Excessive reactive oxygen species (ROS) in seminal plasma can trigger male infertility. Therefore, the development of simple and rapid ROS detection methods is urgently needed, particularly for the early self-screening of preconception couples. Herein, a gold nanobipyramid (Au NBP)-based colorimetric hydrogel for convenient and fast ROS detection is described. In the hydrogel, Au NBP is etched efficiently by ROS under the synergistic effect of Fe2+and I-, which finally causes color variations. Besides, agarose gel with the function of molecular sieve enables the separation of biomacromolecules, improving the interference resistance of the system and the stability of Au NBP. This chemical sensor can complete all the tests within 20 min, covering two detection range of 10-125 mu M at relative low H2O2 concentration and 125-1000 mu M at relative high H2O2 concentration, with the detection limits of 1.76 mu M and 12.10 mu M (S/N = 3) respectively. Furthermore, via visual observation of the color variations, it allows the initial interpretation of ROS concentration without any additional equipment. We applied this device to the detection of ROS in clinical seminal plasma samples and obtained promising results, demonstrating its potential for rapid and convenient detection in clinical applications.

The extracellular domain (ECD) of human epidermal growth factor receptor 2 (HER2) serves as a promising biomarker for the early diagnosis and treatment of breast cancer (BC). However, due to the heterogeneity of tumors, assessing HER2 status through a core needle biopsy presents significant challenges. In this study, we propose a facile and high-performance electrochemiluminescence immunoassay (ECLIA) platform utilizing a herceptin-encapsulated gold nanoclusters (HER-AuNCs)/(diisopropylamino)ethanol (DIPEA-OH) ECL system for the clinical evaluation of HER2 ECD in BC patients. The two-in-one HER-AuNCs ECL probes integrate the immunological recognition capabilities of HER with the ECL performance of AuNCs. Coupled with the low-potential and high ECL intensity of the HER-AuNCs/DIPEA-OH system, this ECL biosensing platform offers advantages in simplicity, high sensitivity, specificity, and sample saving. Consequently, the proposed ECLIA method enables ultrasensitive detection of HER2 in the range of 0.05-10 ng/mL with a detection limit of 11 pg/mL. Notably, the serum HER2 (sHER2) ECD ECLIA analytical strategy demonstrates strong correlation with tissue HER2 expression in clinical specimens. Furthermore, the sHER2 ECD ECLIA method effectively identifies individuals with HER2-negative status within the low HER2 expression population, thereby providing enhanced guidance for treatment decisions involving antibody-drug conjugates (ADC) in BC patients. Thus, the combined diagnostic approach proposed in this work accurately differentiates between HER2-positive, HER2-negative, and low-expression BC patients, facilitating informed, clinically personalized treatment decisions.

BACKGROUND:Gold nanoclusters (AuNCs) obtained by electroreduction have excellent electrochemiluminescence (ECL) properties, and its ECL intensity is regulated by the valence state. In addition, their ECL signals can be rapidly quenched by reactive oxygen species (ROS). Based on this observation, a sensitive ROS biosensor was designed based on valence regulation of AuNCs. Excessive ROS in seminal plasma can lead to male infertility, and the short half-life and instability of ROS pose a challenge for their detection. Since valence regulation can be done quickly and is very sensitive, this ECL biosensor holds promise to address this issue. RESULTS:The ECL mechanism of AuNCs and the quenching mechanism of AuNCs by ROS were explored, mainly because ROS change the valence state of AuNCs. The ECL signals of the biosensor have a linear relationship with logarithm of the target concentration in the range of 1.0 × 10-8 to 1.0 × 10-3 M and 1.0 × 10-3 to 1.0 × 10-1 M, with a detection limit of 0.75 × 10-10 M (S/N = 3). The biosensor enables rapid one-step detection of ROS and has the advantage of being stable and reusable. More notably, the results of 57 real samples showed that the biosensor can be used to accurately assess the concentration of seminal plasma ROS, guiding the monitoring of sperm quality and the diagnosis of male infertility. SIGNIFICANCE:Compared with the traditional strategy of applying AuNCs only as a luminescent body, this strategy of regulating the valence state of AuNCs to achieve sensitive and rapid detection broadens the application of AuNCs in the field of analysis. Compared with other ROS detection strategies, the one-step immediate detection method effectively avoids the inaccuracy caused by the short half-life and natural dissipation of ROS, and is expected to improve the accuracy and efficiency of clinical diagnosis.

Surface-enhanced Raman scattering (SERS) has great potential in biological analysis due to its specificity, sensitivity, and non-invasive nature. However, effectively extracting Raman information and avoiding spectral overlapping from biological background interference remain major challenges. In this study, we developed a background-free SERS nanosensor consisting of gold nanobipyramids (Au NBPs) core-Prussian blue (PB) shell (Au NBPs@PB), for endogenous H2S detection. The PB shell degraded quickly upon contact with endogenous H2S, generating a unique Raman signal response in the Raman silent region (1800-2800 cm(-1)). By taking advantage of the high SERS-activity of Au NBPs and H2S-triggered spectral changes of PB, these SERS nanosensors effectively minimize potential biological interferences. The nanosensor exhibits a detection range of 2.0 mu M to 250 mu M and a limit of detection (LOD) of 0.34 mu M, with good reproducibility and minimal interference. We successfully applied this background-free SERS platform to monitor endogenous H2S concentrations in human serum samples with satisfied results.

The detection of specific DNA sequences and the identification of single nucleotide polymorphisms are important for disease diagnosis. Herein, by combining the high specificity of the base-stacking effect with the high reproducibility of bovine serum albumin (BSA) modified electrodes and the high loading performance of DNA nanoclews (DNA NCs), a novel sandwich-type electrochemiluminescence (ECL) biosensor is reported for the highly specific detection of HPV16 (chosen as the model target). The capture probes are loaded by BSA carrier platforms modified on the gold electrode surface to improve reproducibility. DNA NCs loaded with a large amount of Ru(phen)32+ worked as signal probes. The template probe is composed of the complementary strand of the target and two free nucleic acid anchors at the head and tail. In the presence of the target DNA, the template probes can form stacked base pairs with target, generating high base-stacking energy. This results in the shorter free anchors of template probes being able to bind to the capture and signal probes. This eventually forms a sandwich structure that allows Ru(phen)32+ to be near the electrode surface, producing an ECL signal. There is a linear relationship between the signal and the target concentration range from 10 fM to 100 pM, with a detection limit of 5.03 fM (S/N=3). Moreover, the base-stacking effect has single base recognition ability for base pairs, effectively avoiding false positive signals. The results of this strategy for clinical samples are consistent with classical methods.

Screening high-performance anodic electrochemiluminescence (ECL) systems with low triggering potential is a promising way to broaden their applications. In addition to electrochemiluminophore, co-reactant also plays an important role in the ECL process, since the oxidation of co-reactants is one of the most important steps in the anodic ECL process. Herein, a novel co-reactant-mediated high-performance low-potential Au nanocluster (AuNC)-based ECL system has been successfully developed. Benefiting from the isopropyl substitution and hydroxyl addition to the triethylamine (TEA), the BSA-AuNC/2-(diisopropylamino)ethanol (DIPEA-OH) ECL system achieved higher energy efficiency at a lower potential of 0.75 V. In addition, compared with the BSA-AuNC/TEA system, the ECL intensity and quantum yield (ΦECL) with DIPEA-OH as a co-reactant increased 22.34-fold and 13-fold (as high as 68.17%), respectively. Based on the low potential, high ΦECL of the AuNC/DIPEA-OH ECL system, a sandwich-type immunosensor has been constructed for a highly selective SARS-CoV-2 N protein assay. In the absence of any complex signal amplification strategies, the ECL immunosensor for the SARS-CoV-2 N protein detection showed a linear range of 0.001-100 ng/mL and a detection limit of 0.35 pg/mL. Moreover, the ECL platform had good reproducibility and stability and exhibited acceptable detection performance in the detection of actual serum samples. This work established a framework for in-depth design and study of anode ECL co-reactants for AuNCs and other luminophores, and expanded the potential application of ECL sensors in the clinical diagnosis of COVID-19.

BACKGROUND:Firstly, we aimed to compare the differences of higher-order chromatin structure between nasopharyngeal carcinoma (NPC) and normal nasopharyngeal tissues. The second objective was to analyze the specific chromatin interaction site of NPC and the NPC-related genes regulated by this interaction site.METHODS:We included 6 NPC patients and 6 healthy controls to obtain the sequencing results of highest-throughput chromosome conformation capture (Hi-C) technique, followed by further analysis of the specific chromatin interaction sites in NPC.RESULTS:We found an abnormal ultra-long distance interaction site on the chromosome 7p in the CNE210 sample, which was caused by a fusion gene SEPT7P2-PSPH. Additionally, a significant interaction site between chromosome 8q and 3p was revealed in the samples CNE25, CNE29, and CNE211, which was the interaction between 1.5 kb downstream of ASAP1 and 0.8 kb upstream of CTNNB1 gene. Further quantitative polymerase chain reaction (qPCR) revealed that ASAP1 and CTNNB1 genes were more highly expressed in CNE25, CNE29, and CNE211 than in the Np group, preliminarily indicating that this interaction site was likely related to the high expression of ASAP1 and CTNNB1 in NPC.CONCLUSIONS:Through Hi-C analysis, we analyzed the specific chromatin interaction sites associated with NPC, and found the chromosomal translocation and chromatin interaction sites associated with NPC based on statistical analysis. This study has certain guiding significance for in-depth study of the mechanism of NPC occurrence and development.

Biomolecule-functionalized Au nanoclusters (AuNCs) have drawn great interest in the electrochemiluminescence (ECL) field due to their unique optical/electrical properties, biocompatibility, and versatile bioapplication potentials. Herein, we proposed a two-in-one ECL probe of immunoglobulin G-encapsulated AuNCs (IgG-AuNCs) for the development of a high-performance ECL immunoassay (ECLIA) platform. The IgG-AuNCs were not only used as an ECL probe due to their excellent anodic ECL performance with triethylamine (TEA) as a coreactant but also used as the biorecognition element because of their well-retained bioactivity of the IgG. As a proof of concept, a new type of competitive immunosensing platform has been applied to detect IgG representing several merits of facile preparation, rapid detection, sample saving, and good analytical performance. The sensing platform exhibited a linear range of 0.5-50,000 ng/mL with a limit of detection of 0.06 ng/mL for IgG detection with high selectivity. In addition, this convenient ECLIA platform also performed well in real serum sample detection. Notably, our work not only proved the "two-in-one" immuno-AuNC probe-based ECLIA strategy but also developed a rational framework for study of ECL bioassay platforms based on multifunctional AuNCs and other related nanomaterials.

In recent years, the triplet loss-based deep neural networks (DNN) are widely used in the task of face recognition and achieve the state-of-the-art performance. However, the complexity of training the triplet loss-based DNN is significantly high due to the difficulty in generating high-quality training samples. In this paper, we propose a novel DNN training framework to accelerate the training process of the triplet loss-based DNN and meanwhile to improve the performance of face recognition. More specifically, the proposed framework contains two stages: 1) The DNN initialization. A deep architecture based on the softmax loss function is designed to initialize the DNN. 2) The adaptive fine-tuning. Based on the trained model, a set of high-quality triplet samples is generated and used to fine-tune the network, where an adaptive triplet loss function is introduced to improve the discriminative ability of DNN. Experimental results show that, the model obtained by the proposed DNN training framework achieves 97.3% accuracy on the LFW benchmark with low training complexity, which verifies the efficiency and effectiveness of the proposed framework.