This study aims to propose an effective intelligent model for predicting entrepreneurial intention, which can provide a reasonable reference for the formulation of talent training programs and the guidance of entrepreneurial intention of students. The prediction model is mainly based on the kernel extreme learning machine (KELM) optimized by the improved Harris hawk's optimizer (HHO). In order to obtain better parameters and feature subsets, the Gaussian barebone (GB) strategy is introduced to improve the HHO algorithm, so as to strengthen the optimization ability for tuning parameters of KELM and identifying the compact feature subsets. Then, an optimal KELM model (GBHHO-KELM) is established according to the obtained optimal parameters and feature subsets to predict the entrepreneurial intention of students. In the experiment, GBHHO is compared with the other nine well-known methods in 30 CEC 2014 benchmark problems. The experimental findings suggest that the proposed GBHHO method is significantly superior to the existing methods in most problems. At the same time, GBHHO-KELM is compared with other machine learning methods in the prediction of entrepreneurial intention. The experimental results indicate that the proposed GBHHO-KELM can achieve better classification performance and higher stability in accordance with the four metrics. Therefore, we can conclude that the GBHHO-KELM model is expected to be an effective tool for the prediction of entrepreneurial intention.

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The homology-independent targeted integration (HITI) strategy enables effective CRISPR/Cas9-mediated knockin of therapeutic genes in nondividing cells in vivo, promising general therapeutic solutions for treating genetic diseases like Xlinked juvenile retinoschisis. Herein, supramolecular nanoparticle (SMNP) vectors are used for codelivery of two DNA plasmids-CRISPR-Cas9 genome-editing system and a therapeutic gene, Retinoschisin 1 (RS1)-enabling clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) knockin of the RS1 gene with HITI. Through small-scale combinatorial screenings, two SMNP vectors, with Cas9 and single guide RNA (sgRNA)plasmid in one and Donor-RS1 and green fluorescent protein (GFP)-plasmid in the other, with optimal delivery performances are identified. These SMNP vectors are then employed for CRISPR/Cas9 knockin of RS1/GFP genes into the mouse Rosa26 safe-harbor site in vitro and in vivo. The in vivo study involves intravitreally injecting the two SMNP vectors into the mouse eyes, followed by repeated ocular imaging by fundus camera and optical coherence tomography, and pathological and molecular analyses of the harvested retina tissues. Mice ocular organs retain their anatomical integrity, a single-copy 3.0-kb RS1/GFP gene is precisely integrated into the Rosa26 site in the retinas, and the integrated RS1/GFP gene is expressed in the retinas, demonstrating CRISPR/Cas9 knockin of RS1/GFP gene.

Tumor-derived extracellular vesicles (EVs) play essential roles in intercellular communication during tumor growth and metastatic evolution. Currently, little is known about the possible roles of tumor-derived EVs in sarcoma because the lack of specific surface markers makes it technically challenging to purify sarcomaderived EVs. In this study, a specific purification system is developed for Ewing sarcoma (ES)-derived EVs by coupling covalent chemistry-mediated EV capture/ release within a nanostructure-embedded microchip. The purification platform-ES-EV Click Chip-takes advantage of specific anti-LINGO-1 recognition and sensitive click chemistry-mediated EV capture, followed by disulfide cleavagedriven EV release. Since the device is capable of specific and efficient purification of intact ES EVs with high purity, ES-EV Click Chip is ideal for conducting downstream functional studies of ES EVs. Absolute quantification of the molecular hallmark of ES (i.e., EWS rearrangements) using reverse transcription Droplet Digital PCR enables specific quantification of ES EVs. The purified ES EVs can be internalized by recipient cells and transfer their mRNA cargoes, exhibiting their biological intactness and potential role as biological shuttles in intercellular communication.