DNA-Programmed Orientation-Ordered Multivalent Microfluidic Interface for Liquid Biopsy.

Aptamer-functionalized microfluidic interfaces hold great potential for liquid biopsies owing to their programmable nature. However, most previous studies have focused on development of multivalent aptamers to improve binding affinity, while ignoring aptamer orientation on microfluidic interfaces, resulting in suboptimal accessibility and affinity. Herein, we report a Cubic DNA Nanostructure (CDN)-programmed strategy to precisely control the orientation and valency of the Aptamer on a microfluidic interface (CDN-Apt-Chip) for enhancing the capture and release of circulating tumor cells (CTCs). We demonstrate that the ordered orientation and multivalent configuration can synergistically increase the binding affinity of aptamers toward CTCs. By using CDN-Apt-Chip, we successfully isolated CTCs from the peripheral blood of T-cell leukemia patients and discriminated T-cell leukemia patients from healthy volunteers. Furthermore, the captured CTCs were nondestructively released via nuclease treatment. We then performed T-cell receptor sequencing on the released cells to demonstrate the compatibility with downstream analysis. Overall, this study provides a new paradigm for interface regulation of functional microfluidic chips and advances the clinical translation of aptamer-based liquid biopsy.

Chaiyu-Dixian Formula Exerts Protective Effects on Ovarian Follicular Abnormal Development in Chronic Unpredictable Mild Stress (CUMS) Rat Model.

BACKGROUND: Chronic stress has been known to impair the female reproductive function, but the mechanism remains to be further investigated. Chaiyu-Dixian Formula (CYDXF) has been reported to regulate human endocrine disorders clinically. However, whether this formula can affect chronic stress-induced ovarian follicular development is not clear. AIM OF THE STUDY: To examine effects of CYDXF on follicular development and explore possible mech anisms in a chronic unpredictable mild stress (CUMS) model. MATERIALS AND METHODS: Adult female rats were randomly divided into 5 groups control group, CUMS group (saline treatment), CUMS+Estradiol (E2) (0.1 mg/kg) group, CUMS+CYDXF (2.73 g/kg) group, and CUMS+CYDXF (5.46 g/kg) group. Body weights and behavioral tests were documented. Serum hormone levels were determined by enzyme-linked immunosorbent assay (ELISA). Western blotting was used to detect the protein levels in the PI3K/Akt pathway and brain-derived neurotrophic factor (BDNF). The follicles were analyzed and classified according to their morphological characterization. RESULTS: CYDXF relieved depression-like behaviors and ameliorated the abnormality in rat estrous cycle within the rat model of CUMS. Moreover, CYDXF could regulate endocrine disorders, increase the proportion of antral follicles as well as decrease the proportion of follicular atresia, which suggested that CYDXF could alleviate abnormal follicular development and improve overall ovarian function. Furthermore, CYDXF also activated the BDNF-mediated PI3K/Akt signaling pathway. CONCLUSIONS: CYDXF (at dose of both 2.73 and 5.46 g/kg) attenuated chronic stress-induced abnormal ovarian follicular development by relieving depression-like behaviors and improving ovarian function through partly the regulation of the BDNF-mediated PI3K/Akt pathway.