This study uncovers a new molecular mechanism by which the E3 ubiquitin ligase PIAS4 orchestrates pluripotency exit and lineage commitment in porcine embryonic stem cells (pESCs). Using a genome-wide CRISPR screening approach, the researchers identified PIAS4 as a critical regulator that modulates histone H3K4me3 marks via SUMOylation-mediated stabilization of KDM5B. Loss of PIAS4 impaired stem cell differentiation, disrupted lineage specific gene programs, and altered mesendoderm specification through LEFTY2–SMAD signaling. These findings not only provide fundamental insight into porcine stem cell biology but also pave the way for applications in livestock breeding, artificial meat production, and regenerative medicine.

The senescence of bone marrow-derived mesenchymal stem cells is involved in osteoporosis. The combination of dasatinib and quercetin has been explored to alleviate bone loss by efficiently reducing senescent cell populations. However, senolytic therapy by dasatinib and quercetin requires a precise ratio for better therapeutic effects, which is hard to achieve by oral administration. Meanwhile, the poor water solubility of these compounds limits their bioavailability, and their non-specific action could hamper effective penetration and targeting within relevant tissues. Herein, we developed alendronate-functionalized liposomes carrying dasatinib and quercetin (Aln-Lipo-DQ), focusing mainly on senescence-associated osteoporosis induced by chemotherapy or radiotherapy. Alendronate helps liposomes deliver dasatinib and quercetin to the femur and tibias, effectively removing senescent cells from bone tissue and increasing bone volume fraction from 5.05% to 11.95% in the chemotherapy-induced osteoporosis mouse model. We also found a 2.91-fold increase in bone volume fraction in Aln-Lipo-DQ treated groups compared to the control in radiotherapy models. This selectively targeting bone and reducing senescent cells holds great promise for cancer treatment-related and senescence-associated bone disorders.

Researchers have discovered a novel role of Neuraminidase 1 (NEU1) in the pathophysiology of acute lung injury (ALI) and uncovers NEU1 as a direct target of baicalin and Huanglian Jiedu Decoction (HLJDD) in alleviating ALI. NEU1 binding to the CXCR4 protein, thereby activating the downstream JNK signaling pathway, promoting inflammation and endothelial barrier damage; whereas baicalin can enhance the degradation of NEU1 protein via the lysosomal pathway, thereby improving endothelial dysfunction and acute lung injury.

Antimicrobial peptides (AMPs) exhibit broad-spectrum antimicrobial activity, low propensity to induce bacterial resistance, and multifunctional properties including immunomodulation and tissue regeneration promotion.This study comprehensively reviews the classification, antimicrobial mechanisms, and therapeutic applications of AMPs in major oral diseases such as dental caries, periodontitis, oral cancer, oral candidiasis, and oral mucositis. The research also analyzes key challenges in clinical translation (stability, cytotoxicity, immunogenicity, production costs) and corresponding solutions, while exploring their applications in implant coatings, oral dressings, combination therapy, and diagnostic markers, providing a robust theoretical basis for advancing oral disease treatment.