Drug-resistant bacterial infections in chronic wounds remain a critical challenge, particularly under persistent inflammation. Here, we report the de novo design of high-entropy alloy (HEA, PtFeCuCoNi)-based Janus artificial enzymes with pH-gated redox biocatalysis for sequential antibacterial and repair functions. The multi-metal synergy stabilizes the d -band center, allowing acidic oxidase/peroxidase-like activity and neutral antioxidase-like activity. In infection, the enzymes generate bactericidal reactive oxygen species (ROS) to eliminate methicillin-resistant Staphylococcus aureus ( MRSA ) and biofilms at ultralow concentrations (8 μg/mL). During healing, they scavenge ROS, alleviate oxidative injury and support cellular proliferation. In MRSA -infected wounds, this dual-action system clears bacteria and then accelerates regeneration through enhanced neovascularization and matrix remodeling. Mechanistic analyses reveal PFKFB3 -mediated metabolic reprogramming, suppression of pro-inflammatory cytokines, and macrophage polarization toward the M2 phenotype. Integrating pH-gated antimicrobial and immunomodulatory repair within one nanoplatform, this strategy addresses the conflicting demands of infection control and tissue healing.

Zero‐inflated Poisson (ZIP) and negative binomial (ZINB) models are widely used to model zero‐inflated count responses. These models extend the Poisson and negative binomial (NB) to address excessive zeros in the count response. By adding a degenerate distribution centered at 0 and interpreting it as describing a non‐risk group in the population, the ZIP (ZINB) models a two‐component population mixture. As in applications of Poisson and NB, the key difference between ZIP and ZINB is the allowance for overdispersion by the ZINB in its NB component in modeling the count response for the at‐risk group. Overdispersion arising in practice too often does not follow the NB, and applications of ZINB to such data yield invalid inference. If sources of overdispersion are known, other parametric models may be used to directly model the overdispersion. Such models too are subject to assumed distributions. Further, this approach may not be applicable if information about the sources of overdispersion is unavailable.In this paper, we propose a distribution‐free alternative and compare its performance with these popular parametric models as well as a moment‐based approach proposed by Yuet al.[Statistics in Medicine2013;32: 2390–2405]. Like the generalized estimating equations, the proposed approach requires no elaborate distribution assumptions. Compared with the approach of Yuet al., it is more robust to overdispersed zero‐inflated responses. We illustrate our approach with both simulated and real study data. Copyright © 2015 John Wiley & Sons, Ltd.

Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation, apoptosis, and differentiation, with the Wnt/β-catenin signaling pathway playing a pivotal role. However, the comprehensive regulatory mechanisms of Wnt/β-catenin signaling remain largely unclear. Smad7, a key antagonist of the TGF-β superfamily, is essential for maintaining tissue homeostasis and ensuring proper cellular function. Our previous study has demonstrated that Smad7 knockout in mice leads to impaired proliferative property of tooth germ cells, resulting in small molars. Here, we identified SMAD7 expression in human dental papilla and dental pulp, colocalized with β-CATENIN and cell proliferation-related proteins. RNA sequencing analysis revealed a significant reduction in Wnt signaling activity in Smad7 -deficient mouse tooth germs. Using lentivirus transfection, we established SMAD7 -knockdown human dental papilla stem cells, which manifested remarkably blunt proliferation rate, along with diminished Wnt signaling activity. In vivo transplantation investigations further revealed the indispensable role of SMAD7 in dentin formation. Mechanistically, we revealed that β-CATENIN interacts with P-SMAD2/3 and SMAD7 through co-immunoprecipitation and yeast two-hybrid assays. Inhibition of TGF-β pathway or disruption of SMAD7/β-CATENIN transcription factor complex formation potently impacted Wnt/β-catenin activities, indicating both direct and indirect regulatory mechanisms. These findings highlight the critical role of SMAD7 in the proliferation and differentiation of human dental stem cells, which could contribute to dental tissue regeneration and engineering.

Regeneration of the dentin-pulp complex is essential for tooth integrity and function. However, the inherent cell heterogeneity limits our understanding of lineage-specific subsets critical for efficient odontogenesis and regenerative outcomes. Here, we demonstrated that CD24⁺ human dental papilla cells (hDPCs) exhibit robust odontogenic differentiation capacity and drive coordinated regeneration of well-vascularized pulp and structurally integrated dentin tissues in both ectopic murine and preclinical in situ minipig models, significantly outperforming conventional dental pulp stem cells. Mechanistically, we delineate a BMP2/SIRT1 axis where elevated BMP signaling sustains SIRT1 expression and promotes mitochondrial metabolism and odontogenic capacity. Furthermore, BMP signaling induces VEGF expression, enhancing neovascularization via paracrine effects. CD24 is also a downstream marker of BMP signaling, though it does not directly mediate differentiation. Together, CD24⁺ hDPCs represent a regeneration-competent subpopulation that integrates mitochondrial metabolism and signaling crosstalk to enable coordinated dentin-pulp regeneration, representing a translationally relevant cell source for dental tissue engineering.