Normal view
-
cs.AI, q-bio.NC updates on arXiv.org
-
ShapE-GRPO: Shapley-Enhanced Reward Allocation for Multi-Candidate LLM Training
arXiv:2603.29871v1 Announce Type: new Abstract: In user-agent interaction scenarios such as recommendation, brainstorming, and code suggestion, Large Language Models (LLMs) often generate sets of candidate recommendations where the objective is to maximize the collective utility of the entire set rather than individual candidates independently. However, existing reinforcement learning post-training paradigms, such as Group Relative Policy Optimization (GRPO), typically assign the same set-level
-
Omics in Hepatocellular
-
Curcumol Induces G1 Phase Arrest in SK-Hep-1 Cells by Targeting SKP2-Mediated p27 Degradation
Molecules. 2026 Mar 16;31(6):997. doi: 10.3390/molecules31060997.ABSTRACTCONTEXT: S-phase kinase-associated protein 2 (SKP2) is an oncogene and cell cycle regulator that mediates the ubiquitination of cell cycle regulators. Curcumol, a sesquiterpene natural product, has been reported to regulate SKP2-mediated ubiquitination degradation to overcome drug resistance in cancer cells. However, whether the cell cycle arrest effect of curcumol is related to SKP2's function in cancer cells and its mecha
Curcumol Induces G1 Phase Arrest in SK-Hep-1 Cells by Targeting SKP2-Mediated p27 Degradation
Molecules. 2026 Mar 16;31(6):997. doi: 10.3390/molecules31060997.
ABSTRACT
CONTEXT: S-phase kinase-associated protein 2 (SKP2) is an oncogene and cell cycle regulator that mediates the ubiquitination of cell cycle regulators. Curcumol, a sesquiterpene natural product, has been reported to regulate SKP2-mediated ubiquitination degradation to overcome drug resistance in cancer cells. However, whether the cell cycle arrest effect of curcumol is related to SKP2's function in cancer cells and its mechanisms are still unclear.
OBJECTIVE: To investigate the role of SKP2 in curcumol-induced cell cycle arrest and its underlying mechanisms.
MATERIALS AND METHODS: Transcriptomic and proteomic analyses were used to screen the ubiquitination-related factors in curcumol treated hepatocellular carcinoma cells. Lentiviral overexpression, co-immunoprecipitation assays, ubiquitination analysis, and cell-line-derived xenograft (CDX) models were used to dissect the role and mechanisms of the identified ubiquitination-related factor in the cell cycle arrest effect of curcucmol.
RESULTS: Curcumol modulated the expression of CDK4, CDK6, Cyclin D1, p27 and SKP2. SKP2 was one candidate target of curcumol selected by multi-omics. Overexpressed SKP2 partially reversed curcumol-induced growth inhibition and G1-phase arrest. The increased expression of p27 induced by curcumol was attenuated by overexpressed SKP2. Curcumol impaired the interaction between SKP2 and p27, and led to the ubiquitination and degradation of p27. In vivo, curcumol effectively reduced tumor growth, and its antitumor effect was significantly mitigated by SKP2 overexpression.
DISCUSSION AND CONCLUSIONS: Curcumol reduced SKP2 expression, weakened the interaction between SKP2 and p27, inhibited degradation of p27, and then induced G1 phase cell-cycle arrest in SK-Hep-1 cells.
PMID:41900096 | PMC:PMC13029316 | DOI:10.3390/molecules31060997
-
cs.AI, q-bio.NC updates on arXiv.org
-
Less is More: Improving LLM Alignment via Preference Data Selection
arXiv:2502.14560v4 Announce Type: replace-cross Abstract: Direct Preference Optimization (DPO) has emerged as a promising approach for aligning large language models with human preferences. While prior work mainly extends DPO from the aspect of the objective function, we instead improve DPO from the largely overlooked but critical aspect of data selection. Specifically, we address the issue of parameter shrinkage caused by noisy data by proposing a novel margin-maximization principle for datase