Xu Yan

Background: Age and sex are strong predictors of major brain disorders and are incorporated into most risk models, making it difficult to distinguish demographic discrimination from the additional information contributed by other indicators. Routine health examinations capture potentially informative physical and self-reported indicators, but whether these can add prospective risk information beyond demographic risk across multiple brain health domains is unclear.Methods: Following TRIPOD+AI, we developed an eight-item non-laboratory risk score (MD-BHRS; three physical measurements and five brief self-reported items) for first-line assessment of brain health risk in UK Biobank (n=502,204). Age and sex were deliberately excluded from the assessment and specified as the demographic baseline, so the information added by the assessment could be quantified. In 477,638 participants with complete 10-year follow-up, we assessed the increment over age and sex across five endpoints using changes in C-index, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and case capture. Transportability was evaluated on seven of the eight indicators in each cohort in two independent Chinese cohorts (grip strength unavailable in CKB; diet unavailable in CHARLS, so six were common to both): CKB (n=300,723; 10-year hospital-record stroke) and CHARLS (waves 2–4; n=15,215; self-reported stroke).Findings: The assessment added discrimination beyond age and sex at all five endpoints, with 95% CIs excluding zero. Incremental discrimination varied inversely with baseline discrimination: as the age-and-sex C-index rose from 0.5635 to 0.7792, the increment fell from +0.0604 to +0.0080. The largest increment was for late-life depression (ΔC +0.0604, 95% CI 0.0503–0.0696), a domain excluded from indicator derivation and weighting throughout. Raising the onset-age threshold from unrestricted to ≥65 years reproduced the pattern within the same domain (baseline 0.5635–0.7866; increment +0.0604–+0.0083). In CKB under the primary analysis, 10-year stroke incidence rose from 5.79% to 17.90% across score quintiles (1.75-fold age-standardised); direct projection without parameter re-estimation gave ΔAUC +0.0071 (0.0060–0.0080). In CHARLS, ΔAUC for self-reported stroke was +0.0389 (0.0221–0.0534) under fixed-bin projection and +0.0271 (0.0216–0.0322) under direct projection.Interpretation: Separating demographic risk from the assessment showed that routinely obtainable, non-laboratory indicators add prospective brain health information beyond age and sex, with the largest increment where demographic discrimination is lowest. The assessment stratified risk across multiple brain health domains, and vascular risk ranking transported to two independent Chinese cohorts, although absolute risk scales and thresholds require local derivation. Six of the eight indicators are already collected in routine health examinations; the remaining two add a brief questionnaire and a shared dynamometer.Funding: This work was supported by the National Institute of Hospital Administration, National Health Commission (YLZLXZ25G066), the Liaoning Provincial Federation of Social Sciences (2025lslzdianwtkt-c-2), the Guizhou Provincial Department of Science and Technology (GJHJZ20200731095604013), and the Liaoning Provincial Education Science Planning Leading Group Office (JG25DB480).

Infected bone defects present a major clinical challenge, requiring precise sequential therapy that transitions from antibacterial activity to bone regeneration. Piezoelectric materials can transduce external stimulation into bioelectrical cues, providing a promising controllable handle to regulate antibacterial and osteogenic processes. However, conventional piezoelectric scaffolds often lack the capacity to distinctly separate these multifunctional roles, making it difficult to meet the therapeutic needs of different stages in the treatment of infected bone defects. Here, we develop a programmable NIR-responsive periosteum scaffold featuring a Janus bilayer architecture, in which a PDA-rich photothermal side and a non-photothermal piezoelectric side enable spatially separated antibacterial and osteogenic functions. This system integrates a thermoresponsive hydrogel with a piezoelectric polyvinylidene fluoride/barium titanate (PVDF/BT) electrospun membrane, achieving three switchable functional modes: continuous NIR irradiation for antibacterial therapy, intermittent irradiation for immunomodulation, and no irradiation for mechanical support and Ca²⁺ release to facilitate mineralization. In vitro studies demonstrated effective antibacterial efficacy and enhanced pro-healing M2 macrophage polarization, while comprehensive in vivo studies in rat models of 8 mm infected bone defect models achieved over 60% bone healing rate through programmable sequential therapy at 4 weeks. This programmable multi-mode periosteum scaffold provides a promising strategy for temporally orchestrating complex microenvironments, advancing the regenerative medicine for infected bone repair.

The noninvasive regulation of photocatalytic materials for reactive oxygen species (ROS)‐based antimicrobial strategies offers a promising approach for healing infected wounds under comorbid conditions. However, most ROS‐generating photocatalytic materials rely on ultraviolet (UV) or near‐infrared (NIR) light activation, presenting challenges for convenient application and biosafety. In this study, novel zinc oxide@copper oxide (ZnO@CuO) nanofibers with a robust coaxial structure are developed that could be activated by visible light to generate ROS through photocatalytic reactions. The orderly arrangement of the inner and outer semiconductor layers enhanced the contact efficiency of p‐n heterojunctions, thereby improving the electron‐hole separation efficiency in the nanofibers. The enhanced contact efficiency of p‐n heterojunctions is the key mechanism driving the improved photocatalytic properties and increased ROS generation under visible light, offering greater ease of application and biocompatibility. The ZnO@CuO coaxial nanofibers exhibited excellent antimicrobial properties and accelerated wound healing under visible light in a methicillin‐resistant Staphylococcus aureus (MRSA)‐infected mouse skin wound model. The coaxial nanofibers controlled infection at an early stage and significantly accelerated wound healing. Even in infected diabetic wounds, a healing rate of 92.3% is achieved within 10 days. This innovative approach utilizes biosafe visible light, providing a promising solution for infected wound therapies.

Polyetheretherketone (PEEK) and its fiber-reinforced composites have been indicated as ideal post-and-cores materials due to its mechanical properties. However, the laboratory evidences of post-and-cores restored with fiber-reinforced PEEK are lacking. A total of 120 extracted mandibular premolars were treated endodontically and divided into six groups restored with different post-and-core materials (N = 20): (1) prefabricated quartz fiber-reinforced composite (QFRC), (2) polymer-infiltrated ceramic (PIC), (3) cobalt chromium (CoCr), (4) PEEK, (5) 30% glass fiber-reinforced PEEK (GFR-PEEK), and (6) 30% carbon fiber-reinforced PEEK (CFR-PEEK). Stress distribution was analyzed by finite element analysis (FEA). Then, each group was then divided into two subgroups (n = 10): static loading test and fatigue loading test. The static failure load (SFL) was analyzed by one-way analysis of variance (ANOVA) with least-significant difference (LSD) multiple comparison tests. The fatigue failure load (FFL) and cycles for failure (CFF) were evaluated by Kaplan-Meier survival analysis (P < 0.05). Groups PEEK, GFR-PEEK, and CFR-PEEK exhibited lower maximum peak principal stress and better stress distribution than Group CoCr. The SFL of Groups PEEK and QFRC did not differ from each other, and both were lower than those of Groups CoCr, GFR-PEEK, and CFR-PEEK. In the fatigue loading test, Group CoCr exhibited the best survival; however, with the progression of fatigue, the survival probabilities of Groups PEEK and its composites were close to that of Group CoCr. In all groups apart from Group CoCr, the rate of repairable failure modes was higher than that of irreparable ones. Customized post-and-cores manufactured with PEEK and its fiber-reinforced composites showed superior biomechanical performance, making them potential alternatives for the restoration of massive tooth defects. This study provides a theoretical basis for clinicians to select post-and-core materials for different root canal morphology residual roots and helps to reduce the occurrence of complications such as root fracture and post core debonding.

Background: This study aimed to evaluate stomatological students’ learning efficacy and their attitude towards Lecture-Team-Based Learning (LTBL) on topics regarding the design of removable partial dentures via in-class, online, and both in combination.Methods: Students from seven distinct grades participated in the course in their fourth academic year (Years 2015, 2016, 2017, 2018, 2019, 2020, and 2021). Students of Years 2015–2019 attended in-class LTBL, students of Year 2020 attended online LTBL, and students of Year 2021 attended the combination mode. The scores of three examinations were compared, namely, individual readiness assessment test, team readiness assurance test, and individual application test. Visual Analog Scales (VAS) were used for students to self-assess their mastery of prosthodontics knowledge before and after the course. Anonymous questionnaires were delivered to evaluate their satisfaction with LTBL via a Likert scale.Results: In each academic year, the three exam scores were significantly improved as the course progressed and VAS-post scores were significantly higher than VAS-pre scores. The three examination and VAS scores of students in Year 2020 were significantly lower than those in Years 2019 and 2021. Students were highly satisfied with the LTBL course based on the three parameters of knowledge acquisition, teamwork, and classroom atmosphere.Conclusion: Students were highly satisfied with the LTBL course and their learning performance was improved as the course progressed both in-class and online. Online LTBL could be adopted when students have to study online, while in-class LTBL could perform better when combined with video records of an online LTBL course.

Objective: To determine the critical roles of PU.1/cathepsin S activation in regulating inflammatory responses of macrophages during periodontitis.Background: Cathepsin S (CatS) is a cysteine protease and exerts important roles in the immune response. Elevated CatS has been found in the gingival tissues of periodontitis patients and is involved in alveolar bone destruction. However, the underlying mechanism of CatS‐driven IL‐6 production in periodontitis remains unclear.Methods: Western blot was applied to measure mature cathepsin S(mCatS) and IL‐6 expression in gingival tissues from periodontitis patients and RAW264.7 cells exposed to lipopolysaccharide from Porphyromonas gingivalis (P.g. LPS). Immunofluorescence was applied to confirm the localization of PU.1, and CatS in the gingival tissues of periodontitis patients. ELISA was performed to determine IL‐6 production by the P.g. LPS‐exposed RAW264.7 cells. Knockdown by shRNA was used to determine the effects of PU.1 on p38/ nuclear factor (NF)‐κB activation, mCatS expression and IL‐6 production in RAW264.7 cells.Results: The expressions mCatS and IL‐6 were significantly upregulated in gingival macrophages. In cultured RAW264.7 cells, increased mCatS and IL‐6 protein paralleled the activation of p38 and NF‐κB after exposure to P.g. LPS. CatS knockdown by shRNA significantly decreased P.g. LPS‐induced IL‐6 expression and p38/NF‐κB activation. PU.1 was significantly increased in P.g. LPS‐exposed RAW264.7 cells, and PU.1 knockdown dramatically abolished the P.g. LPS‐induced upregulation of mCatS and IL‐6 and the activation of p38 and NF‐κB. Furthermore, PU.1 and CatS colocalized in macrophages within the gingival tissues of periodontitis patients.Conclusion: PU.1‐dependent CatS drives IL‐6 production in macrophages by activating p38 and NF‐κB in periodontitis.