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Purpose: To find new signaling pathways that may be involved in the cellular response to ionizing radiation. Methods: Two radioresistant subclones (A549/R and SPCA1/R) derived from lung adenocarcinoma cell lines A549 and SPCA1 were established after eight rounds of sublethal irradiation. The new subclones were tested for radioresistant features using clonogenic assay and apoptosis analysis. The genes expressed differentially were screened with cDNA microarray analysis consisting of 48,000 transcript probes and confirmed by quantitative real-time PCR. Results: Stable and significant radioresistance was observed in the screened subclones. The microarray analysis showed 65 genes were up-regulated and 141 genes down-regulated in SPCA1/R cells. The up-regulated and down-regulated genes were 708 and 230 in A549/R cells, respectively. Twenty-seven altered genes were consistent in both subclones. Interestingly, members the of human solute carrier (SLC) gene superfamily were among in 27 genes. Conclusions: The differentially expressed genes in both cell lines may contribute to their radioresistant phenotype. This extensive list of genes identified in the experiment provides a large body of potentially valuable information for studying the molecular mechanism(s) of radiosensitivity and identification of candidate molecular markers of radiation sensitivity. Thus, to our knowledge, the SLC gene superfamily is the first being reported to involve in acquired radioresistance. [ABSTRACT FROM AUTHOR]

Background: Emerging data point to the critical role of snoRNA in the emergence of different types of cancer, but scarcely in breast cancer (BC). This study aimed to clarify the differential expressions and potential diagnostic value of SNORD16, SNORA73B, SCARNA4, and SNORD49B in BC. Methods: We screened differential snoRNAs in BC tissues and adjacent tissues through SNORic datasets, and then we further verified them in the plasma of BC patients and healthy volunteers by quantitative polymerase chain reaction (qPCR). Results: These four snoRNAs: SNORD16, SNORA73B, SCARNA4, and SNORD49B were considerably more abundant in cancerous tissues than in neighboring tissues in the TCGA database. Their plasma levels were also higher in BC and early-stage BC patients when compared to healthy controls. Furthermore, the ROC curve demonstrated that BC (AUC = 0.7521) and early-stage BC (AUC = 0.7305) might be successfully distinguished from healthy people by SNORD16, SNORA73B, SCARNA4, and SNORD49B. Conclusion: Plasma snoRNAs: SNORD16, SNORA73B, SCARNA4, and SNORD49B were upregulated in BC and early-stage BC and can be used as potential diagnostic markers for BC and early-stage BC. [ABSTRACT FROM AUTHOR]

Purpose: The alterations of RNA profile in tumor-educated platelets (TEPs) have been described as a novel biosource for cancer diagnostics. This study aimed to explore the potential snoRNAs in TEP as biomarkers for diagnostics of hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC). Methods: Platelets were isolated using low-speed centrifugation and subjected to a quantitative polymerase chain reaction (qPCR) for snoRNAs detection. Results: Down-regulated SNORD12B and SNORD14E as well as up-regulated SNORA63 were identified in TEP from HBV-related HCC, which could act as diagnostic biomarkers for HBV-related HCC as well as the early disease. Besides, TEP SNORD12B, SNORD14E, and SNORA63 facilitate the diagnostic performance of AFP and achieve favorable diagnostics efficiency for HBV-related HCC when combined with platelet parameters. Conclusions: Aberrant expression of SNORD12B, SNORA63, and SNORD14E in TEPs could serve as the novel and non-invasive biomarkers for HBV-related HCC diagnosis. [ABSTRACT FROM AUTHOR]

KRAS mutations have been reported as a reliable biomarker for epidermal growth factor receptor (EGFR) targeted therapy and are also associated with poor prognosis in colorectal cancer (CRC) patients. However, limitations of detecting KRAS mutations in tissues are obvious. KRAS mutations in the peripheral blood can be detected as an alternative to tissue analysis. The objective of this meta‐analysis was to evaluate the diagnostic value of cfDNA (circulating free DNA) compared with tissues and to investigate the prognostic potential of cfDNA KRAS mutations in CRC patients. Searches were performed in PubMed, Embase, and Cochrane Library for published studies. We extracted true‐positive (TP), false‐positive (FP), false‐negative (FN), true‐negative (TN) values, survival rate of CRC patients with mutant and wild‐type KRAS and calculated pooled sensitivity and specificity, positive/negative likelihood ratios [PLRs/NLRs], diagnostic odds ratios [DORs], and corresponding 95% confidence intervals [95% CIs]. We also generated a summary receiver operating characteristic (SROC) curve to evaluate the overall diagnostic potential. Totally, 31 relevant studies were recruited and used for the meta‐analysis on the efficacy of cfDNA testing in detecting KRAS mutations. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.637 (95% CI: 0.607‐0.666), 0.943 (95% CI: 0.930‐0.954), 10.024 (95% CI: 6.912‐14.535), 0.347 (95% CI: 0.269‐0.447), and 37.882 (95% CI: 22.473‐63.857), respectively. The area under the SROC curve was 0.9392. Together, the results suggest that detecting KRAS mutations in cfDNA has adequate diagnostic efficacy in terms of specificity. There is a promising role for cfDNA in the detection of KRAS mutations in CRC patients. However, prospective studies with larger patient cohorts are still required before definitive conclusions of the prognostic potential of cfDNA KRAS mutations in CRC patients were drawn. Circulating free DNA (cfDNA) has high concordance rate in detecting KRAS mutation status in colorectal cancer (CRC) patients, compared with tumor tissues. cfDNA has adequate diagnostic performance and could act as an effective method to detect KRAS mutation status in CRC patients. Due to its high specificity and non‐invasive nature, cfDNA might be a promising screening tool for CRC. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence has confirmed the role of snoRNAs in a variety of cancer, but rare in renal cell carcinoma (RCC). This study aims to clarify the role of snoRNAs in RCC tumorigenesis and their potential as novel tumor biomarkers. Materials and methods: The snoRNA expression matrix was obtained from the public TCGA and SNORic databases. SNORD15A, SNORD35B and SNORD60 were selected and validated by qPCR, then analyzed combined with related clinical factors using T-test and ROC curve. Results: All three snoRNAs: SNORD15A, SNORD35B and SNORD60 were significantly upregulated in cancer tissues compared to adjacent tissues from TCGA or FFPE detection. These three snoRNAs were also increased in urinary sediment (US) of RCC as well as the early-stage RCC patients compared with the healthy controls. In addition, RNase stability experiments confirmed their stable existence in US. Meanwhile, the ROC curve shows that SNORD15A, SNORD35B and SNORD60 could effectively distinguish RCC (AUC = 0.7421) and early-stage RCC (AUC = 0.7465) from healthy individuals. Conclusion: SNORD15A, SNORD35B and SNORD60 were upregulated in tissues and US of RCC, serving as novel potential biomarkers for RCC diagnosis. [ABSTRACT FROM AUTHOR]

Background: Colon cancer with liver metastases (CCLM) characterized by genetic heterogeneity is an evolutionary process leading to variations in response to selective pressure, but the underlying evolutionary models still remains unclear. Methods: Total of 30 samples, including primary tumor and two to four matched liver metastases from 8 treatment-naïve patients with CCLM were collected, and subjected to whole-exome DNA sequencing. PyClone was used to calculate intra and inter-tumor heterogeneity, LICHeE was used to reconstruct the cancer phylogeny trees and investigate the subclonal composition. Results: The genetic differences were observed between primary and metastatic lesions, as well as among multiple metastases in all patients. The natural history models of colorectal cancer in each case were identified, including parallel, linear, and branching evolution. Liver metastases could originate from primary lesions or other metastases. Pathway and process enrichment analysis also showed obvious heterogeneity and enhancement of several molecular functions. Conclusions: Our data reveal the genetic and heterogeneity between primary and metastatic lesions, as well as among multiple metastases and provide genomic evidence for clonal heterogeneity for CCLM. [ABSTRACT FROM AUTHOR]

Liensinine is a bioactive component of Plumula Nelumbinis extracted from the green embryo of the mature seeds of Nelumbonaceae and exhibits therapeutic functions and noteworthy anti-tumor effects in recent studies. However, the potential anti-tumor property and the underlying mechanisms of liensinine in nonsmall-cell lung cancer (NSCLC) have not been illustrated. In this study, we demonstrated that liensinine has the potential anti-tumor property, and it could inhibit growth of NSCLC in vitro and in vivo. In addition, we found that although it induced significant accumulation of autophagosomes, liensinine could quench them for degradation and blocked autophagic flux. Importantly, we observed that liensinine inhibited the normal function of mitochondrial energy supply and impaired the lysosomal function. This research firstly provides a possibility insight that liensinine could be a novel therapeutic strategy for NSCLC. [ABSTRACT FROM AUTHOR]

Abstract: A novel electrochemiluminescence (ECL) immunosensor based on the peroxydisulfate solution for detection of prostate-specific antigen (PSA) has been developed. In this work, gold nanoparticles (AuNPs) were electrodeposited on the glassy carbon electrode surface, which could increase the surface area to capture a large amount of primary antibodies as well as to improve the electronic transmission rate. The as-prepared bionanolabels, three-dimensional (3D) nanoflower-like MnO2 functionalized graphene (GN/MnO2), with novel hybrid architecture were initially fabricated via electrostatic interaction. Then, to provide an effective matrix for antibody immobilization with good stability and bioactivity, the novel materials were modified by AuNPs with the aid of poly (diallyldimethylammonium chloride) via a simple sonication-induced assembly method. In this immunosensor, MnO2 with the characteristics of well electrochemical behavior, low cost, and environmental-friendly, is used as a substitute for horseradish peroxidase to catalyze H2O2 to produce O2, and its 3D nanoflower-like structure is beneficial for the unparallel surface-to-volume ratio. Furthermore, a simple, low-cost and portable home-made potential transformer was utilized in this system to take the place of conventional electrochemical workstation. With a sandwich-type immunoassay format, the amount of functionalized GN/MnO2 labeled antibodies increased with the increment of antigens in the samples, which implied that the ECL signals enhanced with the increase of in situ generated O2 due to the enhancive catalysis of MnO2 to the H2O2. The immunosensor displayed excellent analytical performance for the detection of PSA in the range of 0.005–10ngmL−1 with a detection limit of 2.5pgmL−1 at 3σ. Moreover, the proposed method showed good precision, acceptable stability and reproducibility, and could be used for the detection of PSA in real samples. The proposed method provides a new promising platform of clinical immunoassay for other biomolecules. [Copyright &y& Elsevier]

Abstract: In this work, electrochemiluminescence (ECL) immunoassay was introduced into the recently proposed microfluidic paper-based analytical device (μPADs) based on directly screen-printed electrodes on paper for the very first time. The screen-printed paper-electrodes will be more important for further development of this paper-based ECL device in simple, low-cost and disposable application than commercialized ones. To further perform high-performance, high-throughput, simple and inexpensive ECL immunoassay on μPAD for point-of-care testing, a wax-patterned three-dimensional (3D) paper-based ECL device was demonstrated for the very first time. In this 3D paper-based ECL device, eight carbon working electrodes including their conductive pads were screen-printed on a piece of square paper and shared the same Ag/AgCl reference and carbon counter electrodes on another piece of square paper after stacking. Using typical tris-(bipyridine)-ruthenium (Ⅱ) - tri-n-propylamine ECL system, the application test of this 3D paper-based ECL device was performed through the diagnosis of four tumor markers in real clinical serum samples. With the aid of a facile device-holder and a section-switch assembled on the analyzer, eight working electrodes were sequentially placed into the circuit to trigger the ECL reaction in the sweeping range from 0.5 to 1.1 V at room temperature. In addition, this 3D paper-based ECL device can be easily integrated and combined with the recently emerging paper electronics to further develop simple, sensitive, low-cost, disposable and portable μPAD for point-of-care testing, public health and environmental monitoring in remote regions, developing or developed countries. [Copyright &y& Elsevier]

Abstract: A novel lab-on-paper device combining the simplicity and low-cost of microfluidic paper-based analytical devices (μPADs) and the sensitivity and selectivity of chemiluminescence ELISA (CL-ELISA) for the high-throughput, rapid, stable and reusable point-of-care testing is presented here. Chitosan was used to modify μPADs to covalently immobilize antibodies on μPADs. Thus, sandwich CL-ELISA on μPADs can be easily realized for further development of this technique in sensitive, specific and low-cost application. The paper device was fabricated by a low-cost, simple, and rapid wax-screen-printing method. Using tumor markers and paper microzone plate as model, the application test of this paper-based CL-ELISA was successfully performed with a linear range of 0.1–35.0ngmL−1 for α-fetoprotein, 0.5–80.0UmL−1 for cancer antigen 125 and 0.1–70.0ngmL−1 for carcinoembryonic antigen. Since the cutoff values of the three tumor markers in clinical diagnosis are 25ngmL−1, 35UmL−1 and 5ngmL−1, the sensitivity and linear ranges of the proposed method were enough for clinical application. In addition, this lab-on-paper immunodevice can provide reproducible results upon storage at 4°C (sealed) for at least 5 weeks. Ultimately, this novel chitosan modification and wax-screen-printing methodology for μPADs can be readily translated to other signal reporting mechanism including electrochemiluminescence and photoelectrochemistry, and other receptors such as enzyme receptors and DNA receptors for determination of DNA, proteins and small molecules in point-of-care testing. [Copyright &y& Elsevier]

Background: tRNA‐derived fragments (tRFs) have been found to play a regulatory role in the occurrence and development of many tumors. The aim of this study was to identify the expression of tRFs in breast cancer and their ability to serve as diagnostic markers for breast cancer. Methods: Total RNA was extracted from breast cancer and paracancerous tissues (n = 83), as well as from the sera of breast cancer patients (n = 214) and healthy donors (n = 113) using trizol reagents. Expression of tRFs was then detected by q‐PCR, and analyzed using t‐test and ROC to illuminate their potential as biomarkers for breast cancer. Results: Our results demonstrated that tRFs: tRF‐Gly‐CCC‐046, tRF‐Tyr‐GTA‐010 and tRF‐Pro‐TGG‐001 were downregulated in both tissues and sera from breast cancer patients as well as early‐stage patients compared with those in the healthy donors. More importantly, the three tRFs were capable of serving as circulating biomarkers of diagnostics and early diagnosis of breast cancer, possessing areas under the curve (AUC) of 0.7871 and 0.7987, respectively. Conclusions: tRFs: tRF‐Gly‐CCC‐046, tRF‐Tyr‐GTA‐010 and tRF‐Pro‐TGG‐001 are downregulated in breast cancer and early breast cancer and act as new potential biomarkers for the diagnosis and early diagnosis of breast cancer. [ABSTRACT FROM AUTHOR]

TIPE1, a newly identified member in TIPE (TNFAIP8) family, plays an important role in tumorigenesis and immune regulation, but its role in ovarian cancer, especially in tumor metastasis, remains unknown. In the current study, we aimed to reveal the protein expression spectrum of TIPE1 in normal human tissues and explored its relationship with metastasis in ovarian cancer. The results of IHC staining showed that TIPE1 protein was not only detected in cytoplasm in most human tissues but also expressed in both cytoplasm and nucleus in squamous epithelium and some epithelial-derived cells with secretory functions, such as esophagus, cervix uteri and ovary, and thyroid gland. Moreover, TIPE1 protein was downregulated in ovarian cancer tissues compared with that in the paracancerous. More importantly, TIPE1 suppressed tumorigenesis and metastasis of ovarian cancer in vitro and in vivo, as evidence shows its ability to suppress growth, colony formation, migration, and epithelial-mesenchymal transition (EMT) of ovarian cancer. Taken together, our results demonstrate the suppressor role of TIPE1 in ovarian cancer metastasis, indicating TIPE1 might be a metastasis predictor and a novel therapeutic target for ovarian cancer. [ABSTRACT FROM AUTHOR]

Purpose: Platelets contain a rich repertoire of RNA species, such as mRNAs and long non-coding RNAs. During the development of tumors, platelets are "educated" by cancer cells, altering their transcriptome and molecular content, thereby, tumor educated platelet (TEP) lncRNA profile has the potential to diagnose lung cancer. The current study was aimed to examine whether TEPs might be a potential biomarker for lung cancer. Methods: Platelet precipitation was obtained by low-speed centrifugation. TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 were selected by lncRNA microarray and validated by qPCR in a large cohort of lung cancer patients and healthy donors. Besides, we analyzed the association of their expression levels with clinicopathological features. Results: TEP linc-GTF2H2-1 and RP3-466P17.2 were significantly downregulated, while lnc-ST8SIA4-12 was significantly upregulated in patients with lung cancer or with early-stage lung cancer as compared to healthy donors, possessing AUCs of 0.781, 0.788, 0.725 for lung cancer and 0.704, 0.771, 0.768 for early-stage lung cancer, respectively. Notably, their combination demonstrated the markedly elevated AUCs of 0.921 for lung cancer and 0.895 for early-stage lung cancer. Besides, the combination of TEP linc-GTF2H2-1 was capable to facilitate diagnostic efficiencies of CEA, Cyfra21-1, or NSE to distinguish advanced-stage lung cancer patients from early ones, with an AUC of 0.899 based on the integration of these four factors. Conclusion: Our data suggested that lncRNAs sequestered in TEPs enabled blood-based lung cancer diagnosis and progression prediction. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the diagnostic and prognostic role of tumor‐educated leukocytes (TELs) mRNA in Chinese patients with non‐small cell lung cancer (NSCLC). Methods: The TELs collected underwent total RNA isolation. RNA‐sequencing (RNA‐seq) technology was used to analyze the transcriptome of the TELs. The mRNA expression levels of differential genes were analyzed by RT‐qPCR. Statistical analyses were performed using Prism and SPSS by Mann–Whitney nonparametric test, Kruskal‐Wallis test and one‐way ANOVA. Results: We used RNA‐seq technology to screen 95 differential genes (DEGs) from seven NSCLC and four controls, wherein 15 genes were upregulated, and 80 were downregulated. Of these, four genes were selected for further analysis, wherein one was upregulated (GPX1) and three were downregulated (BCL9L, MAP3K7CL, PCSK7). RT‐qPCR was performed in 431 samples (237 NSCLC, 194 healthy donors). The four‐gene panel showed significant differences (p < 0.001) in the expression levels between NSCLC and healthy samples. ROC curves of the panel revealed an AUC of 0.803, with a sensitivity of 73.8% and specificity of 75.3%. GPX1, BCL9L and PCSK7 genes distinguished early‐stage NSCLC patients from healthy group (p < 0.05). When the three genes were combined to diagnose early‐stage NSCLC, the diagnostic efficacy was 0.772, sensitivity was 73.7%, and specificity was 72.2%. In addition, the downregulated gene BCL9L was associated with chemotherapeutic effect. Conclusions: The present study provided a systematic description of gene expression profiling in the TELs. It is worth noting that these four genes may be potential candidate genes for NSCLC diagnostic biomarkers and provide a basis for further biological and functional studies. [ABSTRACT FROM AUTHOR]

Background: Despite the emerging insights into many snoRNAs (small nucleolar RNAs) which are detectable in body fluids and serve as noninvasive biomarkers, few studies have previously discussed the role of snoRNAs in tumor‐educated platelets (TEPs). Herein, we systematically estimated dysregulation of snoRNAs in non‐small cell lung cancer (NSCLC) and clarified the biomarker potential of SNORD55 in platelets. Methods: We compared expression of snoRNAs between NSCLC and normal tissues using SNORic datasets. Platelets were isolated from plasma using low‐speed centrifugation and subjected to quantitative polymerase chain reaction (qPCR) for SNORD55 detection. Results: SNORD55 was significantly decreased in TEPs from NSCLC patients especially in early‐stage patients compared with healthy controls. Importantly, we validated that TEP SNORD55 was capable of acting as a promising biomarker for NSCLC. It exerted diagnostic performance for NSCLC diagnosis, possessing an AUC of 0.803, as well as for early NSCLC diagnosis, possessing an AUC of 0.784. Moreover, the combination of TEP SNORD55 and carcinoembryonic antigen (CEA) improved the diagnostic efficiency of cancer progression. In addition, TEP SNORD55 also potentially acts as a noninvasive early biomarker for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) with favorable diagnostic efficiencies. Conclusions: In summary, TEP SNORD55 could potentially serve as a noninvasive biomarker for NSCLC diagnosis and early diagnosis. Key points: SNORD55 was significantly decreased in TEPs from NSCLC patients compared to healthy controls and acted as a novel biomarker for early NSCLC. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence shows that microRNAs are aberrantly expressed and exert essential roles in the tumorigenesis and tumor progression of non‐small cell lung cancer (NSCLC). Methods: The plasma miRNAs from five healthy donors and four NSCLC patients were profiled by miRNA microarray. The differentially expressed miRNAs from 154 primary NSCLC patients and 146 healthy donors were subjected to RNA isolation and verified by quantitative PCR (qPCR). Results: The miRNA microarray analysis revealed that 40 differential miRNAs between NSCLC patients and healthy donors were selected. We found that the plasma miR‐1247‐5p, miR‐301b‐3p and miR‐105‐5p levels of patients were significantly higher than those of healthy controls. The receiver operating characteristic curve (ROC) analyses revealed higher area under the ROC curve (AUC) values and higher sensitivity/specificity of carcinoembryonic antigen (CEA) in combination with miR‐1247‐5p, miR‐301b‐3p, or miR‐105‐5p were superior to that of CEA alone. Conclusions: High miR‐1247‐5p, miR‐301b‐3p and miR‐105‐5p expression have been demonstrated to accelerate tumorigenesis, and these three miRNAs in plasma act as novel biomarkers for the early diagnosis of NSCLC patients. Key points: Plasma miR‐1247‐5p, miR‐301b‐3p and miR‐105‐5p act as novel biomarkers for early NSCLC and NSCLC. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence has demonstrated that snoRNAs play crucial roles in tumorigenesis of various cancer types. However, researches on snoRNAs in ccRCC were very little. This study mainly aimed to validate the differential expression and the potential diagnostic value of SNORD63 and SNORD96A in ccRCC. Methods: SnoRNAs expression was downloaded from the SNORic and TCGA database including 516 patients with ccRCC and 71 control cases. SNORD63 and SNORD96A expression were further detected in 54 tumor and adjacent FFPE ccRCC tissues, 55 plasma and 75 urinary sediment of ccRCC patients. Then, differential expression and diagnostic value of SNORD63 and SNORD96A were further calculated. Results: SNORD63 and SNORD96A expression were significantly increased in ccRCC tissues compared with normal tissues from the TCGA database (both, P < 0.0001). In addition, we found that SNORD63 and SNORD96A localized in plasma and US stably after treating with RNase A. Meanwhile, SNORD63 and SNORD96A in FFPE and US were elevated in ccRCC patients (all, P < 0.0001). However, plasma SNORD63 expression had no significance while SNORD96A significantly increased in plasma of ccRCC patients. Notably, the AUC of SNORD63 in US was 0.7055, by comparison the AUC of plasma SNORD63 was only 0.5161. However, the AUC of plasma SNORD96A was up to 0.8909, by comparison the AUC of SNORD96A in US was 0.6788. Interestingly, the AUC of plasma SNORD96A in early stage ccRCC was highly up to 0.9359. Conclusions: Our findings revealed that SNORD63 in US and SNORD96A in plasma could act as the promising non-invasive diagnostic biomarkers for ccRCC patients. [ABSTRACT FROM AUTHOR]

Background. Evidence has suggested the functional role of exosomal miRNAs in cancer diagnosis. This study aimed to determine whether the serum exosomal biomarkers can improve the diagnosis of patients with non-small-cell lung cancer (NSCLC). Materials and Methods. The exosomes were extracted from the serum of NSCLC patients (n = 235) and healthy donors (n = 231) using ultracentrifugation and then were evaluated by using transmission electron microscopy, qNano, and western blotting. The serum exosomal miRNA expression was validated using qPCR. Results. Exosomal miR-620 was significantly reduced in NSCLC and early-stage NSCLC patients (P < 0.0001) when compared to that of healthy controls, with an area under the curve (AUC) of 0.728 and 0.707, respectively. Exosomal miR-620 expression showed an association with drinking (P = 0.008) and distant metastasis (P = 0.037). Additionally, the downregulated exosomal miR-620 showed association with chemotherapeutic effect (P = 0.044). Conclusion. These findings suggest the serum exosomal miR-620 as a promising diagnostic and prognostic noninvasive biomarker in NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: Exosomal microRNAs (miRNAs) are proposed to be excellent candidate biomarkers for clinical applications. However, little is known about their potential value as diagnostic biomarkers for metastatic non-small cell lung cancer (NSCLC). Methods: In this study, microarrays were used to determine distinct miRNA profiles of plasma exosomes in a discovery cohort of healthy donors, metastatic NSCLC and nonmetastatic NSCLC patients. Three potential candidate miRNAs were selected based on the differential expression profiles. The discovery set data were validated by quantitative real-time polymerase chain reaction using a validation cohort. Results: NSCLC patients (n = 80) and healthy controls (n = 30) had different exosome-related miRNA profiles in plasma. Results demonstrated that the level of let-7f-5p was decreased in plasma exosomes of NSCLC patients (p < 0.0001). Further analysis of three differentially expressed miRNAs revealed that miR-320a, miR-622 and let-7f-5p levels could significantly segregate patients with metastatic NSCLC from patients with nonmetastatic NSCLC (p < 0.0001, p < 0.0001 and p = 0.023, respectively). In addition, the combination of let-7f-5p, CEA and Cyfra21-1 generated an area under the curve (AUC) of 0.981 for the diagnosis of NSCLC patients, and the combination of miR-320a, miR-622, CEA and Cyfra21-1 had an AUC of 0.900 for the diagnosis of patients with metastatic NSCLC. Conclusions: This novel study demonstrated that plasma exosomal miRNAs are promising noninvasive diagnostic biomarkers for metastatic NSCLC. [ABSTRACT FROM AUTHOR]

Background. Procalcitonin (PCT), C-reactive protein (CRP), and neutrophil-to-lymphocyte ratio (NLR) have emerged as important markers of inflammation, and these markers, especially PCT and CRP, have been studied in patients with neutropenia. This study was designed to evaluate their value in differentiating infectious fever from tumor fever (TF) and to investigate their role in assessing outcomes in nonneutropenic lung cancer patients (NNLCPs). Methods. This retrospective clinical study included 588 febrile NNLCPs between January 2019 and December 2019. The levels of PCT, CRP, and conventional inflammatory markers, including white blood cells (WBC) and neutrophils (NEU), were measured. NLR was defined as the ratio of the absolute neutrophil count to the absolute lymphocyte count. Patients' clinical and bacteriological data were recorded. Results. This study included 311 NNLCPs with bacterial infections and 277 with TF. Inflammatory markers such as PCT, CRP, WBC, and NEU levels and NLR were significantly higher in patients with bacterial infections than in those with TF (p < 0.0001). However, PCT level was the best predictor of bacterial infections, with an area under the curve (AUC) of 0.874, followed by CRP level (AUC = 0.855) and NLR (AUC = 0.792) (p < 0.0001). Additionally, PCT level was significantly elevated in patients with bacterial infections with progressive disease after radiotherapy and chemotherapy (p < 0.01). Conclusions. The present study demonstrated the superiority of PCT over CRP and NLR in the diagnosis of febrile patients with bacterial infections. Additionally, PCT can be used to assess the clinical outcomes and cancer progression in NNLCPs. [ABSTRACT FROM AUTHOR]

Background: During the development of tumors, tumors "educate" platelets causing changes in their mRNAs expression profiles and phenotypes, thereby, tumor-educated platelet (TEP) mRNA profile has the potential to diagnose lung cancer. The current study aimed to examine whether TEPs might be a potential biomarker for lung cancer diagnostics. Methods: Platelet precipitation was obtained by low-speed centrifugation and subjected to Trizol for total RNA extraction. Platelet MAX, MTURN, and HLA-B mRNA were selected by microarray, validated by qPCR, and analyzed combined with related clinical factors. Results: Our results showed that a three-platelet mRNA set: MAX, MTURN, and HLA-B was significantly up-regulated in lung cancer patients as well as in early-stage lung cancer patients compared with those from healthy donors, the area under the curve (AUC) was 0.734, 0.787, respectively, among which platelet MTURN mRNA processed a dramatically high diagnostic efficiency in female patients with lung cancer, its AUC for female was 0.825. More importantly, the three-platelet mRNA set: MAX, MTURN, and HLA-B was associated with chemotherapeutic effect, low mRNA expression of this three-platelet set was correlated with "favorable" first chemotherapy response. Conclusions: A three-platelet mRNA set: MAX, MTURN and HLA-B enables blood-based lung cancer diagnosis and chemotherapy response prediction. [ABSTRACT FROM AUTHOR]

Background: Both quantitative and qualitative aspects of plasma cell‐free DNA (plasma cfDNA, pcfDNA) have been well‐studied as potential biomarkers in non‐small cell lung cancer (NSCLC). Accumulating evidence has proven that saliva also has the potential for the detection and analysis of circulating free DNA (saliva cfDNA, scfDNA). Methods: In the current study, we aimed to explore the potential application of scfDNA in NSCLC diagnostics and consistency of epidermal growth factor receptor (EGFR) mutation detection in paired pcfDNA and scfDNA using droplet digital PCR (ddPCR) and analyze the relationship between EGFR mutations and clinical treatment response. Results: In the quantitative cohort study, scfDNA concentration in NSCLC patients was no different from that in healthy donors, or in benign patients. ScfDNA concentration was significantly lower than pcfDNA concentration, yet they were not statistically significant in relevance (Spearman's rank correlation r = −0.123, P = 0.269). In the qualitative cohort study, the overall concordance rate of EGFR mutations between pcfDNA and scfDNA was 83.78% (31 of 37; k = 0.602; P < 0.001). EGFR mutation detection in paired pcfDNA and scfDNA was significantly correlated with the clinical treatment response (Spearman's rank correlation r = 0.664, P = 0.002). Conclusions: Our results demonstrated that saliva might not be the idea material for a cfDNA quantitative test, and scfDNA concentration is not applicable for NSCLC diagnostics. Conversely, scfDNA was capable of acting as the supplement for EGFR mutations due to the coincidence rate of EGFR mutation detection between scfDNA and pcfDNA. [ABSTRACT FROM AUTHOR]

In this paper, a dual-target electrochemical aptasensor has been developed for simultaneous detection of carcinoembryonic antigen and mucin-1 based on metal ion electrochemical labels and Ru(NH 3 ) 6 3+ electronic wires. When targets are present, the interaction between targets and their respective aptamers leads to the dissociation of double-strand DNA because the targets have higher affinity to its aptamer than the complementary strand. And the qualitative and quantitative analyses of the two targets are realized by the differential pulse voltammetry (DPV) peaks generated by metal ion electrochemical labels. For the effective loading of a large number of metal ions, Au/bovine serum albumin (Au/BSA) nanospheres are employed as carriers to develop Au/BSA–metal ions. After Ru(NH 3 ) 6 3+ complexes are embedded into double-strand DNA to form the electronic wires, the electrical conductivity and the electron transfer of the detection system are greatly improved. The detection limit of the proposed assay was calculated as 3.33 fM ranging from 0.01 pM to 100 nM. Therefore, this novel sensing assay provides a new and sensitive platform for detecting several targets simultaneously in biochemical research and clinical diagnosis. [ABSTRACT FROM AUTHOR]

In this paper, a microfluidic paper-based electrochemical DNA biosensor was constructed for sensitive detection of EGFR mutations in patients with saliva. In order to achieve the purpose of detection, oligonucleotides were modified on the electrode surface, and the outputs of the electrochemical signal were gained by analyzing DNA hybridization reaction, after that, the horseradish peroxidase (HRP) recognized the indicator labeled on DNA and exhibited excellent electrocatalytic behavior to H 2 O 2 , bringing the rapid enhancement of current response. Under optimum conditions, the as-prepared biosensor showed a good linear relationship between the current value and logarithm of the target DNA concentration ranging from 0.5 nM to 500.0 nM and a detection limit as low as 0.167 nM. Meanwhile, the DNA biosensor emerged good stability and high specificity in distinguishing single nucleotide polymorphism of target DNA. This work not only opened a different horizon for investigating biomarker in biological fluids but also offered a promising and reliable method in biosensing and clinical diagnosis in general. [ABSTRACT FROM AUTHOR]

The authors describe a new kind of enzymatic glucose assay. The strategy involves three processes: (a) Generation of HO via glucose oxidase catalyzed oxidation of glucose; (b) production of 2,3-diaminophenazine (DAP) from HO and o-phenylenediamine (OPD) via peroxidase-catalyzed oxidation; and (c) a reduction of the blue fluorescence of SiNPs with emission maxima at 445 nm via an inner filter effect that is caused by DAP which is yellow and has an absorption peak at 450 nm. Fluorescence drops with increasing glucose concentrations in the 0.01 to 7 mM concentration range, and the detection limit is 3.5 μM. The assay was successfully applied to the analysis of glucose in human serum. [ABSTRACT FROM AUTHOR]

A fluorescent sensor for the determination of glutathione (GSH) has been developed, which is based on the absorption of a newly designed thiols-specific chromogenic probe (CP) coupled with the use of a thiols-independent fluorophore g-C 3 N 4 nanosheets. It was operated on the inner filter effect (IFE). To construct an efficient IFE system, the CP molecules were adsorbed on the surface of g-C 3 N 4 nanosheets via π–π stacking interaction. When the biothiol introduced the systems, the weak fluorescence would be restored because of “IFE off”. The novel IFE sensor was established for GSH and regarded it as a model target analyte. The IFE sensor had a sensitive response for GSH in a linear range of 0.05 μM L −1 to 1.0 μM L −1 and the limit of detection was 0.01 μM. The sensor was successfully applied for the quantitative detection of biothiols in human serum. Additionally, the proposed sensor shows high specificity and sensitivity. [ABSTRACT FROM AUTHOR]

Background: Mutant Phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit alpha ( PIK3CA) has been shown to be associated with the occurrence, development and prognosis in colorectal cancer (CRC). However, its detection has been limited because of complicated procedures and the low sensitivity of the present approaches. Methods: We established an ultra-sensitive peptide nucleic acid-mediated polymerase chain reaction (PNA-PCR) assay to detect PIK3CA gene mutation in exon 9 and exon 20 with cell-free DNA (cfDNA). Using this technology, we detected the mutation status of PIK3CA in 128 colorectal cancer patients. 6 CRC patients receiving targeted therapy were chosen at random to undergo continuous PIK3CA mutation detection. Results: The results showed that the sensitivity of PNA-PCR clamping method was 0.1% for the exon 9 and 0.2% for the exon 20 variant alleles. When the PIK3CA mutation status was determined by PNA-PCR plus sequencing, 38.3% (49/128) of CRC carried at least one mutation, either E545Kor H1047R. The clinic-pathological parameters of age ( p = 0.358), gender ( p = 0.622), disease stage ( p = 0.353) and disease location ( p = 0.307) were not associated with the PIK3CA mutation. In the continuous monitoring study, we found that the gene status was associated with the effect of treatment. Furthermore, when the PIK3CA variant was determined by only the PNA-PCR method, there was a good linear relationship between ΔCp values and the proportion of variant DNA. The accuracy of PNA-PCR was 93.75 and 92.27% respectively when the cut-off values of ΔCp at 9.0 and 8.0 were set for determining the E545K and H1047R mutations. Conclusions: A simple, noninvasive, ultra-sensitive PNA-PCR technology was developed and was especially suitable for the dynamic detection of PIK3CA variants using cfDNA. [ABSTRACT FROM AUTHOR]

An ultrasensitive photoelectrochemical (PEC) immunosensor for the detection of carcinoembryonic antigen (CEA) was constructed using CdS@Cu 2 O co-sensitized porous ZnO nanosheets as photoactive materials and multiwalled carbon nanotubes (MWCNTs) as electrons sink. Porous ZnO was assembled on the MWCNTs modified indium tin oxides electrode to immobilize capture antibodies. With a sandwich immunoassay format, CEA and signal antibodies labeled CdS@Cu 2 O were introduced in sequence via specific immunoreaction, and the ultrahigh sensitivity of this immunoassay results from the following three aspects. First, the co-sensitization of Cu 2 O and CdS extends the absorption range of ZnO from ultraviolet region to visible light region, which can adequately utilize the light energy. Second, the effective matching of energy levels between the ZnO, CdS and Cu 2 O accelerates the separation and transfer of photogenerated electron-hole pairs and improves the PEC performance, significantly. Finally, the introduced MWCNTs evidently expedite the interfacial electron transfer from ZnO to electrode, further resulting in noticeably increased photocurrent. On the basis of multiple signal amplification strategy, a largely increased linear detection range from 1.0 pg mL −1 to 80 ng mL −1 with a low detection limit (0.4 pg mL −1 ) are obtained. Meanwhile, the prepared materials with attractive properties provide a promising platform for PEC detection. [ABSTRACT FROM AUTHOR]

In this work, a novel sensing platform based on visible light driven biofuel cell (BFC) has been facilely designed for sensitive detection of prostate-specific antigen (PSA) with the photo-response bioanode, realizing the dual route energy conversion of light energy and chemical energy to electricity. The hierarchical branched TiO 2 nanorods (B-TiO 2 NRs) decorated with CdS quantum dots (QDs) act as the substrate to confine glucose dehydrogenase (GDH) for the visible light driven glucose oxidation at the bioanode. Three dimensional flowers like hierarchical carbon/gold nanoparticles/bilirubin oxidase (3D FCM/AuNPs/BOD) bioconjugate served as biocatalyst for O 2 reduction at the biocathode. With an increase in the concentration of PSA, the amount of BOD labels on biocathode increases, thus leading to the higher current output of the as-proposed visible light driven BFC. Based on this, this sensing platform provide great performance in sensitivity and specificity, increasing linear detection range from 0.3 pg mL −1 to 7 μg mL −1 with a detection limit of 0.1 pg mL −1 . Most importantly, our new sensing strategy provided a simple and inexpensive sensing platform for tumor markers detection, suggesting its wide potential applications for clinical diagnostics. [ABSTRACT FROM AUTHOR]

A simple and rapid assay for the detection of peptides is designed based on the specific recognition of aptamer, the quenching effect of graphene oxide (GO) and the efficient signal amplification of hybrid chain reaction (HCR). In this assay, the hairpin structure of aptamer is opened after binding with targets, and the initiation sequence could be exposed to hairpin probe 1 (H1) to open its hairpin structure. Then the opened H1 will open the hairpin structure of hairpin probe 2 (H2), and in turn, the opened initiation sequence of H2 continues to open H1. As a result, the specific recognition of target and fluorescent signals are accumulated through the process in short 1 h. Attentively, the aptamer can not only identify target peptides, but also initiate the HCR between H1 and H2. More importantly, the HCR is initiated only after the target recognition of aptamer. After HCR, the excess hairpin probes will be anchored on the GO surface, and the background is greatly reduced due to the quenching effect of GO. By using Mucin-1(MUC1) as a model peptide, the assay has a wide linear range as two orders of magnitude and the detection range is from 0.01 to 5 nM with low detection limit of 3.33 pM. Therefore, the simple and rapid detection of the target can be realized, and the novel assay has great potential in detecting various peptides and even cancer cells. [ABSTRACT FROM AUTHOR]

On the basis of the absorption and emission spectra overlap, an enhanced resonance energy transfer caused by excition-plasmon resonance between carbon nanotubes-gold nanoparticles (CNTs-Au) and pinnate titanium dioxide nanorods array (P-TiO 2 NA) was obtained. Three-dimensional single crystalline P-TiO 2 were prepared successfully on fluorine-doped tin oxide conducting glass (FTO glass), and its optical absorption properties and photoelectrochemical (PEC) properties were investigated. With the synergy of CNTs-Au as energy acceptor, it resulted in the enhancement of energy transfer between excited P-TiO 2 NA and CNTs-Au. Upon the novel sandwichlike structure formed via DNA hybridization, the exciton produced in P-TiO 2 NA was annihilated and a damped photocurrent was obtained. With the use of carcinoembryonic antigen (CEA) as a model which bonded to its specific aptamer and destroyed the sandwichlike structure, the energy transfer efficiency was lowered, leading to PEC response augment. Thus a signal-on PEC aptasensor was constructed. Under the optimal conditions, the PEC aptasensor for CEA determination exhibited a linear range from 0.001 to 2.5 ng mL −1 with a detection limit of 0.39 pg mL −1 and was satisfactory for clinical sample detection. Furthermore, the proposed aptasensor shows satisfying performance, such as easy preparation, rapid detection and so on. Moreover, since different aptamer can specifically bind to different target molecules, the designed strategy has an expansive application for the construction of versatile PEC platforms. [ABSTRACT FROM AUTHOR]

In this work, we report a rapid, facile, portable, disposable and low-cost fluorescence and visual method for multiplexed monitoring of cancer cells using graphene oxide (GO)-based aptameric nanosensor in microfluidic paper-based analytical devices. This method has combined the exceptional quenching capability of GO and an aptamer with high specificity and affinity employed as the molecular recognition element. The quantum dots coated mesoporous silica nanoparticles labeled aptamers in a flexible single stranded state could be adsorbed on the surface of GO, and the fluorescence was quenched via Förster resonance energy transfer, with subsequent recovery of the fluorescence upon addition of target cells. Furthermore, the design of sensors for other cancer cells only requires change in the recognition element for the target cell and different colored quantum dots. More importantly, three different cancer cells can be simultaneously determined with a single excitation light. The sensitivity and selectivity of this method for GO-based sensing were extremely high. The color changes could be clearly monitored with the naked eye. And their linear range were from 180 to 8 × 10 7 , 210 to 7 × 10 7 , 200 to 7 × 10 7 cells mL −1 and detection limit were 6270 and 65 cells mL −1 for MCF-7, HL-60, and K562 cells, respectively. It could be applied in clinical sample analysis with a satisfactory result. Therefore, GO-based aptameric nanosensor is highly promising for potential applications in the sensitive monitoring of multiple cancer cells for biomedical research and medical diagnostics. [ABSTRACT FROM AUTHOR]

A highly sensitive and selective turn on fluorescent probe P-acid-aldehyde (P-CHO) is developed for the determination of cysteine (Cys) and homocysteine (Hcy). The probe is designed and synthesized by incorporating the specific functional group aldehyde group for thiols into a stable π-conjugated material 4,4′-(2,5-dimethoxy-1,4-phenylene) bis(ethyne-2,1-diyl) dibenzoic acid (P-acid). The probe fluorescence is quenched through donor photoinduced electron transfer (d-PET) between the fluorophore (P-acid) and the recognition group (aldehyde group). In the presence of thiols, Cys and Hcy can selectively react with aldehyde group of the probe because the inhibition of d-PET between fluorophore and recognition group. Therefore, a turn-on fluorescent sensor was established for the fluorescence recovery. Under the optimized conditions, the fluorescence response of probe is directly proportional to the concentration of Cys in the range of 4–95 nM L −1 , with a detection limit 3.0 nM. In addition, the sensing system exhibits good selectively toward Cys and Hcy in the presence of other amino acids. It has been successfully applied for bioimaging of Cys and Hcy in living cells with low cell toxicity. [ABSTRACT FROM AUTHOR]

Herein, a photoelectrochemical (PEC) immunoassay is constructed for squamous cell carcinoma antigen (SCCA) detection using zinc oxide nanoflower-bismuth sulfide (Bi 2 S 3 ) composites as photoactive materials and reduced graphene oxide (rGO) as signal labels. Horseradish peroxidase is used to block sites against nonspecific binding, and then participated in luminol-based chemiluminescence (CL) system. The induced CL emission is acted as an inner light source to excite photoactive materials, simplifying the instrument. A novel signal amplification strategy is stem from rGO because of the rGO acts as an energy acceptor, while luminol serves as a donor to rGO, triggering the CL resonance energy transfer phenomenon between luminol and rGO. Thus, the efficient CL emission to photoactive materials decreases. Furthermore, the signal amplification caused by rGO labeled signal antibodies is related to photogenerated electron–hole pairs: perfect matching of energy levels between rGO and Bi 2 S 3 makes rGO a sink to capture photogenerated electrons from Bi 2 S 3 ; the increased steric hindrance hinders the electron donor to the surface of Bi 2 S 3 for reaction with the photogenerated holes. On the basis of the novel signal amplification strategy, the proposed immunosensor exhibits excellent analytical performance for PEC detection of SCCA, ranging from 0.8 pg mL −1 to 80 ng mL −1 with a low detection limit of 0.21 pg mL −1 . Meanwhile, the designed signal amplification strategy provides a general format for future development of PEC assays. [ABSTRACT FROM AUTHOR]

Background Human epididymis protein 4 (HE4) had been shown to be an ideal biomarker in ovarian cancer. However, there were fewer reports on its application in lung cancer. We explored the diagnostic value of serum HE4 as a biomarker in early lung cancer by comparing it with other biomarkers. Methods 162 individuals including 112 cases of lung cancer at early stage and 50 healthy people as controls were enrolled. The serum concentrations of biomarkers were determined with the Roche Elecsys assays. Results In comparison to the other biomarkers such as carcinoembryonic antigen (CEA), neuron-specific-enolase (NSE), serum cytokeratin 19 fragment (CYFRA 21-1) and progastrinreleasing peptide (proGRP), serum HE4 was one of the biomarkers with the highest sensitivity (43.8%) and specificity (95.0%) for early lung cancer diagnosis. In terms of histological results, serum HE4 was the best biomarker both in adenocarcinoma (AC) and squamous carcinoma (SC), and serum proGRP was the best in small cell lung cancer (SCLC). The combination of proGRP, NSE and HE4 could determine the histological type of lung cancer with a very high accuracy of 93.8%. Conclusions These findings suggested that serum HE4 was a better biomarker in early lung cancer than other frequently-used biomarkers. [ABSTRACT FROM AUTHOR]

Branched zinc oxide nanorods (BZR) arrays, an array with high charge carries collection efficiency and specific surface area, are grown on the reduced graphene oxide-paper working electrode for the first time to construct a paper-based electrochemical (EC) immunosensor. Typically, the BZR are fabricated via a simple hydrothermal process, which can provide abundant sites for antibodies loading. By combining the large surface area of porous zinc oxide (PZS) and good biocompatibility of gold nanoparticles (AuNPs), PZS–AuNPs (PZS@Au) nanocomposites are designed to label horseradish peroxide (HRP) and antigens. After a competitive reaction between antigens and PZS@Au nanocomposites labeled antigens, the signal labels are introduced into the immunosensor, in which, HRP participate in biocatalytic precipitation process. The produced precipitate reduces the electrode surface area and hinders the electron transfer. With the increase of concentration of antigens, the signal labels introduced into the sensor decrease, thus, a signal-on immunoassay for α-fetoprotein detection is constructed. The proposed paper-based EC immunosensor combines enzymatic biocatalytic precipitation reaction and competitive immunoassay mode for the first time, and possesses a wide linear range from 0.2 pg mL −1 to 500 ng mL −1 with a detection limit of 0.08 pg mL −1 . In addition, the proposed method is simple, sensitive and specific and can be a promising platform for other protein detection. [ABSTRACT FROM AUTHOR]

In our work, low potential and sensitive electrochemiluminescence (ECL) detection for CA153 on MCF-7 cell surface was firstly achieved based on a microfluidic paper-based analytical device. Au nanoflowers were grown in paper working electrode (PWE) to construct the ECL platform for primary antibodies immobilizing. After MCF-7 cells were captured in the modified PWE, and subsequently recognized with ECL signal substance labeled secondary antibodies, the sandwich-type cell sensor was fabricated. Graphene quantum dots (GQDs) loaded surface villous Au nanocages were synthesized as the ECL signal substance, and characterized by scanning electron microscope. The specific villous surface structure for Au nanocage permitted more GQDs being carried and electrons transporting, which largely benefited for the ECL performance. As the un-negligible impendence for MCF-7 cell would definitely influence the ECL signal, CA153 labeled HMEpic cell was used as the control cell to obtain more accurate determination result. This low-cost and fast strategy showed acceptable biocompatibility and stability, and will be promising for cellular immunochemistry. [ABSTRACT FROM AUTHOR]

Copper sulfide (CuS), an excellent photoactive material, is introduced into a paper-based photoelectrochemical (PEC) immunosensor for the first time using an in situ electron donor producing approach. ZnO nanoflakes (ZNF) with a large surface area are first electrodeposited onto a gold-paper electrode, and then functionalized with CuS via a simple hydrothermal and ion exchange method. The recombination process of electron–hole pairs in CuS is prevented since the energy levels between ZnO and CuS are matched well, resulting in a high PEC performance. The glucose oxidase (GOx) and signal antibodies co-labeled nanoporous gold (NPG) is then introduced into the immunosensor via sandwich immunoreactions. On the basis of the catalytic chemistry of GOx to produce in situ H2O2 for electron donation, an enhanced photocurrent was achieved. By coupling the brilliant properties of CuS/ZNF, a modified gold-paper electrode with amplified electron donor production through NPG, a sensitive PEC immunosensor for carcinoembryonic antigen (CEA) analysis is proposed. The immunosensor displayed a linear response to CEA in the range from 2 pg mL−1 to 100 ng mL−1 with a relatively low detection limit of 0.7 pg mL−1. The proposed immunosensor exhibited good performance, which has a promising prospect in clinical diagnosis. [ABSTRACT FROM AUTHOR]

An ultrasensitive enzyme-free electrochemical immunosensor is constructed using a gold nanorods (AuNRs) modified paper electrode as the sensor platform and porous zinc oxide spheres (PZS)–silver nanoparticles (AgNPs) nanocomposites as signal labels. Significantly enhanced sensitivity for prostate specific antigen (PSA) comes from a dual signal amplification strategy. First, interconnected AuNRs layers, which can improve the electronic transmission rate, are grown on the surface of cellulose fibers on a paper sample zone to capture primary antibodies. Second, PZS, a porous material with large surface area, is synthesized to provide sites for AgNPs loading, which improves the catalytic capacity of the AgNPs towards H2O2 reduction. Under optimized conditions, the proposed immunosensor for PSA exhibits a wide linear detection range from 0.004 to 60 ng mL−1 with a detection limit of 1.5 pg mL−1. Moreover, the immunosensor shows excellent selectivity, high stability, and acceptable fabrication reproducibility. This strategy appears to be a simple method, which provides a promising platform for the detection of other proteins. [ABSTRACT FROM AUTHOR]

A dual functional analytical device performing both energy conversion and electric energy storage based on biofuel cells to implement self-powered point-of-care testing was developed based on a piece of Ti foil. [ABSTRACT FROM AUTHOR]

A novel electrochemical immunosensor for the detection of carcinoembryonic antigens (CEAs) was developed by using nanogold functionalized flower-like hierarchical carbon material (AuNPs/FCM) labeled with horseradish peroxidase-secondary antibodies as a signal amplification label. The amplified detection was achieved by the increased HRP-electrocatalyzed reduction of hydrogen peroxide. In order to construct the base of the immunosensor, a hybrid platform was generated by the electrostatic attraction between poly(diallyldimethylammonium chloride) functionalized graphene (G-PDDA) and three-dimensional trepang-like gold (3D-TG). The platform with excellent electronic properties, stability, bioactivity and large surface area served as an effective matrix for CEA-primary monoclonal antibodies. Subsequently, a sandwich-type immunocomplex of 3D-TG/G-PDDA and AuNPs/FCM was formed based on the immunoreaction of antibody–antigen in the presence of CEA. Enhanced sensitivity was obtained by combining the advantages of excellent electrical conductivity and bioactivity of the hybrid sensor platform with multilabel signal amplification. Under optimal conditions, our strategy displayed excellent analytical performance for the detection of CEA ranging from 0.0001 to 50 ng mL−1 with a detection limit of 0.026 pg mL−1. The new proposed method provides a new promising platform for the design of the highly sensitive detection method, showing great promise for clinical immunoassays. [ABSTRACT FROM AUTHOR]

In this work, multiplexed photoelectrochemical (PEC) immunoassays are introduced into an indium tin oxide (ITO) device. Firstly, the ITO device is fabricated using a simple acid etch treatment method. Secondly, AuPd alloy nanoparticles are electro-deposited on ITO working electrodes as electron sink to construct the immunosensor platform. After that, ZnO nanotubes (ZNTs) arrays are synthesized via chemical etching of ZnO nanorods that are grown on AuPd surface by electrochemical deposition method. Subsequently, CdS is electro-deposited on ZNTs arrays and used as photoactive material. Then, CuO nanoseeds are labeled with signal antibodies and firstly used as PEC signal amplification label. The introduction of CuO brings signal amplification because of the conduction band (CB) of both CuO and ZnO are lower than that of CdS, CuO will compete the photo-induced electrons in CB of CdS with ZnO, leading to the decrease of the photocurrent intensity. Using cancer antigen 125, prostate specific antigen and α-fetoprotein as model analytes, the proposed immunoassay exhibits excellent precision and sensitivity. Meanwhile, this work provides a promising, addressable and simple strategy for the multi-detection of tumor markers. [ABSTRACT FROM AUTHOR]

We report on the synthesis of flower-like 3D titanium dioxide (fl-TiO) using a hydrothermal method. This material possesses a large specific surface and displays an electrochemiluminescence (ECL) intensity that is much stronger than the one of TiO nanoparticles having smooth surfaces. It was used to label the secondary antibody in a sandwich immunoassay. A thin layer of metallic gold (Au) and palladium (Pd) was deposited on an indium tin oxide (ITO) electrode by code-position at a potential of 0.2 V in the respective chloride solutions. The Au/Pd-modified ITO electrode showed good conductivity. An ECL based immunoassay for the prostate specific antigen (PSA) was then worked out by immobilizing the first antibody on the Au/Pd layer on the ITO electrode, then exposing the electrode to a sample containing PSA, then forming the sandwich with the fl-TiO labeled secondary antibody, and finally measuring the intensity of ECL at a potential of −1.5 V. This ECL sensor has a response range that extends from 0.001 to 600 ng∙mL, a lower detection limit of 0.32 pg∙mL, good specificity, acceptable stability and good reproducibility. It gave satisfactory results when used for the determination of PSA in (spiked) diluted solutions of human serum. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

BACKGROUND: At present no useful factors to predict the sensitivity to neoadjuvant chemoradiotherapy (nCRT) have been established in patients with locally advanced rectal cancer (LARC). OBJECTIVE: The objective of this study was to explore the prognostic role of T cell factor 4 (TCF4) expression in predicting tumor response to nCRT and tumor outcomes for patients with LARC. METHODS: The study enrolled 96 patients who underwent nCRT followed by total mesorectal excision (TME). The TCF4 expression of all patients' biopsies before nCRT was evaluated by Immunohistochemical staining method. RESULTS: After completion of nCRT, 5 cases (5.2%) achieved clinical complete response (cCR) thus the remaining 91 patients underwent a standardized total mesorectal excision (TME) procedure. There were 44 patients (45.8%) achieved good tumor response (including TRG 3-4 and 5 cCR patients) while poor response (TRG 0-2) was achieved in 52 patients (54.2%). Our results demonstrated that patients with low expression of TCF4 were more sensitive to nCRT than those with high TCF4 expression (P=0.031). Low TCF4 expression before nCRT and good response were significantly associated with improved 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariate analysis confirmed that the pretreatment TCF4 expression was an independent prognostic factor. CONCLUSIONs: Our data revealed that low TCF4 protein expression was a useful predictive factor of good tumor response to nCRT and good outcomes in patients with LARC. [ABSTRACT FROM AUTHOR]

A dual signal amplification immunosensing strategy that offers high sensitivity and specificity for the detection of low-abundance biomarkers was designed on a 3D origami electrochemical device. High sensitivity was achieved by using novel Au nanorods modified paper working electrode (AuNRs-PWE) as sensor platform and metal ion-coated Au/bovine serum albumin (Au/BSA) nanospheres as tracing tags. High specificity was further obtained by the simultaneous measurement of two cancer markers on AuNRs-PWE surface using different metal ion-coated Au/BSA tracers. The metal ions could be detected directly through differential pulse voltammetry (DPV) without metal preconcentration, and the distinct voltammetric peaks had a close relationship with each sandwich-type immunoreaction. The position and size of the peaks reflected the identity and level of the corresponding antigen. Integrating the dual-signal amplification strategy, a novel 3D origami electrochemical immunodevice for simultaneous detecting carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125) with linear ranges of over 4 orders of magnitude with detection limits down to 0.08 pg mL −1 and 0.06 mU mL −1 was successfully developed. This strategy exhibits high sensitivity and specificity with excellent performance in real human serum assay. The AuNRs-PWE and the designed tracer on this immunodevice provided a new platform for low-cost, high-throughput and multiplex immunoassay and point-of-care testing in remote regions, developing or developed countries. [ABSTRACT FROM AUTHOR]

We reported here the synthesis of thin MoS 2 nanosheets, which showed a good catalysis of H 2 O 2 . The MoS 2 nanosheets were further synthetized into nano-composite MoS 2 -Au, and the MoS 2 -Au was found with a better catalysis property of H 2 O 2 and well electroconductibility. Furthermore, we composed Ag nanospheres (AgNPs), which have good electricity and large surface area. The prepared AgNPs and MoS 2 -Au were applied in a sandwich-type immunosensor for detecting carcinoembryonic antigen (CEA). In the immunosensor, MoS 2 -Au acted as the solid support for CEA primary antibody and AgNPs were employed as the supporter of glucose oxidase (GOx) and CEA secondary antibody. With the addition of glucose, the hydrogen peroxide was prepared and the MoS 2 -Au catalyzed hydrogen peroxide that the current peak was presented with the differential pulse voltammetry (DPV). The proposed immunosensor enabled CEA concentrations to be determined in the range of 1 pg mL −1 to 50 ng mL −1 , with a detection limit of 0.27 pg mL −1 . The immunosensor showed low detection limit, good specificity, high sensitivity and reproducibility. Satisfactory results were obtained for determination of CEA in human serum albumin samples. This work is to open new avenues in the application of AuNPs dotted MoS 2 composite interface for sensitive electrochemical immunoassay. Hence, the proposed electrochemical immunosensor could become a promising method for tumor marker detection. [ABSTRACT FROM AUTHOR]

Carbon coated magnetic composite nanoparticles (Fe 3 O 4 @C) were prepared and further fabricated into a new kind of the multifunctional core/shell nanoparticles (Fe 3 O 4 @C@CdTe) by a self-assembly of CdTe quantum dots. These nanoparticles exhibited good fluorescence (FL) property. In addition, zinc oxide (ZnO) nanowires (NWs) with high surface area were synthesized via solvothermal reaction under a hydrothermal condition. In a sandwich immune-device for the detection of carcinoembryonic antigen (CEA), the Fe 3 O 4 @C@CdTe nanoparticles were applied as the solid support for CEA-primary monoclonal antibody (CEA-McAb 1 ) and the ZnO NWs were applied as the label of CEA-secondary monoclonal antibody (CEA-McAb 2 ). The Fe 3 O 4 @C@CdTe-McAb 1 was collected at the bottom of the quartz cuvette using a magnet. The ZnO NWs bond with Fe 3 O 4 @C@CdTe after the immune reaction. The Zn 2+ ions are subsequently released from ZnO NWs by dissolution in acidic buffer solution and the enhanced FL intensity is measured. In this way, the proposed FL immune-device displayed excellent analytical performance for the detection of CEA in the range of 0.005–100 ng mL −1 with a low detection limit of 1.6 pg mL −1 , and the assay results of CEA in real serum samples were in a good agreement with the standard enzyme-linked immunosorbent assay (ELISA) tests. [ABSTRACT FROM AUTHOR]

An enzyme-free electrochemical immunoassay is introduced into microfluidic paper-based analytical devices for the first time using novel three dimensional flower-like Au nanoparticles modified paper working electrode (FLAuNPs-PWE) as sensor platform and gold (Au)-silver (Ag) bimetallic nanoparticles (Au-Ag BMNPs) as tracer. FLAuNPs with large surface area serve as an effective matrix for primary antibodies. Au-Ag BMNPs with good biological activity, such as mimicking natural peroxidases, are used for binding of signal antibodies (Ab 2 ). Then the Ab 2 labeled BMNPs is linked to the FLAuNPs-PWE via sandwich immunoreactions. Enhanced sensitivity is achieved by efficient catalysis of the Au-Ag BMNPs toward hydrogen peroxide. Under the optimized experimental conditions, the proposed paper-based electrochemical immunosensor exhibits excellent analytical performance for enzyme-free detection of carcinoembryonic antigen, ranging from 0.001-50 ng mL −1 with a low detection limit of 0.3 pg mL −1 . The immunosensor shows good precision, acceptable stability and reproducibility. The proposed method provides a new promising platform for the design of the highly sensitive detection method, showing great promise for clinical application. [ABSTRACT FROM AUTHOR]

We reported here the preparation of "dioscorea batatas bean"-like silver nanoparticles (AgNPs) and the unique structure provided the AgNPs good localized surface plasmon resonance (LSPR) property. In addition, zinc oxide quantum dots (ZnO QDs) were also synthesized and found with good fluorescent property. Furthermore, the ZnO QDs decorated exfoliated graphene oxide (EGO-ZnO) was prepared via electrostatic interaction. The named nanomaterials were applied in a LSPR-induced fluorescent DNA sensor. To fabricate the DNA sensor, the EGO-ZnO was modified on the silica glass as the supporter for the capture probe ssDNA, and the complementary ssDNA was labeled on the surface of the AgNPs. After the hybridization step by step, the AgNPs was fastened on the surface of the EGO-ZnO, and the fluorescent intensity of the EGO-ZnO increased as a result. The prepared DNA sensor enabled the target ssDNA to be detected in the concentration range of 10-19-10-14M, and the limit of detection was 4.3×10-20M. [ABSTRACT FROM AUTHOR]

Abstract: We reported here the synthesis of zinc ferrite (ZnFe2O4), which was further fabricated into gold nanoparticles (AuNPs) functionalized ZnFe2O4 (ZnFe2O4@Au) through a layer-by-layer (LBL) self-assembly method. The prepared ZnFe2O4@Au showed excellent catalytic performance to the reduction reaction procedure of hydrogen peroxide (H2O2), and the coated AuNPs provided the nanoparticles with good biocompatibility. In addition, the CdTe quantum dots dotted graphene (G–CdTe) was prepared and was found with good electrochemiluminescence (ECL) property. The prepared ZnFe2O4@Au and G–CdTe were applied in a simple sandwich-type ECL immunosensor for carcinoembryonic antigen (CEA). In the immunosensor, G–CdTe acted as the solid support for CEA primary antibody and ZnFe2O4@Au was employed as the supporter of CEA secondary antibody. The ZnFe2O4@Au could quench the ECL signal of the G–CdTe and the quenching ECL intensity could be obtained. The proposed immunosensor enabled CEA concentrations to be determined in the 0.01–50ngmL−1 concentration range, with a detection limit of 4pgmL−1. [Copyright &y& Elsevier]