Background: Tanshinone IIA (Tan IIA) is a lipophilic active constituent derived from the rhizomes and roots of Salvia miltiorrhiza Bunge (Danshen), a common Chinese medicinal herb. However, clinical applications of Tan IIA are limited due to its poor solubility in water. Methods: To overcome this limitation, we developed a calcium alginate hydrogel (CA) as a hydrophilic carrier for Tan IIA, which significantly improved its solubility. We also prepared nanoparticles with pH-responsive properties to explore their potential for controlled drug delivery. The physicochemical properties of Tan IIA/CA nanoparticles were evaluated, including their size, stability, and release profile. We also utilized RNA sequencing to further investigate the underlying anticancer mechanisms of Tan IIA/CA nanoparticles. Results: The Tan IIA/CA nanoparticles demonstrated enhanced solubility and exhibited potent anticancer activity in vitro. Additionally, the nanoparticles showed promising pH-responsive behavior, which is beneficial for controlled release applications. Further investigation into the molecular mechanisms revealed that the anticancer effects of Tan IIA/CA were mediated through apoptosis, ferroptosis, and autophagy pathways. Conclusions: This study confirms the anticancer potential and mechanisms of Tan IIA, while also presenting an innovative approach to enhance the solubility of this poorly soluble compound. The use of CA-based nanoparticles could be a valuable strategy for improving the therapeutic efficacy of Tan IIA in cancer treatment.

The plant Di19 (drought-induced 19) protein belongs to zinc finger transcription factors, which play crucial roles in drought stress acclimatization. OsDi19-3, a drought-induced transcription factor in rice, has not been fully characterized for its biological role in stress acclimatization. In this study, transgenic rice overexpressing OsDi19-3 was generated. Water deprivation experiments showed that transgenic plants exhibited higher drought tolerance than wild-type (WT) plants, indicating that OsDi19-3 positively regulates drought stress acclimatization. Consistent with this, stomata in overexpression lines closed more significantly than those in WT under drought stress. To explore the molecular mechanism, yeast two-hybrid and bimolecular fluorescence complementation (BiFC) experiments identified two interacting proteins of OsDi19-3: OsCAMK1 and OsNEK6. Notably, these two proteins also interacted with each other. A transcriptome analysis of OsDi19-3 transgenic plants revealed 224 upregulated and 167 downregulated genes (log₂(OE/WT) > 1, p-value < 0.05), including multiple stress-responsive genes. Furthermore, a ChIP-PCR analysis confirmed that OsDi19-3 directly binds to three target genes. This study provides insights into the role of OsDi19-3 in drought acclimatization and its regulatory network in rice.

Background: The potent topoisomerase I inhibitor SN-38, the active metabolite of irinotecan, is limited in clinical application due to severe systemic toxicity. Prodrug strategies enabling selective activation in the tumor microenvironment offer a promising approach to improve its therapeutic index. This study aims to rationally design, synthesize, and systematically evaluate novel disulfide-based SN-38 prodrugs engineered for redox-responsive activation in hypoxic tumors. Methods: Two novel disulfide-based SN-38 prodrugs (SN-38-CSS and SN-38-LSS) were designed and synthesized; SN-38-CSS incorporates a constrained cis-piperazine-fused six-membered cyclic disulfide linker, while SN-38-LSS contains a linear disulfide tether, to differentially exploit the upregulated thioredoxin (Trx/TrxR) system in hypoxic tumor microenvironments. Results: Both prodrugs demonstrated high stability under physiological pH conditions and in human plasma, minimizing premature release. Crucially, they exhibited selective, rapid degradation in the presence of dithiol reductants (TCEP and DTT), mimicking Trx system activity, while remaining stable towards monothiols (GSH, L-Cys). In vitro cytotoxicity assays revealed that the prodrugs exhibited significantly reduced toxicity compared to SN-38 under normoxic conditions across most tested cell lines. However, under hypoxic conditions, their activity was significantly restored. Specifically, SN-38-CSS exhibited cytotoxicity comparable to SN-38 against MCF-7 and NCI-N87 cells, whereas SN-38-LSS showed lower activation efficiency. Conclusions: SN-38-CSS is identified as a promising redox and hypoxia dual-responsive prodrug candidate, highlighting the strategic use of cyclic disulfide linkers for achieving high selectivity and controlled drug release within the tumor microenvironment.

Actin cytoskeleton is a fundamental cellular structure governing stress signal transduction and cellular homeostasis in plants. While its involvement in heat stress adaptation has been documented, the transcriptional and cytoskeletal regulatory networks underlying rice thermotolerance remain poorly defined. Here, we report that the actin-depolymerizing factor OsADF7 acts as a negative regulator of rice heat acclimation through modulating microfilament dynamics, and is transcriptionally controlled by the R2R3-MYB transcription factor OsMYB30. Heat stress markedly suppresses the expression of both OsMYB30 and OsADF7. Functional characterization demonstrated that knockout of Osadf significantly enhances heat acclimation by preserving microfilament polymerization, whereas overexpression (OE) of OsADF7 confers heat acclimation in rice seedlings. Physiological analyses including survival rate, electrolyte leakage, MDA, ROS, chlorophyll content and Fv/Fm further validated the heat acclimation phenotypes. Mechanistically, OsMYB30 directly binds to the TATCC cis-element in the OsADF7 promoter and may positively regulate OsADF7 transcription. Consequently, knockout of Osmyb30 enhances heat tolerance, while OE of OsMYB30 induces OsADF7 expression and leads to heat hypersensitivity. Genetic epistasis analyses support that the OsMYB30-OsADF7 transcriptional module may serve as a potential regulatory module involved in actin cytoskeleton-associated heat acclimation in rice. Collectively, our findings provide preliminary mechanistic clues linking MYB-related transcriptional regulation to actin cytoskeletal dynamics during rice thermotolerance responses, and provide a promising target for genetic improvement of heat-resistant rice varieties.