Isobutyric acid promotes colorectal cancer metastasis through activating RACK1.

Colorectal cancer (CRC) metastasis plays a crucial role in disease progression, yet the regulatory mechanisms underlying metastasis remain incompletely understood. Isobutyric acid (IBA), a short-chain fatty acid found at high levels in serum of CRC patients, has been shown to be a critical metabolite influencing CRC proliferation. However, its role in tumor metastasis remains unknown. Here, utilizing liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis, we found that levels of IBA were significantly higher in patients with distant organ metastasis of CRC than in those without. Furthermore, IBA promoted CRC metastasis both in vitro and in vivo. Mass spectrometry, immunofluorescence, and cellular thermal shift assay revealed that IBA interacts with RACK1. Mechanistically, IBA binding to and activating RACK1 promotes regulation of downstream Akt and FAK signaling and CRC metastasis. Collectively, our study highlights the critical interplay between IBA and RACK1 and its impact on tumor metastasis. This study suggests that targeting the IBA-RACK1 signaling axis may be an effective therapeutic strategy for controlling CRC metastasis.

In Situ Visualization of Epidermal Growth Factor Receptor Nuclear Translocation with Circular Bivalent Aptamer.

Epidermal growth factor receptor (EGFR) nuclear translocation correlates with the abnormal proliferation, migration, and anti-apoptosis of tumor cells. Monitoring EGFR nuclear translocation provides insights into the molecular mechanisms underlying cancers. EGFR nuclear translocation includes two processes, EGFR phosphorylation and phosphorylated EGFR translocation to the nucleus. With the help of aptamers, probes that can achieve the first step of anchoring phosphorylated EGFR have been developed. However, the EGFR nuclear translocation can last for hours, posing a challenge to monitor the entire nuclear translocation in living cells. Herein, we designed a circular bivalent aptamer-functionalized optical probe with greatly enhanced stability for long-term visualization of EGFR nuclear translocation in situ. The results of cell experiments show that the probe could monitor the entire nuclear translocation of EGFR. The findings of tissue and in vivo experiments demonstrate that the probe can evaluate the development and progression of tumors by imaging EGFR nuclear translocation in situ. The proposed approach allows us to monitor EGFR nuclear translocation in the long term, indicating its great potential in investigating the mechanisms of cancers and guiding for tumor treatment.

Ultrasensitive Glutathione-Mediated Facile Split-Type Electrochemiluminescence Nanoswitch Sensing Platform.

Seeking for an advanced electrochemiluminescence (ECL) platform is still an active and continuous theme in the ECL-sensing realm. This work outlines a femtomolar-level and highly selective glutathione (GSH) and adenosine triphosphate (ATP) ECL assay strategy using a facile split-type gold nanocluster (AuNC) probe-based ECL platform. The system utilizes GSH as an efficient etching agent to turn on the MnO2/AuNC-based ECL nanoswitch platform. This method successfully achieves an ultrasensitive detection of GSH, which significantly outperformed other sensors. Based on the above excellent results, GSH-related biological assays have been further established by taking ATP as a model. Combined with the high catalytic oxidation ability of DNAzyme, this ECL sensor can realize ATP assay as low as 1.4 fmol without other complicated exonuclease amplification strategies. Thus, we successfully achieved an ultrahigh sensitivity, extremely wide dynamic range, great simplicity, and strong anti-interference detection of ATP. In addition, the actual sample detection for GSH and ATP exhibits satisfactory results. We believe that our proposed high-performance platform will provide more possibilities for the detection of other GSH-related substances and show great prospect in disease diagnosis and biochemical research.

Split-type electrochemiluminescent gene assay platform based on gold nanocluster probe for human papillomavirus diagnosis.

Persistent high-risk human papillomavirus (HPV) infection is the leading cause of cervical cancer. Efficient detection of HPV16 E7 is necessary for early diagnosis and cure of the disease. Here, a novel and high-performance Au nanocluster (AuNC) probe-based split-type electrochemiluminescent (ECL) assay platform has been established to detect these oncogenes, in which the nucleic acid hybridization assay and the ECL measurements are performed independently. The proposed approach combines superior magnetic nanobead enrichment and separation technology, specific nucleic acid hybridization technology, and high-efficiency AuNC probe ECL strategy, and shows excellent advantages. First, the split-type ECL sensing platform can effectively avoid interference from biological samples and adequately uses the ECL efficiency of the AuNC probe. Furthermore, the ultrahigh sensitivity assay of HPV DNA can be achieved without any complex nucleic acid amplification technique. Taking advantage of the above merits of split-type detection, the ECL DNA sensor achieved ideal low detection of 6.8 aM and a wide dynamic range bridging 10 orders of magnitude HPV16 E7. Furthermore, together with its favorable and powerful specificity, high sensitivity, and good selectivity, this strategy could detect HPV16 E7 DNA in human samples, which showed great consistency with the FDA-approved approach (Hybrid capture 2, HC2). Therefore, this work proposes a facile and reliable split-type ECL platform for HPV diagnosis and shows great potential for the early diagnosis of other diseases.

Mechanistic Insight into a Novel Ultrasensitive Nicotine Assay Base on High-Efficiency Quenching of Gold Nanocluster Cathodic Electrochemiluminescence.

Monitoring nicotine concentrations in human fluids is extremely crucial owing to the harmful effect of nicotine on human health. Herein, it is shown that nicotine could quench the cathodic electrochemiluminescence (ECL) of gold nanoclusters (AuNCs) with high efficiency. The ECL quenching mechanism of nicotine was studied in detail using various experimental tools and theoretical calculations. It was concluded that the strongly oxidizing intermediate SO4•-, produced from K2S2O8, could oxidized nicotine, resulting in ECL emission quenching. On the basis of this high-efficiency ECL quenching of the AuNCs/K2S2O8 system, a recyclable, ultrasensitive, and selective ECL sensing platform for nicotine detection was proposed. Even in the absence of any complex signal amplification techniques, the ECL sensor for nicotine detection showed an unprecedentedly low detection limit of 7.0 × 10-13 M (S/N = 3) and a wide linear range over 8 orders of magnitude. Most remarkably, it could be successfully used for nicotine detection in human urine samples. This is expected to promote the investigations and applications on nicotine-related diseases. We believe that the proposed ECL platform can hold great prospects for commercialization in biomedical fields and tobacco industries.

Facile and highly sensitive photoelectrochemical biosensing platform based on hierarchical architectured polydopamine/tungsten oxide nanocomposite film.

The fabrication of photosensitive interface and molecular recognition layer at the biosensing surface are of vital importance in photoelectrochemical (PEC) biosensor construction. Developing facial methods with favorable biomolecule immobilization as well as excellent photoelectric activity still need to be explored. In this work, by integration of the merits of tungsten oxide (WO3) semiconductor nanomaterial and polydopamine (PDA) polymer, a novel biofunctional PDA/WO3 nanocomposites (PDA/WO3 NCs) modified ITO hierarchical architecture was fabricated by simple thermal annealing and self-polymerization methods. The proposed PEC biosensor platform based on PDA/WO3/ITO not only have preponderances in simple preparation, but also possesses excellent PEC activity, high specific surface area and good microenvironment for biomolecule immobilization. Utilizing CYFRA 21-1 as a model target, label-free PEC immunosensor was developed successfully, which exhibited great sensitivity and broad dynamic range with four orders of magnitude (10 pg mL-1 to 100 ng mL-1), and the limit of detection was as low as 2.5 pg mL-1. Moreover, owing to the great sensitivity and selectivity of the proposed platform, this convenient sensor also performed well in real serum sample analysis. It is worth noting that our work not only helps in gaining a better understanding of the applicability of the PEC properties of PDA/WO3 NCs, but also sheds novel light on the design and development of PEC biosensing platform based on PDA/WO3 NCs.

Facile electrochemiluminescence sensing platform based on high-quantum-yield gold nanocluster probe for ultrasensitive glutathione detection.

This report outlines a highly sensitive and facile electrochemiluminescence (ECL) sensing platform based on a novel high-quantum-yield Au-nanocluster (AuNC) probe for glutathione (GSH) detection. Owing to the prominent quenching effect of GSH on the ECL of the AuNCs, the proposed ECL nanosensor showed a wide response to GSH in the ranges of 1.0 × 10-9-1.0 × 10-5M and 1.0 × 10-5-1.0 × 10-1M and a low detection limit of 3.2 × 10-10M. In addition, the proposed system exhibited good selectivity for GSH in the presence of other chemical/biological interferences. Moreover, since no further functionalization of AuNC-based sensor interface was necessary, together with the stability, high sensitivity and selectivity of the proposed nanosensor, this convenient approach was able to successfully detect GSH in both of human urine samples and blood samples with excellent recoveries, which indicated its promising application under physiological conditions. Of significant importance is that this study not only helps in gaining a better understanding of the applicability of the ECL properties of AuNCs, but also provides a new avenue for the design and development of ECL sensors based on the novel high-quantum-yield AuNC-based probe and other functional-metal-based NC probes.

Valence States Effect on Electrogenerated Chemiluminescence of Gold Nanocluster.

This work elucidated the valence states effect on the electrogenerated chemiluminescence (ECL) performance of gold nanocluster (AuNC). The N-acetyl-l-cysteine-AuNCs (NAC-AuNCs) and the electrochemical reduction method for reducing the AuNCs were first employed to this study. Results demonstrate that the electrochemical reduction degree of the AuNCs depended on the reduction potential, and the enhancement of the ECL signals was positively correlated with the reduction degree of AuNCs, which indicated that the valence state of Au plays a vital role in the ECL performance of AuNCs. Furthermore, the proposed method has been successfully extended to the chemical reduction technique and other nanoclusters. Therefore, an excellent AuNC-based ECL method with various advantages, such as simple preparation, lower toxicity, high sensitivity, and ΦECL, and excellent stability, has been proposed. This approach not only opens up a new avenue for designing and developing ECL device from other functional-metal based NCs, but also extends the huge potential application in the ECL sensing.