Cell-free DNA methylation markers for differential diagnosis of hepatocellular carcinoma.

BACKGROUND: Aberrant DNA methylation may offer opportunities in revolutionizing cancer screening and diagnosis. We sought to identify a non-invasive DNA methylation-based screening approach using cell-free DNA (cfDNA) for early detection of hepatocellular carcinoma (HCC). METHODS: Differentially, DNA methylation blocks were determined by comparing methylation profiles of biopsy-proven HCC, liver cirrhosis, and normal tissue samples with high throughput DNA bisulfite sequencing. A multi-layer HCC screening model was subsequently constructed based on tissue-derived differentially methylated blocks (DMBs). This model was tested in a cohort consisting of 120 HCC, 92 liver cirrhotic, and 290 healthy plasma samples including 65 hepatitis B surface antigen-seropositive (HBsAg+) samples, independently validated in a cohort consisting of 67 HCC, 111 liver cirrhotic, and 242 healthy plasma samples including 56 HBsAg+ samples. RESULTS: Based on methylation profiling of tissue samples, 2321 DMBs were identified, which were subsequently used to construct a cfDNA-based HCC screening model, achieved a sensitivity of 86% and specificity of 98% in the training cohort and a sensitivity of 84% and specificity of 96% in the independent validation cohort. This model obtained a sensitivity of 76% in 37 early-stage HCC (Barcelona clinical liver cancer [BCLC] stage 0-A) patients. The screening model can effectively discriminate HCC patients from non-HCC controls, including liver cirrhotic patients, asymptomatic HBsAg+ and healthy individuals, achieving an AUC of 0.957(95% CI 0.939-0.975), whereas serum α-fetoprotein (AFP) only achieved an AUC of 0.803 (95% CI 0.758-0.847). Besides detecting patients with early-stage HCC from non-HCC controls, this model showed high capacity for distinguishing early-stage HCC from a high risk population (AUC=0.934; 95% CI 0.905-0.963), also significantly outperforming AFP. Furthermore, our model also showed superior performance in distinguishing HCC with normal AFP (< 20ng ml-1) from high risk population (AUC=0.93; 95% CI 0.892-0.969). CONCLUSIONS: We have developed a sensitive blood-based non-invasive HCC screening model which can effectively distinguish early-stage HCC patients from high risk population and demonstrated its performance through an independent validation cohort. TRIAL REGISTRATION: The study was approved by the ethic committee of The Second Xiangya Hospital of Central South University (KYLL2018072) and Chongqing University Cancer Hospital (2019167). The study is registered at ClinicalTrials.gov(# NCT04383353 ).

Oxygen-Functionalized Polyacrylonitrile Nanofibers with Enhanced Performance for Lithium-Ion Storage.

Functionalization and morphological construction can promote lithium-ion storage performance of organic polymers. In this contribution, exceptional lithium ion storage performance is empowered to porous polyacrylonitrile (PAN) nanofibers via the integration of template-assisted electrospinning technology and thermal treatment. It is found that the atmosphere adopted during the annealing process controls the storage behaviors of Li+. Impressively, the samples annealed in air present competitive capacities, rate capabilities, and a stable lifetime, compared with other counterparts (PAN powders and PAN fibers treated in N2). Such enhancement in performance is attributed to the enriched oxygen-based functionalities (mainly C=O group) which guarantee a high specific capacity and the porous structure which facilitates the transportation of Li+ and electrons to improve the rate capability. It is envisioned that such morphology control and surface functionalization open up new horizons in the development of organic electrode materials with enhanced lithium-ion storage performances.

3D-Structured Polyoxometalate Microcrystals with Enhanced Rate Capability and Cycle Stability for Lithium-Ion Storage.

The unsatisfactory rate capability and poor cycle stability are two major obstacles for polyoxometalates (POMs) in lithium-ion storage. On the other hand, how to endow POMs with 3D macrostructures for further practice is a challenge. To this end, a facile hydrothermal strategy was practiced to fabricate Co8W12O42(OH)4(H2O)8 microcrystals or CoWO4 aggregates onto the foamed substrate (denoted as CoW-POM and CoW-Salt, respectively). Integrating the extraordinary redox stability and lattice deformability of POMs with the excellent volume accommodation, the as-prepared CoW-POM presents an extraordinary better electrochemical performance (specific capacity, rate capability, and cycle life) than that of CoW-Salt. In detail, the CoW-POM can deliver a reversible capacity of 737.8 mA h g-1 at the current density of 0.1 A g-1 and provide a capacity retention of 90.1% even after 100 cycles. This work not only promotes the application of POMs in energy storage and conversion but also guides an effect methodology to endow POMs with 3D structures.

Metal complexes of folic acid for lithium ion storage.

As a natural abundant biomolecule, folic acid (FA) was explored for the first time as a material for lithium ion storage. Most impressively, after the cooperation of metal ions (Co2+, Ni2+ and Fe3+), the fabricated complexes presented an enhancement in capacity retention as well as a long cycling life. This work suggests an effective strategy to enhance the performance of organic electrode materials.