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Lynch syndrome (LS) carriers develop mismatch repair–deficient neoplasia with high neoantigen (neoAg) rates. No detailed information on targetable neoAgs from LS precancers exists, which is crucial for vaccine development and immune-interception strategies. We report a focused somatic mutation and frameshift-neoAg landscape of microsatellite loci from colorectal polyps without malignant potential (PWOMP), precancers, and early-stage cancers in LS carriers. We generated paired whole-exome and transcriptomic sequencing data from 8 colorectal PWOMP, 41 precancers, 8 advanced precancers, and 12 early-stage cancers of 43 LS carriers. A computational pipeline was developed to predict, rank, and prioritize the top 100 detected mutated neoAgs that were validated in vitro using ELISpot and tetramer assays. Mutation calling revealed >10 mut/Mb in 83% of cancers, 63% of advanced precancers, and 20% of precancers. Cancers displayed an average of 616 MHC-I neoAgs/sample, 294 in advanced precancers, and 107 in precancers. No neoAgs were detected in PWOMP. A total of 65% of our top 100 predicted neoAgs were immunogenic in vitro, and were present in 92% of cancers, 50% of advanced precancers, and 29% of precancers. We observed increased levels of naïve CD8+ and memory CD4+ T cells in mismatch repair–deficient cancers and precancers via transcriptomics analysis. Shared frameshift-neoAgs are generated within unstable microsatellite loci at initial stages of LS carcinogenesis and can induce T-cell responses, generating opportunities for vaccine development, targeting LS precancers and early-stage cancers. This study provides the combined mutational and transcriptomic landscape along with a catalog of immunologically validated neoantigens in Lynch syndrome colonic precancers and tumors that will facilitate cancer immunoprevention strategies. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the practice and the associated outcomes of surgical treatment for young-onset colorectal cancer (YOCRC) patients presenting with synchronous liver metastases. The study cohort was divided into two groups according to surgery date: 131 patients in the early era (EE, 1998–2011) and 179 in the contemporary era (CE, 2012–2020). The CE had a higher rate of node-positive primary tumors, higher carcinoembryonic antigen level, and lower rate of RAS/BRAF mutations. The CE had higher rates of reverse or combined resection, multi-drug prehepatectomy chemotherapy, and two-stage hepatectomy. The median survival was 8.4 years in the CE and 4.3 years in the EE (p = 0.011). On multivariate analysis, hepatectomy in the CE was independently associated with improved overall survival (HR 0.48, p = 0.001). With a combination of perioperative systemic therapy, careful selection of treatment approach, and coordinated resections, durable cure can be achieved in YOCRC patients. [ABSTRACT FROM AUTHOR]

Aqueous zinc-ion batteries (AZIBs) are attracting worldwide attention due to their multiple merits such as extreme safety, low cost, feasible assembly, and environmentally friendly enabled by water-based electrolytes. At present, AZIBs have experienced systematic advances in battery components including cathode, anode, and electrolyte, whereas research involving separators is insufficient. The separator is the crucial component of AZIBs through providing ion transport, forming contact with electrodes, serving as a container for electrolyte, and ensuring the efficient battery operation. Considering this great yet ignored significance, it is timely to present the latest advances in design strategies, the systematic classification and summary of separators. We summarize the separator optimization strategies mainly along two approaches including the modification of the frequently used glass fiber and the exploitation of new separators. The advantages and disadvantages of the two strategies are analyzed from the material types and the characteristics of different strategies. The effects and mechanisms of various materials on regulating the uniform migration and deposition of Zn 2+ , balancing the excessively concentrated nucleation points, inhibiting the growth of dendrites, and the occurrence of side reactions were discussed using confinement, electric field regulation, ion interaction force, desolvation, etc. Finally, potential directions for further improvement and development of AZIBs separators are proposed, aiming at providing helpful guidance for this booming field., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)