Integration of multiomics features for blood-based early detection of colorectal cancer.

BACKGROUND: Early detection of colorectal cancer (CRC) significantly enhances patient outcomes. Conventional CRC screening tools, like endoscopy and stool-based tests, have constraints due to their invasiveness or suboptimal patient adherence. Recently, liquid biopsy employing plasma cell-free DNA (cfDNA) has emerged as a potential noninvasive screening technique for various malignancies. METHODS: In this research, we harnessed the Mutation Capsule Plus (MCP) technology to profile an array of genomic characteristics from cfDNA procured from a single blood draw. This profiling encompassed DNA methylation, the 5' end motif, copy number variation (CNV), and genetic mutations. An integrated model built upon selected multiomics biomarkers was trained using a cohort of 93 CRC patients and 96 healthy controls. RESULTS: This model was subsequently validated in another cohort comprising 89 CRC patients and 95 healthy controls. Remarkably, the model achieved an area under the curve (AUC) of 0.981 (95% confidence interval (CI), 0.965-0.998) in the validation set, boasting a sensitivity of 92.1% (95% CI, 84.5%-96.8%) and a specificity of 94.7% (95% CI, 88.1%-98.3%). These numbers surpassed the performance of any single genomic feature. Importantly, the sensitivities reached 80% for stage I, 89.2% for stage II, and were 100% for stages III and IV. CONCLUSION: Our findings underscore the clinical potential of our multiomics liquid biopsy test, indicating its prospective role as a noninvasive method for early-stage CRC detection. This multiomics approach holds promise for further refinement and broader clinical application.

Radiation-Assisted Assembly of a Highly Dispersed Nanomolybdenum-Functionalized Covalent Organic Framework.

Two-dimensional covalent organic frameworks (2D COFs), featuring a large surface area and 1D pore structure, serve as promising scaffolds for anchoring functional guest compounds, which can significantly enhance their performance and thus expand their potential applications. Postsynthetic strategy for COFs functionalization is versatile but challenging because of their tedious procedure with high time and energy consumption, generation of excess reaction waste, and damage to COF crystallinity. We report in this work a general strategy for the synthesis of inorganic nanocompound-functionalized COF composites in a one-pot way. Specifically, a high-crystallinity nanoscale molybdenum compound is successfully introduced into a COF skeleton with high dispersion in situ during the crystallization process of the COF induced by gamma ray radiation under ambient conditions. The obtained COF@Mo composites exhibit remarkable sorption performance for methylene blue and many other organic dyes in aqueous solution with the advantages of ultrarapid uptake dynamics and high removal efficiency.

Record High Iodate Anion Capture by a Redox-Active Cationic Polymer Network.

As a critical radioactive anionic contaminant, traditional adsorbents primarily remove iodate (IO3 -) through ion exchange or hard acid-hard base interactions, but suffer from limited affinity and capacity. Herein, employing the synergistic effect of ion exchange and redox, we successfully synthesized a redox-active cationic polymer network (SCU-CPN-6, [C9H10O2N5 ⋅ Cl]n) by merging guanidino groups with ion-exchange capability and phenolic groups with redox ability via a Schiff base reaction. SCU-CPN-6 exhibits a groundbreaking adsorption capacity of 896 mg/g for IO3 -. The inferior adsorption capacities of polymeric networks containing only redox (~0 mg/g) or ion exchange (232 mg/g) fragments underscore the synergistic "1+1>2" effect of the two mechanisms. Besides, SCU-CPN-6 shows excellent uptake selectivity for IO3 - in the presence of high concentrations of SO4 2-, Cl-, and NO3 -. Meanwhile, a high distribution coefficient indicates its exemplary deep-removal performance for low IO3 - concentration. The synergic strategy not only presents a breakthrough solution for the efficient removal of IO3 - but also establishes a promising avenue for the design of advanced adsorbents for diverse applications.

Distinct molecular profiles drive multifaceted characteristics of colorectal cancer metastatic seeds.

Metastasis of primary tumors remains a challenge for early diagnosis and prevention. The cellular properties and molecular drivers of metastatically competent clones within primary tumors remain unclear. Here, we generated 10-16 single cell-derived lines from each of three colorectal cancer (CRC) tumors to identify and characterize metastatic seeds. We found that intrinsic factors conferred clones with distinct metastatic potential and cellular communication capabilities, determining organ-specific metastasis. Poorly differentiated or highly metastatic clones, rather than drug-resistant clones, exhibited poor clinical prognostic impact. Personalized genetic alterations, instead of mutation burden, determined the occurrence of metastatic potential during clonal evolution. Additionally, we developed a gene signature for capturing metastatic potential of primary CRC tumors and demonstrated a strategy for identifying metastatic drivers using isogenic clones with distinct metastatic potential in primary tumors. This study provides insight into the origin and mechanisms of metastasis and will help develop potential anti-metastatic therapeutic targets for CRC patients.

Analysis of the Genetic Characteristics and Metastatic Pathways of G1 and G2 Colorectal Neuroendocrine Neoplasms.

Objective: G1 and G2 colorectal neuroendocrine neoplasms (NENs) are a group of rare and indolent diseases. We aimed to delineate their genetic characteristics and explore their metastatic mechanisms. Methods: We used next-generation sequencing technology for targeted sequencing for 54 patients with G1 and G2 colorectal NENs. We delineated their genetic features and compared the genetic characteristics between metastatic NENs and nonmetastatic NENs. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was utilized to explore their abnormal pathways and study their potential metastatic mechanisms. Results: We collected 23 metastatic NENs and 31 nonmetastatic NENs. In the whole cohort, the common mutated genes were NCOR2, BRD4, MDC1, ARID1A, AXIN2, etc. The common copy number variations (CNVs) included amplification of HIST1H3D, amplification of HIST1H3E, and loss of PTEN. The KEGG enrichment analysis revealed that PI3K-Akt, MAPK, and Rap1 were the major abnormal pathways. There were significantly different genetic features between metastatic NENs and nonmetastatic NENs. The metastatic NENs shared only 47 (22.5%) mutated genes and 6 (13.3%) CNVs with nonmetastatic NENs. NCOR2, BRD4, CDKN1B, CYP3A5, and EIF1AX were the commonly mutated genes in metastatic NENs, while NCOR2, MDC1, AXIN2, PIK3C2G, and PTPRT were the commonly mutated genes in nonmetastatic NENs. Metastatic NENs presented a significantly higher proportion of abnormal pathways of cell senescence (56.5% vs 25.8%, P = .022) and lysine degradation (43.5% vs 16.1%, P = .027) than nonmetastatic NENs. Conclusion: G1 and G2 colorectal NENs are a group of heterogeneous diseases that might obtain an increased invasive ability through aberrant cell senescence and lysine degradation pathways.

How and When Inclusive Human Resource Management Promotes Employee Well-Being: The Roles of Ambidextrous Fit and Affective Leadership.

Researchers and practitioners have largely recognized the importance of human resource management in addressing the growing trend of workforce diversity to improve employee well-being. However, empirical research on inclusive human resource management (IHRM) remains scarce. Drawing on the conservation of resources theory and the person-environment fit framework, the current study constructs a moderated dual-mediation model to explore how IHRM influences employee well-being through ambidextrous fit (i.e., supplementary fit and complementary fit) and further examine the moderating role of affective leadership. Using three-wave data from 382 employees through the questionnaire survey, the empirical findings indicate that IHRM positively affects employee well-being and that this linkage is mediated by supplementary fit and complementary fit. In addition, we find that affective leadership strengthens the positive influences of IHRM on employee well-being, supplementary fit, and complementary fit as well as the indirect effect of IHRM on employee well-being through ambidextrous fit. We discuss some theoretical and practical implications of our findings and provide research directions.