Shibao Li

Tumor-derived exosomes (TDEs) have emerged as clinically significant liquid biopsies for noninvasive early cancer diagnosis. Although serum prostate-specific antigens (PSA) are widely used for prostate cancer (PCa) screening, their diagnostic accuracy is compromised by elevated levels in nonmalignant conditions. B7H3, a protein overexpressed on cancer cell membranes, shows promise as a tumor diagnostic marker but lacks PCa specificity. To address these limitations, we developed an analytical platform for high-accuracy PCa screening via the co-recognition of dual exosomal markers (PSA and B7H3) using a paper-based electrochemical immunosensor. Magnetic Fe3O4 nanoparticles functionalized with multivalent PSA aptamers captured PSA+ TDEs, while anti-B7H3-conjugated iron–manganese silicate nanozymes (IMSNs) amplified the electrochemical signals. A specific electrochemical response occurred only when both markers were highly expressed on TDEs, eliminating false positives from inflammation-induced PSA elevation. Coupled with high sensitivity (detection limit: 81 particles/mL) and specificity for TDEs detection, the assay successfully screened 50 PCa patients, 33 benign prostatic hyperplasia (BPH) patients, and 20 healthy controls, enabling enhanced-accuracy diagnosis of PCa.

Myocarditis, an inflammatory disorder of myocardium, poses significant clinical challenges due to its heterogeneous progression. While a majority of patients achieve spontaneous recovery, approxima...

Investigations on epithelial-mesenchymal transition (EMT) events occurring on circulating tumor cells (CTCs) are poised to significantly advance nanoliquid biopsy methodologies. This study presented a colorimetric multiplex lateral flow immunoassay strip (mLFIA) for the simultaneous detection of EpCAM and Vimentin, two representative EMT biomarkers, on heterogeneous CTCs. The assay utilized an engineered magnetic probe (pCF-Apt-H1/H2), characterized by a zwitterionic polymer coating on Fe₃O₄ nanoparticles, which conferred anti-fouling properties. This probe also incorporated dual aptamers specific for EpCAM and Vimentin for recognition, along with two complementary strands (H1/H2) that enabled fluorescent detection. Upon recognition, a cascade of strand displacement and entropy-driven amplification reactions was initiated, generating abundant single-stranded DNA co-labeled with biotin and fluorescein, which were subsequently detected by a gold nanoparticle-based mLFIA strip. Coupled with a custom-fabricated 3D-printed reader, the platform facilitated a rapid colorimetric readout for EpCAM and Vimentin, achieving low limits of detection at 0.22 and 0.16 ng/mL, respectively. Remarkably, this assay also demonstrated the capability to detect these two biomarkers on CTCs down to 10 cells/mL, and to track dynamic EMT processes. Machine learning algorithms were subsequently employed to classify and predict the colorimetric signals. Ultimately, this sensing platform proved effective in differentiating healthy individuals from colon cancer patients.

Chemotherapy serves as the primary therapeutic approach for triple-negative breast cancer (TNBC), yet its efficacy remains unsatisfactory. This study was a single-arm, open-label, single-center clinical trial (NCT05447702) involving patients with newly diagnosed stage II-III TNBC at West China Hospital. The treatment regimen consisted of camrelizumab (200 mg intravenously every 2 weeks, 12 cycles), apatinib (250 mg orally daily), and alternating chemotherapy [nab-paclitaxel (d1, 8, 15 every 4 weeks) for 4 cycles and epirubicin plus cyclophosphamide (every 2 weeks) for 4 cycles]. From June 2023 to April 2024, 35 patients were enrolled, of whom 1 patient withdrew due to adverse reaction intolerance. At treatment completion, the total pathological complete response (tpCR, ypT0/is, ypN0) rate was 67.6% (23/34), and the breast pCR (ypT0/is) rate was 70.6% (24/34). The overall response rate following neoadjuvant treatment reached 94.1% (32/34). Elevated levels of alanine aminotransferase (38.2%) and aspartate aminotransferase (29.4%) were the most common grade 3-4 adverse events, with no significant toxicities or treatment-related deaths reported. Comprehensive analysis of serum and tissue samples collected before and after neoadjuvant therapy via Olink and RNA sequencing revealed that the treatment induced a complex systemic immune response. These findings enabled the development of two novel scoring systems: a pretreatment response predictive score system for stratification and an efficacy assessment score system for treatment response evaluation. In conclusion, camrelizumab and apatinib combined with chemotherapy have good clinical efficacy and good safety as neoadjuvant treatments for stage II-III TNBC, warranting further investigation and potential clinical application.

Lateral flow assays (LFAs) are widely applicable in clinical point‐of‐care testing (POCT) due to their unique advantages such as simplicity, rapidity, and cost‐effectiveness. However, their sensitivity is often constrained by the background autofluorescence of the biological sample, the self‐matrix, or the readout technique, thereby leading to overlooking trace amounts of biomarkers present in early disease. In recent years, various nanomaterials‐based methods have been developed to address this issue, including the time‐gated technique, wavelength‐differentiated strategy and external modulated strategy for separation of background autofluorescence to minimize interference from biological samples. This review provides a comprehensive overview of various low‐background luminescent nanoparticles (LBLNPs)‐enhanced LFA systems, focusing on analyzing the underlying mechanism of these nanomaterials in improving the sensitivity and accuracy of the LFAs platform in clinical diagnosis. Representative examples are selected to demonstrate the clinical potential of these nanomaterials in detecting disease‐associated biomarkers in various samples including blood, urine, saliva et al. Finally, unresolved challenges and future development prospects are briefly discussed.

Response to Letter in regards to Response to Article “Ultrasensitive Hierarchical AuNRs@SiO2@Ag SERS Probes for Enrichment and Detection of Insulin and C-Peptide in Serum” [Letter]

Cyclophilin A (CypA) is a peptidyl-prolyl isomerase that participates in multiple cancer events, but the molecular mechanisms of abnormal expression and regulation of CypA in ovarian cancer (OC) have never been considered. This study identifies CypA as a key driver of epithelial-mesenchymal transition (EMT) in ovarian cancer and explores the mechanisms that underly this process. We show that CypA is upregulated in tissues and serum of ovarian cancer patients and that CypA overexpression correlates with poor prognosis. CypA facilitates tumor growth and metastasis in vivo in subcutaneous tumor xenograft and abdominal metastatic models, and in vitro studies suggest a mechanism, showing that CypA accelerates ovarian cancer cell epithelial-mesenchymal transition by activating a PI3K/AKT signaling pathway. Mechanistic studies showed that STAT5A binds pri-miR-514a-3p and inhibits its activity, whereas miR-514a-3p directly binds to the 3ʹ-UTR of CypA to suppress its expression, resulting in STAT5A promoting the expression of CypA, forming the STAT5A/miR-514a-3p/CypA axis. Furthermore, immunoprecipitates and mass spectrometry analysis identifies a CypA interaction with TAF15 that stabilizes TAF15 by suppressing its proteasome degradation and promotes its entry into the nucleus. While STAT5A is positively regulated by TAF15. Our findings identify a novel feedback loop for CypA that drives EMT and ovarian tumor growth and metastasis via a TAF15/STAT5A/miR-514a-3p pathway in ovarian cancer and facilitates the release of CypA into the extracellular, which provides a promising therapeutic target for OC treatment and a diagnostic biomarker.