Metabolic rewiring is considered as a primary feature of cancer. Malignant cells reprogram metabolism pathway in response to various intrinsic and extrinsic drawback to fuel cell survival and growth. Among the complex metabolic pathways, pyrimidine biosynthesis is conserved in all living organism and is necessary to maintain cellular fundamental function (i.e. DNA and RNA biosynthesis). A wealth of evidence has demonstrated that dysfunction of pyrimidine metabolism is closely related to cancer progression and numerous drugs targeting pyrimidine metabolism have been approved for multiple types of cancer. However, the non-negligible side effects and limited efficacy warrants a better strategy for negating pyrimidine metabolism in cancer. In recent years, increased studies have evidenced the interplay of oncogenic signaling and pyrimidine synthesis in tumorigenesis. Here, we review the recent conceptual advances on pyrimidine metabolism, especially dihydroorotate dehydrogenase (DHODH), in the framework of precision oncology medicine and prospect how this would guide the development of new drug precisely targeting the pyrimidine metabolism in cancer.

Monoclonal antibody therapy has played an important role against SARS-CoV-2. Strategies to deliver functional, antibody-based therapeutics with improved in vivo durability are needed to supplement current efforts and reach underserved populations. Here, we compare recombinant mAbs COV2-2196 and COV2-2130, which compromise clinical cocktail Tixagevimab/Cilgavimab, with optimized nucleic acid-launched forms. Functional profiling of in vivo-expressed, DNA-encoded monoclonal antibodies (DMAbs) demonstrated similar specificity, broad antiviral potency and equivalent protective efficacy in multiple animal challenge models of SARS-CoV-2 prophylaxis compared to protein delivery. In PK studies, DNA-delivery drove significant serum antibody titers that were better maintained compared to protein administration. Furthermore, cryo-EM studies performed on serum-derived DMAbs provide the first high-resolution visualization of in vivo-launched antibodies, revealing new interactions that may promote cooperative binding to trimeric antigen and broad activity against VoC including Omicron lineages. These data support the further study of DMAb technology in the development and delivery of valuable biologics.

An iron-catalyzed highly anti-Markovnikov selective, enantioselective hydrosilylation of vinylcyclopropanes with PhSiH 3 was reported for the preparation of valuable chiral allylic silanes via stereospecific C-C bond cleavage. Simultaneously, difficultly prepared chiral VCPs could be also obtained with moderate to excellent enantioselectivity via this kinetic resolution pathway. The chiral Zallylic silanes could be converted to various chiral allylic derivatives. A possible mechanism via an iron-silyl species was proposed based on experimental and computational studies.

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Background Atherosclerosis (AS) is the greatest contributor to pathogenesis of atherosclerotic cardiovascular disease (ASCVD), which is associated with increased mortality and reduced quality of life. Early intervention to mitigate AS is key to prevention of ASCVD. Salvianolic acid B (Sal B) is mainly extracted from root and rhizome of Salvia Miltiorrhiza Bunge, and exerts anti-atherosclerotic effect. The purpose of this study was to screen for anti-AS targets of Sal B and to characterize immune cell infiltration in AS. Methods We identified targets of Sal B using SEA (http://sea.bkslab.org/) and SIB (https://www.sib.swiss/) databases. GSE28829 and GSE43292 datasets were obtained from Gene Expression Omnibus database. We identified differentially expressed genes (DEGs) and performed enrichment analysis. Weighted gene co-expression network analysis (WGCNA) was used to determine the most relevant module associated with atherosclerotic plaque stability. Intersecting candidate genes were evaluated by generating receiver operating characteristic (ROC) curves and molecular docking. Then, immune cell types were identified using CIBERSOFT and single-sample gene set enrichment analysis (ssGSEA), the relationship between candidate genes and immune cell infiltration was evaluated. Finally, a network-based approach to explore the candidate genes relationship with microRNAs (miRNAs) and Transcription factors (TFs). Results MMP9 and MMP12 were been selected as candidate genes from 64 Sal B-related genes, 81 DEGs and turquoise module with 220 genes. ROC curve results showed that MMP9 (AUC = 0.815, P<0.001) and MMP12 (AUC = 0.763, P<0.001) were positively associated with advanced atherosclerotic plaques. The results of immune infiltration showed that B cells naive, B cells memory, Plasma cells, T cells CD8, T cells CD4 memory resting, T cells CD4 memory activated, T cells regulatory (Tregs), T cells gamma delta, NK cells activated, Monocytes, and Macrophages M0 may be involved in development of AS, and the candidate genes MMP9 and MMP12 were associated with these immune cells to different degrees. What’ s more, miR-34a-5p and FOXC1, JUN maybe the most important miRNA and TFs. Conclusion The anti-AS effects of Sal B may be related to MMP9 and MMP12 and associated with immune cell infiltration, which is expected to be used in the early intervention of AS.