Circulating extracellular vesicles (EVs) were recognized as a promising source of diagnostic biomarker. However, there are limited studies published in this area, partly due to the limited number of detection platforms capable of detecting extracellular vesicles. In this study, extracellular vesicle immunoassays were developed using the Single Molecule array technology (SiMoa) and their clinical applications to cancer diagnosis were evaluated. Two extracellular vesicle detection assays, CD9-CD63 and Epcam-CD63, were designed to detect universal extracellular vesicles and tumour-derived extracellular vesicles, respectively. Our results show that CD9-CD63 and Epcam-CD63 SiMoa assays specifically detect extracellular vesicles but not free proteins with high sensitivities. The Epcam-CD63 levels detected in cancer cell culture media were consistent with levels of Epcam-expressing EVs isolated from the same cancer cell lines and detected by Western blot. Furthermore, the assays distinguish cancerous from non-cancerous plasma samples. The highest CD9-CD63 and Epcam-CD63 signals were observed in colorectal cancer patients comparing to healthy and benign controls. Both assays showed superior diagnostic performance for colorectal cancer. In addition, our results show that CD9-CD63 detection is an independent prognosis factor for both progression free survival and overall survival, while Epcam-CD63 detectionis an independent prognosis factor for OS.

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Prevention of muscle fiber degeneration is a key issue in the treatment of muscular dystrophies such as Duchenne Muscular Dystrophy (DMD). It is widely postulated that existing pharmaceutical compounds might potentially be beneficial to DMD patients, but tools to identify them are lacking. Here, by using a Caenorhabditis elegans model of dystrophin-dependent muscular dystrophy, we show that the neurohormone serotonin and some of its agonists are potent suppressors of muscle degeneration. Inhibitors of serotonin reuptake transporters, which prolong the action of endogenous serotonin, have a similar effect. Moreover, reduction of serotonin levels leads to degeneration of non-dystrophic muscles. Our results demonstrate that serotonin is critical to C. elegans striated muscles. These findings reveal a new function of serotonin in striated muscles.

Hepatocellular carcinoma (HCC) accounts for 90% of cases of liver cancer and is one of the most common and lethal malignancies among all cancers. Current screening practices in high‐risk populations using ultrasound and serological α‐fetoprotein (AFP) have significantly reduced HCC mortality. However, considering the highly operative‐dependent nature of ultrasound and dissatisfactory diagnostic performance of AFP, there is an unfulfilled need for a biomarker that can be used in HCC‐related at‐risk population screening. Here, sera from 322 patients, including 105 cases of chronic hepatitis (CH), 116 of liver cirrhosis (LC), and 101 of HCC, were collected. Two biomarkers, osteopontin (OPN) and dickkopf WNT signaling pathway inhibitor 1 (DKK1), were evaluated and compared with AFP alone and in combination. In our data, the serum OPN level increased significantly in HCC even in tumors of less than 2 cm. The area under the curve (AUC) reached 0.851, much higher than AFP and DKK1, with 79.21% sensitivity and 79.64% specificity at optimal cutoff in all of the samples. In AFP‐negative samples, serum OPN also performed well with an AUC of 0.838. The combination of AFP and OPN improved diagnosis performance significantly when compared with AFP alone. However, the DKK1 level showed an increase in HCC only compared with the LC group. The AUC does not improve significantly when added into the binary logistic model. We conclude that OPN, but not DKK1, is a promising biomarker for HCC diagnosis.