BackgroundPANoptosis is a comprehensive form of cell death regulation that involves the interplay of pyroptosis, apoptosis, and necrosis. As a key regulator of PANoptosis, TAK1 plays a crucial role in multiple cell death pathways. However, its specific mechanism in the process of diabetic wound (DW) healing remains unclear. This study aimed to explore the role of TAK1 in regulating PANoptosis and its impact on DW healing.MethodsWe used immunofluorescence, TUNEL staining, and EthD-III staining to analyse the relationship between TAK1 activity and PANoptosis. RNA sequencing was used to investigate the regulatory role of TAK1 and the NF-κB pathway under high-glucose conditions. Additionally, molecular docking and coimmunoprecipitation experiments were performed to verify the interaction between TAK1 and p65. Finally, a mouse model was used to study the effects of TAK1 knockdown on wound healing.ResultsOur findings revealed that PANoptosis is significantly present in DW, with markedly upregulated TAK1 expression under high-glucose conditions. The inhibition of TAK1 expression significantly reduced cell death and promoted cell proliferation and migration. Mechanistically, TAK1 interacts with p65 through the NF-κB pathway, activating downstream signals that exacerbate cell damage in a high-glucose environment. TAK1 knockdown significantly suppressed PANoptosis, promoted microvascular and collagen formation, reduced inflammation, and further accelerated wound healing.ConclusionTAK1 regulates PANoptosis by activating the NF-κB signalling pathway, thereby playing a crucial role in DW healing. Inhibiting TAK1 may represent a potential strategy to improve wound healing, with significant potential for clinical application.

Sepsis is a life-threatening condition characterized by profound immune dysregulation and organ dysfunction. The functional impairment of dendritic cells (DCs) in septic patients is well-documented and contributes significantly to sepsis-induced immunosuppression; yet the underlying mechanisms remain poorly understood. Tripartite motif 13 (TRIM13) has been identified as an immune regulator with predominantly suppressive effects. Here, we aimed to investigate the potential role of TRIM13 restriction in promoting the DC-mediated immune response during sepsis. Splenic DCs were isolated from wild-type (WT) and DC-specific Trim13 conditional knockout (Trim13 cKO) mice post-cecum ligation and puncture (CLP). These cells were subsequently analyzed by proteomics, immunoblotting, flow cytometry, and transmission electron microscopy (TEM). DC2.4 cells were infected with either Trim13 shRNA or a Trim13 overexpression lentiviral vector and treated with different pharmacological inhibitors. Protein interactions were examined via coimmunoprecipitation (Co-IP) and confocal microscopy. Cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA), and organ lesions were assessed through hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) for CD45, and TUNEL assays. TRIM13 expression was rapidly upregulated in DCs following septic challenge. Deletion of TRIM13 in DCs disrupted the endoplasmic reticulum (ER)-associated degradation (ERAD) and ER-selective autophagy (ER-phagy)-mediated degradation of the stimulator of interferon genes (STING), leading to sustained STING activation and enhanced DC function. STING signaling promoted the p-IRF3 nuclear translocation, NLRP3 inflammasome priming, and transient DC pyroptosis, thereby exacerbating hyperinflammation in the acute phase of sepsis. Over the longer term, prolonged STING signaling inhibited DCs from adopting the immunosuppressive phenotype and promoting the DC-mediated immune response. Ultimately, TRIM13 deficiency in DCs ameliorated sepsis-induced immunosuppression, preserved organ function in the late phase of sepsis, and reduced overall mortality in septic mice. TRIM13 acts as a key negative regulator of DC function during sepsis. Restricting TRIM13 sustains DC immunostimulatory property, counteracts sepsis-induced immunosuppression, and improves survival outcomes. These findings highlight TRIM13 as a potential therapeutic target for sepsis management.

Tendon–bone interface injuries, such as rotator cuff tears and anterior cruciate ligament ruptures, remain challenging due to the enthesis’s complex structure and poor healing capacity. Conventional repair often fails to restore the fibrocartilaginous transition, causing mismatched integration and high retear rates. Biomaterial-based scaffolds provide biomechanical support and bioactive regulation, showing great promise for regeneration. Recent advances span natural polymers, synthetic polymers, bioceramics, and composites, with designs evolving from monophasic to multiphasic, gradient-based, and functionalized scaffolds. Emerging strategies emphasize immunomodulation, bio-signal delivery, and physical responsiveness, establishing a structure–signal–function paradigm to guide multi-tissue integration. However, translation faces major barriers, including inadequate animal models, manufacturing and scalability challenges, long-term safety concerns, and regulatory complexity, as well as the need to balance personalization with cost. Future directions point to intelligent biomaterials, AI-driven design, and integrated translational frameworks to bridge preclinical research and clinical application. Overall, advanced scaffold engineering offers transformative potential for functional tendon–bone regeneration, but successful translation will depend on close collaboration among biology, materials science, engineering, and medicine.

Trauma represents a significant global health issue, often resulting in devastating and long-lasting effects on the body throughout a patient's life. Organ inflammation and dysfunction caused by trauma present additional challenges for clinicians. Therefore, understanding the cellular and molecular mechanisms of post-trauma systemic inflammation and organ dysfunction is essential for improving the management of trauma. This review aims to summarize current updates on the findings that explore different mechanisms of trauma-induced inflammation and organ dysfunction, highlighting the recent understanding of the vital roles of damage-associated molecular patterns, trauma-induced cell death, organ-organ cross-talk pathways, and the gut microbiota in the development and progression of post-traumatic systemic inflammation. We also discuss new approaches that can potentially guide further investigations of trauma diagnosis, treatment, and prognosis.

Diabetic foot (DF) is a prevalent and significant complication of diabetes mellitus. The primary factors that contribute to amputation and mortality in DF patients are multifaceted and include foot deformities, ulcers, ischemia, and potential concurrent infections. To further standardize DF prevention and treatment in China, improve consistency in DF diagnosis and treatment, and promote the development of a specialized tiered care system, the Chinese Burn Association, the Yangtze River Delta Integrated Diabetic Foot Alliance, and the Editorial Committee of the Chinese Journal of Burns and Wound Repair established a multidisciplinary expert team. The team identified clinical issues concerning the diagnosis, treatment, and prevention of DF via the population, interventions, comparisons, outcomes framework, assessed the quality of relevant evidence using the Grading of Recommendations Assessment, Development and Evaluation system, and ultimately formulated a consensus titled “Practical Guidelines for the Prevention and Management of Diabetic Foot Disease in China.” The guidelines include 46 recommendations that address comprehensive medical assessment; internal medical treatments, including treatments related to blood glucose, blood pressure, and blood lipid control; antithrombotic and anti-infection therapy; perioperative risk assessment and management; surgical interventions, such as debridement, vascular reconstruction, and tissue repair; foot disease prevention; multidisciplinary collaboration; and the establishment of a hierarchical diagnosis and treatment system, with the objective of guiding clinical practice for managing DF in China.

Burn injury remains a major global health challenge, causing an estimated 180 000 deaths annually. The marked heterogeneity in burn severity, complications, and outcomes highlights the need for more objective and efficient evaluation strategies. Artificial intelligence (AI) has emerged as a promising approach to support clinical decision-making and improve patient care in this field. In this narrative review, we summarize the growing applications of AI in burn care, including the assessment of burn depth and total body surface area, monitoring of wound healing, prediction of postburn complications, and estimation of clinical outcomes. AI-based models have demonstrated strong performance in automating wound assessment, optimizing fluid resuscitation, and predicting complications such as sepsis, inhalation injury, and acute kidney injury. Furthermore, AI-driven prediction of mortality risk and hospital length of stay has shown potential to inform early interventions and improve resource allocation. Despite encouraging progress, most studies to date rely on small, single-center datasets and limited model validation, underscoring the need for larger, multi-institutional efforts, and standardized data sharing. Integrating AI into burn management holds great promise for enhancing diagnostic precision, forecasting outcomes, and personalizing treatment strategies. As these technologies advance, clinician familiarity and collaboration with AI tools will be critical to fully realize their potential in transforming burn care.

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.