Osteosarcoma remains a major clinical challenge owing to its high recurrence rate, metastatic potential, and the frequent need for postoperative bone reconstruction. Here, we report a multifunctional platform consisting of doxorubicin-loaded mesoporous silica nanoparticles (DOX@MSN) embedded within chitosan microspheres (DMCS). The DMCS microspheres, with diameters of 100-200 µm, were fabricated by emulsion crosslinking and achieved a DOX encapsulation efficiency of 71.82% and a drug loading content of 17.95%. The platform exhibited pH-responsive drug release, with markedly enhanced DOX release under mildly acidic conditions relevant to the tumor microenvironment. In vitro, DMCS demonstrated favorable hemostatic and antitumor effects, while DOX@MSN showed preferential uptake by K7M2-WT osteosarcoma cells compared with MC3T3-E1 preosteoblasts. In addition, MCS microspheres, used as the DOX-free analog of DMCS, promoted osteogenic differentiation of MC3T3-E1 cells, as evidenced by increased alkaline phosphatase activity, matrix mineralization, and upregulation of osteogenesis-related genes, including Runx2, Col1A1, OPN, and OCN. In vivo, the platform enabled rapid hemostasis, effective inhibition of residual osteosarcoma after resection, and enhanced bone regeneration. Given that this is, to the best of our knowledge, the first attempt to integrate these three key functions within a single postoperative osteosarcoma-oriented system, the primary objective of this proof-of-concept study was to establish clear evidence for each function individually. This work defines key design principles and a functional validation framework for the development of next-generation integrated platforms for postoperative osteosarcoma management.

Soil salinization/alkalization represents a universal challenge that severely constrains crop productivity. Elucidating the molecular mechanisms underpinning saline/alkaline tolerance of wheat (Triticum aestivum) holds profound significance for global food security and sustainable agriculture. In this study, we functionally characterized a wheat alkaline sensitive locus designated Wheat Alkaline Sensitive 1 (WAS1), through whole exome-capture sequencing-based bulked segregant analysis and fine mapping of was1 mutant populations. This locus encodes TaIAA25, a canonical member of the Auxin/Indole-3-Acetic Acid (Aux/IAA) protein family. A C to T transition in TaIAA25 leads to a Pro-to-Ser substitution within its Aux/IAA degron motif. This amino acid substitution enhances the stability of TaIAA25 protein, thereby rendering wheat hypersensitive to alkaline stress. The overexpression of TaIAA25 significantly increased sensitivity of wheat to alkaline treatment, whereas iaa25 knockout mutants displayed enhanced tolerance to alkaline stress. Consistent with established auxin signaling transduction, TaIAA25 interacts with auxin response factor 16 (TaARF16) to repress the TaARF16-mediated transcriptional activation of small auxin-up RNA gene TaSAUR215. This cascade potentiates the inhibitory effect of D-clade type 2C protein phosphatase (TaPP2C.D) on plasma membrane (PM) H+-ATPase activity. Notably, TaIAA25 also directly interacts with the phosphorylation (P) domain in central loop of PM H+-ATPase 2 (TaHA2) and represses its binding with the actuator (A) domain, thereby blocking TaHA2-driven proton efflux. Collectively, our findings clarified the crucial role of the classical auxin signaling pathway in plant responses to alkaline stress. Furthermore, we revealed a mechanism wherein an Aux/IAA protein directly modulates PM H+-ATPase activity to orchestrate auxin-mediated alkaline stress response.

Osteoporosis is characterized by progressive bone loss and structural deterioration caused by an imbalance between bone resorption and formation. Although mesenchymal stem cells (MSCs) possess strong osteogenic potential, their therapeutic use is limited by poor retention, low survival, and insufficient maturation after direct injection. Here, we report an injectable, self-healing polysaccharide hydrogel designed to enhance MSC delivery and osteogenic differentiation for bone regeneration. The hydrogel forms through dynamic Schiff-base crosslinking between succinylated chitosan and aldehyde-modified hyaluronic acid, enabling rapid in situ gelation, uniform cell encapsulation, and structural recovery after mechanical disruption. The system exhibits tunable mechanical properties compatible with osteogenic mechanotransduction. Encapsulated MSCs maintained high viability, formed spheroid-like structures, and showed accelerated osteogenic maturation, evidenced by increased alkaline phosphatase activity, enhanced mineral deposition, and upregulation of osteoblast and osteocyte markers. Notably, the hydrogel microenvironment promoted osteogenic commitment even without differentiation supplements. These findings demonstrate that the hydrogel provides a mechanically instructive and biologically supportive environment for MSC-mediated bone regeneration and represents a promising minimally invasive strategy for osteoporotic bone repair.

Currently, the repair of bone defects faces multiple challenges, including insufficient angiogenesis and limited osteogenic differentiation capacity, which pose significant obstacles to treatment. In this study, a ternary composite scaffold composed of PCL-nHA-nMgO (PHM) was fabricated using 3D printing technology. After surface modification with a photothermal polydopamine (PDA) coating, a PHM@PDA composite scaffold was obtained. Metformin (Met) and PDA were loaded into GelMA hydrogels to produce GPM hydrogels. The GPM hydrogels were then packed into the PHM@PDA composite scaffolds, resulting in near-infrared region-I (NIR-I)-responsive PHM@PDA/GPM composite scaffolds. The outer GPM layer serves as a three-dimensional in vivo-like microenvironment, providing physical transport channels for cellular nutrient exchange. Upon stimulation by NIR-I, the scaffold enables the dynamic release of Mg2+ and Met, upregulates the expression of the VEGF and KDR, accelerates vascular network reconstruction, and creates a mild microenvironment conducive to cell proliferation. Furthermore, by activating the PI3K/AKT signaling pathway, it promotes the expression of osteogenesis-related factors (such as transcription factor Sp7, alkaline phosphatase, and osteocalcin), thereby accelerating the osteogenic differentiation process. In vivo animal experiments, micro-CT and tissue staining confirmed that, under near-infrared light (NIR-I) stimulation, this scaffold significantly increased bone mineral density, trabecular bone thickness, and trabecular bone count and demonstrated excellent angiogenic effects. In summary, this NIR-I-responsive composite scaffold can meet the dual requirements of reconstructing the vascular network and promoting osteogenic differentiation, enabling personalized precision therapy and offering a promising new treatment strategy for complex bone defects where vascular regeneration and osteogenic differentiation are challenging.

Because its elastic modulus is closer to that of cortical bone, polyetheretherketone (PEEK) has been considered a potential alternative to titanium for dental implants. However, the biological inertness and lack of intrinsic antibacterial activity of pristine PEEK limit its osseointegration and increase the risk of peri-implant infection. In this study, Zn-, Mg-, and Zn/Mg-implanted PEEK were prepared using a metal vapor vacuum arc ion source, with untreated PEEK as the control. Surface chemical composition, ion release, roughness, and wettability were characterized, and the osteogenic responses of MG-63 cells and antibacterial activity against Staphylococcus aureus and Fusobacterium nucleatum were evaluated. Ion implantation introduced Zn and/or Mg into the near-surface region of PEEK and was accompanied by increased surface roughness and improved hydrophilicity. Mg-containing surfaces, particularly the Zn/Mg group, promoted cell spreading, proliferation, alkaline phosphatase activity, and the expression of osteogenesis-related genes, including ALP, IBSP, and BGLAP. Antibacterial activity was more evident on Zn-containing surfaces, whereas Mg alone showed only limited antibacterial effects. Although Zn alone showed stronger inhibition of Fusobacterium nucleatum, Zn/Mg co-implantation achieved a more favorable overall balance between osteogenic and antibacterial performance. Zn/Mg co-implantation improved osteogenesis-related responses while adding antibacterial activity to PEEK surfaces, suggesting its potential as a coating-free modification strategy for PEEK-based implant materials.

Bone fracture healing requires coordinated osteoclast-mediated resorption and osteoblast-driven formation. Saposhnikovia divaricata Schischkin (SDS) is a traditional East Asian medicine with anti-inflammatory and immunomodulatory activities, but its role in bone regeneration remains unclear. This study evaluated the osteogenic potential of SDS using integrated in vitro, in vivo, and in silico approaches. Mouse-derived osteoblasts were treated with SDS, and cell viability, alkaline phosphatase (ALP) activity, and mineralization were assessed by CCK-8, ALP assay, and Alizarin Red O staining. A femoral drill-hole injury model was established in C57BL/6 mice, followed by oral administration of SDS (100, 200, or 400 mg/kg). Bone healing was evaluated by micro-computed tomography and histological analyses. SDS enhanced osteoblast viability, ALP activity, mineral deposition, and osteogenic marker expression in vitro. In vivo, SDS increased bone volume fraction and bone mineral density at 1 week after injury, accompanied by reduced TRAP-positive osteoclasts and increased osteocalcin staining. Molecular docking predicted favorable interactions between major chromone-derived constituents of SDS and the bone-related proteins RUNX2 and RANK. Collectively, these findings suggest that SDS may promote cellular processes associated with early bone repair and warrant further investigation into its mechanisms and long-term therapeutic potential.

Although the cancer treatment efficacy has significantly improved, delayed and isolated evaluation methods are difficult to prevent excessive or insufficient treatment. Therefore, the single molecule for simultaneous therapy and feedback has become a promising tool. Herein, we develop an in situ self-assembled probe (HPO-CYFF-TPP) for cascade-instructed therapy and feedback imaging. Under the dephosphorylation of alkaline phosphatase, HPO-CYFF-TPP converts to HO-CYFF-TPP and self-assembles into nanoparticles (NPs) with quenched fluorescent (FL) and opened photoacoustic (PA) signal. After laser irradiation, NPs can produce abundant singlet oxygen for photodynamic therapy (PDT) of tumor cells, which leading to the increase of intracellular viscosity. At high viscosity, NPs opens FL and further enhances PA signal. HPO-CY-TPP without self-assembly group is a control probe. HPO-CYFF-TPP or HPO-CY-TPP exhibits effective PDT against tumor cells and high tumor inhibition in tumor-bearing mice, while HPO-CYFF-TPP is more effective than HPO-CY-TPP due to the formation of NPs in situ. Importantly, HPO-CYFF-TPP or HPO-CY-TPP can monitor the viscosity during PDT on tumor cells and tumor-bearing mice for treatment feedback, while HPO-CYFF-TPP is more accurate than HPO-CY-TPP with higher FL/PA sensitivity. We envision that this self-assembled probe will be a powerful tool for tumor therapy and real-time treatment feedback imaging in the future.

Oxidative stress has a key role in paraquat (PQ)-mediated hepatic failure. Considering the known antioxidant and anti-inflammatory properties of nonselective phosphodiesterase inhibitors, this study investigated the potential of pentoxifylline (PTX) to counteract acute PQ-induced liver damage. The molecular interactions of PQ and PTX with key oxidative stress enzymes (NADPH oxidase, xanthine oxidase) were investigated by molecular docking using AutoDock 4.2.6. For in vivo studies, thirty-six mice were randomized into six groups: a normal saline control, a PQ-intoxicated group (20 mg/kg, single dose), a PTX control group (100 mg/kg for 3 days), and three treatment groups that received PTX (25, 50, or 100 mg/kg) for three consecutive days, starting one hour after PQ administration. Blood and liver tissues were collected 24 hours after the final dose for biochemical and histological analysis. The PQ administration resulted in a significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), hepatic lipid peroxidation (LPO), and nitric oxide (NO) levels, while concurrently decreasing antioxidant capacity (TAC), total thiol molecule (TTM), and superoxide dismutase (SOD) activity in liver tissue. PTX treatment effectively improved serum hepatic enzymes, LPO, TTM, and SOD levels, as corroborated by histological findings. Moreover, molecular docking analysis suggests that PTX may reduce PQ-induced oxidative stress by competitively inhibiting the FAD-binding site of xanthine oxidase, and by engaging a non-active-site region of NADPH oxidase. This study indicates PTX administration may prevent PQ-induced hepatic damage in mice, potentially by inhibiting free radical formation. Further research is needed to validate the proposed enzymes inhibition mechanisms and assess PTX's potential in acute PQ poisoning.