Peking University Stomatological Hospital

Clinical management of periodontitis requires addressing both bacterial infection and the deficient osteogenic microenvironment to optimize tissue regeneration. Electroactive biomaterials have demonstrated promise in bone regeneration, but are insufficient to enduringly synergize antibacterial properties with optimal immunomodulatory and tissue remodeling effects within the complex inflammatory microenvironment. Here, this study proposes an efficient, dynamic magnetoelectric conversion-based therapeutic strategy, which integrates antibacterial activity and immunomodulation to optimize periodontal tissue regeneration. Magnetic field-sensitive CoFe2O4-BiFeO3 nanoparticles (CFO-BFO NPs) are developed as a pioneering magnetoelectric biomaterial for periodontitis therapy. Magnetoelectric CFO-BFO NPs significantly enhance osteogenesis of periodontal ligament stem cells (PDLSCs) and exhibit potent antibacterial activity in vitro. Crucially, magnetoelectric coupling stimulation can program macrophage from the M1 to M2 phenotype via the PI3K-Akt signaling pathway, thereby enhancing osteogenesis. Moreover, magnetoelectric CFO-BFO NPs can also alleviate tissue inflammation and accelerate infected periodontal bone regeneration in Porphyromonas gingivalis (P. gingivalis)-mediated periodontitis mice models. After 4 weeks of treatment, the bone volume fraction (BV/TV) in the magnetoelectric CFO-BFO NPs group approached healthy levels. This study pioneers the application of magnetoelectric coupling materials for periodontitis treatment and provides a novel strategy for enhancing the therapeutic effects of electroactive biomaterials on periodontitis.

Evaluating the potential toxicity of pharmaceuticals and biomaterials to ectodermal epithelia, such as the oral mucosa and skin, is indispensable in pre-clinical assessments. However, this remains a challenge primarily owing to the lack of physiologically relevant and accurate screening models. To address this need, we referred to developmental patterns of the ectodermal epithelium in vivo and adopted the strategic downregulation of the TGF-β signaling pathway in organoid fabrication. Our novel ectodermal epithelial organoids (EEOs) recapitulate the cellular and histological complexities of native epithelial tissues and improve fabrication efficiency. EEOs can accurately capture essential barrier components, including the stratum corneum and intercellular junctions, which are crucial for maintaining epithelial barrier integrity. Validation studies revealed that EEOs are capable of modeling the dose-dependent cytotoxic effects of pharmaceuticals on the oral mucosa and identifying previously undetectable nanomaterial-induced damage to intercellular junctions. These findings indicate that the model system is a robust platform for epithelial barrier stimulation tests, and that this technology is poised to transform pre-clinical assessment paradigms by enabling more accurate toxicity prediction and accelerating the development of safer pharmaceuticals and biomaterials.

With the rapid progress of Multimodal LLMs, evaluating their mathematical reasoning capabilities has become an increasingly important research direction. In particular, visual-textual mathematical reasoning serves as a key indicator of an MLLM's ability to comprehend and solve complex, multi-step quantitative problems. While existing benchmarks such as MathVista and MathVerse have advanced the evaluation of multimodal math proficiency, they primarily rely on digitally rendered content and fall short in capturing the complexity of real-world scenarios. To bridge this gap, we introduce MathScape, a novel benchmark focused on assessing MLLMs' reasoning ability in realistic mathematical contexts. MathScape comprises 1,369 high-quality math problems paired with human-captured real-world images, closely reflecting the challenges encountered in practical educational settings. We conduct a thorough multi-dimensional evaluation across nine leading closed-source MLLMs, three open-source MLLMs with over 20 billion parameters, and seven smaller-scale MLLMs. Our results show that even SOTA models struggle with real-world math tasks, lagging behind human performance-highlighting critical limitations in current model capabilities. Moreover, we find that strong performance on synthetic or digitally rendered images does not guarantee similar effectiveness on real-world tasks. This underscores the necessity of MathScape in the next stage of multimodal mathematical reasoning.

Introduction and Objective: Glucokinase (GCK) maintains glucose homeostasis. Gck heterozygous inactivation mutation leads to maturity onset diabetes of the young 2 with clinical features of mild hyperglycemia and low insulin levels, and the incidence of microvascular complications is significantly low. ATP-Sensitive K+ Channel (K-ATP) is vital in regulating insulin secretion. Inactivated variants of Abcc8 encoding SUR1 subunit of the K-ATP can lead to hyperinsulinemia and kidney injury. Our study aims to elucidate the role of GCK and hyperinsulinemia in the development of kidney injury. Methods: Gck knockout mouse (Gck+/-) and Abcc8 R306C mutation mouse (Abcc8mut/+) were constructed using CRISPR-Cas9. After hybridization, we obtained Gck knockout and Abcc8 mutant heterozygote mouse (G&A), observed metabolic phenotype and evaluated the kidney injury. Results: Gck +/- mice showed hyperglycemia and impaired glucose toleranc. Abcc8mut/+ mice showed normal blood sugar, elevated fasting insulin, and significant kidney injury. Compared to Abcc8mut/+ mice, G&A mice developed elevated fasting blood glucose but lower insulin levels, and alleviated kidney injury. (Figure 1) Conclusion: Hyperinsulinemia leads to severe renal injury independent of hyperglycemia. Suppression of glucokinase on the basis of hyperinsulinemia can partially alleviate renal injury. Disclosure H. Lian: None. C. Yang: None. L. Ji: None. X. Han: None. Funding National Natural Science Foundation of China (82170814)