Our study revealed the influence of m6A RNA methylation regulators on thyroid carcinoma through biological experiments and three-gene prognostic model.
Mammalian target of rapamycin (mTOR) is a core component of raptor-mTOR (mTORCI) and rictor-mTOR (mTORC2) complexes that control diverse cellular processes. Both mTORC1 and mTORC2 regulate several ...elements downstream of type I insulin-like growth factor receptor (IGF-IR) and insulin receptor (InsR). However, it is unknown whether and how roTOR regulates IGF-IR and InsR themselves. Here we show that mTOR possesses unex- pected tyrosine kinase activity and activates IGF-IR/InsR. Rapamycin induces the tyrosine phosphorylation and ac- tivation of IGF-IR/InsR, which is largely dependent on rictor and mTOIL Moreover, mTORC2 promotes ligand-induced activation of IGF-IR/InsR. IGF- and insulin-induced IGF-IR/InsR phosphorylation is significantly compromised in rictor-null cells. Insulin receptor substrate (IRS) directly interacts with SIN1 thereby recruiting mTORC2 to IGF-IR/InsR and promoting rapamyeinor ligand-induced phosphorylation of IGF-IR/InsR. mTOR exhibits tyrosine kinase activity towards the general tyrosine kinase substrate poly(Glu-Tyr) and IGF-IR/InsR. Both recombi- nant mTOR and immunoprecipitated mTORC2 phosphorylate IGF-IR and InsR on Tyr1131/1136 and Tyr1146/llS1, respectively. These effects are independent of the intrinsic kinase activity of IGF-IR/InsR, as determined by assays on kinase-dead IGF-IR/InsR mutants. While both rictor and mTOR immunoprecitates from rictor+/+ MCF-10A cells exhibit tyrosine kinase activity towards IGF-IR and InsR, mTOR immunoprecipitates from rictor-/- MCF-10A cells do not induce IGF-IR and InsR phosphorylation. Phosphorylation-deficient mutation of residue Tyrll31 in IGF-IR or Tyrl146 in InsR abrogates the activation of IGF-IR/InsR by mTOR. Finally, overexpression of rictor promotes IGF-induced cell proliferation. Our work identifies mTOR as a dual-specificity kinase and clarifies how mTORC2 promotes IGF-IR/InsR activation.