Given specific microenvironment of bone repair, the bio-functionally decorated implant endowed with self-regulated bone healing procedure was committed to pursuing. Inspired by the microstructure and chemical composition of natural bone, a kind of bionic bone-like bioactive coating, namely micro/nano gradient morphological calcium titanate containing trace ions, was in-situ hydrothermally grown on 3D printed porous titanium alloy scaffold. Surface features of the decorated porous titanium alloy scaffolds, by itself, could modulate microenvironment, and enhance neurovascular bone regeneration and reconstruction via surface topography and sustainably released bioactive ions, as verified by in vitro and in vivo biological evaluation. The underlying immunoregulation mechanism was surface feature-modulated macrophage oxidative phosphorylation and ATP production in energy metabolism, which advocates M2 macrophage phenotypic switch. It provided an insightful foundation for bio-functional decoration of bone repair implants.

Infected bone defects, especially irregular or long-segment defects, pose great clinical challenges. By performing bone defect reconstruction on patients with complex infected bone defects admitted to our hospital, this study explores the clinical efficacy of a novel customized 3D prosthesis combined with the induced membrane technique in the treatment of complex infected bone defects and the feasibility of relevant prosthesis design strategies. It also discusses its positive effects on infection control and improvement of patients’ quality of life. (1) Measurement and Design: A 256-slice spiral CT was used to perform thin-layer scanning (layer thickness 1 mm) of the patient’s infected bone defect area and the corresponding healthy side. The data were saved in DICOM format and reconstructed into 3D using Mimics software. Using the healthy side as a template and applying the mirror principle, the data from the defect area were matched with those from the healthy side. First, the corresponding anatomical landmark points were identified, and a digital model of the implant was designed, with the debrided normal bone tissue serving as the boundary and an osteotomy plane of 5 mm depth. The model was saved in STL format. The STL file was imported into Materialise’s 3-matic software, and the model was designed starting from the osteotomy surface to facilitate mold testing. (2) Printing and Surgical Simulation: The scanned CT data was sent to Dimension (Xi’an) Biomedical Technology Co., Ltd. Engineers employed computer-aided technology to eliminate metallic artifacts from the bone prosthesis. Based on the patient’s specific bone defect location, anatomical position, and characteristics of the surrounding bone tissue, they designed a prosthesis tailored to the bone defect. Using 3D printing technology, the customized porous titanium alloy prosthesis was then simulated and printed. (3) Application and Indicator Analysis: This study summarizes and analyzes the 3D prosthesis design process for four patients with infected femoral osteomyelitis complicated by bone defects who received personalized 3D-printed porous titanium alloy prostheses at our hospital between May 2023 and May 2025. Treatment was conducted in two phases: In the first phase, following the induced membrane technique protocol, all four patients underwent thorough debridement followed by bone cement placement. In the second phase, the personalized 3D-printed prostheses were used to reconstruct and repair the infected bone defects. Postoperative follow-ups were performed at 1, 3, 6, and 12 months, with X-ray and CT examinations used to assess the integration of the reconstructed prostheses with the bone ends, evaluating the clinical efficacy of personalized 3D-printed prostheses in the repair and reconstruction of complex infectious bone defects. A 3D-printed porous titanium alloy prosthesis was adopted, with a porosity of approximately 70

The complex pathological microenvironment of bone defects (resulting from trauma, tumors, or infections) poses significant clinical challenges, wherein adverse conditions (e.g., inflammation and vascular damage) impede bone regeneration and complicate treatment. Although bone grafting remains the primary clinical approach, its therapeutic efficacy is limited under these circumstances. To address this, we developed a gentiopicroside-strontium complex (GPS-Sr) to leverage the synergistic effects of both components, subsequently encapsulating it within a gelatin methacrylate (GelMA) hydrogel to create an injectable GelMA/GPS-Sr system with sustained-release properties. In vitrostudies demonstrated that GPS-Sr promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) via the PI3K/AKT pathway, polarizes M2 macrophages to mitigate inflammation, and enhances angiogenesis. These in vitrofindings were corroborated in vivo, where the GelMA/GPS-Sr hydrogel significantly enhanced bone regeneration in a rat defect model, exhibiting high biocompatibility and achieving a 45

Postoperative treatment of osteosarcoma faces the dual challenges of tumor recurrence and extensive bone defect repair, necessitating the development of a synergistic strategy capable of simultaneously eliminating residual tumor cells and promoting bone regeneration. Existing prosthetic implants are often limited by their singular functionality, leading to issues such as high recurrence rates and non-union. This study innovatively constructs a functional titanium alloy scaffold system synergistically driven by a biodegradable "shell-like" triboelectric nanogenerator (BS-TENG). The BS-TENG efficiently converts natural joint movement into electricity. Within the acidic tumor microenvironment, this electrical output accelerates the breakdown of the scaffold's MgxFe1-xS2 coating, leading to the localized release of H2S gas and Fe2+ ions. The H2S upregulates HMOX1 protein expression, which synergizes with heightened Fe2+ levels to induce intense lipid peroxidation, thereby activating a selective ferroptosis cascade in osteosarcoma cells and drastically lowering their survival. In physiological conditions, the scaffold shows excellent biocompatibility. Concurrent electrical stimulation and controlled Mg2+ release significantly boost alkaline phosphatase activity and calcium nodule formation, effectively promoting bone regeneration. In vivo validation confirms a 90% tumor inhibition rate alongside robust biosafety, offering a novel self-powered paradigm for integrated therapy and repair post-osteosarcoma surgery.

3D‐printed titanium implants are extensively utilized in bone reconstruction. However, their bioinertness and lack of antibacterial activity increase risks of aseptic loosening and implant‐associated infection—the primary causes of implant failure. To address these limitations, we developed a dual‐functional 3D‐printed porous titanium–hydrogel composite scaffold to enhance the osteogenic and antibacterial capacities of titanium. This composite scaffold was fabricated by integrating quaternized chitosan (QCS)/aldehyde‐terminated Pluronic F127 (PF127‐CHO) hydrogel loaded with magnesium ions (Mg2+) and zeolitic imidazolate framework‐8 (ZIF‐8) into polydopamine‐coated 3D‐printed porous titanium scaffold. The composite scaffold exhibited sustained and controlled release of Mg2+ and ZIF‐8 with enhanced binding strength at titanium–hydrogel interface. In vitro experiments demonstrated that the composite scaffold possessed favorable biocompatibility, promoted the adhesion and proliferation of MC3T3‐E1 cells, and facilitated their osteogenic differentiation through synergistic effect of Mg2+ and ZIF‐8. Furthermore, it also inhibited bacterial growth via synergistic action of QCS/PF127‐CHO hydrogel and ZIF‐8. In vivo experiments confirmed enhanced bone ingrowth into the composite scaffold and its effective antibacterial activity. In summary, this composite scaffold provides a promising strategy to simultaneously improve the osteogenic and antibacterial capacities of titanium implants.

Infected bone defects are a challenging issue in clinical orthopedics. Traditional scaffolds are prone to bacterial adhesion, colonization, and biofilm formation under infected conditions, making infection difficult to control. Additionally, severe infections can lead to tissue cell necrosis, hindering the bone repair process. In recent years, advancements in materials science and biomedical technology have driven the development of porous titanium alloy scaffolds that combine infection control with osteogenic functionality. By integrating antimicrobial properties with osteogenic potential, these scaffolds hold promise to overcome the limitations of traditional treatments and achieve early repair of infectious bone defects. Therefore, developing a porous titanium alloy scaffold that can effectively control infection and promote bone tissue regeneration under infected conditions is of significant importance for the clinical treatment of infectious bone defects.This study aims to explore the design and preparation of a dual-functional porous titanium alloy scaffold with antibacterial and bone repair capabilities, and to validate its application efficacy in infectious bone defects, with the goal of providing a more efficient and safer solution for clinical treatment.

Up to now, how to implement the optimal regenerative repair of large load-bearing bone defects using artificial bone prosthesis remains to be an enormous challenge in clinical practice. Titanium-based alloys, especially Ti6Al4V, are applied as artificial bone grafts due to their favorable mechanical property and biocompatibility, assisted by personalized customization of 3D-printing to completely match with the bone defect. However, their bioinert peculiarity restricts osteointegration at the interface between bone and titanium-based implants and bone growth into porous titanium-based scaffolds, for lack of bone regeneration with the aid of blood vessels and neural networks. Of note, ample blood delivery and integral innervation are pivotal to the survival of artificially tissue-engineered bones. Herein, the functionalized surface of 3D printed titanium alloy scaffolds driven immunoregulatory neuro-vascularized osseointegration is delved. Bone-like micro/nano morphology and chemical composition of calcium-rich formula are scrutinized to accelerate the process of bone defect repair, including inflammatory response, angiogenesis, neurogenesis, and osseointegration. Micro/nano-topographic calcium titanate (CaTiO3) coating, especially 10%H2O2-Ca, driven immunoregulatory neuro-vascularized osseointegration is validated and its underlying mechanism is attributed to the signaling pathway of TNF-α /oxidative phosphorylation, providing an effective tactic of the bone tissue-engineered scaffold with surface functionalization-driven immunoregulatory neuro-vascularized osseointegration for clinical large segmental bone defects.

3D-printed customized titanium alloy (Ti6Al4V, TC4) as load-bearing prostheses and implants, such as intervertebral cages, have been widely used in clinical practice. Native biological inertia and inadequate bone in-growth of porous titanium alloy scaffolds hampered their clinical application efficiency and then extended the healing period. To improve the osseointegration capacity of 3D-printed intervertebral cages, sandblasting was selected to execute their surface treatment. On the one hand, sandblasting treatment can efficiently eliminate incomplete unmelted powder that adheres to struts in intervertebral cages during the manufacture of 3D printing, resulting in high surface area and low surface flatness induced by the rough surface could favor osseointegration. On the other hand, sandblasting can also induce ultrafine grains and nanograins in the near-surface layer that are conductive to mechanical strength enhancement. This can be verified by both microhardness and residual compressive stress reaching peak values (404.2 HV, 539.1 MPa) in the transverse section of its near-surface layer along the depth from the surface. This is attributed to the fact that more grain boundaries can impede dislocation movement. Sandblasting surfaces in intervertebral cages could favor osseointegration and in-growth, providing a foundation for sandblasting treatment of 3D-printed intervertebral cages in clinical applications.

Sulfur mustard (SM), a well-known vesicant chemical warfare agent, induces acute lung injury through mechanisms that remain incompletely understood. This study aimed to delineate the specific contributions of oxidative stress and inflammatory pathways in SM-mediated pulmonary damage. A C57BL/6 J mouse model exposed to aerosolized 2-chloroethyl ethyl sulfide (CEES, a sulfur mustard analogue) and an in vitro macrophage model were established. Evaluations were conducted using pulmonary function tests, transcriptome sequencing, RT-qPCR, Western blot, and ELISA. Functional validation was performed through pharmacological activation of peroxisome proliferator-activated receptor γ (PPARγ) and application of a NADPH oxidase 4 (NOX4) inhibitor. CEES exposure was found to induce airway obstruction in mice, accompanied by alveolar structural damage and significant infiltration of pro-inflammatory macrophages. Levels of ROS and MDA were elevated in lung tissues, and antioxidant enzyme activity showed an initial compensatory increase followed by exhaustion. Increased levels of TNF-α and IL-6, together with decreased levels of Arg-1 and IL-10, were observed in serum and lung homogenates. Transcriptomic analysis and subsequent validation experiments indicated that CEES up-regulated the expression of NOX4 and suppressed PPARγ. In vitro, overexpression of PPARγ promoted the expression of IL-10, Arg-1, and CD206, while suppressing TNF-α, IL-6, and iNOS. Inhibition of NOX4 expression reduced ROS and MDA levels, restored PPARγ expression, and promoted a shift from M1 to M2 polarization. Collectively, these findings elucidate a central regulatory axis wherein CEES triggers macrophage polarization imbalance via the NOX4/PPARγ-mediated integration of oxidative stress and inflammatory signaling, thereby amplifying lung injury. This study lays the foundation for developing targeted dual-action therapeutic strategies addressing both oxidative and inflammatory injury, with significant relevance to the field of chemical warfare agent protection.

Stroke significantly alters microglial immune status beyond the traditional M1/M2 classification. We analyzed single-cell RNA sequencing data from the striatum of hemorrhagic, ischemic, and control mice, revealing activation of mitochondrial autophagy and assembly processes after stroke. Gene Ontology functional enrichment analysis indicated that stroke-associated genes predominantly regulate mitochondrial maintenance, with leucyl-tRNA synthetase 2 (Lars2) markedly upregulated in post-stroke microglia. A distinct microglial subset (Mc) was identified with notably low Lars2 expression. In vitro, Lars2 overexpression enhanced mitochondrial function, reduced pro-inflammatory cytokine release, and suppressed Mc marker gene expression. Cell-cell communication analysis revealed Mc as the most interactive microglial subset following stroke, particularly engaging with neurons. Among neuron-Mc signaling pairs, the neurotrophic factor pleiotrophin-syndecan-4 (PTN-SDC4) ligand-receptor pair emerged as a key mediator. Conditioned media from stressed microglia upregulated neuronal Ptn expression, likely recruiting microglia, as exogenous PTN promoted microglial migration. These findings identify Mc as a stroke-induced microglial population with low Lars2 expression and pro-inflammatory features. The lack of compensatory mitochondrial repair in Mc contributes to pro-inflammatory polarization, positioning Lars2 as a mitochondrial checkpoint linking stroke-induced microglial reprogramming to neuroinflammation.

INTRODUCTION:Bone fracture is increasing in patients with type 2 diabetes mellitus (T2DM) due to skeletal fragility. Most antidiabetics are expected to reduce the incidence of fracture in patients with T2DM, however the results are disappointing. Metformin and GLP-1 receptor agonists have a neutral or minor positive effect in reducing fractures. OBJECTIVES:We aim to reveal the mechanism of fracture in patients with T2DM treated with metformin or exendin-4, explore the key regulators responsible for bone fragility in T2DM. METHODS:Trabecular and cortical masses in mice with T2DM were analyzed using micro-computed tomography. Biomechanical strength of bone was determined according to three-point bending, and the expression of bone-associated factors was examined with enzyme-linked immunosorbent assays. Important proteins and miRNAs were identified using proteomics analysis and deep screening analysis. Lastly, immunoprecipitation-mass spectrometry and dual-luciferase reporter analysis were used to identify key molecular signals. RESULTS:We found that sermaphorin 4D (Sema4D) is the key regulator of bone fragility in T2DM. Exendin-4 increased the biomechanical properties of bone by decreasing serum Sema4D levels, and metformin has little effect on Sema4D. Anti-sema4D treatment could improve bone strength in T2DM mice compared with metformin or exendin-4. The biomechanical properties of bone were comparable between anti-Sema 4D and the combination of metformin and exendin-4. Exendin-4 promoted osteogenesis of BMSCs by activating CRMP2 to reverse the effect of sema4D. Metformin increased miR-140-3p levels, which decreased plexin B1 expression in bone mesenchymal stem cells. Metformin increased the effect of exendin-4 with more GLP-1 receptor expression to increase the biomechanical strength of bone via miR-140-3p-STAT3-miR-3657 signaling. CONCLUSION:Blood glucose level is not the major factor contributing to impairment in bone remodeling. Sema4D is responsible for the increase in the incidence of bone fractures in T2DM. Accordingly, we proposed an effective therapeutic strategy to eliminate the effect of sema4D.

Bone regeneration is synergistically regulated by growth factors, which are expressed in a coordinated cascade of events. An ideal guided bone regeneration membrane (GBRM) shall present barrier and antibacterial functions, and promote osteogenesis through time-controlled release of growth factors. In this study, a coordinated cascade therapy-based Janus fibrous membrane is fabricated by coaxial electrospinning and layer-by-layer self-assembly technology (LBL). Specifically, the oriented PCL/PLGA fibers loaded with zinc oxide nanoparticles (ZnO NPs) are designed as the outer layer, and randomly arranged core-shell Gelatin/PLLA nanofibers are employed as the inner layer to rapidly release aFGF and sustainedly release BMP-2. Results demonstrated that the Janus fibrous membrane achieved multiple functions to satisfy essential requirement of bone regeneration, which exhibited remarkable antibacterial ability, barrier function, osteoinductive ability. Interestingly, the significant enhancement of oxidative phosphorylation (OXPHOS) as the major energy supply pathway is the decisive factor to drive osteogenic differentiation of BMSCs induced by Janus fibrous membranes. This study provides a novel strategy to fabricate multifunctional membranes/scaffolds, displaying great potential applications in tissue engineering. Besides, understanding the synergistic mechanism of time-controlled release of growth factors on the cellular energy metabolism process can provide deeper insights into growth factors-mediated tissue regeneration and optimizing healing outcomes.

Osteonecrosis of the femoral head (ONFH) is a common condition that greatly affects patients’ quality of life, yet current treatments often have limited effectiveness. This study aimed to explore how a porous titanium alloy scaffold coated with barium titanate (BaTiO3) could promote bone regeneration in ONFH. We employed various research methods including cell culture, piezoelectric property measurements, tissue-engineered scaffold fabrication, and in vitro and in vivo biocompatibility assessments. Our results showed that macrophages had better attachment and growth on the BaTiO3-coated porous titanium alloy (PTB) scaffold than on the uncoated porous titanium alloy (PT) scaffold, with no significant differences in apoptosis rates between the two groups. Furthermore, the PTB scaffolds reduced the expression of bone resorption markers, such as Cathepsin K, TRAP, and RANK, under dynamic loading conditions. This finding indicates their potential to inhibit osteoclast differentiation. Moreover, the BaTiO3 coating enhanced the mechanical properties and biocompatibility of the scaffolds, evidenced by significantly higher alkaline phosphatase activity and calcium nodule formation in MC3T3-E1 osteoblasts cultured on PTB scaffolds. These findings underscore the dual role of BaTiO3 in facilitating cellular responses and modulating signaling pathways involved in bone metabolism. Our study highlights the promise of BaTiO3-coated titanium alloy scaffolds as an innovative approach to enhance bone regeneration in ONFH, paving the way for future clinical applications and the development of advanced biomaterials for bone healing.

Three-dimensional-printed porous titanium alloy implants have shown significant potential for addressing large segmental bone defects in weight-bearing applications. Nevertheless, existing limitations, particularly stress concentration within porous structures and biologically inert surfaces, often result in suboptimal bone ingrowth and reconstruction failure. Therefore, optimizing the scaffold structure to homogenize the stress distribution and endowing the implant with osteogenic capabilities are critical approaches to improve the success rate of bone defect reconstruction. In this context, a dual-bionic titanium scaffold combining a triply periodic minimal surface (TPMS) architecture for mechanical optimization with a barium titanate (BaTiO _3 ) piezoelectric coating to enhance electromechanical conversion was constructed. Structural and functional characterization validated the improved mechanical performance and efficient electromechanical response of the scaffold. In vitro and in vivo studies further revealed that BaTiO _3 coated TPMS scaffolds promoted osteogenesis and bone remodeling by activating the focal adhesion kinase and PI3K/AKT signaling pathways through electromechanical stimulation during defect repair. This biohybrid design paradigm provides a promising solution for load-bearing bone regeneration through simultaneous mechanical optimization and electromechanical microenvironment regulation.

Pulmonary fibrosis is a severe lung disease characterized by the epithelial-mesenchymal transition (EMT) of alveolar epithelial cells, leading to an increase in fibroblasts or myofibroblasts. Currently, effective therapeutic options for PF remain limited, rendering the inhibition or reversal of EMT a clinically imperative goal. Caffeic acid phenethyl ester (CAPE), a natural flavonoid, exhibits various biological activities, including antioxidant, anti-inflammatory, anticancer, antiviral, and immunomodulatory effects. However, the role of CAPE in EMT-related diseases such as pulmonary fibrosis remains unclear. This study aimed to investigate whether CAPE can target the Sirtuin 1 (Sirt1)/Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) pathway to regulate mitochondrial function, thereby inhibiting EMT and pulmonary fibrosis. Our in vitro and in vivo findings demonstrate that CAPE significantly improves the quantity and function of mitochondria including mitochondrial DNA (mtDNA) content, ATP level, or mitochondrial membrane potential in altered alveolar epithelial cells, increases the ratio of alveolar epithelial to mesenchymal cell markers, and reduces ROS level or collagen expression, ultimately alleviating the degree of fibrosis. These findings establish a robust preclinical foundation for the translational application of CAPE in EMT-related diseases. In conclusion, CAPE may serve as a potential therapeutic agent for pulmonary fibrosis by modulating mitochondrial function through the Sirt1/PGC-1α pathway, underscoring its potential for clinical translation and merit for further investigative efforts in other EMT-associated conditions.

Marbling traits serve as a key determinant of meat quality in livestock, with interspecies genetic variations significantly influencing intramuscular fat (IMF) deposition. Through systematic analysis of public databases and cross-species RNA sequencing data from cattle, sheep, and pigs exhibiting divergent IMF levels, we identified PCK2 as a conserved regulatory factor governing lipogenesis. Functional analyses demonstrated that targeted PCK2 silencing significantly impaired cell cycle dynamics and suppressed adipocyte proliferation, which mechanistically involved transcriptional downregulation of key cell cycle regulators (CCNB1, CCND1, CCNE2) and functional inhibition of critical proliferative mediators (CDK1, CDK2, PCNA). Furthermore, PCK2 silencing impaired lipid accumulation by decreasing triglyceride synthesis and lipid droplet formation, while down-regulating adipogenic transcription factors PPARγ and C/EBPα, as well as lipid metabolism factors SCD1, ACSL1 and FABP4. Integrated multi-omics analysis revealed PCK2 modulates bovine IMF deposition through the regulation of lipolysis in adipocyte. Notably, patatin-like phospholipase domain containing 2 (PNPLA2) suppression as a novel mechanism underlying PCK2-mediated enhancement of bovine intramuscular adipocyte differentiation. These findings establish a molecular framework for understanding PCK2’s regulatory role in marbling beef production.

The treatment of large bone defects is rendered challenging owing to ischemia, hypoxia, and insufficient osteogenesis in the defect sites. Consequently, the use of oxygen-releasing osteogenic materials has been studied extensively in recent years. This study aimed to construct and test a 3D-printed composite scaffold with both angiogenic and bone-repair functions. A “sandwich”-like structure containing polycaprolactone, hydroxyapatite, and calcium peroxide was fabricated using fused deposition modeling 3D printing technology. The polycaprolactone/hydroxyapatite/calcium peroxide composite scaffolds exhibited excellent mechanical properties and sustained oxygen release for over three weeks. Compared to the control groups, the polycaprolactone/hydroxyapatite/calcium peroxide scaffolds also significantly promoted rat bone marrow mesenchymal stem cell proliferation, migration, adhesion, and osteogenic differentiation, with the scaffold containing 1% calcium peroxide showing the most potent pro-angiogenic and bone-repairing effects. In a rat calvarial defect model, radiographic and histological analyses revealed that the synergistic effects of calcium peroxide and hydroxyapatite significantly induced vascular network formation, accelerated bone regeneration across the entire defect area, and markedly enhanced new bone formation. In summary, this work proposes a novel strategy for fabricating cell- and growth factor-free bone tissue engineering scaffolds with potential for tissue regeneration and clinical replacement.

Sulfur mustard (SM), a typical alkylating agent, poses significant threats. Inhalational SM exposure causes acute lung injury (ALI) with complex mechanisms and no effective antidotes. we established a murine inhalation model and an in vitro alveolar epithelial cell (MLE-12) model using chloroethyl ethyl sulfide (CEES), a well-characterized SM analog, to explore therapeutic interventions. We found that dexmedetomidine (DEX), a clinically anesthetic with multi-mechanistic properties, effectively mitigated CEES-induced pulmonary histopathological and functional damage, enhancing survival rates in vivo. Transcriptomic profiling revealed that DEX reversed CEES-mediated downregulation of genes involved in hematopoietic lineage differentiation in lung tissues. Further histopathological and hematological analyses revealed that DEX mitigated CEES-triggered bone marrow suppression, splenic white pulp atrophy, peripheral neutrophilia, and serum inflammatory cytokine elevation. DEX also suppressed pulmonary infiltration of neutrophils and monocyte-macrophages, along with reduced inflammatory mediators. Mechanistically, DEX inhibited mitochondria-mediated apoptosis in both lung tissues and MLE-12 cells. Additionally, DEX reduced reactive oxygen species (ROS) and mitochondrial ROS levels, while enhancing SOD1 and glutathione content. Finally, DEX reversed CEES-induced mitochondrial structural damage in type II alveolar epithelial cells and the increase in mtDNA content in lung tissue, ameliorated the decline of mitochondrial membrane potential in MLE-12 cells, and inhibited the downregulation of the mitochondrial Mfn1 in both in vivo and in vitro models. Collectively, our findings underscore DEX's multifaceted protective mechanisms, including modulation of inflammation, apoptosis, oxidative stress, and mitochondrial homeostasis against SM analog-induced ALI.