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Cell-free RNA (cfRNA) allows assessment of health, status, and phenotype of a variety of human organs and is a potential biomarker to non-invasively diagnose numerous diseases. Nevertheless, there is a lack of highly efficient and bias-free cfRNA isolation technologies due to the low abundance and instability of cfRNA. Here, we developed a reproducible and high-efficiency isolation technology for different types of cell-free nucleic acids (containing cfRNA and viral RNA) in serum/plasma based on the inclusion of nucleic acids by metal-organic framework (MOF) materials, which greatly improved the isolation efficiency and was able to preserve RNA integrity compared with the most widely used research kit method. Importantly, the quality of cfRNA extracted by the MOF method is about 10-fold that of the kit method, and the MOF method isolates more than three times as many different RNA types as the kit method. The whole transcriptome mapping characteristics of cfRNA in serum from patients with liver cancer was described and a cfRNA signature with six cfRNAs was identified to diagnose liver cancer with high diagnostic efficiency (area under curve = 0.905 in the independent validation cohort) using this MOF method. Thus, this new MOF isolation technique will advance the field of liquid biopsy, with the potential to diagnose liver cancer.

The structural characterization of sublayer surfaces of MIL‐101 is reported by low‐dose spherical aberration‐corrected high‐resolution transmission electron microscopy (HRTEM). The state‐of‐the‐art microscopy directly images atomic/molecular configurations in thin crystals from charge density projections, and uncovers the structures of sublayer surfaces and their evolution to stable surfaces regulated by inorganic Cr₃(μ₃‐O) trimers. This study provides compelling evidence of metal–organic frameworks (MOFs) crystal growth via the assembly of sublayer surfaces and has important implications in understanding the crystal growth and surface‐related properties of MOFs.

The structural characterization of sublayer surfaces of MIL‐101 is reported by low‐dose spherical aberration‐corrected high‐resolution transmission electron microscopy (HRTEM). The state‐of‐the‐art microscopy directly images atomic/molecular configurations in thin crystals from charge density projections, and uncovers the structures of sublayer surfaces and their evolution to stable surfaces regulated by inorganic Cr₃(μ₃‐O) trimers. This study provides compelling evidence of metal–organic frameworks (MOFs) crystal growth via the assembly of sublayer surfaces and has important implications in understanding the crystal growth and surface‐related properties of MOFs.