BackgroundThe expression of CX3CR1 is regulated by the gut microbiota and is correlated with the prognosis of sepsis in patients. However, the underlying mechanism has remained uncertain. This study aims to explore the role of gut microbiota components in regulating CX3CR1 expression and its impact on pneumonia-induced lung injury during sepsis.MethodsMice were fed a mixture of antibiotics to establish a pseudogerm-free mouse model and then infected with Klebsiella pneumoniae. Fecal microbiota transplantation (FMT) was performed on microbiota-depleted mice, and 16S rRNA gene sequencing and targeted metabolomics were used to identify the key metabolites. Flow cytometry was employed to analyze the phenotypes of natural killer (NK) cells. Butyric acid was added as a supplement for rescue. Next, NK92 cells were pretreated with butyric acid to explore the potential signaling pathways involved.ResultsIn the animal study, we revealed that the expression of CX3CR1 on NK cells depended on the intestinal microbiota and its metabolites, which were related to the survival rates of gut microbiota-depleted mice after K. pneumoniae infection. FMT increased the percentage of CX3CR1+ NK cells in the lungs of these mice, restored the disordered microbiota and metabolites, and alleviated the lung injury induced by infection. Among the metabolites, butyric acid was identified as the key metabolite and was shown to increase the proportion of CX3CR1+ NK cells and interferon (IFN)-γ secretion, reduce bacterial loads, increase lung tissue damage, and increase survival rates. In vitro, butyric acid activated the PI3K/AKT pathway in NK92 cells, promoted CX3CR1 expression, and enhanced NK cell activity and migration ability.ConclusionsWe concluded that butyric acid alleviated K. pneumoniae-induced lung injury by regulating CX3CR1+ NK cells via the PI3K/AKT pathway.

Sepsis-associated encephalopathy (SAE) is a secondary cerebral dysfunction of the central nervous system (CNS) caused by sepsis and is associated with high mortality rate and poor prognosis. It significantly affects the quality of life of survivors. The pathological mechanisms associated with SAE include dysfunction of the blood–brain barrier (BBB), activation of glial cells, ischemic injury, leukocyte transmigration, and disturbances in neurotransmitters. The mechanisms of SAE interact with and contribute to its development. Numerous studies have demonstrated that the intestinal microbiota affects not only the health of the gut but also that of other organs. Throughout the progression of SAE, alterations in the gut microbiome composition lead to the production of toxic substances that damage the intestinal barrier and enter the bloodstream. This damage negatively affects BBB permeability and initiates a cascade of neuroinflammatory responses that result in neuronal injury. Conversely, specific microbiome-derived derivatives play exhibit a neuroprotective role in regulating brain function. Therefore, gut–brain crosstalk may be a crucial factor in brain dysfunction. This paper reviews the relationship between the intestinal microbiota and SAE, aiming to explore the role of the intestinal microbiota in SAE and potential therapeutic targets.

Children constitute a key population for scar prevention and treatment because of the unique features of their skin’s physiological structure and psychosomatic growth. Currently, most approaches to pediatric scar management are formulated with reference to adult-related consensuses and guidelines, which fail to fully account for the specific characteristics of pediatric scars and their distinct needs in relation to growth and development. As a result, there are controversies regarding specific prevention and treatment strategies. To address this limitation, the Chinese Burn Association brought together domestic and international experts from disciplines relevant to the field of scar prevention and treatment. Guided by evidence-based medical evidence, drawing on domestic and international literature, and integrating the clinical experience of specialist physicians, the branch first conducted consultations on clinical issues and then organized multiple rounds of expert meetings for discussions. Eventually, the Clinical practice guideline for pediatric scar prevention and treatment (2025 edition) was developed. Focusing on 10 key aspects of pediatric scar prevention and treatment, the guideline formulates 20 recommendation opinions. It also elaborates on the remaining controversial issues in this field, aiming to provide scientific guidance for the entire process of prevention, treatment, and rehabilitation of scars in children aged 1–14 years.

Research shows that the microbiome of the skin is present as an active contributor to wound healing processes by moving past its historical infection-related function. The review investigates how commensal and probiotic bacteria affect immunomodulation while accelerating epithelial growth, together with tissue repair processes. Researchers use modern methods to link immunological concepts with material science along with synthetic biological techniques to study engineered probiotics which transform current wound treatments. The research study represents an extensive integration of recent findings concerning probiotic-mediated immunomodulatory operations and engineered approaches that improve probiotic delivery systems and their performance during skin wound healing procedures. Recent genetically engineered Lactobacillus reuteri strains that express chemokines like CXCL12 have been found to promote wound healing to an accelerated rate in animal models, and pre-clinical phases of clinical trials in the setting of diabetic foot ulcers (DFU) has demonstrated safety and therapeutic potential. Simultaneously, another live biotherapeutic product has been validated in terms of regenerative and immunomodulatory properties in animal models and in a clinical trial, a multi-cytokine-integrated strain of Lactococcus cremoris secreting FGF-2, IL-4, and CSF-1 promoted faster wound healing in diabetic mice and healed 83% of subjects in a Phase I DFU study. The range of probiotic therapies for trauma care expands due to advancements in probiotic delivery using materials and membrane vesicles derived from probiotics. This review builds a detailed framework that connects core immune functions with modern engineering methods for developing smart wound healing systems that combine engineered probiotics with bioresponsive materials and real-time monitoring systems. Engineered probiotics promise to become an alternative strategy for treating chronic wounds and infection-related complications that currently create significant medical problems.

BackgroundKeloids are a common skin fibroproliferative disease that can result in severe aesthetic and functional concerns. Pruritus and pain are the most prevalent clinical manifestations of keloids. Schwann cells (SCs) variation and neuropathy within keloids contribute to these uncomfortable sensations; however the underlying mechanisms remain unclear. This study aims to explore the potential role of fibroblasts (FBs) and SCs in pruritic and pain keloids.MethodsThe activity of FBs and SCs was investigated using single-cell RNA sequencing (scRNA-seq) data of keloids. These bioinformatics analysis results were validated through in vitro cell culture, clinical samples, and in vivo experiments. The selected molecule was confirmed to be correlated with pain and itch and was subsequently used to treat cells in order to investigate its role in keloids. The in vivo inhibition assay was performed to evaluate its therapeutic potential.ResultsOur scRNA-seq analysis identified specific types of FBs and SCs were present in higher proportions in keloids and exhibited neurogenesis-related functions. Upon conducting an interaction analysis of these two cell types, we identified a critical molecule, Midkine (MDK), which is positively correlated with the patients’ pain and itching levels. Besides, MDK treatment facilitated the proliferation of SCs and their transition to a repairing phenotype, resulting in neuronal axonogenesis. This activation of repairing SCs promoted the release of substance P from nerve fibers, leading to clinical symptoms of pain and pruritus in keloid patients. Targeting MDK effectively reduces abnormal Schwann cell proliferation and subsequently inhibits the secretion of neuropeptides that trigger pain and pruritus.ConclusionsOur study uncovered the interaction between FBs and SCs in the development of keloidal pain and pruritus, offering a novel therapeutic strategy to alleviate the distressing symptoms of keloids.

BackgroundCirculating lactate is associated with poor prognosis in sepsis-induced acute lung injury (S-ALI). However, it remains unclear whether microvascular dysfunction, a hallmark of S-ALI, is related to circulating lactate levels and what the underlying mechanisms are. The aim of this study was to investigate the role and mechanisms of lactate in pulmonary microvascular dysfunction in S-ALI.MethodsThe effects of lactate on pulmonary microvascular function were assessed in a septic mouse model. Primary mouse pulmonary microvascular endothelial cells (MPMVECs) were isolated to evaluate the impact of lactate on MPMVEC permeability. Transcriptomic sequencing was employed to investigate the involvement of lactate in regulating MPMVEC ferroptosis, and the results were validated by in vivo and in vitro experiments. Histone lactylation was identified as a regulator of lipid peroxidation and iron homeostasis dysregulation in lactate-induced ferroptosis in MPMVECs. Gain- and loss-of-function approaches were used to assess the role of histone lactylation in regulating ferroptosis and pulmonary microvascular dysfunction. Correlations between serum lactate and ferroptosis levels and their associations with patient prognosis were investigated in patients with sepsis-associated acute respiratory distress syndrome (S-ARDS).ResultsThe mouse serum lactate level reached a peak at 18 h after caecal ligation and puncture surgery. Elevated lactate levels during sepsis promoted ferroptosis in PMVECs, leading to increased pulmonary vascular permeability and exacerbation of ALI. Mechanistically, lactate increased the lactylation of histone H3 at K18 (H3K18la), which promoted ACSL4 transcription in MPMVECs, resulting in excessive lipid peroxidation. Additionally, elevated H3K18la promoted LC3 transcription and indirectly upregulated NCOA4 expression through the transcription factor GATA2, facilitating ferritinophagy. Serum lactate levels were significantly correlated with ferroptosis levels in S-ARDS patients, and both were associated with poor patient prognosis.ConclusionsThis study revealed a critical role for high lactate-derived histone lactylation in PMVEC ferroptosis and the progression of ALI during sepsis, providing new insights and potential therapeutic mechanisms.

BackgroundSepsis-associated acute lung injury (ALI) is driven by endothelial barrier dysfunction and endothelial–mesenchymal transition (EndoMT), mediated by TGF-β1/SMAD3 signaling. Despite the therapeutic potential of SMAD3, current inhibitors face limitations. As endogenous small molecules that are closely related to physiological regulatory processes, microRNAs (miRNAs) have more potential research value for regulating SMAD3. Therefore, this study aimed to investigate the protective effect and molecular mechanism of a key miRNA targeting SMAD3 in sepsis-ALI.MethodsScreening multiple databases revealed that miR-23b-3p was the sole miRNA targeting SMAD3. Lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs) and cecal ligation/puncture (CLP) mice were used to model sepsis. Lentivirus was used to construct stable strains. The functional performance and mechanism were verified by key techniques, including dual-luciferase assays, rescue experiments, reverse transcription–quantitative polymerase chain reaction (qPCR)/Western blotting, monocyte adhesion/permeability assays, and histopathology.ResultsIn LPS-stimulated HUVECs, miR-23b-3p downregulation correlated with TGF-β1/SMAD3 activation, EndoMT progression, and barrier disruption. miR-23b-3p overexpression reversed these effects by restoring the expression of junctional proteins and suppressing the expression of mesenchymal markers. Chromatin isolation by RNA purification–qPCR, RNA pull-down, and dual-luciferase assays confirmed the direct miR-23b-3p–SMAD3 3′UTR interaction. Rescue experiments demonstrated that miR-23b-3p counteracts TGF-β1/SMAD3 hyperactivation. In CLP mice, intratracheal agomiR-23b-3p attenuated lung injury, normalized alveolar architecture, and reduced vascular leakage by suppressing endothelial Smad3 upregulation.ConclusionmiR-23b-3p is a SMAD3-targeting regulator that inhibits EndoMT and repairs endothelial barrier integrity. Mechanistically, miR-23b-3p preserves endothelial homeostasis via SMAD3-dependent EndoMT inhibition. This study provides mechanistic insights and a miRNA-based therapeutic strategy for sepsis-induced ALI.

BackgroundBurns and wounds cause significant physical and psychological distress, with pain being a major barrier to recovery. Traditional pharmacological methods for pain management carry risks such as side effects and dependency. Virtual reality has emerged as a non-invasive, distraction-based technique that may reduce pain perception during wound care by modulating sensory input.MethodsThis systematic review and meta-analysis, conducted following PRISMA guidelines and registered in PROSPERO (CRD420251005004), assessed the effectiveness of virtual reality in managing pain during wound and burn care. A comprehensive search of PubMed, Web of Science, Scopus, and Cochrane Library was conducted in March 2025. Eligible studies included randomized controlled trials comparing virtual reality interventions to standard care or other distraction techniques in patients with active wounds or burns. Data on pain outcomes, as well as physiological indicators, were extracted. Meta-analysis was performed using a random-effects model and Hedges’ g as the effect size estimator. The analysis was performed with SPSS version 29 and the risk of bias was assessed using the RoB 2.0 tool.ResultsEleven studies (n = 936 participants) were included, with diverse wound types (burns, surgical, limb injuries) and virtual reality setups, predominantly immersive. The overall pooled effect showed a statistically significant reduction in pain using virtual reality (g = −1.528; 95% CI: −2.259 to −0.797; p < 0.001), indicating a moderate-to-large effect. Subgroup analysis revealed that virtual reality was most effective in children (g = −2.348), followed by adolescents (g = −0.538), while adults showed a non-significant effect (g = −1.453). High heterogeneity (I2 = 95.5%) was explained by age group differences and sensitivity analysis. No significant publication bias was detected.ConclusionsVirtual reality appears to be a promising tool for reducing procedural pain, particularly in children with wounds or burns. Its efficacy in adolescents is moderate, while evidence in adults remains inconclusive. Given its non-pharmacological nature and potential to improve patient experience, virtual reality warrants broader implementation and further age-specific research in wound care settings.

Fibrosis is a pathological process marked by excessive extracellular matrix deposition, ultimately resulting in irreversible tissue damage. This aberrant process manifests across multiple organs, including the skin, lung, cardiovascular system, liver, kidneys, and eyes. However, the underlying mechanisms driving tissue fibrosis remain incompletely elucidated, and effective therapeutics are still lacking. In recent years, increasing attention has turned toward the contribution of mechanical signals to fibrotic progression. Within this context, the Piezo family of mechanosensitive ion channels, recently identified as key mediators of mechanotransduction, has emerged as a compelling focus of investigation in diverse pathological settings. This review summarizes current evidence on the central role of Piezo1 in orchestrating fibrotic responses across various tissues. Moreover, we examine the application of Piezo1 modulators in experimental models and their potential to modulate fibrosis, thereby informing the development of novel antifibrotic interventions. By integrating mechanobiological insights into the study of fibrosis, this work highlights promising translational avenues for advancing therapeutic strategies and improving clinical outcomes in fibrotic disease.

BackgroundSepsis-induced myocardial injury (SIMI) is recognized as a severe complication of sepsis which characterized by a high mortality rate. Notably, the pathophysiology of SIMI involves complex mechanisms, including dysregulation of autophagy. Exosomes contribute to crucial biological processes during sepsis， modulating autophagy processes and facilitating communication between cells. PIWI-interacting RNAs (piRNAs) are highly expressed in myocardial tissue and exert cardiovascular regulation properties. Therefore, we investigated the role of macrophage-derived exosome piRNAs, specifically piR-50971, in SIMI and their impact on autophagy through N6-Methyladenosine (m6A) modification of mTOR.MethodsA cecal ligation and puncture model was established to mimic the pathophysiological features of SIMI. Plasma exosomes were isolated and sequenced to characterize the expression of sepsis-related piRNAs. Bioinformatics analysis was employed to predict the potential regulatory mechanisms involving piR-50971. To investigate the direct interaction between piR-50971 and mTOR, a dual-luciferase reporter assay was conducted. Moreover, a methylated RNA immunoprecipitation assay was conducted to verify the involvement of piR-50971 in the m6A methylation modification of mTOR transcripts. Additionally, the m6A methylation level was assessed using dot blotting. Left ventricular ejection fraction and left ventricular fractional shortening of rats were detected by animal echocardiography. Transmission electron microscopy was used to detect autophagy flux in the myocardial tissue of rats in vivo. Cardiac enzymes were detected using a biochemical analyzer.ResultspiR-50971 was identified as a key piRNA upregulated in plasma exosomes during SIMI, which was correlated with the inhibition of autophagy. Increased macrophage infiltration was observed in the myocardium of rats with SIMI. Additionally, cardiomyocytes treated with macrophage-derived exosomes exhibited impaired autophagy. RNA binding protein immunoprecipitation assay demonstrated an interaction between Wilms’ tumor 1-associated protein (WTAP) protein and mTOR mRNA. piR-50971 interacted with mTOR, leading to increased m6A modification through the regulation of WTAP and subsequent suppression of autophagy. Notably, this regulation upregulated mTOR translation, thereby inhibiting autophagy and exacerbating myocardial injury under septic conditions. In vivo experiments demonstrated that piR-50971 inhibition ameliorated myocardial injury and improved autophagy in rats with SIMI.ConclusionsOur findings reveal a novel mechanism by which macrophage-derived exosome piR-50971 contributes to SIMI by suppressing autophagy via m6A modification of mTOR. Overall, our results implicate piR-50971 as a potential target for therapeutic intervention in sepsis-related myocardial dysfunction.