Background Emerging evidence suggest the critical role of circular RNAs (circRNAs) in disease development especially in various cancers. However, the oncogenic role of circRNAs in hepatocellular carcinoma (HCC) is still largely unknown. Methods RNA sequencing was performed to identify significantly upregulated circRNAs in paired HCC tissues and non-tumor tissues. CCK-8 assay, colony formation, transwell, and xenograft mouse models were used to investigate the role of circRNAs in HCC proliferation and metastasis. Small interfering RNA (siRNA) was used to silence gene expression. RNA immunoprecipitation, biotin pull-down, RNA pull-down, luciferase reporter assay and western blot were used to explore the underlying molecular mechanisms. Results Hsa_circ_0095868, derived from exon 5 of the MDK gene (named circMDK), was identified as a new oncogenic circRNA that was significantly upregulated in HCC. The upregulation of circMDK was associated with the modification of N6-methyladenosine (m6A) and poor survival in HCC patients. Mechanistically, circMDK sponged miR-346 and miR-874-3p to upregulate ATG16L1 (Autophagy Related 16 Like 1), resulting to the activation of PI3K/AKT/mTOR signaling pathway to promote cell proliferation, migration and invasion. Poly (β-amino esters) (PAEs) were synthesized to assist the delivery of circMDK siRNA (PAE-siRNA), which effectively inhibited tumor progression without obvious adverse effects in four liver tumor models including subcutaneous, metastatic, orthotopic and patient-derived xenograft (PDX) models. Conclusions CircMDK could serve as a potential tumor biomarker that promotes the progression of HCC via the miR-346/874-3p-ATG16L1 axis. The PAE-based delivery of siRNA improved the stability and efficiency of siRNA targeting circMDK. The PAE-siRNA nanoparticles effectively inhibited HCC proliferation and metastasis in vivo. Our current findings offer a promising nanotherapeutic strategy for the treatment of HCC. Graphical Abstract

DNA is a one-dimensional nanowire in nature, and it may not be used in nanodevices due to its low conductivity. In order to improve the conducting property of DNA, divalent Ni(2+) are incorporated into the base pairs of DNA at pH≥8.5 and nickel DNA (Ni-DNA) is formed. Conducting scanning probe microscopy (SPM) analysis reveals that the Ni-DNA is a semiconducting biopolymer and the Schottky barrier of Ni-DNA reduces to 2 eV. Meanwhile, electrochemical analysis by cyclic voltammetry and AC impedance shows that the conductance of Ni-DNA is better than that of native DNA by a factor of approximately 20-fold. UV spectroscopy and DNA base pair mismatch analyses show that the conducting mechanism of Ni-DNA is due to electrons hopping through the π-π stacking of DNA base pairs. This biomaterial is a designable one-dimensional semiconducting polymer for usage in nanodevices.

The study aimed to compare the application values of endoscopic-laparoscopic cholecystolithotomy (ELC) and laparoscopic cholecystectomy (LC) for patients with cholecystolithiasis. It did a retrospective analysis of 107 patients with cholecystolithiasis who underwent ELC and 144 patients with cholecystolithiasis who underwent LC. There is no significant difference in operating time and expenses when comparing ELC with LC (P>0.05). ELC showed significantly less blood loss during operation compared with LC (P<0.01). Shortened exhaust time (P<0.05) and hospital stay (P<0.01) were present in patients who underwent ELC. Moreover, ELC showed decreased occurrence rate of dyspepsia and diarrhea in comparison with LC (P<0.01). The stone recurrence rate of ELC was 16.67%. ELC decreased the recurrence of stone in common bile duct in comparison with LC. The contractile function of gallbladder was close to normal (P<0.05), and the thickness of gallbladder wall significantly decreased (P<0.001). Patients who underwent ELC showed less digestive symptom, good recovery, and low stone recurrence compared with those who underwent LC.

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Competitive endogenous RNA (ceRNA) networks play crucial roles in multiple biological processes and development of diseases. They might serve as diagnostic and prognosis markers as well as therapeutic targets. The purpose of this study was to identify a novel ceRNA network involving KCNQ1OT1, hsa-miR-24-3p, and VWF in acute traumatic coagulopathy (ATC) based on databases search. We searched the CTD, GeneCards, and PharmGKB databases for ATC-related target genes using Coagulopathy as a keyword. Upstream miRNAs and lncRNAs of the candidate target VWF were then explored using the miRWalk, microT, TargetScan, RNA22 and Tarbase, and DIANA-LncBase and Starbase databases, respectively. A KCNQ1OT1-hsa-miR-24-3p-VWF ceRNA network was constructed by R “ggalluvial” package. Interaction between KCNQ1OT1, hsa-miR-24-3p, and VWF was examined, and their expression was quantified in the peripheral blood samples from 30 ATC patients and liver tissues of ATC rat models. Forty-one ATC-related target genes were identified following data retrieval from publicly available databases, of which VWF was selected as the target and used for the subsequent analysis. KCNQ1OT1 and hsa-miR-24-3p were confirmed to be the key upstream regulatory factors of VWF. KCNQ1OT1-hsa-miR-24-3p-VWF coexpression regulatory network was constructed where KCNQ1OT1 competitively bound to hsa-miR-24-3p and attenuated its binding to VWF. Both the liver tissues of ATC rats and peripheral blood samples from ATC patients showed increased hsa-miR-24-3p expression and decreased VWF and KCNQ1OT1 expression. Collectively, we described the KCNQ1OT1-hsa-miR-24-3p-VWF ceRNA network in the development of ATC. We propose a new ceRNA that could help in the diagnosis and treatment of ATC.