Quantification of steroids possesses a crucial clinical value in early diagnosis and prognosis evaluation of various endocrine diseases. However, it is still challenging to realize feasible analysis ...of estrogens, androgens, progestogens, and corticoids within one single workflow. In this study, two derivatization reactions were newly designed for improvement: (1) acylation of phenolic hydroxyl on estrogens with isonicotinoyl chloride (INC) under the catalysis of 4-dimethylaminopyridine and (2) post-modification of oxime hydroxyl on hydroxylamine-pretreated ketosteroids with INC. Both reactions could conduct instantaneously at room temperature under aqueous conditions. Moreover, the resulting phenolic-INC and oxime-INC esters exhibited favorable MS responses. Through integrating these derivatization strategies with cold-induced phase separation technology, a feasible LC–MS/MS method was developed for simultaneous quantification of 15 multiclass steroids with proper sample consumption (50 μL serum), satisfying sensitivity (lower limit of quantitation at 0.01–5.00 ng/mL) and high throughput (40 min for sample-preparation). The practical applicability was tested by detecting 30 real samples from pregnant and non-pregnant women. The obtained results showed a good agreement with a previous validated methodology.
•The steroid profile was first analyzed by LC–MS/MS in pregnant women affected with trisomy 21.•We found that steroid hormones perturbations occurred in pregnant women affected with trisomy ...21.•Decreased 11-deoxycortisol levels were associated with trisomy 21.
Trisomy 21 is a serious chromosome abnormality. The conventional Down’s screening test is the most widely used for trisomy 21 screening. However, this method could lead to a higher false positive rate. Therefore, we aim to analyze steroid profile in second-trimester pregnant women and identify novel serum biomarkers of trisomy 21.
We employed an LC–MS/MS method to measure the steroid profile. The concentrations and product-to-substrate ratios in 71 second-trimester pregnant women were determined and statistically analyzed to identify novel biomarkers for trisomy 21 screening.
We found that there were significant differences in levels of E3, 11-deoxycortisol, and 11-deoxycortisol /17-hydroxyprogesterone between two groups. The OPLS-DA plots revealed obvious separation between two groups. Combining VIP analysis (VIP > 1.0) with volcano plot (P < 0.05 and fold change >1.2 or < 0.83), 11-deoxycortisol was identified as a novel biomarker for trisomy 21. After controlling for confounders, we found 11-deoxycortisol was associated with trisomy 21 (adjusted P = 0.009), and the fully adjusted OR (95 % CI) was 0.098 (0.016−0.593) in highest quartile versus lowest quartile of 11-deoxycortisol (P = 0.011).
Steroid profile analysis for the first time showed that steroid hormones perturbations occurred in pregnant women carrying a fetus affected by trisomy 21 and decreased 11-deoxycortisol levels were associated with trisomy 21.
A 423.5-450 MHz low-power OOK/FSK/QPSK wireless transmitter is proposed with multi-phase injection locking and frequency multiplication techniques. A low-frequency phase-rotation-based frequency ...synthesizer is employed to provide multichannel support and FSK modulation. The far-out phase noise caused by the quantization noise of the <inline-formula> <tex-math notation="LaTeX">\Delta \Sigma </tex-math></inline-formula> modulator is filtered through a proposed N-path filter and two-stage injection-locked ring oscillators (ILROs). Phase modulation is achieved by changing the offset frequency between the oscillator free-running frequency and the injected frequency to control the steady-state phase offset of the injection-locked oscillator. Finally, a current mode class-D edge-combining power amplifier with high energy efficiency is used to achieve 5X frequency multiplication to generate the required carrier frequency. A prototype transmitter is fabricated in TSMC 90 nm CMOS process. It is shown that the device delivers an output power of −7 dBm with a power consumption of <inline-formula> <tex-math notation="LaTeX">870 \mu \text{W} </tex-math></inline-formula> under a 0.75 V supply voltage and supports data rates of 40/5/80 Mbps under OOK/BFSK/QPSK modulation, respectively, achieving the energy efficiency of 11 pJ/bit and 23% global efficiency.
BACKGROUNDThe detection of 25-hydroxyvitamin D (25OHD) from dried blood spots (DBS) has been widely studied. However, the existing pretreatment methods suffer from limitations in terms of throughput ...(usually exceeding 2 h), complexity (involving liquid-liquid extraction or solid-phase extraction), and contamination (including multiple steps of organic solvent evaporation).RESULTSWe first released 25OHD from DBS samples by 50% acetonitrile solution through ultrasonication. Subsequently, the cold-induced phase separation technique was introduced for in-situ concentration and purification. Afterward, the PTAD derivatization of 25OHD was performed directly, profiting from the high acetonitrile content in the concentrated solution. In the end, the resulting solution was submitted to LC-MS/MS for quantification. The established LC-MS/MS methodology possessed favorable analytical performance, possessing lower limit of quantification of 1 ng/mL pointing to plasma, accuracy of 86.8-110.1% and imprecision of 5.4-16.8%. Method comparison with plasma samples demonstrated that over 93% of the detections met the acceptance limit for cross-validation of ±20%.SIGNIFICANCE AND NOVELTYThe novel sample preparation can be finished within 15 min and eliminated the traditional steps of extraction and organic solvent evaporation. Based on this high-throughput, reliable and applicable LC-MS/MS method, the detection of 25OHD in DBS samples can be better achieved for clinical patients and researchers with relevant demands.
We fabricated nanomaterials comprising amino-functionalized and nitrogen-doped graphene quantum dots (amino-N-GQDs) and investigated their photostability and intrinsic luminescence in the ...near-infrared spectrum to determine their suitability as contrast agents in two-photon imaging (TPI). We observed that amino-N-GQDs with a higher amount of bonded nitrogen and amino-functionalized groups (6.2%) exhibited superior two-photon properties to those with a lower amount of such nitrogen and groups (4.9%). These materials were conjugated with polymers containing sulfur (polystyrene sulfonate, PSS) and nitrogen atoms (polyethylenimine, PEI), forming amino-N-GQD-PSS-PEI specimens (amino-N-GQD-polymers). The polymers exhibited a high quantum yield, remarkable stability, and notable two-photon properties and generated no reactive oxygen species, rendering them excellent two-photon contrast agents for bioimaging. An antiepidermal growth factor receptor (Ab
) was used for labeling to increase specificity. Two-photon imaging (TPI) of amino-N-GQD (6.2%)-polymer-Ab
-treated A431 cancer cells revealed remarkable brightness, intensity, and signal-to-noise ratios for each observation at a two-photon excitation power of 16.9 nJ pixel
under 30 scans and a three-dimensional (3D) depth of 105 µm, indicating that amino-N-GQD (6.2%)-polymer-Ab
-treated cells can achieve two-photon luminescence with 71 times less power required for two-photon autofluorescence (1322.8 nJ pixel
with 500 scans) of similar intensity. This economy can minimize photodamage to cells, rendering amino-N-GQD-polymers suitable for noninvasive 3D bioimaging.
Objectives:
Oral squamous cell carcinoma (OSCC) is the most common oral cancer with a poor prognosis owing to limited understanding of the disease mechanisms. The aim of this study was to explore and ...identify the potential biomarkers in OSCC by integrated bioinformatics analysis.
Materials and Methods:
Expression profiles of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) were downloaded from The Cancer Genome Atlas (TCGA) and differentially expressed RNAs (DERNAs) were subsequently identified in OSCC by bioinformatics analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyze DERNAs. Then, the competing endogenous RNA (ceRNA) network was constructed in Cytoscape and the protein -protein interaction (PPI) network was established in the STRING database. We established a risk model to predict the overall survival of OSCC on the basis of DElncRNAs with Kaplan–Meier analysis and combined with logrank p test. Furthermore, we identified potential biomarkers by combining univariate Cox regression with overall survival rate, which were then validated in Gene Expression Omnibus (GEO), OSCC cell lines and OSCC specimens.
Results:
A total of 1,919 DEmRNAs, 286 DElncRNAs and 111 DEmiRNAs were found to be dysregulated in OSCC. A ceRNA network included 46 DElncRNAs,7 DEmiRNAs and 10 DEmRNAs, and the PPI network included 712 DEmRNAs including 31 hub genes. Moreover, a 7 lncRNAs risk model was established and four genes (CMA1, GNA14, HCG22, HOTTIP) were identified as biomarkers on overall survival in patients with OSCC.
Conclusions:
This study successfully constructed a ceRNA network and a PPI network which play a crucial role in OSCC. A risk model was established to predict the prognosis, and four DERNAs are revealed with overall survival in patients with OSCC, suggesting that they may be potential biomarkers in tumor diagnosis and treatment.
Tourism destinations are the important research objects of tourism geography. And destination songs, as a media of tourism destination image, play a very important role in it. Based on the SOR model, ...this study constructs a theoretical relationship between destination song perception and tourism intention. A total of 317 valid questionnaires were collected from potential tourists through the Internet and SPSS v.26.0 and AMOS v.24.0 were used for data processing to verify these theories. The study found that destination song perception has a positive effect on travel intention, emotion induced, and destination image perception; Emotion induced has a positive effect on destination image perception and travel intention; Destination image perception has a positive effect on travel intention. Emotion induced and destination image play a mediating role individually and play a chain mediating role together in the effect of destination song perception on travel intention, and there is no significant difference between different mediating effects. This study attempts to explain the influence of destination songs on the travel intentions of potential tourists, and might be used for tourism destination marketing, especially in creation, promotion and management of destination songs.
A rapid, sensitive and automated in-tube solid-phase microextraction-liquid chromatography–mass spectrometry (in-tube SPME/LC–MS) method was developed for the analysis of ten antidepressants in urine ...and plasma. A hybrid organic–inorganic silica monolith with cyanoethyl functional groups was prepared and used as a sorbent for in-tube SPME. Integration of the sample extraction, LC separation and MS detection into a single system permitted direct injection of the diluted urine or plasma after filtration. Under the optimized conditions, good extraction efficiencies for the targets were obtained with no matrix interference in the subsequent LC–MS. Automation of the sampling, extraction and separation procedures was realized under the control of a program in this study. The total process time was 30
min and only 30
μL of urine or plasma was required in one analysis cycle. Good linearities were obtained for ten antidepressants with the correlation coefficients (
R) above 0.9933. The limits of detection (
S/
N
=
3) for ten antidepressants were found to be 0.06–2.84
ng/mL in urine and 0.07–2.95
ng/mL in plasma. The recoveries of antidepressants spiked in urine and plasma were from 75.2% to 113.0%, with relative standard deviations less than 16.5%. The developed method was successfully used to analyze urine sample from ageing patients undergoing therapy with antidepressants.
A new ionic current rectification device responsive to a broad range of pH stimuli is established using highly ordered nanochannels of porous anodic alumina membrane with abrupt surface charge ...discontinuity. The asymmetric surface charge distribution is achieved by patterning the nanochannels with surface amine functional groups at designed positions using a two‐step anodization process. Due to the protonation/deprotonation of the patterned amine and the remaining intrinsic hydroxyl groups upon solution pH variation, the nanochannel‐array‐based device is able to regulate ion transport selectivity and has ionic current rectification properties. The rectification ratio of the device is mainly determined by the nanochannel size, and the rectification ratio is less sensitive to the patterned length of the amine groups when the nanochannels size is defined. Thus, the isoelectric point of nanochannels can be easily estimated to be the pH value with a unit rectification ratio. The present ionic device is promising for biosensing, molecular transport and separation, and drug delivery in confined environments.
A new ionic current rectification device responsive to a broad range of pH stimuli is established using highly ordered nanochannels of porous anodic alumina membrane with abrupt surface charge discontinuity. Due to the protonation/deprotonation of the patterned amine and the remaining intrinsic hydroxyl groups, the nanochannel‐array‐based device is able to regulate ion transport selectivity and has ionic current rectification properties.