Aiming to develop novel Type-I inhibitors of ALK to overcome extensive resistance mutations, especially the L1196M mutation surrounding the ATP pocket, two series of 2-arylaminopyrimidine derivatives (11a-f and 22a-t) were designed based on scaffold hopping. The extensive structural elaboration discovered compound 22o which possessed excellent IC values of 0.06 and 0.23 μM against ALK-positive Karpas299 and H2228 cell lines, respectively. Meanwhile, 22o displayed encouraging inhibitory potency in the ALK (2.5 nM) and ALK (6.5 nM) enzymatic assays. Furthermore, the AO/EB and Hoechst 33258 assays illustrated 22o could induce cell apoptosis in a dose-dependent manner. Eventually, the molecular docking of 22o with ALK clearly presented the vital interactions within the active site, which was in accordance with Type-I inhibitor binding mode.

Cyanobacterial monoglucosyldiacylglycerol (MGlcDG) not only serves as a precursor for monogalactosyldiacylglycerol (MGDG) synthesis, but also participates in stress acclimation. Two genes (mgdA and mgdE) related to MGDG synthesis of Synechococcus sp. PCC 7942 were identified. The mgdE-suppressed mutant (AE) accumulated MGlcDG (4.2%) and showed better growth and photosynthetic activities compared with WT and other mutants (mgdA/mgdE-overexpressed and mgdA-suppressed strains), which suggested that MGlcDG was involved in phosphate stress adaptation for Synechococcus sp. PCC 7942. A notable increase in contents of 18:1 fatty acid (FA) of MGDG (127%), DGDG (68%), and SQDG (105%) in AE were found under phosphate starvation. However, the expression of △9 desaturase (desC) was not higher in AE than that in WT during phosphate-starved period. These results suggested that MGlcDG might be involved in the process of FA desaturation, which contributed to membrane fluidity and cell basic metabolism for stress acclimation in cyanobacteria. In complementary experiments of E. coli, although the expression of mgdA and desC in the mgdA and desC coexpressed strain (OEAC) reduced by 22% and 35% compared with that of the strains only overexpressing mgdA (OEA) or desC (OEC), the content of unsaturated FA in OEAC was the highest. This further implied that the accumulation of MGlcDG could prompt FA desaturation in E. coli. Therefore, we propose that an overproduction of MGlcDG is responsible for FA desaturation and participates in phosphate stress adaptation in cyanobacteria.

Laser reduction of graphene oxide (GO) produces graphene effectively. As a low-power laser source, commercial DVD drives provide a versatile platform to produce reduced graphene films in designed 2D patterns. However, research on how GO characteristics affect its laser reduction efficiency in DVD drives is rarely conducted. Here, we investigate how heating the GO dispersion affects the photoreduction process of GO films in a LightScribe DVD drive. Without noticeably changing the oxygen content, such mild heat treatment significantly improves GO's absorption in the visible region, resulting in significant enhancement on GO's laser reduction efficiency. We demonstrate that, the laser reduction efficiency increases with the increasing treatment time. The enhanced reduction level greatly improves the performance of laser scribed graphene (LSG) electrodes in applications such as glucose sensors (with optimal linear response range up to 2550 μM) and supercapacitors (with optimal areal capacity of 1.37 mF cm at the scan rate of 50 mV s). This proposed approach provides general insights to the production of laser reduced graphene with low-power laser sources, for advanced device applications such as wearable electronics and flexible microelectronics.

Interpreting disease-causing variants, especially in noncoding regions by genome-wide association studies (GWAS), has become one of the most challenging and demanding tasks. We hypothesized that functional lncRNAs variants in GWAS-identified loci might alter expression level of genes associated with persistent HBV infection and hepatocellular carcinoma (HCC). Integrated bioinformatics approaches were used to prioritize potentially functional variants and a two-stage case-control study (2473 HBV positive HCC patients, 2248 persistent HBV carriers and 2294 spontaneously recovered subjects) was performed to assess the roles of these variants. The rs2844512 G > C variant in LINC01149 was identified to facilitate HBV spontaneous recovery (OR = 0.84, 95% CI = 0.77-0.92) but increase the risk of HCC (OR = 1.21, 95% CI = 1.11-1.32) in combined samples. Subsequent biological assays indicated this variant created a binding site for miR-128-3p and upregulated MICA expression by serving as a miRNA sponge, which might recruit NK-cells to lyse infected cells, but release highly soluble MICA by shedding to induce NK-cells exhaustion and tumor immune evasion. These findings highlight a regulatory circuit between LINC01149 and MICA, mediating by miR-128-3p, and the important role of upregulated MICA in conferring susceptibility to persistent HBV infection and HCC.

IL-6/STAT3 signaling pathway is required for the development of psoriatic lesions and tripartite motif-containing 27 (TRIM27) as a protein inhibitor of activated STAT3 (PIAS3)-interacting protein that could modulate IL-6-induced STAT3 activation. However, whether TRIM27 associates with the IL-6/STAT3 signaling pathway in psoriasis remains enigmatic. TRIM27 expression and Gene set enrichment analysis (GSEA) in psoriasis patients were determined using bioinformatics. Human keratinocyte HaCaT cells treated with recombinant protein IL-6 (rh-IL-6) were transduced with lentivirus silencing TRIM27 and/or PIAS3, otherwise transduced with lentivirus expressing TRIM27 and/or lentivirus silencing STAT3, or MG132, a proteasome-specific protease inhibitor. Cell proliferation and inflammation factor production were measured using CCK-8 and ELISA, respectively. TRIM27, Ki67, phospho-STAT3 (p-STAT3), STAT3 and PIAS3 expressions were determined using Real-time quantitative PCR, immunofluorescence staining or western blotting. Co-immunoprecipitation combined with ubiquitination analysis was performed to explore the interaction between TRIM27 and PIAS3. In the present study, TRIM27 expression was increased in psoriasis lesions, associated with IL-6 signaling pathway and induced by rh-IL-6 in a time-dependent manner. The increased cell proliferation, inflammation factor production, and expression of Ki67 and p-STAT3/STAT3 induced by rh-IL-6 and TRIM27 overexpression were significantly inhibited by TRIM27 silencing and STAT3 silencing, respectively. More importantly, TRIM27 interacted with PIAS3, and its overexpression promoted PIAS3 ubiquitination in HaCaT cells. PIAS3 silencing also significantly promoted TRIM27-dependent and IL6-induced STAT3 activation, cell proliferation and inflammation factor production. In conclusion, our results highlight the TRIM27 expression significantly increased by IL-6 and suggest a TRIM27/STAT3-dependent mechanism for regulation of inflammation and proliferation-associated development of psoriasis.

Leaves are one of the most important organs of plants, and yet, the association between leaf color and consumable traits remains largely unclear. Tea leaves are an ideal study system with which to investigate the mechanism of how leaf coloration affects palatability, since tea is made from the leaves of the crop . Our genomic resequencing analysis of a tea cultivar ZiJuan (ZJ) with purple leaves and altered flavor revealed genetic variants when compared with the green-leaf, wild type cultivar YunKang(YK). RNA-Seq based transcriptomic comparisons of the bud and two youngest leaves in ZJ and YK identified 93%, 9% and 5% expressed genes that were shared in YK- and ZJ-specific cultivars, respectively. A comparison of both transcript abundance and particular metabolites revealed that the high expression of gene for anthocyanin biosynthesis is responsible for purple coloration, which competes with the intermediates for catechin-like flavanol biosynthesis. Genes with differential expression are enriched in response to stress, heat and defense, and are casually correlated with the environmental stress of ZJ plant origin in the Himalayas. In addition, the highly expressed and genes for synthesizing flavanol precursors, ZJ-specific for degrading chlorophyll, alternatively spliced and and low photosynthesis also contributed to the altered color and flavor of ZJ. Thus, our study provides a better molecular understanding of the effect of purple coloration on leaf flavor, and helps to guide future engineering improvement of palatability.

Most wild fish caught by anglers (WFAs) are likely to be contaminated by toxic metals, particularly the fish collected from the waterways in urban and suburban areas; hence, the determination of health risk caused by WFAs consumption associated with toxic metals is vital. Therefore, Liuzhou, one of the largest industrial cities in China, was considered as an example city in this study. Eight toxic elements were analysed to uncover the pollution status and consumption safety of WFAs. Moreover, the suitable angling waterways were identified in the urban and suburban areas. The obtained results suggested relatively high concentrations of Zn, Cr and Cd, which were also found to be beyond corresponding Maximum Residue Limit. Among all analysed elements, only the mean pollution indices of Cr and Cd were observed to be beyond 0.2, revealing that the observed WFAs were generally contaminated by these metals. However, the potential health risk of WFAs can be predominately attributed to Cr, confirmed by the significantly higher Target hazard quotients (THQ). For adults, all the THQ values were below 1, indicating no significant health risk being associated with WFAs consumption in the case of adults. On the contrary, all the THQ values for Children were beyond 1, suggesting children being susceptible to great health risks due to WFAs consumption. Furthermore, the weekly recommended consumption of WFAs in urban area is remarkably lower than the current rate of fish consumption observed among urban residents; therefore, the waterways in urban areas can be evaded for fish angling.

Information on the occurrence and trophodynamics of per- and polyfluoroalkyl substances (PFASs) in the Antarctic region is limited. We investigated the occurrence of PFASs in an ecosystem in the Fildes Peninsula at King George Island and Ardley Island, Antarctica. The profiles, spatial distribution, and trophic transfer behavior of PFASs were further studied. ∑PFASs ranged from 0.50 ± 38.0 ng/g dw (dry weight) in algae to 4.97 ± 1.17 ng/g dw in Neogastropoda (Ngas), which was lower than those in the low- and mid-latitude regions and even Arctic regions. Perfluorobutyric acid (PFBA) was predominant with detection frequencies above 50% in all types of samples, and the relative contribution of PFBA ranged from 22% to 57% in the biota samples. The biomagnification factors of PFBA, perfluoroheptanoate (PFHpA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) between Archaeogastropoda (Agas) and Ngas were 0.67 ± 0.54, 0.77 ± 0.38, 1.04 ± 1.56, 3.30 ± 4.07, and 1.61 ± 0.89, respectively. The trophic magnification factors of PFHxS and PFOS were 2.09 and 2.92, respectively, which indicated that they could be biomagnified through the food chain. Considering the increasing production and uncertain toxicological risks of emerging PFASs and the sensitive ecosystems in Antarctic regions, more attention should be paid, especially for the short-chain ones in the Antarctic region.

Hexagonal boron nitride (h-BN) is an important member of two-dimensional (2D) materials with a large direct bandgap, and has attracted growing interest in ultraviolet optoelectronics and nanoelectronics. Compared with graphene and graphite, h-BN has weak Raman effect because of the far off-resonance excitation, hence it is difficult to exploit Raman spectroscopy to characterize important properties of 2D h-BN, such as thickness, doping and strain effects. Here, we applied stimulated Raman scattering (SRS) to enhance the sensitivity of E2g Raman mode of h-BN. We showed that SRS microscopy achieves rapid high resolution imaging of h-BN with a pixel dwell time four orders of magnitude smaller than conventional spontaneous Raman microscopy. Moreover, the near perfect linear dependence of signal intensity on h-BN thickness and isotropic polarization dependence allow convenient determination of flake thickness with SRS imaging. Our results indicated that SRS microscopy provides a promising tool for high-speed quantification of h-BN and holds potential for vibrational imaging of 2D materials.

Background MRI performed with echo-planar imaging (EPI) sequences is sensitive to susceptibility artifacts in the presence of metallic objects, which presents a substantial barrier for performing functional MRI and diffusion tensor imaging (DTI) in patients with metallic orthodontic material and other head implants. Purpose To evaluate the ability to reduce susceptibility artifacts in healthy human participants wearing metallic orthodontic braces for two alternative approaches: T2-prepared functional MRI and diffusion-prepared DTI with three-dimensional fast gradient-echo readout. Materials and Methods In this prospective study conducted from February to September 2018, T2-prepared functional MRI and diffusion-prepared DTI were performed in healthy human participants. Removable dental braces with bonding trays were used so that MRI could be performed with braces and without braces in the same participants. Results were evaluated in regions with strong (EPI dropout regions for functional MRI and the inferior fronto-occipital fasciculus for DTI) and minimal (motor cortex for functional MRI and the posterior limb of internal capsule for DTI) susceptibility artifacts. Signal-to-noise ratio (SNR), contrast-to-noise ratio for functional MRI, apparent diffusion coefficient and fractional anisotropy for DTI, and degree of distortion (quantified with the Jaccard index, which measures the similarity of geometric shapes) were compared in regions with strong or minimal susceptibility effects between the current standard EPI sequences and the proposed alternatives by using paired test. Results Six participants were evaluated (mean age ± standard deviation, 40 years ± 6; three women). In brain regions with strong susceptibility effects from the metallic braces, T2-prepared functional MRI showed significantly higher SNR (37.8 ± 2.4 vs 15.5 ± 5.3; < .001) and contrast-to-noise ratio (0.83 ± 0.16 vs 0.29 ± 0.10; < .001), whereas diffusion-prepared DTI showed higher SNR (5.8 ± 1.5 vs 3.8 ± 0.7; = .03) than did conventional EPI methods. Apparent diffusion coefficient and fractional anisotropy were consistent with the literature. Geometric distortion was substantially reduced throughout the brain with the proposed methods (significantly higher Jaccard index, 0.95 ± 0.12 vs 0.81 ± 0.61; < .001). Conclusion T2-prepared functional MRI and diffusion-prepared diffusion tensor imaging can acquire functional and diffusion MRI, respectively, in healthy human participants wearing metallic dental braces with less susceptibility artifacts and geometric distortion than with conventional echo-planar imaging. © RSNA, 2019 See also the editorial by Dietrich in this issue.

Double-stranded RNA (dsRNA)-induced genes are usually related to RNA interference (RNAi) mechanisms and are involved in immune-related pathways. In a previous study, we found a lepidopteran-specific nuclease gene that was up-regulated by dsRNA and that affected RNAi efficiency in Asian corn borer (). In this study, to verify the function of , the homologous gene in cotton bollworm () was knocked out using CRISPR/Cas9 system. We found that the midgut epithelium structure was apparently not affected in the Δ mutant [Knock out (KO)]. Transcript sequencing results showed that most of the known insect immune-related genes were up-regulated in KO. When second instar larvae were fed artificial diet with Cry1Ac, a protoxin from (), in sublethal doses (2.5 or 4 μg/g), the growth rate of KO was repressed significantly. The dsRNA stability was also enhanced in midgut extraction of KO; however, RNAi efficiency was not obviously improved compared with the wild type (WT). The KO and WT were injected with dsEGFP (Enhanced green fluorescent protein) and subjected to transcriptome sequencing. The results showed that the expression levels of 14 nuclease genes were enhanced in KO after the dsRNA treatment. These findings revealed that expression level was not only related with dsRNA stability, but also with resistance in cotton bollworm. When was knocked out, other immune- or nuclease-related genes were enhanced significantly. These results remind us that insect immune system is complex and pest control for cotton bollworm is an arduous task.

Linoleic acid is an important polyunsaturated fatty acid, required for all eukaryotes. Microsomal delta-12 (Δ) oleate desaturase (FAD2) is a key enzyme for linoleic acid biosynthesis. Desert shrub Artemisia sphaerocephala is rich in linoleic acid, it has a large FAD2 gene family with twenty-six members. The aim of this work is to unveil the difference and potentially functionality of AsFAD2 family members.

A majority of nurses struggled with a negative emotion of anger, doubt, fear, or anxious, uncomfortable in the face of death and dying. However, little was known about community health care providers' in China. Therefore, we conducted a study to investigate their knowledge and attitudes toward end-of-life care and analyze its influencing factors. To provide reference for developing effective strategies to promote end-of-life care in China.A total of 132 community health care providers of 10 community health care centers in Changzhi city were investigated by a Questionnaire of Knowledge and Attitudes toward Caring for the Dying from May, 2017 to December, 2017, and data was analyzed by SPSS 22.0 software.Of the 132 community health care providers who were under investigation, 70 knew about hospice care, but they rated their overall content on end-of-life care as inadequacy, especially in communication skills and knowledge of pain management. The average score of attitudes was 3.47 (SD = 0.44), the lowest score was in the subscale of nurse-patient communication, which was 2.91 (SD = 0.65). Health care providers who had worked for more than 11 years, who had experiences of the death of relatives or friends, and who had previous experiences of caring for terminal patients had more positive attitudes toward caring for the dying (P < .05 for all). There was a significant relationship between community health care providers' attitudes toward death and their attitudes toward end-of-life care (r = -0.282, P < .01). The significant predictors of attitudes toward end-of-life care were attitudes toward death (β = -0.342), experiences of the death of relatives (β=-0.207), experiences of caring for the dying (β = 0.185), and working experience (β = 0.171).Community health care providers had positive attitudes toward end-of-life care, but they lacked systematic and professional knowledge and skills of caring for the terminal patients. Education is the top priority. It is imperative to set up palliative care courses and life-death education courses, establish an indigenous end-of-life care model, and improve policies, systems, and laws to promote end-of-life care.

Non-small cell lung cancer (NSCLC) is the main type of lung malignancy. Early diagnosis and treatments for NSCLC are far from satisfactory due to the limited knowledge of the molecular mechanisms regarding NSCLC progression. Long noncoding RNA (lncRNA) ZNFX1 antisense RNA1 (ZFAS1) has been implicated for its functional role in the progression of malignant tumors. This study aimed to determine the ZFAS1 expression from lung cancer clinical samples and to explore the molecular mechanisms underlying ZFAS1-modulated NSCLC progression. Experimental assays revealed that clinical samples and cell lines of lung malignant tumors showed an upregulation of ZFSA1. ZFAS1 expression was markedly upregulated in the lung tissues from patients with advanced stage of this malignancy. The loss-of-function assays showed that knockdown of ZFAS1-suppressed NSCLC cell proliferative, as well as invasive potentials, increased NSCLC cell apoptotic rates in vitro and also attenuated tumor growth of NSCLC cells in the nude mice. Further experimental evidence showed that ZFAS1 inversely affected miR-150-5p expression and positively affected high-mobility group AT-hook 2 (HMGA2) expression in NSCLC cell lines. MiR-150-5p inhibition or HMGA2 overexpression counteracted the effects of ZFAS1 knockdown on NSCLC cell proliferative, invasive potentials and apoptotic rates. In light of examining the clinical lung cancer samples, miR-150-5p expression was downregulated and the HMGA2 expression was highly expressed in the lung cancer tissues compared with normal ones; the ZFAS1 expression showed a negative correlation with miR-150-5p expression but a positive correlation with HMGA2 expression in lung cancer tissues. To summarize, we, for the first time, demonstrated the inhibitory effects of ZFAS1 knockdown on NSCLC cell progression, and the results from mechanistic studies indicated that ZFAS1-mediated NSCLC progression cells via targeting miR-150-5p/HMGA2 signaling.

Treatment of idiopathic sensorineural hearing loss (ISSNHL) is problematic due to the unclear etiology of the illness. Corticosteroid is recommended by some papers, and hyperbaric oxygen (HBO2) by others. Recently HBO2 has been shown to be an important therapy for ISSNHL, with an increasing number of studies demonstrating its beneficial results. Recovery from ISSNHL depends on the interval period between onset and treatment, hearing loss severity and audiogram type used to determine damage. Treatment of ISSNHL requires a detailed analysis. In this retrospective study we reviewed data from 56 patients with moderate ISSNHL. These patients were divided into three groups based on different treatments: corticosteroid group; corticosteroid + HBO2 (combination)group; and HBO2-only group. Additionally, all patients received intravenous vasodilator treatment. Hearing levels before and after treatment were compared. All three groups had a similar recovery rate, with an effective rate of more than 50%, and a hearing gain average of 17.38 decibels (dB). HBO2 treatment got a higher recovery rate. The combination therapy, which included corticosteroid and HBO2, did not elevate the recovery rate.

Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus. Patients with LN mostly die of sclerosing glomerulonephritis and renal failure. The inhibition of glomerular mesangial matrix deposition is an efficient method to restrict the progress of renal injury. By recognizing and binding extracellular and intracellular ligands, Toll-like receptor 2 (TLR2) contributes to the pathogenesis of most immune diseases. However, the relationship between TLR2 and LN is still unknown. Our previous studies confirmed that high-mobility group box 1 (HMGB1), an important ligand of TLR2, promotes the progression of LN by inducing the proliferation of glomerular mesangial cells. However, whether or not HMGB1 participates in the pathogenesis of glomerular mesangial matrix deposition in LN remains unknown. In this study, we observed the upregulated expression of TLR2 in the glomeruli of LN patients and MRL/lpr mice. The inhibition of either TLR2 or HMGB1 inhibited the release of fibronectin and the activation of the MyD88/NF-κB pathway in mesangial cells cultured with LN plasma. In addition, both TLR2- and HMGB1-deficient mice showed reduced 24 hr urine protein levels and improved glomerular histological changes and sclerosis levels. These results indicate that TLR2 regulates glomerular mesangial matrix deposition in LN through the activation of the MyD88/NF-κB pathway by binding to HMGB1.

Given the lack of research on the schoolchildren exposure to PM2.5-bound PHAs in northeast China, we investigated the effects of exposure to ambient benzo[b]fluoranthene (BbFA) and dibenz[a,h]anthracene (DahA) bound to PM2.5 on pulmonary ventilation dysfunction (PVD) and small airway dysfunction (SAD). PM2.5 samples at two schools (A and B) were collected, and the concentrations of PM2.5-bound 4-6-ring PAHs were analyzed. PVD and SAD were evaluated by pulmonary function tests in 306 students while urinary MDA and CRP levels were measured. The results confirmed that ambient PM2.5-bound 4-6-ring PHA levels were significantly higher and the PVD and SAD incidence in schools A and B were increased during the heating season. We found that PM2.5-bound BbFA, BkFA, BaP, and DahA levels were only correlated with SAD in schoolchildren; the correlation coefficients of BbFA and DahA were the highest effect estimates, possibly due to altered MDA levels. Therefore, this research enables us to better understand the effects of exposure to ambient PM2.5-bound PHAs on pulmonary function parameters. Our results also showed that identification of hazardous PM2.5-bound BbFA and DahA to health is crucial for preventing the respiratory-related diseases.

Influenza poses a severe threat to human health in the world. However, developing a universal anti-viral strategy has remained challenging due to the presence of diverse subtypes as well as its high mutation rate, resulting in antigenic shift and drift. Here we developed an antiviral strategy using iron oxide nanozymes (IONzymes) to target the lipid envelope of the influenza virus. We evaluated the antiviral activities of our IONzymes using a hemagglutination assay, together with a 50% tissue culture infectious doses (TCID) method. Lipid peroxidation of the viral envelope was analyzed using a maleic dialdehyde (MDA) assay and transmission electron microscopy (TEM). The neighboring viral proteins were detected by western blotting. We show that IONzymes induce envelope lipid peroxidation and destroy the integrity of neighboring proteins, including hemagglutinin, neuraminidase, and matrix protein 1, causing the inactivation of influenza A viruses (IAVs). Furthermore, we show that our IONzymes possess a broad-spectrum antiviral activity on 12 subtypes of IAVs (H1~H12). Lastly, we demonstrate that applying IONzymes to a facemask improves the ability of virus protection against 3 important subtypes that pose a threat to human, including H1N1, H5N1, and H7N9 subtype. Together, our results clearly demonstrate that IONzymes can catalyze lipid peroxidation of the viral lipid envelope to inactivate enveloped viruses and provide protection from viral transmission and infection.

Insertional Achilles tendinopathy (IAT) is a common finding in the clinic. However, consensus on its mechanism, pathological process, diagnosis, treatment, and rehabilitation is lacking. Thus, the Chinese Society of Sports Medicine organized and invited experts representing the fields of ankle disease and tendinopathy to jointly develop an expert consensus on IAT.

An electrochemical method is described for ultrasensitive determination of protein tyrosine kinase-7 (PTK7). It is based on (a) the use of positively charged gold nanoparticles (AuNPs) and negatively charged graphene oxide (GO), and (b) of toehold-mediated strand displacement amplification. A hairpin probe 2 (HP) containing the sgc8 aptamer was used to modify a glassy carbon electrode (GCE). Its hairpin structure is opened in the presence of PTK7 to form the PTK7-HP complex. The exposed part of HP partly hybridizes with hairpin probe 1 (HP) that was immobilizing on the AuNPs and GO modified GCE. On addition of the hairpin probe 3 that was labeled with the redox probe Methylene Blue (MB-HP), toehold-mediated strand displacement occurs due to complementary hybridization of HP with MB-HP. This causes the release of PTK7-HP into the solution and makes it available for the next reaction. Under optimal conditions, PTK7 can be quantified by voltammetry (typically performed at -0.18 V) with a detection limit of 1.8 fM. The assay possesses high selectivity for PTK7 due to the employment of the aptamer. It was successfully applied to the determination of PTK7 in the debris of malignant melanoma A375 cells. Graphical abstract Schematic representation of the enzyme-free electrochemical sensor for ultrasensitive determination of protein tyrosine kinase-7 (PTK7) based on the toehold-mediated strand displacement reaction amplification on gold nanoparticles and graphene oxide.