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1.
Int J Mol Med ; 49(1)2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34850962

RESUMO

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that the OGD + HYSA and OGD + HYSA + AKBA plots in Fig. 5B on p. 1507 appeared to share a similar patterning with respect to many of the data points. The authors have re-examined their original data and realize that they made inadvertent errors during the assembly of this figure. The FCS files were read and analyzed by FlowJo cell analysis software. The authors have carefully examined the raw data (fcs files), and have identified the errors that occurred when applying the setting to all files and saving the resulting fluorescence data to dot-plot graphs. The corrected version of Fig. 5, showing the correct flow cytometric analysis data in Fig. 5B and a re-evaluation of the quantification of the data in the associated bar chart, is shown on the next page. Note that the errors made during the assembly of this figure did not affect the major conclusions reported in the paper. All the authors have agreed to this Corrigendum, and thank the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this. The authors regret these errors went unnoticed prior to the publication of the paper, and apologize to the readership for any confusion that this may have caused. [the original article was published in International Journal of Molecular Medicine 37: 1501-1510, 2016; DOI: 10.3892/ijmm.2016.2571].

2.
Phys Chem Chem Phys ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34850795

RESUMO

We have explored the chemical reaction of the photoisomerization and thermal reaction of the photochromic spiropyran (SP) 1',3'-Dihydro-1',3',3' trimethyl-6-nitrospiro[2H-1 benzopyran-2,2'-(2H)-indole] molecule deposited on the atomic thin channel of a MoS2 field-effect transistor (FET) through the analysis of the FET property. With four monolayers of SP molecules on the channel, we observed a clear shift of the threshold voltage in the drain-current vs gate-voltage plot with UV-light injection on the molecule, which was due to the change of the SP molecule to merocyanine (MC). A complete reset from MC to SP molecule was achieved by thermal annealing, while the injection of green light could revert the FET property to the original condition. In the process of change from MC to SP, two types of decay rates were confirmed. The quick- and slow-decay components corresponded to the molecules attached directly to the substrate and those in the upper layer, respectively. The activation energies for the conversion of MC to SP molecules were estimated as 71 kJ/mol and 90 kJ/mol for the former and latter, respectively. Combined with DFT calculations, we concluded that the Id-Vg shift with photoisomerization from SP to MC is due to the upper layer molecules and the dipole moment in the surface normal direction. Based on the estimated activation energy of 90 kJ/mol for the reset process, we calculated the conversion rate in a controllable temperature range. From these values, we consider that the chemical state of MC can be maintained and switched in a designated time period, which demonstrates the possibility of this system in logical operation applications.

3.
Opt Express ; 29(23): 38904-38914, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34808933

RESUMO

A plasmonic fiber-tip based on the metallic metasurface and the multimode fiber (MMF) alleviates the limitation of the inevitable large sensing size caused by fiber side wall functionalization. Localized surface plasmon resonance (LSPR) based on metasurface on the fiber-tip provides a promising way to manipulate and interrogate the transmitted and reflection light in sub-wavelength range. Combining the advantages of plasmonic fiber-tip and magnetic fluid, a compact magnetic field fiber-optic sensor is proposed and verified by experiments. The developed fiber-optic magnetic field sensor has linear response and high magnetic strength sensitivity of 0.532 nm/mT over a range of 0-20 mT. In addition, the results also prove the feasibility of pseudo-vector magnetic field sensing.

4.
Front Genet ; 12: 753748, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721540

RESUMO

Copy number variations (CNVs) are important structural variations that can cause significant phenotypic diversity. Reliable CNVs mapping can be achieved by identification of CNVs from different genetic backgrounds. Investigations on the characteristics of overlapping between CNV regions (CNVRs) and protein-coding genes (CNV genes) or miRNAs (CNV-miRNAs) can reveal the potential mechanisms of their regulation. In this study, we used 50 K SNP arrays to detect CNVs in Duroc purebred pig. A total number of 211 CNVRs were detected with a total length of 118.48 Mb, accounting for 5.23% of the autosomal genome sequence. Of these CNVRs, 32 were gains, 175 losses, and four contained both types (loss and gain within the same region). The CNVRs we detected were non-randomly distributed in the swine genome and were significantly enriched in the segmental duplication and gene density region. Additionally, these CNVRs were overlapping with 1,096 protein-coding genes (CNV-genes), and 39 miRNAs (CNV-miRNAs), respectively. The CNV-genes were enriched in terms of dosage-sensitive gene list. The expression of the CNV genes was significantly higher than that of the non-CNV genes in the adult Duroc prostate. Of all detected CNV genes, 22.99% genes were tissue-specific (TSI > 0.9). Strong negative selection had been underway in the CNV-genes as the ones that were located entirely within the loss CNVRs appeared to be evolving rapidly as determined by the median dN plus dS values. Non-CNV genes tended to be miRNA target than CNV-genes. Furthermore, CNV-miRNAs tended to target more genes compared to non-CNV-miRNAs, and a combination of two CNV-miRNAs preferentially synergistically regulated the same target genes. We also focused our efforts on examining CNV genes and CNV-miRNAs functions, which were also involved in the lipid metabolism, including DGAT1, DGAT2, MOGAT2, miR143, miR335, and miRLET7. Further molecular experiments and independent large studies are needed to confirm our findings.

5.
Opt Lett ; 46(21): 5453-5456, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724499

RESUMO

In traditional imaging system design, the optical lens is often optimized toward the artificial optimization target like modulation transfer function and field-of-view (FoV). This usually leads to complex stacks of lenses. In order to reduce the complexity, we propose an end-to-end single lens imaging system design method. First, the imaging and processing model is established, whose input end is the ground truth image, and the output end is the restored image by Res-Unet. Then, with the optimization target of minimizing the difference between the restored image and the ground truth image, the parameters of the lens surface and the parameters of the restoration algorithm are optimized simultaneously by deep learning. In order to realize the end-to-end design, the imaging model is required to be differentiable to the lens parameters, so a fast differentiable ray tracing model is proposed. A single lens imaging system with high-quality large FoV (47°) has been designed by the end-to-end method. This method will have a wide application prospects in the design of light and small optoelectronic imaging systems.

6.
Mar Drugs ; 19(11)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34822467

RESUMO

(1) Background: Chitooligosaccharides (COS) have numerous applications due to their excellent properties. Chitosan hydrolysis using chitosanases has been proposed as an advisable method for COS preparation. Although many chitosanases from various sources have been identified, the cold-adapted ones with high stability are still rather rare but required. (2) Methods: A novel chitosanase named CsnY from marine bacterium Renibacterium sp. Y82 was expressed in Escherichia coli, following sequence analysis. Then, the characterizations of recombinant CsnY purified through Ni-NTA affinity chromatography were conducted, including effects of pH and temperature, effects of metal ions and chemicals, and final product analysis. (3) Results: The GH46 family chitosanase CsnY possessed promising thermostability at broad temperature range (0-50 °C), and with optimal activity at 40 °C and pH 6.0, especially showing relatively high activity (over 80% of its maximum activity) at low temperatures (20-30 °C), which demonstrated the cold-adapted property. Common metal ions or chemicals had no obvious effect on CsnY except Mn2+ and Co2+. Finally, CsnY was determined to be an endo-type chitosanase generating chitodisaccharides and -trisaccharides as main products, whose total concentration reached 56.74 mM within 2 h against 2% (w/v) initial chitosan substrate. (4) Conclusions: The results suggest the cold-adapted CsnY with favorable stability has desirable potential for the industrial production of COS.

7.
Antibiotics (Basel) ; 10(11)2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34827285

RESUMO

The objective of this study was to assess the effects of dietary supplementation with Clostridium butyricum (CB) and a bacteriophage cocktail (BP) on growth performance, serum biochemical parameters, intestinal digestive and oxidase enzymes, intestinal morphology, immune responses, and the cecum microbiota in rabbits. In total, 108 New Zealand rabbits (5 weeks old) were randomly and equally allotted into three dietary treatment groups (four replicates per treatment, n = 36/treatment): (1) the control (CN) group-rabbits fed the basal diet; (2) CB group-rabbits fed the basal diet supplemented with 100 mg/kg diet Clostridium butyricum; and (3) BP group-rabbits fed the basal diet supplemented with 200 mg/kg diet BP cocktail, respectively, for 6 weeks. Compared with the CN diet, dietary CB and BP inclusion increased the average daily gain (ADG) and average daily feed intake (ADFI) and decreased the feed/gain (F/G) ratio of rabbits. Furthermore, CB increased the digestive enzyme activity (α-amylase and trypsin in the ileum); the chymotrypsin activity was also significantly increased in the duodenum and jejunum. Supplementation with CB significantly enhanced antioxidant capacity (SOD and GSH-Px) in the jejunum and ileum and reduced MDA levels. Additionally, rabbits fed CB had significantly elevated villus height (V) and (V/C) ratios but reduced crypt depth (C). Moreover, dietary CB supplementation markedly increased the ileal expression of tight junction proteins (occludin, ZO-1, and claudin-1) and increased secretory immunoglobulin A (sIgA) production. High-throughput sequencing indicated that the microbiota in the rabbit intestine was altered by CB and BP. Venn diagrams and heatmap plots revealed that the gut microbial community composition varied obviously among rabbits fed different diets. Specifically, CB increased the relative abundance of beneficial bacteria to maintain intestinal barrier homeostasis, whereas BP decreased the relative abundance of Gammaproteobacteria, which included a plenty of pathogenic bacteria.

8.
Sheng Wu Gong Cheng Xue Bao ; 37(9): 3253-3267, 2021 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-34622633

RESUMO

Members of the ferric uptake regulator (Fur) protein family are bacterial transcriptional repressors that control iron uptake and storage in response to iron availability, thereby playing a crucial role in the maintenance of iron homeostasis. The fur null mutants of Pseudomonas aeruginosa could not be obtained because fur is an essential gene. In this study, We constructed a Fur inducibly expression strain Δfur/attB::PBAD-fur in order to study the effect of fur on the growth, biofilm formation, motilities and oxidative stress response of P. aeruginosa. The results showed that a low level of fur expression retarded the growth of P. aeruginosa at an iron-depleted condition, or under high concentration of iron, or in the presence of H2O2. Fur affected the biofilm formation and the motilities (swimming, twitching, and swarming) of strain PAO1. The production of pyoverdine is regulated by Fur. Interestingly, proteins from Magnetospirillum gryphiswaldense MSR-1, which shares homology with Fur, can partially recover the pyoverdine production of strain Δfur/attB::PBAD-fur. This study provides new clues for the prevention and treatment of P. aeruginosa infections.


Assuntos
Peróxido de Hidrogênio , Pseudomonas aeruginosa , Proteínas de Bactérias/genética , Magnetospirillum , Pseudomonas aeruginosa/genética , Proteínas Repressoras/genética
9.
Artigo em Inglês | MEDLINE | ID: mdl-34630616

RESUMO

Kunxian capsules (KCs), a Chinese patent medicine, have been clinically proven to be effective in the treatment of rheumatoid arthritis (RA). However, the chemical profile of KC remains to be characterized, and the mechanism underlying the protective effect against RA is yet to be elucidated. Here, a network pharmacology-based approach was adopted, integrated with the chemical profiling of KC by UHPLC-Q-TOF/MS. As a result, a total of 67 compounds have been identified from KC extract, among which 43 were authenticated by comparison to the mass spectrum of standard chemicals. ADME behaviors of the chemical constituents of KC were predicted, resulting in 35 putative active ingredients. Through target prediction of both active ingredients of KC and RA and PPI analysis, core targets were screened out, followed by biological process and related pathway enrichment. Then, a TCM-herb-ingredient-target-pathway network was constructed and a multicomponent, multitarget, and multipathway synergistic mechanism was proposed, providing an information basis for further investigation. The active pharmaceutical ingredients included mainly terpenoids (such as triptolide and celastrol), sesquiterpene pyridines (such as wilforgine and wilforine), and flavonoids (such as icariin, epimedin A, B, and C, and 2″-O-rhamnosylicariside II).

10.
Polymers (Basel) ; 13(20)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34685219

RESUMO

A cyclophosphazene derivative containing multiple cyano groups, denoted as hexa(4-cyanophenoxy)cyclotriphosphazene (CN-CP), was synthesized by a one-step nucleophilic substitution reaction for a phosphorus-nitrogen flame retardant. To meet the strict requirement of safe and environment-protective insulation materials, a series of composites based on low-density polyethylene-poly(ethylene-co-vinyl acetate) containing CN-CP/Mg(OH)2/Al(OH)3 organic-inorganic synergistic flame retardants was fabricated. High-energy electron beam irradiation was subsequently applied to obtain a halogen-free flame-retardant crosslinked system. The relationship between crosslinking degree and irradiation dose was studied, and crosslinking degrees ranging within 63-85% were obtained under 100-190 kGy. Furthermore, the effects of CN-CP filler and irradiation dose on the properties of the composites were carefully investigated. The maximum tensile stress and limiting oxygen index values of most composites irradiated by EB were more than 15 MPa and 28%. Results revealed that the obtained materials had excellent thermal and mechanical, flame-retardant, and insulation properties, thereby suggesting their promising prospects for wire and cable applications.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34634172

RESUMO

DNA-protein cross-links (DPCs) between DNA epigenetic mark 5-formylC and lysine residues of histone proteins spontaneously form in human cells. Such conjugates are likely to influence chromatin structure and mediate DNA replication, transcription, and repair, but are challenging to study due to their reversible nature. Here we report the construction of site specific, hydrolytically stable DPCs between 5fdC in DNA and K4 of histone H3 and an investigation of their effects on DNA replication. Our approach employs oxime ligation, allowing for site-specific conjugation of histones to DNA under physiological conditions. Primer extension experiments revealed that histone H3-DNA crosslinks blocked DNA synthesis by hPol η polymerase, but were bypassed following proteolytic processing.

12.
ACS Appl Mater Interfaces ; 13(43): 51736-51745, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34668690

RESUMO

Optical security involving the use of light to achieve distinctive vision effects has become a widely used approach for anticounterfeiting. Holographic multiplexing has attracted considerable interest in multiplexing security due to its high degree of freedom for manipulating the optical parameters of incident laser beams. However, the complex and time-consuming fabrication process of metasurface-based holograms and the sophisticated nature of holographic imaging systems have hindered the practical application of holographic multiplexing in anticounterfeiting. Combining holography with shape memory polymers to construct reconfigurable holograms provides a simple and efficient way for holographic multiplexing. This paper proposes a reconfigurable four-level amplitude hologram fabricated on a heat-shrinkable shape memory polymer using spatially modulated femtosecond laser pulses. Simply by triggering the shape recovery of the polymer through heating, the amplitude modulation of light by the hologram is reconfigured through the shrinking of processed microcrater pixels with three diameters, which enables variation to be achieved in reconstructed holographic images. Examples of holographic multiplexing and data encryption are used to validate the proposed method. The proposed economic and simple approach for holographic multiplexing provides an integrated and single-material solution to packaging and optical security, which has extensive potential in anticounterfeiting and optical encryption.

13.
Bioresour Technol ; 344(Pt A): 126117, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34653631

RESUMO

Fucoxanthin (Fx) has gained a growing attention due to the remarkable biological activities. The limited biomass of was the restrictive factor for Fx production in Phaeodactylum tricornutum. In this study, Laminaria japonica hydrolysate (LPH) with a low addition proportion of 1.5 ml/L, was proved to promote fucoxanthin accumulation and cell growth simultaneously. Fx topped at 27.9 mg/L after 10-d cultivation in the LPH group, with a biomass of 1.59 g/L and a Fx content of 17.55 mg/g. Three key plant hormones in LPH were screened responsible for promoting fucoxanthin accumulation. Transcriptomic analysis and qRT-PCR results showed that genes related to Fx formation were generally up- regulated. The study demonstrated that LPH addition was a feasible and efficient strategy to enhance production of fucoxanthin, facilitating the scale-up production of Fx in autotrophic culture.

15.
Cancer Manag Res ; 13: 6833-6845, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512023

RESUMO

Purpose: To investigate the survival benefit and safety of individualized schedules for sunitinib in patients with metastatic renal cell carcinoma (mRCC) through plasma concentration monitoring. Methods: A total of 105 patients with mRCC were enrolled. The schedule was adjusted in two ways: therapeutic drug monitoring (TDM) and toxicity-adjusted schedule (TAS). One group of patients were without any schedule adjustment (maintained schedule, MAS). Progression-free survival (PFS), overall survival (OS), tumor response, and adverse events (AEs) were compared. The relationship between AEs and steady-state concentration or consecutive monitoring curves was explored. Further monitoring of individualized schedules was also conducted. Results: Based on the plasma concentration, the schedules of 18 patients were adjusted in the TDM group. The schedules were adjusted in 37 patients due to severe AEs in the TAS group, while 50 patients were without any schedule adjustment. The median PFS and OS were better in the TDM group than the other two groups (p = 0.001 and p = 0.004, respectively). Univariate and multivariate analyses indicated that TDM could decrease the risk of death independently (p = 0.026). Moreover, the incidence of grades 3/4 AEs decreased from 88.9% to 33.3% in the TDM group (p = 0.001). Sunitinib concentration in 150-200ng/mL was regarded as a "transitional zone" due to severe AEs mainly happened when concentration elevated over it. After TDM, further plasma concentration monitoring indicated that individualized schedules enabled sunitinib concentration to fluctuate in a much safer range. Conclusion: Treatment-related toxicities could be minimized through plasma concentration monitoring. Patients with adjusted schedules by therapeutic drug monitoring could achieve better survival benefits.

16.
Cancer Cell Int ; 21(1): 485, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521413

RESUMO

As an efficient drug carrier, exosome has been widely used in the delivery of genetic drugs, chemotherapeutic drugs, and anti-inflammatory drugs. As a genetic drug carrier, exosomes are beneficial to improve transfection efficiency and weaken side effects at the same time. Here, we use genetic engineering to prepare engineered exosomes (miR-449a Exo) that can actively deliver miR-449a. It was verified that miR-449a Exo had good homology targeting capacity and was specifically taken up by A549 cells. Moreover, miR-449a Exo had high delivery efficiency of miR-449a in vitro and in vivo. We demonstrated that miR-449a Exo effectively inhibited the proliferation of A549 cells and promoted their apoptosis. In addition, miR-449a Exo was found to control the progression of mouse tumors and prolong their survival in vivo. Our research provides new ideas for exosomes to efficiently and actively load gene drugs, and finds promising methods for the treatment of non-small cell lung cancer.

17.
Biotechnol Biofuels ; 14(1): 181, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526122

RESUMO

BACKGROUND: Raw materials composed of easily assimilated monosaccharides have been employed as carbon source for production of microbial lipids. Nevertheless, agro-industrial wastes rich in galactose-based carbohydrates have not been introduced as feedstocks for oleaginous yeasts. RESULTS: In this study, Aureobasidium namibiae A12 was found to efficiently accumulate lipid from soy molasses and whey powder containing galactose-based carbohydrates, with lipid productions of 5.30 g/L and 5.23 g/L, respectively. Over 80% of the fatty acids was C16:0, C18:0, C18:1, and C18:2. All kinds of single sugar components in the two byproducts were readily converted into lipids, with yields ranging between 0.116 g/g and 0.138 g/g. Three α-galactosidases and five ß-galactosidases in the strain were cloned and analyzed. Changes of transcriptional levels indicated GalB and GalC were key α-galactosidases, and GalG was key ß-galactosidase. In 10 L fermentor, lipid production from SM and WP achieved 6.45 g/L and 6.13 g/L, respectively. ß-galactosidase was responsible for lactose hydrolysis; sucrase and α-galactosidase both contributed to the efficient hydrolysis of raffinose and stachyose in a cooperation manner. CONCLUSIONS: This is a new way to produce lipids from raw materials containing galactose-based carbohydrates. This finding revealed the significance of sucrase in the direct hydrolysis of galactose-based carbohydrates in raw materials for the first time and facilitated the understanding of the efficient utilization of galactose-based carbohydrates to manufacture lipid or other chemicals in bioprocess.

18.
Evol Bioinform Online ; 17: 11769343211041382, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471342

RESUMO

The CCAAT/enhancer binding protein (C/EBP) transcription factors (TFs) regulate many important biological processes, such as energy metabolism, inflammation, cell proliferation etc. A genome-wide gene identification revealed the presence of a total of 99 C/EBP genes in pig and 19 eukaryote genomes. Phylogenetic analysis showed that all C/EBP TFs were classified into 6 subgroups named C/EBPα, C/EBPß, C/EBPδ, C/EBPε, C/EBPγ, and C/EBPζ. Gene expression analysis showed that the C/EBPα, C/EBPß, C/EBPδ, C/EBPγ, and C/EBPζ genes were expressed ubiquitously with inconsistent expression patterns in various pig tissues. Moreover, a pig C/EBP regulatory network was constructed, including C/EBP genes, TFs and miRNAs. A total of 27 feed-forward loop (FFL) motifs were detected in the pig C/EBP regulatory network. Based on the RNA-seq data, gene expression patterns related to FFL sub-network were analyzed in 27 adult pig tissues. Certain FFL motifs may be tissue specific. Functional enrichment analysis indicated that C/EBP and its target genes are involved in many important biological pathways. These results provide valuable information that clarifies the evolutionary relationships of the C/EBP family and contributes to the understanding of the biological function of C/EBP genes.

19.
Int J Gen Med ; 14: 4783-4792, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34466023

RESUMO

Objective: To investigate the risk factors related to new-onset diabetes mellitus (NODM) and the significance of IL-6. Methods: A retrospective analysis was conducted on clinical data from 64 patients who received either a living donor liver transplantation or a donation after circulatory death from September 2013 to October 2020 and attended regular follow-up visits for six or more months. During follow-up, patients were randomized into groups and followed up until the completion of the study or the death of the patient. Results: The incidence of NODM was 31.25% (n = 20). The median age in the NODM group was 52.15 years (p < 0.01). Age (OR = 1.089; 95% CI: 0.0211-0.1495, p = 0.003) and elevated preoperative IL-6 (OR = 1.122; 95% CI: 0.0619-0.1677, p = 0.029) were found to be independent risk factors for NODM. HBV-induced liver cirrhosis, warm ischemia time (WIT), body mass index (BMI), and high preoperative fasting blood glucose (FBG) were also found to be risk factors for NODM. The recipient had a higher risk of NODM if the donor had a high BMI and poor hepatic function. The concentrations of IL-6, procalcitonin (PCT), FBG, and tacrolimus (TAC) in the first month postoperatively were significantly higher in the NODM group than in the NO-NODM group. The survival rate of the patients was not affected by NODM. Conclusion: HBV-induced liver cirrhosis, WIT, BMI, and high preoperative FBG levels are risk factors for NODM, and age and preoperative IL-6 levels are independent risk factors. To a certain extent, higher BMI and poor hepatic function had reference significance for the incidence of NODM. Patients with a high concentration of FBG, IL-6, and TAC in the first month postoperatively had an increased risk of suffering from NODM.

20.
Int J Anal Chem ; 2021: 5524361, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567122

RESUMO

Objective: To develop a new method for quantitatively analyzing six tyrosine kinase inhibitors (gefitinib, erlotinib, icotinib, afatinib, osimertinib, and crizotinib) used in the treatment of non-small cell lung cancer (NSCLC) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methods: The analytes were detected in the selected reaction monitoring mode on a triple quadrupole mass spectrometer with the positive ionization mode. Carbamazepine was utilized as the internal standard. The pretreatment of the plasma sample was completed based on protein precipitation with acetonitrile, and the analytes were separated on an Agilent Zorbax SB-C18 reversed-phase column (2.1 mm × 100 mm, 3.5 µm, Agilent, USA) using gradient elution. The mobile phase consisted of 0.1% formic acid in water (phase A) and 0.1% formic acid in acetonitrile (phase B). The flow rate was 0.3 mL/min, and the injection volume was 5 µL. The column temperature was set and maintained at 35°C. Results: The calibration curves were linear over the range from 5.0 to 1000.0 ng/mL for gefitinib, crizotinib, and osimertinib; from 50.0 to 4000.0 ng/mL for icotinib and erlotinib; and from 5.0 to 400.0 ng/mL for afatinib. Linear correlation coefficients were >0.990 for all regression curves. The intra- and interday accuracy and precision of the method were within ±15.0% and not more than 15.0%, respectively. The mean recovery of all the analytes ranged from 70.18% to 110.76%, the matrix effect was from 88.85% to 127.58%, and stability was within ±15.0%. Conclusion: This newly developed method was sensitive, simple, and robust and could be used in therapeutic drug monitoring of six tyrosine kinase inhibitors in NSCLC patients.

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