Background and objective: Impaired healing of diabetic chronic wounds is closely associated with persistent inflammation, insufficient angiogenesis, impaired cell migration, and oxidative stress. Rosuvastatin (RSV) possesses anti-inflammatory and pro-angiogenic properties, but its topical application is limited by poor solubility and low bioavailability. This study aimed to construct an RSV-loaded multifunctional composite hydrogel (RSV@PMO-GNS@PCT) and evaluate its therapeutic efficacy and underlying mechanisms in diabetic wound repair. Methods: RSV was encapsulated into periodic mesoporous organosilica-gold nanostar complexes (PMO-GNS) and incorporated into a PVA-Ca-TA hydrogel to form RSV@PMO-GNS@PCT. In vitro assays assessed cytocompatibility, antioxidant and anti-inflammatory effects, fibroblast migration, endothelial tube formation, and antibacterial activity. In vivo efficacy was evaluated using a streptozotocin-induced diabetic mouse full-thickness wound model by monitoring wound closure, macrophage polarization, histological changes, and angiogenesis. Transcriptome sequencing and western blotting were performed to explore molecular mechanisms, and biosafety was systematically assessed. Results: RSV@PMO-GNS@PCT exhibited a uniform nanocomposite structure, a porous three-dimensional network, and sustained drug release. It showed excellent biocompatibility, potent antioxidant and antiinflammatory activity, enhanced fibroblast migration and HUVEC tube formation, and strong inhibition of E. coli and S. aureus. In vivo, the hydrogel significantly accelerated wound closure, improved collagen deposition, promoted angiogenesis, suppressed M1 macrophage polarization, and enhanced M2 polarization. Mechanistic studies revealed regulation of the cGMP-PKG and RhoA-MLCK-MLC pathways, leading to reduced inflammation, enhanced angiogenesis, and cytoskeletal remodeling. Biosafety evaluation confirmed good tissue compatibility and systemic safety. Conclusion: The RSV@PMO-GNS@PCT multifunctional hydrogel achieves efficient RSV delivery and exerts synergistic anti-inflammatory, antibacterial, and pro-angiogenic effects, thereby markedly accelerating diabetic wound healing. This study provides a promising localized therapeutic strategy with potential clinical application.

Chronic wounds remain a severe clinical challenge worldwide due to persistent inflammation, impaired tissue regeneration, and refractory infection control. Recently, magnesium-based materials have garnered tremendous attention for chronic wound healing owing to their exceptional biocompatibility, biodegradability, and multifaceted biological functions in remodeling the wound immune microenvironment. Well-established preclinical evidence demonstrates that magnesium and its derivatives facilitate chronic wound repair by regulating inflammatory responses, promoting angiogenesis, enhancing cellular proliferation and migration, and exerting antibacterial effects, thus constructing a favorable microenvironment for tissue regeneration. Emerging (though still partly speculative) findings suggest that degradation products of magnesium, particularly Mg2⁺ ions, play a central role in directing immune cell polarization, optimizing endothelial cell activity, and alleviating oxidative stress. Magnesium-based inorganic materials, nanostructured systems, and hybrid platforms integrated with hydrogels or other bioactive components also exhibit outstanding preclinical therapeutic potential. It is important to note that the vast majority of current evidence remains at the preclinical stage, and any interpretation of translational readiness should be made with caution. However, the clinical translation of these materials is still severely restricted by multiple bottlenecks: the lack of precise control over magnesium degradation and Mg2⁺ release kinetics, safety risks arising from local pH elevation and hydrogen gas generation, deficient long-term toxicological data, and the absence of standardized evaluation systems for magnesium-based wound dressings. Future research should prioritize the development of tunable and stimuli-responsive delivery systems, deepening mechanistic insights into magnesium-mediated immunomodulation, and incorporating advanced manufacturing technologies to realize personalized therapeutic strategies. Rigorous biosafety evaluations and clinically relevant preclinical models are also imperative. In conclusion, magnesium-based materials stand as a highly promising and versatile strategy for chronic wound repair, holding great potential to be developed as multifunctional platforms that integrate antibacterial, immunoregulatory, and tissue-regenerative properties for clinical translational applications.

OBJECTIVES: Sepsis triggers both excessive inflammation and immunosuppression, the latter partly characterized by CD4+ T-cell depletion. The mechanisms underlying this depletion, especially its interplay with cytokine storms driven by inflammatory factors such as interleukin (IL)-6, remain unclear. This study aimed to elucidate the molecular mechanisms contributing to CD4+ T-cell depletion in sepsis, focusing specifically on the IL-6/Janus kinases (JAKs)/signal transducer and activator of transcription 3 (STAT3) signaling axis and programmed cell death. DESIGN: Prospective cohort study. SETTING: Adult ICUs at a university hospital. PATIENTS: Adult sepsis and septic shock patients without any documented immune comorbidity. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A prospective analysis enrolled 151 patients (93 sepsis, 58 septic shock) and 20 controls. Flow cytometry and enzyme-linked immunosorbent assay were used to assess immune cell populations and cytokine profiles, with multivariate analyses exploring their interrelationships. An additional 30 sepsis patients and ten controls were recruited to investigate mechanisms. Peripheral blood mononuclear cells (PBMCs) underwent RNA sequencing (RNA-seq). Isolated CD4+ T cells were stimulated with IL-6 in vitro, followed by treatment with specific inhibitors targeting pyroptosis, apoptosis, necroptosis, the JAKs/STAT3 pathway, or receptor-interacting protein kinase 1 (RIPK1). Western blotting, flow cytometry, immunofluorescence, Cell Counting Kit-8 assays, and interferon-gamma staining evaluated cell death pathways, PANoptosome (a complex mediating apoptosis, pyroptosis and necroptosis)-assembly, and function. Significant CD4+ T-cell loss occurred in both sepsis and septic shock groups, strongly correlating with elevated IL-6 levels. Sepsis PBMC RNA-seq revealed activated IL-6/JAKs/STAT3 signaling and upregulated apoptosis/pyroptosis/necroptosis genes. In vitro, IL-6 induced pyroptosis, apoptosis, and necroptosis (PANoptosis) in CD4+ T cells via IL-6/JAKs/STAT3-dependent RIPK1-PANoptosome assembly. Inhibiting JAKs/STAT3 or RIPK1 significantly reduced PANoptosis, partially restored CD4+ T-cell viability and functional capacity. CONCLUSIONS: PANoptosis has been observed to be a form of CD4+ T-cell death in sepsis patients. Evidence suggests that IL-6 may be associated with the exhaustion process, mechanistically involving the activation of the JAKs/STAT3 pathway. It is also hypothesized that this process might be linked to RIPK1-PANoptosome-mediated PANoptosis.

Sepsis is a serious, life-threatening widespread inflammatory response in the body to infection that can result in multiple organ damage and has a relatively high death rate. Traditional antibiotics and supportive treatments have certain deficiencies, such as poor drug accumulation at the site of infection, delayed identification of pathogens, and an inability to precisely regulate the host immune response. New developments in micro- and nanorobotics have provided new paths for sepsis diagnosis and treatment by means of active motion, intelligent sensing and targeted intervention. Biohybrid microrobots containing DNA nanodevices or enzyme sensors can be used for diagnosis to rapidly detect bacterial pathogens, endotoxins and other markers such as procalcitonin. Motivated micro-robots can overcome the biofilm barrier to deliver drugs and increase the local concentration of antibiotics to inhibit bacterial toxins. Functionalised nanobots of cell membrane or enzyme types can target cytokines, reactive oxygen species and circulating mitochondrial DNA to suppress inflammation and organ damage. The above-mentioned multi-functional platforms have combined pathogen clearance, immune modulation and tissue repair into one treatment. Although the above are promising, there are still some problems in biosafety, propulsion efficiency under complex physiological conditions, large-scale production, and the development of clinically relevant animal models. Future work will focus on building intelligent, biocompatible systems capable of autonomous navigation and adaptation to sepsis. Micro- and nanorobots are generally considered to be a new type of devices for treating sepsis that can achieve targeted and personalised therapy through intelligence.

Diabetic chronic wounds heal slowly due to persistent inflammation, impaired macrophage polarization, and compromised angiogenesis, while conventional therapies fail to effectively modulate the wound microenvironment. This study aimed to develop pagoda-like microneedle (MN) patches incorporating isoliquiritigenin (ISL)-loaded hollow mesoporous copper sulfide nanoparticles (HMCuS@ISL MNs) with near-infrared (NIR) photothermal functionality to achieve local immunometabolic regulation and promote angiogenesis, antibacterial activity, and wound repair. HMCuS@ISL nanoparticles were integrated into a collagen/hyaluronic acid matrix to form pagoda-like MN patches. Nanoparticles were characterized by TEM, DLS, and UV–vis–NIR spectroscopy, and their photothermal performance under 808 nm irradiation was evaluated. MN mechanical strength, dissolution, cytocompatibility, antibacterial activity, and in vitro angiogenesis were systematically assessed. ISL-mediated macrophage polarization was analyzed via RNA sequencing, qPCR, flow cytometry, and metabolic flux assays. In vivo efficacy and biosafety were evaluated in streptozotocin-induced diabetic mouse wound models. HMCuS@ISL nanoparticles displayed uniform hollow–mesoporous morphology with strong NIR absorption and efficient photothermal conversion. MN patches exhibited excellent mechanical strength, rapid dissolution, and good biocompatibility. ISL promoted M2 macrophage polarization by suppressing glycolysis and enhancing fatty acid oxidation. HMCuS@ISL MNs, especially under NIR irradiation, significantly enhanced fibroblast migration, angiogenesis, antibacterial activity, and accelerated wound closure. Histological and immunostaining analyses confirmed improved re-epithelialization, collagen deposition, vascularization, and immune microenvironment balance without systemic toxicity. HMCuS@ISL MN patches integrating metabolic immune modulation with photothermal therapy provide an effective, safe, and minimally invasive strategy for diabetic wound healing.

Background:Diabetic chronic wounds are characterized by persistent infection, excessive oxidative stress, impaired angiogenesis, and prolonged inflammation, resulting in delayed healing. Current wound dressings lack the ability to simultaneously regulate these pathological processes. Methods:A multifunctional composite hydrogel was developed by incorporating benzalkonium chloride (BAC)-loaded selenium-doped mesoporous silica nanoparticles (Se-MSNs) into a PF127 matrix. In this system, BAC provides antibacterial activity, Se-MSNs enable redox regulation and immunomodulation, and PF127 serves as a delivery platform for localized retention and sustained release. The physicochemical properties, antibacterial activity, antioxidant capacity, pro-angiogenic effects, and anti-inflammatory performance were evaluated in vitro, followed by therapeutic assessment in a diabetic mouse wound model. Results:The composite hydrogel exhibited effective antibacterial activity against Staphylococcus aureus and Escherichia coli, reduced intracellular reactive oxygen species, promoted endothelial cell migration and tube formation, and modulated inflammatory cytokine expression in vitro. In vivo, the hydrogel significantly accelerated wound closure, enhanced collagen deposition and angiogenesis, and alleviated excessive inflammation in diabetic wounds. Conclusion:The therapeutic effects of the composite hydrogel are attributed to the restoration of redox homeostasis and the coordinated regulation of inflammation resolution and vascular regeneration. This study presents a multifunctional biomaterial strategy for improving the healing of diabetic chronic wounds.

Objective Gasdermin D (GSDMD), a key pyroptosis effector, is implicated in systemic inflammation during sepsis. However, its role in skeletal muscle metabolism remains largely unexplored.Methods GSDMD-knockout (GSDMD-KO) and wild-type (WT) mice were used to establish a septic model. Skeletal muscle samples were collected and subjected to non-targeted metabolomic analysis via UHPLC-QE-MS. Multivariate statistical analysis and KEGG pathway enrichment were performed to identify differential metabolites and explore the underlying metabolic alterations.Results GSDMD knockout resulted in significant changes in skeletal muscle metabolism, notably in pathways related to taurine and hypotaurine metabolism, amino acid biosynthesis, bile acid biosynthesis, oxidative stress response, and nucleotide metabolism. These alterations suggest that GSDMD regulates energy, amino acid, lipid, and redox metabolism during sepsis. A panel of potential biomarkers was identified, which may contribute to muscle injury and repair.Conclusions GSDMD deficiency profoundly alters skeletal muscle metabolic profiles in sepsis. Identified metabolites may serve as diagnostic markers and therapeutic targets for sepsis-associated myopathy, offering insights into GSDMD's role in muscle metabolism and potential intervention strategies.

Cell membrane-coated nanoparticles (CMNPs) have emerged as a promising platform for targeted drug delivery and therapeutic applications due to their unique properties, such as improved biocompatibility, prolonged circulation time, and ability to mimic natural cell functions. The preparation of CMNPs involves three critical stages: extraction of the cell membrane, preparation of the nanoparticle core, and membrane coating. The cell membrane is isolated through various methods, including hypotonic lysis, freeze-thaw cycles, and centrifugation, with careful attention paid to preserving its integrity and functionality. Nanoparticle cores, which can be organic (eg, PLGA, liposomes) or inorganic (eg, metal-based cores), offer distinct advantages in terms of drug loading capacity, stability, and therapeutic potential. The fusion of the core and the membrane is typically achieved through techniques such as membrane extrusion, sonication, and electroporation. These methods enable the efficient formation of core-shell nanostructures, which can be utilized for a range of biomedical applications, particularly in drug delivery, cancer therapy, and tissue regeneration. This review discusses the key aspects of CMNP preparation, including membrane extraction and purification techniques, core selection, and fusion methods, as well as the current trends and future directions in the development of CMNPs for therapeutic purposes.

Sepsis-induced cardiomyopathy (SICM) is a frequent and clinically important complication of sepsis, characterized by acute and often reversible myocardial dysfunction and associated with poor outcomes in critically ill patients. Despite growing recognition of its clinical significance, effective mechanism-based therapies remain unavailable, largely because SICM is highly heterogeneous and driven by a complex interplay of inflammatory activation, endothelial and microcirculatory dysfunction, oxidative stress, mitochondrial injury, calcium-handling abnormalities, metabolic reprogramming, and dynamic cardiomyocyte adaptation. In recent years, increasing attention has been directed toward epigenetic regulation, as it provides a mechanistic framework linking septic stress to sustained transcriptional and post-transcriptional remodeling in the myocardium and its immune microenvironment. Numerous studies have therefore investigated epigenetic mechanisms in SICM, including DNA methylation, histone modifications, and non-coding RNA-mediated regulation. This review summarizes recent advances in the understanding of epigenetic mechanisms underlying SICM, with emphasis on their roles in inflammation, mitochondrial dysfunction, immune-cardiac crosstalk, and cardiomyocyte injury. We further discuss the translational relevance of epigenetic remodeling and highlight the emerging therapeutic potential of epigenetically targeted interventions. Collectively, these findings provide important mechanistic insights into SICM and may support the development of biomarker-guided stratification and more precise therapeutic strategies for septic myocardial dysfunction.

Chronic wounds represent a major clinical challenge due to persistent infection, excessive inflammation, impaired angiogenesis, and defective tissue remodeling. Carbon dots (CDs)-based nanomaterials are promising candidates for addressing these issues, owing to their unique physicochemical properties, tunable surface functionalities, and excellent enzyme-mimetic activities. This review presents a comprehensive overview of recent advances in CDs-based nanomaterials for chronic wound repair under a framework from fundamental principles to translational applications. We first outline the pathophysiological features of chronic wounds and summarize the classification, synthesis, and functionalization strategies of CDs. We then elaborate on the rational design of CDs-based nanomaterials, including stimuli-responsive systems, nanozymes, and multifunctional composites. The multilevel therapeutic mechanisms are dissected, covering infection control, selective ROS scavenging, inflammatory modulation, angiogenesis, and extracellular matrix remodeling. We further highlight applications in real-time wound monitoring, dynamic phase-adaptive therapy, and smart dressings. Key challenges remain in scalable synthesis, long-term biosafety, and clinical translation. Future efforts should focus on green synthesis, engineering optimization, and AI-assisted development to link laboratory research with clinical practice. This review provides a systematic roadmap for the design and translation of next-generation CDs-based wound therapies.

BackgroundMesenchymal stem cells (MSCs) show promise for diabetic wound healing, but global research trends and hotspots lack comprehensive analysis.ObjectiveThis scientific metrology study aims to reveal the research trends of MSCs and diabetic wounds and to showcase the evolving trends in this field.MethodsPublications on MSCs and diabetic wounds (2010-2025) were extracted from the Web of Science (WOS). Bibliometric tools (VOSviewer, R-bibliometrix, and CiteSpace) analyzed publication trends, core journals, author/institutional distribution, collaboration networks, and keyword evolution.ResultsA total of 3943 publications were included. The annual number of publications increased rapidly from 2016, peaking at 535 in 2024. Core journals were primarily focused on wound healing and diabetes management. China ranked first globally in terms of publication volume and citation frequency, followed by the United States (US) and European countries. Keyword analysis indicated that early research primarily focused on "diabetic foot ulcer" and "wound healing," whereas recent studies have shifted toward themes related to mechanisms and clinical applications, such as "angiogenesis," "inflammation," "wound care," and MSC-derived exosomes, suggesting a transition from basic exploration to clinical translation.ConclusionsMSC research for diabetic wounds is rapidly evolving, with global collaboration centered on China and the US. Hotspots now span mechanistic studies to clinical applications, guiding future therapeutic innovation.

Sepsis remains a major global health burden and is characterized by a dysregulated host immune response that evolves from early hyperinflammation to late-stage immunosuppression. Despite advances in supportive care, effective pharmacological therapies capable of modulating this dynamic immune landscape are still lacking. Messenger RNA (mRNA)–based therapeutics have emerged as a promising approach due to their ability to enable transient, controllable expression of immunomodulatory proteins; however, their clinical translation is hindered by intrinsic instability, rapid degradation, and inefficient tissue delivery. Nanotechnology offers innovative solutions to overcome these limitations by improving mRNA protection, cellular uptake, and targeted delivery. A variety of nanocarriers, including lipid nanoparticles, polymeric systems, inorganic nanomaterials, and biomimetic vectors, have been developed for mRNA delivery in sepsis. Emerging strategies incorporating macrophage-targeting ligands and stimuli-responsive release mechanisms further enhance delivery precision and therapeutic efficacy. Preclinical studies demonstrate that mRNA-based nanotherapeutics can suppress cytokine storms, restore immune function, and attenuate organ injury in experimental models of sepsis. This review summarizes recent advances in mRNA-based nanotherapeutics for sepsis, with a focus on delivery strategies, immunomodulatory mechanisms, and translational potential. Key challenges related to delivery efficiency, safety, and regulatory considerations are discussed. Finally, future directions are proposed for the development of individualized, stage-specific mRNA nanotherapies aimed at restoring immune homeostasis in critically ill patients.

Trauma surgical intensive care unit (TSICU) patients frequently present with metabolic dysregulation. However, the combined prognostic value of the triglyceride-glucose–body mass index (TyG-BMI) and the stress hyperglycemia ratio (SHR) remains unclear. A retrospective cohort study was conducted using the MIMIC-IV database, with external validation in a TSICU cohort from Tongji Hospital. Adult patients admitted to the TSICU were classified into four groups based on joint TyG-BMI and SHR categories. The endpoints were 28-day and 180-day all-cause mortality. Cox regression, restricted cubic splines, Kaplan–Meier survival curves, and 33 machine learning models were employed to evaluate associations and predictive performance. A total of 872 patients were included in the training cohort and 525 in the validation cohort. Overall, 19.0

ABSTRACT Background Sepsis‐induced myopathy (SIM) is a severe complication that contributes to late‐stage mortality and functional impairment in sepsis patients. The NLRP3 inflammasome plays a pivotal role in the pathogenesis of SIM, and its selective inhibitor MCC950 has shown promising therapeutic potential. However, systemic administration of MCC950 is limited by hepatotoxicity, necessitating the development of targeted delivery systems to enhance efficacy while minimizing toxicity. Methods To improve the therapeutic profile of MCC950, we designed M12‐functionalized liposomal nanoparticles (M12‐Liposome@MCC950 NPs) as the carrier material, with surface modification by the muscle‐homing peptide M12 for targeted delivery to skeletal muscle tissue. Nanoparticle characteristics were assessed using transmission electron microscopy (TEM), dynamic light scattering (DLS) and in vitro drug release assays. The targeting efficiency was evaluated in vivo using fluorescence imaging and in vitro via cellular uptake studies in C2C12 myoblasts. The anti‐inflammatory and anti‐atrophic effects were investigated in an LPS‐induced myotube atrophy model and a cecal ligation and puncture (CLP)‐induced sepsis mouse model. Biocompatibility and systemic safety were assessed through histological analysis and serum biochemical assays. Results M12‐Liposome@MCC950 NPs exhibited a uniform spherical morphology, an average diameter of 150 ± 10 nm and a zeta potential of −15.73 ± 6.03 mV, ensuring good colloidal stability. The nanoparticles demonstrated sustained drug release over 14 days. In vivo fluorescence imaging confirmed enhanced skeletal muscle accumulation of M12‐conjugated nanoparticles, with a 3.47‐ to 5.31‐fold increase compared to nontargeted controls. Cellular uptake studies revealed a 2.28‐fold improvement in intracellular delivery efficiency. In vitro, M12‐Liposome@MCC950 NPs significantly inhibited NLRP3 inflammasome activation, reducing caspase‐1 cleavage and IL‐1β/IL‐18 secretion, while also preventing LPS‐induced myotube atrophy. In the CLP‐induced sepsis model, treatment with M12‐Liposome@MCC950 NPs markedly reduced muscle atrophy, improved grip strength and decreased expression of atrophy‐related proteins Atrogin‐1 and MuRF1. Additionally, histological and biochemical assessments confirmed that the nanoparticles did not induce hepatic or renal toxicity, demonstrating excellent biocompatibility. Conclusions M12‐Liposome@MCC950 NPs provide a targeted and sustained‐release strategy for delivering MCC950 to skeletal muscle, effectively inhibiting NLRP3 inflammasome activation and alleviating SIM. This approach enhances therapeutic efficacy while mitigating systemic toxicity, highlighting the potential of nanomedicine‐based interventions for treating inflammation‐related myopathies.

Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response, is characterized by a dynamic progression from hyperinflammation to immunosuppression. Its persistently high mortality underscores the limitations of therapies focused solely on immune homeostasis. This review advocates a paradigm shift that positions the nervous system as a central orchestrator of host defense through a hierarchical neuroimmune axis. This axis comprises three interconnected tiers: (1) peripheral effector pathways-the cholinergic anti-inflammatory pathway and the sympathetic-adrenal-medullary axis; (2) central integrative hubs in the brainstem (eg, nucleus tractus solitarius) and limbic system; and (3) molecular translators that convert neural signals into cellular immune responses. In sepsis, maladaptive plasticity within these circuits leads to a pathological "uncoupling" of immune sensing from neural control, driving organ dysfunction and perpetuating both runaway inflammation and subsequent immunosuppression. We critically evaluate emerging neuromodulation strategies-including bioelectronic vagus nerve stimulation, splenic focused ultrasound, precise electroacupuncture, and receptor-specific pharmacology-with careful distinction between established mechanistic evidence, preclinical findings, and early-stage clinical data. The future direction lies in precision neuromodulation, an evolving concept encompassing closed-loop systems responsive to dynamic biomarkers, chronotherapy, and targeted nanomedicine, though these approaches require substantial technical and clinical validation. This framework charts a roadmap for evolving sepsis management from supportive care toward proactive modulation of endogenous regulatory networks, while emphasizing that further mechanistic studies, biomarker validation, and well-designed clinical trials are essential prerequisites for clinical translation.

OBJECTIVE:Sepsis-induced muscle atrophy significantly impairs patient quality of life, yet effective therapeutic strategies remain limited. This study aimed to investigate the protective effects of selenomethionine (Se-Met) on sepsis-induced skeletal muscle atrophy and explore the underlying molecular mechanisms, with the goal of providing a novel theoretical foundation and potential therapeutic approach for sepsis-associated muscle injury. METHODS:A murine sepsis model was established via cecal ligation and puncture, followed by treatment with varying doses of Se-Met. Survival rate, body weight, skeletal muscle mass, and muscle strength were evaluated. Histological analysis [hematoxylin and eosin (HE) staining] was used to assess muscle fiber cross-sectional area. Protein expression levels of Atrogin-1, MuRF1, and pyroptosis-related markers (NLRP3, Caspase-1, GSDMD, IL-18, and IL-1β) were examined via Western blot. In vitro , C2C12 myoblasts were stimulated with lipopolysaccharide and treated with Se-Met to assess oxidative stress markers [reactive oxygen species (ROS), malondialdehyde, superoxide dismutase, glutathione peroxidase], pyroptosis-related proteins, and inflammatory cytokines (e.g., IL-6 and IL-18). ROS scavenger N-acetylcysteine, NLRP3 agonist, and ROS inducer were employed in mechanistic studies to further elucidate the molecular mechanisms. RESULTS:Se-Met significantly improved survival, body weight, and muscle strength in septic mice and alleviated skeletal muscle atrophy. Mechanistically, Se-Met inhibited the NLRP3/Caspase-1/GSDMD signaling axis, thereby reducing pyroptosis and the expression of inflammatory cytokines such as IL-6, IL-18, and IL-1β. Furthermore, Se-Met decreased ROS accumulation, enhanced antioxidant enzyme activities, and suppressed pyroptosis through regulation of the ROS/NLRP3 pathway, ultimately reducing protein degradation mediated by Atrogin-1 and MuRF1. CONCLUSION:This study demonstrates that Se-Met mitigates sepsis-induced skeletal muscle atrophy by exerting antioxidant effects, inhibiting pyroptosis, and modulating inflammatory responses. The findings highlight the critical role of the ROS/NLRP3 signaling pathway in the protective action of Se-Met, providing new experimental evidence for its potential application in sepsis and other oxidative stress-related diseases.

Sepsis is a life-threatening systemic inflammatory syndrome, typically triggered by infection, that can lead to multi-organ failure and high mortality rates. Traditional treatments for sepsis often have limited efficacy and significant side effects, necessitating the exploration of innovative therapeutic strategies. In recent years, the application of nanotechnology in sepsis therapy has garnered widespread attention due to its potential to modulate immune responses, reduce inflammation and oxidative stress, and eliminate bacterial toxins. This review aims to provide an overview of the latest advancements, challenges, and future prospects of nanotechnology in sepsis treatment. By analyzing recent developments in anti-inflammatory, immunomodulatory, antioxidant, and detoxification applications of nanotechnology, key findings and therapeutic potential are summarized, including the use of nanocarriers, biomimetic nanoparticles, and self-assembled nanomaterials. Furthermore, this review addresses the challenges in clinical translation, such as drug targeting, long-term safety, and biocompatibility. Future research will require large-scale clinical trials and interdisciplinary collaboration to validate the efficacy of nanotechnology in sepsis treatment and facilitate its integration into clinical practice. Overall, nanotechnology presents unprecedented opportunities for sepsis management, and this review seeks to offer insights into ongoing research while promoting further advancements in this field.

Background Burns among children and adolescents represent a significant global health burden, leading to substantial morbidity and disability. This study aimed to analyze the trends in burn incidence, prevalence, and years lived with disability (YLDs) from 1990 to 2021, and to project future trends to 2035, highlighting global and regional disparities. Methods We utilized data from the Global Burden of Disease (GBD) database covering 204 countries and territories. Burn data were extracted from multiple sources including hospital records, health surveys, and national health databases. Trend analysis was projected using the Bayesian age-period-cohort (BAPC) model. Health inequality was assessed using the slope index of inequality (SII) and the concentration index (CI). Results In 2021, the global incidence of burns among children and adolescents was 8,484,254 cases, with an age-standardized incidence rate (ASIR) of 1,315.94 per 100,000 population, showing an annual reduction of 1.33% from 1990. The prevalence and YLDs also showed significant annual declines. Males had higher incidence rates than females. Younger children (0-4 years) experienced the highest incidence rates, while adolescents (15-19 years) had the highest prevalence. Regional disparities were evident, with Central Asia and Central Europe having the highest ASIRs. The SII and CI indicated persistent socio-economic health disparities, with lower socio-demographic index (SDI) countries bearing a disproportionate burden. Predictive analysis suggests a continued decline in burn incidence, prevalence, and YLDs through 2035. Additionally, burns among adolescents and young adults result in significant loss of labor force, exacerbating socio-economic challenges in affected regions. Conclusion The global burden of burns in children and adolescents has decreased significantly, yet substantial disparities persist across different regions and socio-economic strata. Continued efforts in improving burn prevention, treatment, and rehabilitation are essential to further reduce the burden and address health inequalities.

BACKGROUND:Spinal cord injuries (SCI) are major contributors to global disability, with high incidence rates, substantial medical costs, and profound long-term impacts. Cervical spinal cord injuries (cSCI), in particular, lead to severe outcomes, making them a critical public health challenge. While the rising global burden of SCI, including cSCI, is well-known, comprehensive and updated epidemiological studies specifically focused on cSCI, especially those that project future trends and analyze regional disparities, remain limited. This study aims to provide novel insights into the evolving burden of cSCI by offering an updated, global analysis using the most recent data and advanced modeling techniques. METHODS:We used data from the Global Burden of Disease (GBD) 2021 database to analyze the incidence, prevalence, and Years Lived with Disability (YLDs) of cSCI from 1990 to 2021 across 204 countries and territories. The DisMod-MR 2.1 Bayesian meta-regression tool was employed to estimate the burden of cSCI, while inequality analyses were conducted using the Gini coefficient and concentration index. Risk factor attribution was performed using the Comparative Risk Assessment framework. Additionally, Bayesian Age-Period-Cohort (BAPC) analysis was used to predict the future burden of cSCI to 2045. RESULTS:While the global incidence of cSCI has increased from 249,122 cases (95% CI: 183,942 to 345,205) in 1990 to 306,568 cases (95% CI: 216,989 to 456,717) in 2021, the age-standardized incidence rate (ASR) has decreased from 4.88 to 3.78 per 100,000 population. This decrease, despite rising absolute numbers, reflects known factors such as improvements in trauma prevention, healthcare access, and better management of degenerative conditions. Regional disparities in cSCI burden and the influence of socio-economic and healthcare inequalities have been highlighted, underscoring the need for targeted interventions. Predictive modeling suggests a continued rise in cSCI incidence, particularly in regions with expanding aging populations. CONCLUSION:This study provides a comprehensive, up-to-date analysis of the global burden of cSCI, including regional disparities and future projections. The findings highlight the urgent need for tailored healthcare interventions and resource allocation strategies, particularly in regions with limited healthcare access. By identifying high-risk populations and regions, this study offers critical insights that can inform future public health policies and interventions to mitigate the growing burden of cSCI.

BACKGROUND AND OBJECTIVE:Sepsis, a systemic inflammatory syndrome, frequently leads to substantial skeletal muscle loss and dysfunction, severely impairing patient prognosis. The P2X7 receptor is an adenosine triphosphate-gated cation channel implicated in inflammation and cell death. Although its role in the immune system has been extensively studied, its expression profile and pathogenic mechanism in sepsis-induced skeletal muscle atrophy remain unclear. This study aimed to investigate the functional role of the P2X7 receptor in sepsis-associated muscle injury and its potential as a therapeutic target. METHODS:A murine sepsis model was established using cecal ligation and puncture (CLP) surgery. Temporal changes in P2X7 receptor expression in the gastrocnemius (GP) and tibialis anterior (TA) muscles were assessed. Functional studies were performed using P2X7 knockout (P2X7 - / - ) mice and the P2X7-specific antagonist A-740003. Skeletal muscle atrophy, inflammatory responses, and activation of the NLRP3 inflammasome signaling pathway were systematically evaluated through Western blotting, qPCR, hematoxylin-eosin staining, muscle fiber cross-sectional area analysis, and measurement of inflammatory cytokines. RESULTS:In the CLP-induced sepsis model, P2X7 receptor expression in both GP and TA muscles was upregulated in a time-dependent manner. P2X7 gene deletion significantly attenuated body weight loss, muscle mass reduction, and muscle fiber atrophy, restored grip strength, and suppressed the expression of atrophy-related genes (Myostatin, Atrogin-1, and MuRF1). Moreover, it markedly reduced IL-6, IL-18, and IL-1β levels in both skeletal muscle and plasma, indicating an anti-inflammatory effect. P2X7 deficiency also significantly inhibited the expression of NLRP3 inflammasome components, caspase-1, and gasdermin D, thereby blocking the pyroptosis signaling pathway. Pharmacological inhibition with A-740003 showed dose-dependent mitigation of muscle atrophy, further supporting the therapeutic potential of targeting P2X7. CONCLUSIONS:The P2X7 receptor contributes to sepsis-induced skeletal muscle atrophy by promoting inflammation and muscle protein degradation through activation of the NLRP3 inflammasome and pyroptosis pathways. Genetic or pharmacological inhibition of P2X7 significantly alleviates muscle damage and functional loss. These findings provide strong experimental evidence supporting P2X7 as a potential therapeutic target for sepsis-associated myopathy.