Non-healing wounds are an intractable problem of major clinical relevance. Evidence has shown that dermal papilla cells (DPCs) may regulate the wound-healing process by secreting extracellular vesicles (EVs). However, low isolation efficiency and restricted cell viability hinder the applications of DPC-EVs in wound healing. In this study, we aimed to develop novel 3D-DPC spheroids (tdDPCs) based on self-feeder 3D culture and to evaluate the roles of tdDPC-EVs in stimulating angiogenesis and skin wound healing. To address the current limitations of DPC-EVs, we previously developed a self-feeder 3D culture method to construct tdDPCs. DPCs and tdDPCs were identified using immunofluorescence staining and flow cytometry. Subsequently, we extracted EVs from the cells and compared the effects of DPC-EVs and tdDPC-EVs on human umbilical vein endothelial cells (HUVECs) in vitro using immunofluorescence staining, a scratch-wound assay and a Transwell assay. We simultaneously established a murine model of full-thickness skin injury and evaluated the effects of DPC-EVs and tdDPC-EVs on wound-healing efficiency in vivo using laser Doppler, as well as hematoxylin and eosin, Masson, CD31 and α-SMA staining. To elucidate the underlying mechanism, we conducted RNA sequencing (RNA-seq) of tdDPC-EV- and phosphate-buffered saline-treated HUVECs. To validate the RNA-seq data, we constructed knockdown and overexpression vectors of Krüppel-like factor 4 (KLF4). Western blotting, a scratch-wound assay, a Transwell assay and a tubule-formation test were performed to detect the protein expression, cell migration and lumen-formation ability of KLF4 and vascular endothelial growth factor A (VEGFA) in HUVECs incubated with tdDPC-EVs after KLF4 knockdown or overexpression. Dual-luciferase reporter gene assays were conducted to verify the activation effect of KLF4 on VEGFA. We successfully cultured tdDPCs and extracted EVs from DPCs and tdDPCs. The tdDPC-EVs significantly promoted the proliferation, lumen formation and migration of HUVECs. Unlike DPC-EVs, tdDPC-EVs exhibited significant advantages in terms of promoting angiogenesis, accelerating wound healing and enhancing wound-healing efficiency both in vitro and in vivo. Bioinformatics analysis and further functional experiments verified that the tdDPC-EV-regulated KLF4/VEGFA axis is pivotal in accelerating wound healing. 3D cultivation can be utilized as an innovative optimization strategy to effectively develop DPC-derived EVs for the treatment of skin wounds. tdDPC-EVs significantly enhance wound healing via KLF4/VEGFA-driven angiogenesis.

This study sought to perform a meta-analysis of the risk factors for the complications of oral and maxillofacial space infections (OMSI), aiming to provide insights for identifying cases at elevated risk and facilitating the further clinical prevention strategies. A comprehensive search of international (PubMed, Web of Science, Cochrane Library and CTdatabase) and Chinese (CNKI, Wanfang and VIP) databases was conducted through August 2024. The identified literature was assessed for quality, and meta-analysis was conducted using RevMan 5.0 software. A total of 12 studies were included, comprising 2,205 participants, among whom 417 experienced complications, yielding a complication rate of 18.91%. Meta-analysis identified the following as significant risk factors for OMSI-associated complications: age [odds ratio(OR): 1.59; 95% confidence interval(CI): 1.33–1.90], body temperature upon admission (OR: 2.97; 95% CI: 2.03–4.33), diabetes mellitus (OR: 2.70; 95% CI: 2.03–3.60), multiple space infections (OR: 2.90; 95% CI: 1.98–4.25), white blood cell (WBC) count (OR: 1.86; 95% CI: 1.48–2.35), neutrophil (NEUT) count (OR: 2.50; 95% CI: 1.60–3.93), and C-reactive protein (CRP) level (OR: 1.01; 95% CI: 1.00–1.01). The incidence of OMSI-associated complications is high. Independent risk factors include advanced age, elevated body temperature on admission, diabetes mellitus, involvement of multiple anatomical spaces, and increased levels of WBC, NEUT, and CRP. These factors may exacerbate infection severity, amplifying the risks of complications such as mediastinitis or sepsis. Therefore, it is crucial to closely monitor patients with these risk factors and implement early interventions to attenuate the incidence of OMSI-associated complications and enhance patient outcomes. While our findings provide valuable insights into risk factors for OMSI-related complications, several limitations—including the predominance of retrospective study designs, heterogeneity in diagnostic criteria and biomarker thresholds—may affect generalizability. Future large-scale and high-quality studies are needed to further validate these findings. Not applicable.

Hypertrophic scar (HS) is a fibroproliferative disorder characterized by fibroblast hyperactivation and aberrant extracellular matrix deposition. This study identifies macrophage-derived lactate as a key mediator of fibroblast phenotypic remodeling via monocarboxylate transporter 1 (MCT1)-mediated histone H3 lysine 23 lactylation (H3K23la) in HS. Elevated lactate levels and MCT1 expression were observed in HS tissues, with macrophages in stiff mechanical microenvironments identified as the primary lactate source. Lactate influx through MCT1 upregulated H3K23la, thereby promoting transcriptional activation of profibrotic genes HEY2 and COL11A1. Mechanistically, HEY2 activated YAP1/SMAD2 signaling, while COL11A1 stabilized MCT1 to enhance lactate transport, forming a positive loop that amplified fibrosis. Fibroblast-specific Mct1 deletion or pharmacological inhibition of Mct1 in male mice reduced collagen deposition, accelerated wound healing, and attenuated scar formation. Our findings redefine the macrophage-fibroblast crosstalk in HS and establish the MCT1-H3K23la-HEY2/COL11A1 axis, particularly its self-reinforcing loop, as a novel therapeutic target.

Adipose-derived stem cells (ADSCs) hold significant potential in regenerative medicine, yet their therapeutic efficacy is often limited by low survival rates in the presence of oxidative stress. While mechanical cues regulate cytoskeletal dynamics, their roles in modulating cellular metabolism and mitochondrial adaptation remain unexplored. This study aimed to elucidate how physiological-range cyclic mechanical stretching (CMS) enhances ADSCs resistance to oxidative stress through the Piezo1/ATP signaling axis, thereby establishing an innovative strategy for developing antioxidant-functionalized stem cell therapies.

Gas explosion injuries are a severe form of trauma with high incidence and mortality rates, both in daily life and industrial settings. Acute lung injury (ALI) is one of the most serious complications of gas explosion injuries and is a leading cause of mortality in such cases. However, the mechanisms underlying gas explosion-induced ALI have not been fully elucidated, and the treatment process consumes a significant amount of medical resources. Therefore, it is crucial to conduct research on the injury mechanisms of gas explosion injuries, especially the mechanisms of gas explosion-induced ALI, which can effectively improve the treatment rate of this condition. In this study, we analyzed the relationship between a novel form of cell death, ferroptosis, and gas explosion-induced ALI, and explored its specific mechanisms. We established ALI rat model by Shock tube biological injury system, and detected lung injury-related indexes as well as ferroptosis related indexes, such as glutathione peroxidase 4（GPX4）, 4-hydroxynonenal（4HNE）, Malondialdehyde（MDA）, Fe2 + . We also investigated the therapeutic effects of the ferroptosis inhibitor ferrostatin-1 (Fer-1) in ALI induced by gas explosion, as well as its specific mechanisms of action. A rat ALI model by gas explosion was successfully established. After the gas explosion treatment, we observed that the systemic inflammatory reaction of rats was increased, and lung function, liver function, kidney function and cardiac function were damaged to different degrees. The inflammatory infiltration in the lung tissue was more severe, and the degree of lung injury and pulmonary edema increased. The ferroptosis markers GPX4 was decreased, while the levels of 4HNE, MDA and Fe2 + were increased. Treatment with Fer-1 significantly ameliorated gas explosion ALI damage and down-regulated the expression level of ferroptosis. Gas explosion-induced ALI in rats is characterized by enhanced inflammatory responses and reduced antioxidant capacity in lung tissues. The specific mechanism of injury involves ferroptosis. Fer-1 has been shown to mitigate the severity of ALI caused by gas explosion by suppressing ferroptosis expression levels in lung tissues via the Nrf2/GPX4 axis.

Background: Diagnosing sternal wound infection (SWI) following median sternotomy remains laborious and troublesome, resulting in high mortality rates and great harm to patients. Early intervention and prevention are critical and challenging. This study aimed to develop a simple risk prediction model to identify high-risk populations of SWI and to guide examination programs and intervention strategies. Methods: A retrospective analysis was conducted on the clinical data obtained from 6715 patients who underwent median sternotomy between January 2016 and December 2020. The least absolute shrink and selection operator (LASSO) regression method selected the optimal subset of predictors, and multivariate logistic regression helped screen the significant factors. The nomogram model was built based on all significant factors. Area under the curve (AUC), calibration curve and decision curve analysis (DCA) were used to assess the model's performance. Results: LASSO regression analysis selected an optimal subset containing nine predictors that were all statistically significant in multivariate logistic regression analysis. Independent risk factors of SWI included female [odds ratio (OR) = 3.405, 95% confidence interval (CI) = 2.535–4.573], chronic obstructive pulmonary disease (OR = 4.679, 95% CI = 2.916–7.508), drinking (OR = 2.025, 95% CI = 1.437–2.855), smoking (OR = 7.059, 95% CI = 5.034–9.898), re-operation (OR = 3.235, 95% CI = 1.087–9.623), heart failure (OR = 1.555, 95% CI = 1.200–2.016) and repeated endotracheal intubation (OR = 1.975, 95% CI = 1.405–2.774). Protective factors included bone wax (OR = 0.674, 95% CI = 0.538–0.843) and chest physiotherapy (OR = 0.446, 95% CI = 0.248–0.802). The AUC of the nomogram was 0.770 (95% CI = 0.745–0.795) with relatively good sensitivity (0.798) and accuracy (0.620), exhibiting moderately good discernment. The model also showed an excellent fitting degree on the calibration curve. Finally, the DCA presented a remarkable net benefit. Conclusions: A visual and convenient nomogram-based risk calculator built on disease-associated predictors might help clinicians with the early identification of high-risk patients of SWI and timely intervention.