Local oxidative stress in diseases or injury severely hinders cell homeostasis and organ regeneration. Antioxidant therapy is an effective strategy for oxidative stress treatment. Biomaterials with good biocompatibility and reactive oxygen species (ROS) scavenging ability are good choices for antioxidant therapeutics. However, there are few natural biomaterials that are identified with both biocompatibility and strong antioxidant activity. Here, we show, for the first time, that silk fibroin (SF) is a strong antioxidant, which can eliminate ROS in both cells and zebrafish. We further demonstrate that the β-sheet structures turn into a random coiled structure when SF is treated with hydrogen peroxide. The content of β-sheet structures can be increased by heating, thus enhancing the antioxidation properties of SF. Therefore, SF can serve as a good antioxidant biomaterial for therapeutics, and its β-sheet structure-based antioxidation mechanism provides a novel theoretical basis, which could be a new cue for more antioxidant biomaterial discovery and identification.

N ⁶ -methyladenosine (m ⁶ A)–modified mRNAs and their cytoplasmic reader YTHDFs are colocalized with stress granules (SGs) under stress conditions, but the interplay between m ⁶ A modification and SG stability remains unclear. Here, we presented a spatiotemporal m ⁶ A imaging system (SMIS) that can monitor the m ⁶ A modification and the translation of mRNAs with high specificity and sensitivity in a single live cell. SMIS showed that m ⁶ A-modified reporter mRNAs dynamically enriched into SGs under arsenite stress and gradually partitioned into the cytosol as SG disassembled. SMIS revealed that knockdown of YTHDF2 contributed to SG disassembly, resulting in the fast redistribution of mRNAs from SGs and rapid recovery of stalled translation. The mechanism is that YTHDF2 can regulate SG stability through the interaction with G3BP1 in m ⁶ A-modified RNA-dependent manner. Our results suggest a mechanism for the interplay between m ⁶ A modification and SG through YTHDF2 regulation.

Genome architecture and organization play critical roles in cell life. However, it remains largely unknown how genomic loci are dynamically coordinated to regulate gene expression and determine cell fate at the single cell level. We have developed an inducible system which allows Simultaneous Imaging and Manipulation of genomic loci by Biomolecular Assemblies (SIMBA) in living cells. In SIMBA, the human heterochromatin protein 1α (HP1α) is fused to mCherry and FRB, which can be induced to form biomolecular assemblies (BAs) with FKBP-scFv, guided to specific genomic loci by a nuclease-defective Cas9 (dCas9) or a transcriptional factor (TF) carrying tandem repeats of SunTag. The induced BAs can not only enhance the imaging signals at target genomic loci using a single sgRNA, either at repetitive or non-repetitive sequences, but also recruit epigenetic modulators such as histone methyltransferase SUV39H1 to locally repress transcription. As such, SIMBA can be applied to simultaneously visualize and manipulate, in principle, any genomic locus with controllable timing in living cells.

High‐magnitude cyclic stretch from arterial blood pressure significantly contributes to the excessive proliferation and migration of vascular smooth muscle cells (VSMCs), leading to neointima formation in vein grafts. However, the molecular mechanisms remain unclear. This study highlights the critical role of cytosolic Phospholipase A2 (cPLA2)/ Yin Yang 1 (YY1)/ carnitine palmitoyltransferase 1b (CPT1B) signaling in coordinating VSMC mechanical activation by inhibiting fatty acid β‐oxidation. Metabolomic analysis showed that a 15%–1 Hz arterial cyclic stretch, compared to a 5%–1 Hz venous stretch, increased long‐chain fatty acids in VSMCs. cPLA2, identified as a mechanoresponsive molecule, produces excessive arachidonic acid (ArAc) under the 15%–1 Hz stretch, inhibiting CPT1B expression, a key enzyme in fatty acid β‐oxidation. ArAc promotes transcription factor YY1 degradation, downregulating CPT1B. Inadequate fatty acid oxidation caused by knockdown of CPT1B or YY1, or etomoxir treatment, increased nuclear membrane tension, orchestrating the activation of cPLA2. Overexpressing CPT1B or inhibiting cPLA2 reduced VSMC proliferation and migration in vein grafts, decreasing neointimal hyperplasia. This study uncovers a novel mechanism in lipid metabolic reprogramming in vein grafts, suggesting a new therapeutic target for vein graft hyperplasia.

The interplay between nuclear architecture and extracellular matrix stiffness orchestrates cell fate decisions, yet the molecular mechanisms remain poorly defined. Here, we investigate the role of Lamin A ( LMNA ), a nuclear structural protein whose expression correlates with tissue stiffness, in regulating cellular differentiation and fate decision. Using myoblasts and fibroblasts as models, it was observed that cells with low LMNA expression showed that higher cell deformation elevated expression of neurological genes and exhibited potential for differentiation into a neural-like fate. CUT&Tag sequencing of LMNA -knockdown cells revealed a reduction in the size of Lamin B1-associated domains, with enhanced Lamin B1 binding at muscle-related genes ( Myf5 and Myf6 ) and diminished binding at the neural gene Nes , suggesting that changes in gene expression are associated with alterations in chromatin structure. Further analysis identified the dissolution of H3K9me2/3-labeled heterochromatin regions and their redistribution in the nucleoplasm following LMNA inhibition. Soft substrates (0.2 kPa) amplify the neural differentiation capacity in LMNA -knockout cells. Additionally, retinoic acid was shown to enhance the expression of neurologically related genes by suppressing LMNA expression. These findings reveal a novel substrate stiffness-induced mechanism by which Lamin A regulates cell fate transitions and provide a new approach for neural cell generation.