TP53-specific mutations serve as a potential biomarker for homologous recombination deficiency in breast cancer: a clinical next-generation sequencing study.

Background: TP53 mutations and homologous recombination deficiency (HRD) occur frequently in breast cancer. However, the characteristics of TP53 pathogenic mutations in breast cancer patients with/without HRD are not clear. Methods: Clinical next-generation sequencing (NGS) of both tumor and paired blood DNA from 119 breast cancer patients (BRCA-119 cohort) was performed with a 520-gene panel. Mutations, tumor mutation burden (TMB), and genomic HRD scores were assessed from NGS data. NGS data from 47 breast cancer patients in the HRD test cohort were analyzed for further verification. Results: All TP53 pathogenic mutations in patients had somatic origin, which was associated with the protein expression of estrogen receptor and progestogen receptor. Compared to patients without TP53 pathologic mutations, patients with TP53 pathologic mutations had higher levels of HRD scores and different genomic alterations. The frequency of TP53 pathologic mutation was higher in the HRD-high group (HRD score ≥ 42) relative to that in the HRD-low group (HRD score < 42). TP53 has different mutational characteristics between the HRD-low and HRD-high groups. TP53-specific mutation subgroups had diverse genomic features and TMB. Notably, TP53 pathogenic mutations predicted the HRD status of breast cancer patients with an area under the curve (AUC) of 0.61. TP53-specific mutations, namely HRD-low mutation, HRD-high mutation, and HRD common mutation, predicted the HRD status of breast cancer patients with AUC values of 0.32, 0.72, and 0.58, respectively. Interestingly, TP53 HRD-high mutation and HRD common mutation combinations showed the highest AUC values (0.80) in predicting HRD status. Conclusions: TP53-specific mutation combinations predict the HRD status of patients, indicating that TP53 pathogenic mutations could serve as a potential biomarker for poly-ADP-ribose polymerase (PARP) inhibitors in breast cancer patients .

The impact of eco-preneurship and green technology on greenhouse gas emissions - An analysis of East Asian economies.

The pressing need to address the effects of rising greenhouse gas emissions on the environment has become a global concern. Policymakers, governments, and stakeholders advocate a sustainable clean environment. Therefore, green technology and eco-entrepreneurship initiatives are being implemented to reduce these emissions. Despite their efforts in sustainable environments, there is insufficient research on how these initiatives impact economies. This study explores the impact of eco-entrepreneurship and green technology on reducing greenhouse gas emissions in East Asia. Using China and Japan, ranked the first and fifth highest greenhouse gas emitters globally, as case studies, the study employed ARDL and NARDL models for empirical analysis. The findings show that short-run linear estimates of eco-entrepreneurship are significant only in China, while nonlinear short-run estimates are significant for both China and Japan. Comparably, short-run linear estimates of green technology are significant for both China and Japan, while nonlinear coefficient estimates are significant only in Japan. The linear estimate of eco-entrepreneurship was significant and negative in both countries. The coefficient estimates for green technology are significant and negative for both countries. In the nonlinear model, the positive shock coefficient estimates for eco-entrepreneurship are negative and significant in China and Japan. These initiatives are vital for reducing greenhouse gas emissions and improving East Asian economies.

Somatic mutations in four novel genes contribute to homologous recombination deficiency in breast cancer: a real-world clinical tumor sequencing study.

Breast cancers involving mutations in homologous recombination (HR) genes, most commonly BRCA1 and BRCA2 (BRCA1/2), respond well to PARP inhibitors and platinum-based chemotherapy. However, except for these specific HR genes, it is not clear which other mutations contribute to homologous recombination defects (HRD). Here, we performed next-generation sequencing of tumor tissues and matched blood samples from 119 breast cancer patients using the OncoScreen Plus panel. Genomic mutation characteristics and HRD scores were analyzed. In the HR genes, we found that BRCA1/2 and PLAB2 mutations were related to HRD. HRD was also detected in a subset of patients without germline or somatic mutations in BRCA1/2, PLAB2, or other HR-related genes. Notably, LRP1B, NOTCH3, GATA2, and CARD11 (abbreviated as LNGC) mutations were associated with high HRD scores in breast cancer patients. Furthermore, functional experiments demonstrated that silencing CARD11 and GATA2 impairs HR repair efficiency and enhances the sensitivity of tumor cells to olaparib treatment. In summary, in the absence of mutations in the HR genes, the sensitivity of tumor cells to PARP inhibitors and platinum-based chemotherapy may be enhanced in a subset of breast cancer patients with LNGC somatic mutations.

Abnormal genetic and epigenetic patterns of m6A regulators associated with tumor microenvironment in colorectal cancer.

Background: N6-methyladenosine (m6A) has a critical role in the development and progression of cancer. However, the genetic and epigenetic patterns, as well as tumor microenvironment (TME) infiltration characteristics of m6A regulators in colorectal cancer (CRC) remain largely unknown. Methods: Molecular patterns of m6A modifications of 24 m6A regulators in CRC samples were evaluated using data from The Cancer Genome Atlas (TCGA). Mutations, copy number variations (CNVs), DNA methylation, and chromatin accessibility were examined to investigate the underlying mechanisms of the aberrant expression of m6A regulators. Correlations between m6A-related genes and TME cell-infiltrating characteristics were evaluated using Tumor Immune Estimation Resource (TIMER). Results: The m6A regulators were frequently dysregulated in CRC, with two downregulated and 16 upregulated. All the m6A regulators had mutations (frequency ranging from 0.9% to 7%), with active mutations tending to occur in RBM15 and inactive mutations in ZC3H13. Only five m6A regulators had CNV frequency greater than 1%: YTHDC2 (2.4%), YTHDF1 (7.0%), YTHDF3 (1.9%), VIRMA (1.7%), and ZC3H13 (3.0%). The copy numbers of these five genes were positively correlated with their expression levels. The m6A regulators frequently showed imbalanced methylation in CRC, with hypomethylation of YTHDF2, IGF2BP3, FTO, and hypermethylation of HNRNPC, METTL3, and WTAP. Most m6A regulators had high chromatin accessibility, which was positively correlated with their gene expression. IGF2BP1 was identified as an independent prognostic factor for overall survival. Moreover, the expression of most m6A regulators was positively correlated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Conclusions: Aberrant expression of m6A regulators is associated with mutation, CNV, and chromatin accessibility, owing to both genetic and epigenetic modifications. The TME infiltration characterization of m6A regulators could guide the development of more effective immunotherapy strategies in CRC.

Jun-APOE-LRP1 axis promotes tumor metastasis in colorectal cancer.

Apolipoprotein E (apoE) has previously been reported to play vital roles in tumor progression. However, the impact of apoE on colorectal cancer (CRC) metastasis remains largely unexplored. This study aimed to investigate the role of apoE in CRC metastasis and to identify the transcription factor and receptor of apoE involved in regulation of CRC metastasis. Bioinformatic analyses were conducted to examine the expression pattern and prognosis of apolipoproteins. APOE-overexpressing cell lines were utilized to explore the effects of apoE on proliferation, migration and invasion of CRC cells. Additionally, the transcription factor and receptor of apoE were screened via bioinformatics, and further validated through knockdown experiments. We discovered that the mRNA levels of APOC1, APOC2, APOD and APOE were higher in lymphatic invasion group, and a higher apoE level indicated poorer overall survival and progression-free interval. In vitro studies demonstrated that APOE-overexpression did not affect proliferation but promoted the migration and invasion of CRC cells. We also reported that APOE-expression was modulated by the transcription factor Jun by activating the proximal promoter region of APOE, and APOE-overexpression reversed the metastasis suppression of JUN knockdown. Furthermore, bioinformatics analysis suggested an interaction between apoE and low-density lipoprotein receptor-related protein 1 (LRP1). LRP1 was highly expressed in both the lymphatic invasion group and the APOEHigh group. Additionally, we found that APOE-overexpression upregulated LRP1 protein levels, and LRP1 knockdown attenuated the metastasis-promoting function of APOE. Overall, our study suggests that the Jun-APOE-LRP1 axis contributes to tumor metastasis in CRC.

Liposome-assisted chemical redox cycling strategy for advanced signal amplification: A proof-of-concept toward sensitive electrochemiluminescence immunoassay.

This work presents a novel signal amplification strategy for electrochemiluminescence (ECL) biosensor based on liposome-assisted chemical redox cycling for in situ formation of Au nanoparticles (Au NPs) on TiO2 nanotubes (TiO2 NTs) electrode. The system was exemplified by ascorbic acid (AA)-loaded liposome, the redox cycling of AA utilizing tris (2-carboxyethyl) phosphine (TCEP) as reductant, and the use of Au nanoclusters (Au NCs)/TiO2 NTs as working electrode to implement the ECL detection of prostate specific antigen (PSA). Specifically, the AA-loaded liposomes were used as tags to label the captured PSA through a sandwich immunoreaction. After the lysate of the liposome was transferred onto the interface of Au NCs/TiO2 NTs in the presence of Au3+ and TECP, the chemical redox cycling was triggered. In the cycling, Au3+ was directly reduced in situ by AA to form Au NPs on Au NCs/TiO2 NTs electrode, whereas the oxidation product of AA was reduced by TCEP to regenerate AA. The large loading capacity of the liposome and chemical redox cycling resulted in the incomplete reduction of the Au NCs to Au NPs on the TiO2 NTs electrode, enhancing the ECL intensity greatly. The multiple signal amplification strategy achieved an ultrasensitive detection for PSA with a detection limit down to 6.7 × 10-15 g mL-1 and a wide linear concentration range from 1.0 × 10-14 to 1.0 × 10-8 g mL-1. It is believed that this work is anticipated to extend the employment of advanced chemical redox cycling reaction in the field of ECL bioassays.

In Situ Formation of Bi2MoO6-Bi2S3 Heterostructure: A Proof-Of-Concept Study for Photoelectrochemical Bioassay of l-Cysteine.

A novel signal-increased photoelectrochemical (PEC) biosensor for l-cysteine (L-Cys) was proposed based on the Bi2MoO6-Bi2S3 heterostructure formed in situ on the indium-tin oxide (ITO) electrode. To fabricate the PEC biosensor, Bi2MoO6 nanoparticles were prepared by a hydrothermal method and coated on a bare ITO electrode. When L-Cys existed, Bi2S3 was formed in situ on the interface of the Bi2MoO6/ITO electrode by a chemical displacement reaction. Under the visible light irradiation, the Bi2MoO6-Bi2S3/ITO electrode exhibited evident enhancement in photocurrent response compared with the Bi2MoO6/ITO electrode, owing to the signal-increased sensing system and the excellent property of the formed Bi2MoO6-Bi2S3 heterostructure such as the widened light absorption range and efficient separation of photo-induced electron-hole pairs. Under the optimal conditions, the sensor for L-Cys detection has a linear range from 5.0 × 10-11 to 1.0 × 10-4 mol L-1 and a detection limit of 5.0 × 10-12 mol L-1. The recoveries ranging from 90.0% to 110.0% for determining L-Cys in human serum samples validated the applicability of the biosensor. This strategy not only provides a method for L-Cys detection but also broadens the application of the PEC bioanalysis based on in situ formation of photoactive materials.

A Pan-Cancer Analysis of the Oncogenic Role of Nuclear Transport Factor 2 in Human Cancers.

Nuclear transport factor 2 (NUTF2) is a GDP-binding protein that participates in the nucleocytoplasmic transport process. The role of NUTF2 in cancer development is largely unknown and lacks systemic assessment across human cancers. In this study, we performed a pan-cancer analysis of NUTF2 in human cancers. Out of 33 types of cancers, 19 types had significantly different expression of NUTF2 between tumor and normal tissues. Meanwhile, survival analysis showed that NUTF2 could be an independent prognostic factor in several tumor types. Further analysis suggested that the expression of NUTF2 expression was correlated with the infiltration of immune cells, such as CD8+ T cells, effector memory CD4+ T cells, and cancer-associated fibroblasts in kidney renal clear cell carcinoma. Moreover, co-expression analysis showed the positive association between NUTF2 and cell proliferation biomarkers (MKI67and PCNA) and epithelial-mesenchymal transition markers (VIM, TWIST1, SNAI1, SNAI2, FN1, and CDH2), suggesting that NUTF2 plays important roles in regulating cancer proliferation and metastasis. This pan-cancer analysis of NUTF2 provides a systemic understanding of its oncogenic role across different types of cancers.

Lnc00892 competes with c-Jun to block NCL transcription, reducing the stability of RhoA/RhoC mRNA and impairing bladder cancer invasion.

Metastasis of bladder cancer is a complex process and has been associated with poor clinical outcomes. However, the mechanisms of bladder cancer metastasis remain largely unknown. The present study found that the long noncoding RNA lnc00892 was significantly downregulated in bladder cancer tissues, with low lnc00892 expression associated with poor prognosis of bladder cancer patients. Lnc00892 significantly inhibited the migration, invasion, and metastasis of bladder cancer cells in vitro and in vivo. In-depth analysis showed that RhoA/C acted downstream of lnc00892 to inhibit bladder cancer metastasis. Mechanistically, lnc00892 reduces nucleolin gene transcription by competitively binding the promoter of nucleolin with c-Jun, thereby inhibiting nucleolin-mediated stabilization of RhoA/RhoC mRNA. Taken together, these findings provide novel insights into understanding the mechanisms of bladder cancer metastasis and suggest that lnc00892 can serve as a potential therapeutic target in patients with invasive bladder cancer.

A novel chemiluminescence imaging immunosensor for prostate specific antigen detection based on a multiple signal amplification strategy.

A novel chemiluminescence (CL) imaging platform was constructed for prostate specific antigen (PSA) detection in a multiple signal amplifying manner. To construct the platform, the primary antibody for PSA was firstly immobilized on a O-ring area of a glass slide for recognizing the PSA. The horseradish peroxidase (HRP) and the secondary antibody of PSA (Ab2) functionalized Au NPs (HRP-Au NPs-Ab2) were modified on the platform through immunoreaction between PSA and Ab2. The excellent catalytic effect of Au NPs and HRP on the HRP-Au NPs-Ab2 to the luminol-H2O2 CL system provided the dual-signal amplification for PSA detection. To further enhance the sensitivity, tyramine signal amplification (TSA) strategy was introduced: tyramine-HRP conjugates were added into the O-ring reservoir and thus tyramine-HRP repeats formed in the presence of H2O2, generating a multiple signal amplification because of the large amounts of HRP on the sensing interface. The excellent performance of HRP-Au NPs-Ab2 and TSA strategy endows the CL platform with high sensitivity. The PSA was detected with a photomultiplier tube (PMT) and visually analyzed by a charge coupled device (CCD), respectively. The linear ranges of PMT and CCD for PSA are 0.1-100.0 ng mL-1 with a detection limit of 0.05 pg mL-1 and 0.5 - 100.0 ng mL-1 with a detection limit of 0.1 pg mL-1, respectively. The levels of PSA in several human serum samples were determined and the recoveries are ranged from 82.5% - 117.0%. This CL immunosensing platform holds great potential for bioactive molecules detection visually and sensitively.

Effect of Graves' disease on the prognosis of differentiated thyroid carcinoma: a meta-analysis.

PURPOSE: Several studies have reported different findings on the prognosis of differentiated thyroid carcinoma combined with Graves' disease. To assess the effect of Graves' disease on differentiated thyroid carcinoma, a meta-analysis was undertaken. METHODS: PubMed, OVID and the Cochrane Library were systematically searched for trials published prior to Oct. 2018. Studies containing data on the outcomes of Graves' disease with differentiated thyroid carcinoma were included. Summary estimates of the prevalence of recurrence/disease progression/persistence and mortality as well as odds ratios and weighted mean differences were calculated with a random-effects model. RESULTS: Of the 916 related articles found, 13 fulfilled the inclusion criteria. The recurrence/disease progression/persistent rate was not significantly different between the Graves' disease group and the non-Graves' disease group (P = 0.86). However, the analysis of three studies with K-M curves or HRs showed that there was a significant difference between the two groups (P = 0.04). Subgroup analysis showed that the contradictory results could be due to the location/race assessed in the studies. Graves' disease almost acted as a risk factor (OR = 1.77, 95%C.I. = 0.99-3.16) for differentiated thyroid carcinoma in European studies. When heterogeneous studies were excluded, the analyses show that GD was a risk factor for recurrence/disease progression/persistence (P = 0.03, OR = 1.75, 95%C.I. = 1.04-2.95). The overall mortality rate was significantly higher in the Graves' disease group than in the non-Graves' disease group (P = 0.02, OR = 2.93, 95%C.I. = 1.17-7.37). CONCLUSIONS: Graves' disease acts as a risk factor for the prognosis of differentiated thyroid carcinoma. The recurrence/disease progression/persistent rate may be affected by TSAbs in a specific location/race and with a genetic immunization background. However, the histotypes and subtypes may play an important role in mortality rate.

Inhibition of UBE2N-dependent CDK6 protein degradation by miR-934 promotes human bladder cancer cell growth.

Because bladder cancer (BC) is one of the most common malignant cancers of the urinary system, identification of BC cell growth-associated effectors is of great significance. Cyclin-dependent kinase (CDK)6 is a member of the CDK family of cell cycle-related proteins and plays an important role in cancer cell growth. This is borne out by the fact that a CDK6 inhibitor had been approved to treat several types of cancers. Nevertheless, underlying molecular mechanisms concerning how to regulate CDK6 expression in BC remains unclear. In the present study, it was observed that miR-934 was much higher in human BCs and human BC cell lines as well. The results also revealed that miR-934 inhibition dramatically decreased human BC cell monolayer growth in vitro and xenograft tumor growth in vivo; the outcomes were accompanied by CDK6 protein down-regulation and G0-G1 cell cycle arrest. Moreover, overexpression of CDK6 reversed the inhibition of BC cell growth induced by miR-934. Further studies showed that miR-934 binds to a 3'-UTR of ubiquitin-conjugating enzyme 2N (ube2n) mRNA, down-regulated UBE2N protein expression; this, in turn, attenuated CDK6 protein degradation and led to CDK6 protein accumulation as well as the promotion of BC tumor growth. Collectively, this study not only establishes a novel regulatory axis of miR-934/UBE2N of CDK6 but also provides data suggesting that miR-934 and UBE2N may be potentially promising targets for therapeutic strategies against BC.-Yan, H., Ren, S., Lin, Q., Yu, Y., Chen, C., Hua, X., Jin, H., Lu, Y., Zhang, H., Xie, Q., Huang, C., Huang, H. Inhibition of UBE2N-dependent CDK6 protein degradation by miR-934 promotes human bladder cancer cell growth.

miR-3687 Overexpression Promotes Bladder Cancer Cell Growth by Inhibiting the Negative Effect of FOXP1 on Cyclin E2 Transcription.

Cyclin E2, a member of the cyclin family, is a key cell cycle-related protein. This protein plays essential roles in cancer progression, and, as such, an inhibitor of cyclin E2 has been approved to treat several types of cancers. Even so, mechanisms underlying how to regulate cyclin E2 expression in cancer remain largely unknown. In the current study, miR-3687 was upregulated in clinical bladder cancer (BC) tumor tissues, The Cancer Genome Atlas (TCGA) database, and human BC cell lines. Inhibition of miR-3687 expression significantly reduced human BC cell proliferation in vitro and tumor growth in vivo, which coincided with the induction of G0/G1 cell cycle arrest and downregulation of cyclin E2 protein expression. Interestingly, overexpression of cyclin E2 reversed the inhibition of BC proliferation induced by miR-3687. Mechanistic studies suggested that miR-3687 binds to the 3' UTR of foxp1 mRNA, downregulates FOXP1 protein expression, and in turn promotes the transcription of cyclin E2, thereby promoting the growth of BC cells. Collectively, the current study not only establishes a novel regulatory axis of miR-3687/FOXP1 regarding regulation of cyclin E2 expression in BC cells, but also provides strong suggestive evidence that miR-3687 and FOXP1 may be promising targets in therapeutic strategies for human BC.

A novel electrochemiluminescence resonance energy transfer system for simultaneous determination of two acute myocardial infarction markers using versatile gold nanorods as energy acceptors.

A novel electrochemiluminescence resonance energy transfer (ECL-RET) system using versatile gold nanorods as energy acceptors was introduced into the ECL biochemical analysis. A spatial- and potential-resolved platform coupled with the ECL-RET strategy was developed for simultaneous determination of two acute myocardial infarction markers.

Ru(NH3)63+/Ru(NH3)62+-Mediated Redox Cycling: Toward Enhanced Triple Signal Amplification for Photoelectrochemical Immunoassay.

Herein we report an effective Ru(NH3)63+/Ru(NH3)62+-mediated photoelectrochemical-chemical-chemical (PECCC) redox cycling amplification (RCA) strategy toward enhanced triple signal amplification for advanced split-type PEC immunoassay application. Specifically, alkaline phosphatase (ALP) label was confined via a sandwich immunorecognition to convert 4-aminophenyl phosphate to the signal reporter 4-aminophenol (AP), which was then directed to interact with Ru(NH3)62+ as a redox mediator and tris (2-carboxyethyl) phosphine (TCEP) as reducing agent in the detection buffer. Upon illumination, the system was then operated upon the oxidation of Ru(NH3)62+ by the photogenerated holes on the Bi2S3/BiVO4 photoelectrode, starting the chain reaction in which the Ru(NH3)62+ was regenerated by Ru(NH3)63+-enabled oxidization of AP to p-quinoneimine, which was simultaneously recovered by TCEP. Exemplified by interleukin-6 (IL-6) as the analyte, the Ru(NH3)63+/Ru(NH3)62+-mediated, AP-involved PECCC RCA coupled with ALP enzymatic amplification could achieve triple signal amplification toward the ultrasensitive PEC IL-6 immunoassay. This protocol can be extended as a general basis for other numerous targets of interest. Besides, we believe this work could offer a new perspective for the further exploration of advanced RCA-based PEC bioanalysis.

Electrochemiluminescence energy resonance transfer in 2D/2D heterostructured g-C3N4/MnO2 for glutathione detection.

The energy transfer efficiency, strongly depending on the distance of donor-acceptor pair, is always a crucial factor for the construction of elegant electrochemiluminescence resonance energy transfer (ECL-RET)-based biosensors. In this paper, a novel and efficient ECL-RET in 2D/2D heterostructured g-C3N4/MnO2 was developed using g-C3N4 nanosheets (g-C3N4 NSs) as energy donor and MnO2 nanosheets (MnO2 NSs) as energy acceptor. In this system, MnO2 NSs in-situ grew on g-C3N4 NSs to form the 2D/2D heterostructure, greatly shortening the distance of the donor-acceptor pair (g-C3N4-MnO2) and thus greatly enhancing the RET efficiency. To demonstrate the performance of the system, a signal "off-on" ECL sensor was designed for glutathione (GSH) analysis. In the absence of GSH, MnO2 significantly quenched the ECL intensity of g-C3N4 owing to ECL-RET in this 2D/2D g-C3N4/MnO2 heterostructure (ECL signal "off"). Upon the addition of GSH, MnO2 was reduced to Mn2+ by GSH and g-C3N4 was released from the heterostructured g-C3N4/MnO2, generating a recovery of ECL intensity (ECL signal "on"). Under the optimal conditions, the designed ECL-RET signal "off-on" sensor realized the sensitive detection of GSH ranged from 0.2-100 µM with the detection limit of 0.05 µM. Furthermore, the as-prepared ECL-RET sensor exhibits good performance in the determination of GSH in human serum samples. The ECL-RET in 2D/2D heterostructure provides an ingenious way for the exploitation of novel ECL biosensing systems.

Immuno-Electrochemiluminescent Imaging of a Single Cell Based on Functional Nanoprobes of Heterogeneous Ru(bpy)32+@SiO2/Au Nanoparticles.

It is valuable to develop a sensing platform for not only detecting a tumor marker in body fluids but also measuring its expression at single cells. In the present study, a simple closed bipolar electrodes-based electrochemiluminescence (BPEs-ECL) imaging strategy was developed for visual immunoassay of prostate specific antigen (PSA) at single cells using functional nanoprobes of heterogeneous Ru(bpy)32+@SiO2/Au nanoparticles. Multiple-assisted ECL signal amplification strategy was introduced into the detection system on the basis of the synergetic amplifying effect of the anodic and cathodic amplification. On the basis of the synergetic amplifying effect, the detection limits of PSA by using photomultiplier tube and charge-coupled device (CCD) imaging are 3.0 and 31 pg/mL, respectively. The obtained immunosensor was employed to evaluate PSA levels in serum samples with a satisfying result. Moreover, the obtained functional nanoprobes were used to visually profile the PSA expression on the surface of single LNCaP cells (a kind of prostate cancer cells) based on a bare BPE. The results show that the functional nanoprobes-based ECL imaging immunoassay provides a promising visual platform for detecting tumor markers (proteins and cancer cells) and thus shows a high potential in cancer diagnosis.

Spatial-resolved dual-signal-output electrochemiluminescent ratiometric strategy for accurate and sensitive immunoassay.

The identification of tumor markers is of great importance for clinical diagnosis but accurate detection with high sensitivity is still a great challenge. In present work, a spatial-resolved dual-signal-output electrochemiluminescent (ECL) ratiometric assay platform was constructed for sensitive detection of prostate specific antigen (PSA) on a dual-disk glassy carbon electrode. To fabricate the platform, flower-like CdS three-dimensional (3D) assemblies and Ru(bpy)32+-conjugated silica nanoparticles (Ru(bpy)32+@RuSi NPs), were immobilized onto the two disks as cathodic and anodic ECL emitters, respectively. After the stepwise modification of the gold nanoparticles, antibody for PSA, and bovine serum albumin onto the two disks respectively, the Ru(bpy)32+@RuSi NPs-based disk were incubated with varied concentration of PSA as working electrode, whereas the flower-like CdS 3D assemblies-based disk with fixed concentration of PSA were taken as internal reference electrode. The label free assay of PSA was realized by the ratio of anodic ECL signal from working electrode to the cathodic ECL signal from the internal reference electrode (ECLanode/ECLcathode). On the basis of the spatial-resolved dual-signal-output ratiometric ECL sensor, the PSA can be detected accurately with a linear range of 0.001 - 50ng/mL at a concentration as low as 0.34pg/mL. Furthermore, the proposed method was applied for PSA determination in human serum samples with satisfying results. Thanks to the same modified process of the two disks, this universal design well avoids environmental errors including the interference caused in the biological recognition process, which effectively reduces the false positive or negative errors, exhibiting a greatly improved accuracy, reliability and sensitivity.

Ferrocene-graphene sheets for high-efficiency quenching of electrochemiluminescence from Au nanoparticles functionalized cadmium sulfide flower-like three dimensional assemblies and sensitive detection of prostate specific antigen.

A signal-switchable electrochemiluminescence (ECL) aptasensor was presented for sensitive prostate specific antigen (PSA) assay using ferrocene-graphene sheets (Fc-GNs) for high-efficiency quenching of ECL from Au nanoparticles functionalized cadmium sulfide flower-like three dimensional (3D) assemblies (Au-CdS flower-like 3D assemblies). Au-CdS flower-like 3D assemblies were synthesized and employed as luminophore, exhibiting strong and stable ECL intensity, and followed by assembling captured DNA (cDNA) and hybridizing it with half of base sequence of PSA aptamer on the Au-CdS flower-like 3D assemblies modified electrode. The remaining part of the non-complementary base of the aptamer could preferentially adsorb GN with the signal switched "off" state. While in the presence of the PSA, the binding of PSA with aptamer caused desorption of aptamer from the surface of Fc-GNs and was then released from electrode surface, thus allowing the ECL signal enhancement. With the transformation of luminescence signal from "off" to "on", the aptasensor displays high sensitivity for PSA detection with a linear range from 1pgmL-1 to 25ngmL-1 and a detection limit of 0.38pgmL-1S/N=3). Moreover, this developed method could be successfully applied to the determination of PSA in human serum samples with recoveries of 85.8-104.0%, suggesting great potential applications in biochemical analysis.

Dual-signal amplification strategy for ultrasensitive chemiluminescence detection of PDGF-BB in capillary electrophoresis.

Many efforts have been made toward the achievement of high sensitivity in capillary electrophoresis coupled with chemiluminescence detection (CE-CL). This work describes a novel dual-signal amplification strategy for highly specific and ultrasensitive CL detection of human platelet-derived growth factor-BB (PDGF-BB) using both aptamer and horseradish peroxidase (HRP) modified gold nanoparticles (HRP-AuNPs-aptamer) as nanoprobes in CE. Both AuNPs and HRP in the nanoprobes could amplify the CL signals in the luminol-H2 O2 CL system, owing to the excellent catalytic behavior of AuNPs and HRP in the CL system. Meanwhile, the high affinity of aptamer modified on the AuNPs allows detection with high specificity. As proof-of-concept, the proposed method was employed to quantify the concentration of PDGF-BB from 0.50 to 250 fm with a detection limit of 0.21 fm. The applicability of the assay was further demonstrated in the analysis of PDGF-BB in human serum samples with acceptable accuracy and reliability. The result of this study exhibits distinct advantages, such as high sensitivity, good specificity, simplicity, and very small sample consumption. The good performances of the proposed strategy provide a powerful avenue for ultrasensitive detection of rare proteins in biological sample, showing great promise in biochemical analysis.