Glutathione decline coordinates mitochondria to license histone acetylation and zygotic genome activation.

Alpha-lipoic acid (ALA), a potent antioxidant, anti-inflammatory and cytoprotective drug, has revealed potential efficacy in pre-clinical studies in reducing radiation induced oral mucositis (RIOM). This study aims to evaluate the protective effects of ALA on RIOM. In this randomized controlled study, 70 head and neck cancer (HNC) patients receiving definitive radiotherapy were assigned to receive either oral ALA (600 mg twice daily) or placebo tablets throughout the radiotherapy period. The primary outcome was the assessment of the incidence and severity of RIOM using the Radiotherapy Oncology Group (RTOG) grading system. Secondary outcomes were the onset and duration of severe RIOM (Grades 3 and 4), quality of life (QOL), and serum total antioxidant capacity (TAC) and C-reactive protein (CRP). The incidence of severe RIOM was 16.7% with the use of ALA, while in the control group it was 41.3% (p value = 0.036). Moreover, ALA significantly delayed the occurrence of severe RIOM (p value = 0.033) and resulted in significantly shorter healing time (p value = 0.042). At the end of the study, ALA resulted in a mean percent change in QOL score from baseline of 43.33, which was non-significantly different from the control group with a mean of 44.84. ALA significantly improved TAC levels but had no effect on CRP. The use of ALA was safe and tolerable. ALA showed a significant reduction in the severity and delayed the onset of RIOM with a high safety profile through its potent antioxidant effects.

Alpha-lipoic acid (ALA) is a natural compound present in plants, animals, and humans. It provides neuroprotection through its antioxidantaction, reducing oxidative stress and inflammation via pathways such as the Nrf-2 signalling pathway. It has shown protective effect against neuronal damage in Alzheimer's disease and Parkinson's disease. The traumatic brain injury (TBI) is a major cause of cognitive and motor impairments. TBI primarily initiates a series of secondary injury pathways, with glutamate excitotoxicity being a critical factor in neuronal degeneration. In this study, we investigated the protective effects of ALA on TBI induced by controlled cortical impact (CCI) in the cerebral cortex (CC) and hippocampus (HC) regions of the Wistar rats. TBI parameters were analysed using behavioural assays, including the Barnes maze test (BMT), beam balance test, grip strength, and Y-maze test (YMT). In addition, we measuredbrain water content, and analyzedhistological alterationsby light microscopy, microglial changes bythe immunofluorescencetechnique, and ultrastructural changes by the transmission electron microscopy (TEM). Expression of markers of glutaminergic and calcium (Ca2⁺) pathways wasanalysed by qRT-PCR and western blotting. ALA was administered following TBI induction in rats. It was shown that ALA downregulated S100B and the N-methyl-D-aspartate (NMDA) receptor subunit 2B (GRIN2B) mRNA expression. However, TBI-dependent alterations in excitatory amino acid transporter (EAAT) expression were downregulated in the CC region of adult rats with TBI. Protein expression of S100B, stromal interaction molecule (STIM), ubiquitin C-terminal hydrolase L1 (UCHL1), nuclear factor kappa (NF-ƙB), and glial fibrillary acidic protein (GFAP) was increased in the TBI group, as analysed by immunoblotting. Furthermore, expression ofIba1+, a marker of microglial activation, was increased in TBI and mitigated by ALA. Overall, this study helps us understand the role of ALA as a mitigating compound in the TBI-induced rat model.

Intervening in the aberrant redox homeostasis of tumors, particularly toward reactive oxygen species (ROS) overload, holds considerable promise for cancer therapy, yet, is severely constrained by the robust compensatory antioxidant defense system (ADS) and the unavoidable disruption of redox homeostasis in normal tissues. Here, we present a catalytic redox-cycling nanoreactor, TEMPO radical-modified cross-linked lipoic acid nanoparticles (T@cLAN), designed to achieve robust oxidative stress amplification for cancer therapy. Lipoic acid (LA) characterized by a cyclic disulfide backbone enables intermolecular thiol-disulfide exchange to from GSH-responsive crosslinked networks, while enabling reversible interconversion with dihydrolipoic acid (DHLA), which can further participate in redox modulation. Mechanistically, T@cLAN depletes intracellular glutathione (GSH) and undergoes depolymerization to generate dihydrolipoic acid (DHLA), which actively participates in redox processes to enhance ROS production. TEMPO, functions as a catalyst rather than a stoichiometric scavenger, directly accelerating the endogenous LA/DHLA redox cycle, thereby further amplifying DHLA generation and sustaining both GSH depletion and ROS amplification. As validated by both in vitro and in vivo results, T@cLAN dismantles the major ADS barrier limiting tumor oxidative stress, achieving an overall 85% GSH depletion and elevating ROS levels by 37-fold compared to untreated tumor cells. Concurrently, it induces both apoptosis and ferroptosis, attaining a tumor inhibition rate of 80% while causing minimal impact on normal cells and tissues, underscoring its substantial potential for cancer therapy. STATEMENT OF SIGNIFICANCE: We engineer a nanoreactor (T@cLAN) as an innovative modality to address a central limitation of oxidative stress-mediated anticancer therapy, that is, the therapeutic attenuation imposed by the highly developed antioxidant defense machinery of tumor cells. T@cLAN is activated by intracellular glutathione, a key redox buffer, to engage two interlinked redox catalytic cycles, enabling sustained glutathione depletion and the amplified accumulation of cytotoxic reactive oxygen species. Through this cooperative redox reprogramming, T@cLAN promotes tumor cell apoptosis and ferroptosis, leading to pronounced anticancer activity. Notably, T@cLAN is activated within the tumor microenvironment while remaining largely quiescent in normal cells, reflecting an active and highly selective intervention mechanism that offers new directions for oxidative stress driven therapeutic innovation.

To assess the efficacy and safety of alpha-lipoic acid (ALA) and pregabalin, both as mono and combination therapy, for treating painful diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus, with the hypothesis that pregabalin monotherapy is non-inferior to combination therapy. A phase 4 randomized, active-controlled, open-label, multicentre trial was conducted over 12 weeks to investigate changes in visual analogue scale (VAS) pain scores from baseline as a primary efficacy endpoint. A total of 151 eligible subjects were randomly assigned to ALA (480 mg/day), pregabalin (150 mg/day), and combination groups in a 1:1:1 ratio. The pregabalin monotherapy group showed a VAS change of -19.73 ± 18.94 mm, while the combination group showed -23.28 ± 18.15 mm at Week 12. The least square mean (LSM) difference between the two groups was 3.46 mm (95% CI: [-4.94, 11.87]), demonstrating that pregabalin monotherapy is non-inferior to combination therapy. Safety analysis revealed no significant differences across treatment groups. Cluster analysis revealed statistically significant differences in VAS scores between the pregabalin monotherapy and combination therapy groups at 12 weeks in cluster 1, characterized by a relatively shorter duration of DPN, and the LSM difference between both groups was 14.79 mm [4.59, 24.99] (p = 0.0055). The pregabalin monotherapy demonstrated non-inferiority compared to the combination therapy in alleviating DPN pain. Cluster analysis supported the identification of patient groups where combination therapy could be more effective, but future comprehensive studies are required for further verification. ClinicalTrials.gov, NCT04846673.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder increasingly associated with aberrant astrocyte activation. Hydrogen sulfide (H2S) has recently emerged as a key regulator of astrocyte function, yet its role in ASD remains largely unexplored. Here, we investigated the association between H₂S modulation, ASD-like phenotypes, and astrocyte activation. In valproic acid (VPA)-exposed rats, H₂S were modulated using α-lipoic acid (LA) or aminooxyacetic acid (AOAA), a cystathionine β-synthase (CBS) inhibitor. Behavioral performance, neuronal injury, astrocyte phenotypes, H₂S levels, CBS expression and the homocysteine/cystathionine ratio were evaluated in vivo and in primary astrocytes. VPA-exposed rats exhibited reduced H₂S levels and CBS expression, an increased homocysteine/cystathionine ratio, ASD-like behavioral deficits and neuronal injury, and astrocyte activation toward a neurotoxic A1 phenotype. Elevation of H2S by LA was associated with improvements in ASD behavioral performance, reduced neuronal damage, reduced inflammatory cytokines and suppressed astrocyte activation, with changes in astrocyte marker expression towards a more A2-like, neuroprotective profile. Conversely, AOAA reversed these beneficial effects. Collectively, these findings suggested enhanced H₂S signaling is linked to improvements in ASD-like behavioral and neuropathological abnormalities, alongside modulation of astrocyte activation involving the CBS/H₂S pathway. These findings highlight the potential involvement of the CBS/H₂S axis in ASD-related pathology.

Oral mucosal wound repair remains a crucial clinical challenge, as the humid and highly dynamic oral microenvironment creates complex conditions that limit the efficacy of conventional treatment strategies. Bioadhesives have emerged as promising biomaterials that effectively address the key limitations of conventional treatments and open new avenues for oral mucosal wound repair. Herein, an ultrasound-responsive lipoic acid-based bioadhesive with in situ polymerization and targeted adhesion capabilities for oral mucosal wounds has been designed. Lipoic acid (LA) was used as the monomer and dissolved in tris(hydroxymethyl) aminomethane (Tris) solution to prepare the hydrogel precursor. Due to the unique disulfide five-membered ring in LA, the precursor rapidly gelled in situ under ultrasound stimulation after being injected onto oral wounds, ensuring precise and stable adhesion. The results demonstrated that the ultrasound-responsive polylipoic acid (UPLA) hydrogel exhibited appropriate adhesive strength and mechanical properties, while cell experiments indicated that this material possessed satisfactory biocompatibility and could promote the migration of human oral keratinocytes (HOKs). In vivo animal experiments further showed that the hydrogel achieved reliable adhesion to the rat oral mucosa and significantly accelerated wound healing processes. Notably, this therapeutic effect was attributed to the hydrogel's ability to promote epithelial regeneration and restoration of epithelial integrity, while simultaneously reducing local inflammatory responses at the wound site. This UPLA bioadhesive integrates in situ gelation, stable mucosal adhesion, and active wound-healing promotion, thereby providing a novel and promising candidate material for clinical oral mucosal wound repair.

The stability and dispersibility of nanoparticles (NPs) directly affect their physicochemical properties and functional performance. In this study, we systematically investigate how ligand structure influences the colloidal stability of gold nanoparticles (Au NPs) under aggregation-inducing chemical conditions. Key structural parameters of ligands, including dendricity, binding groups, and spacer length, are varied to establish design principles for protecting the NPs. Au NPs of varying diameters (and thus surface curvatures), synthesized in both organic and aqueous media, are functionalized with these customized ligands to evaluate how ligand architecture influences colloidal stability and phase transfer efficiency. Oleylamine (OLAM)- or citrate-coated Au NPs are functionalized with these customized ligands via direct ligand exchange and subsequently exposed to a reactive solution of 1,4-butanedithiol (BDT) that triggers ligand displacement and aggregation. Our findings emphasize that the bidentate chelating effect of the lipoic acid (LA) binding group and the diverging terminal chains in the dendritic structures are pivotal in preventing ligand competition-induced clustering and aggregation. Higher-generation dendrons confer greater stability compared to small-molecule ligands, whereas ligands bearing a LA binding group are pivotal for successful phase transfer and stabilization of Au@citrate.

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance, hyperandrogenism, oxidative stress, and disrupted folliculogenesis. The present study aimed to investigate whether combined alpha-lipoic acid (ALA) and vitamin D therapy exerts synergistic effects on metabolic, oxidative, endocrine, and histomorphological parameters in a letrozole-induced rat model of PCOS. Sixty female Wistar Albino rats were randomly divided into six groups: Control, PCOS, PCOS+Metformin (500mg/kg/day), PCOS+Vitamin D (1000 IU/kg/day), PCOS + ALA (100mg/kg/day), and PCOS + ALA+Vitamin D. PCOS was induced with letrozole (1mg/kg/day) for 21 days, followed by 30 days of treatment. Fasting blood glucose (FBG), insulin, and HOMA-IR were assessed to evaluate metabolic status. Ovarian oxidative stress markers (MDA, SOD, CAT, GSH), serum hormonal parameters (testosterone, LH, FSH, LH/FSH ratio), and detailed histomorphometric analyses were performed. Statistical analyses included one-way and two-way ANOVA. Letrozole administration induced persistent diestrus, hyperandrogenemia, increased ovarian weight, elevated HOMA-IR (6.61 ± 1.18 vs. 2.24 ± 0.42, p < 0.001), and marked oxidative stress (MDA: 5.84 ± 0.72 vs. 2.31 ± 0.34 nmol/mg, p < 0.001). ALA and vitamin D monotherapies significantly improved metabolic, oxidative, and endocrine parameters compared with untreated PCOS rats (p < 0.05). The combination therapy group demonstrated the most pronounced improvements, with HOMA-IR (2.43 ± 0.47), MDA (2.52 ± 0.39 nmol/mg), testosterone (1.29 ± 0.27 ng/mL), and LH/FSH ratio (1.03 ± 0.19) values approaching control levels (all p < 0.01 vs. PCOS). Histologically, combined treatment markedly reduced cystic follicles and restored granulosa and theca thickness. Two-way ANOVA revealed significant interaction effects for HOMA-IR, MDA, testosterone, and LH/FSH ratio (p < 0.05). Combined ALA and vitamin D therapy produced enhanced improvements in insulin resistance, oxidative stress, endocrine imbalance, and ovarian morphology in experimental PCOS. Simultaneous targeting of mitochondrial redox dysfunction and endocrine-metabolic signaling pathways may represent a promising multidimensional therapeutic approach in PCOS.

Supramolecular polymer materials derived from biological entities are of paramount importance for the construction of next-generation functional materials. In this study, we employed the flame-retardant monomer HEMA-DPC (HDP) and the aggregation-induced emission monomer (2-(4-vinylphenyl)ethene-1,1,2-triyl)tribenzene (TPEE) to synthesize a novel flame-retardant fluorescent supramolecular polymer material via solvent-free modification of lipoic acid. This is a new strategy for the synthesis and application of double bond addition flame retardant fluorescent lipoic acid supramolecular polymers. Compared with existing lipoic acid polymer materials, this polymer material has a wide range of applications. It serves as a flame-retardant adhesive for fluorescent tracing at post-combustion ash sites. It also acts as a fluorescent encryption material for the encryption of digital information and the decryption of underwater quick response (QR) codes. Furthermore, it can be formulated into a safe, non-toxic, waterproof fluorescent ink, which is cost-effective, environmentally friendly, and holds promise for mass production and widespread application.

The global food security is threatened by the accumulation of anthropogenic nanomaterials in the environment. We investigated the phytotoxic effects of elevated zinc oxide nanoparticles ([ZnO]NPs: 300-400 mg L⁻1) on wheat (Triticum aestivum L.) and evaluated a novel detoxification strategy using successive redox-priming. Wheat caryopses were primed with alpha-lipoic acid (LA) and sodium nitroprusside (SNP, a nitric oxide donor) either individually or in successive sequences (LA→SNP and SNP→LA). Exposure to [ZnO]NPs resulted in significant growth inhibition, reduction of biomass and degradation of chlorophyll. However, successive priming, particularly the LA+SNP combination, significantly attenuated these negative effects. This treatment effectively restored seedling growth by creating a strong antioxidant shield, greatly increasing the activities of SOD, POD, CAT, and APX, and raising metal chelating activity to 98.1%.Furthermore, Density Functional Theory (DFT) calculations, including HOMO-LUMO and molecular electrostatic potential (MEP) analyses, gave mechanistic insights into the molecular interactions of the priming agents and ZnO, highlighting their role as potent radical scavengers and stabilizers. The results indicate that a successive redox priming is an effective and sustainable approach to enhance crop tolerance to high concentrations of nanoparticle toxicity.

Although injectable hydrogels hold promise as dressings for chronic diabetic wounds, their clinical potential is often limited by non-specific actions and modest efficacy. To address these limitations, we developed a novel injectable hydrogel by integrating Bletilla striata polysaccharide (BSP)-known for its biocompatibility and wound-healing properties-with alpha-lipoic acid (LA), a potent antioxidant and antimicrobial agent. The preparation process is straightforward, requiring only the mixing of LA dissolved in Tris buffer (LA-Tris) and BSP solutions, and the gelation time was inversely correlated with BSP content. The resulting BSP/LA hydrogel displayed excellent injectability, appropriate mechanical strength, reliable tissue adhesion, and tunable degradation and swelling behaviors. By leveraging the synergistic effects of BSP and LA, the hydrogel exhibited strong broad-spectrum antimicrobial and antioxidant activities. Both in vitro and in vivo evaluations confirmed its high biocompatibility. Notably, in a diabetic rat wound model, the BSP/LA hydrogel significantly accelerated wound closure, attenuated inflammatory responses, stimulated collagen deposition, and enhanced neovascularization compared to control groups. These collective findings underscore the potential of this multifunctional injectable hydrogel as an effective and clinically viable dressing for the management of complex chronic wounds.

UHPLC-Q-Exactive Orbitrap MS-based brain-gut metabolomics implicates multi-pathway modulation by Ginseng stem-leaf saponins in chronic fatigue syndrome mice.

The development of delivery systems that deliver ALA as a cryoprotectant to sperm in a controlled manner could provide a promising strategy to minimize the toxicity associated with direct use of alpha-lipoic acid (ALA) during cryopreservation. Therefore, the aim of this study was to design and evaluate a nanocarrier based on sericin (SER) and a polysaccharide extracted from Physalis alkekengi for ALA encapsulation in a way that minimizes the toxicity resulting from direct use of ALA by controlling the release. To find the optimal ratio of SER and polysaccharide (pro/poly), a polysaccharide-SER-based nanocarrier (Ph-SER-NC) was synthesized using different ratios of pro/poly. Then, based on the optimization results, Ph-SER-NC was synthesized by the nanoprecipitation method, and ALA was loaded into the nanocarriers by direct system of dissolution into the aqueous phase (ALA-Ph-SER-NC). Its physicochemical characteristics were determined by the dynamic light scattering (DLS) technique. Furthermore, Fourier transform infrared spectroscopy (FTIR) was used to characterize the chemical composition, molecular properties, and surface adsorption of functional groups of the ALA-Ph-SER-NC. Then, the effects of ALA-Ph-SER-NC on biological properties after cryopreservation were investigated. The results showed that the optimal ratio of pro/poly for Ph-SER-NC synthesis was 1:2, and the resulting Ph-SER-NC had a Z-average and PDI of 109nm and 0.21, respectively. After ALA loading, the physicochemical properties of the ALA-Ph-SER-NC, including Z-average, PDI, and zeta potential of 186.9nm, 0.456, and - 11.8 mV, were determined, respectively. The encapsulation efficiency for ALA was determined to be 93.7%. Biological evaluation showed that at concentrations of 0.02 and 0.05 mmol/mL, the ALA-Ph-SER-NC group significantly improved sperm parameters, including increases of approximately 26% in total motility, 24% in morphology, and 12% in viability, along with a 28% reduction in DNA fragmentation index (DFI). The results indicated that ALA-Ph-SER-NC, through controlled release of ALA, preserved key biological properties of sperm. Thus, the synthesized ALA-Ph-SER-NC offers a novel and effective approach to preserve sperm quality during cryopreservation in men at risk of reduced fertility.

α-Lipoic acid (LA), a natural cyclic disulfide, has emerged as a versatile building block for next-generation adhesives because of its ring-opening polymerization and dynamic disulfide exchange. This review summarizes recent advances in LA-based adhesives, focusing on strategies for stabilizing poly(LA) networks through radical quenching, supramolecular assembly, metal-ligand coordination, and deep eutectic architectures. We discuss the interfacial mechanisms underlying robust wet and underwater adhesion, where dense carboxyl groups enable multivalent hydrogen-bonding and ionic interactions. LA-based adhesives also integrate self-healing, recyclability, and intrinsic bioactivity, including antioxidant and antimicrobial functions. These features support applications in hemostasis, wound repair, wearable iontronics, and sustainable industrial bonding. Finally, key challenges, including the trade-off between network stability and dynamicity and the need for scalable manufacturing, are highlighted to guide the future development of circular, smart, and bioactive adhesive materials.

Wound closure by suture and staple demands surgical skills and carries risks of traumatic complications, whereas current tissue adhesives exhibit insufficient wet adhesion strength, unsatisfactory in vivo biodegradability, and durability. Inspired by the robust underwater adhesion of mussels, whose underwater adhesion derives from the synergy of hydrophobic and adhesive matrix, a tough bioadhesive (PLD) was developed by coassembly of lipoic acid (LA) and a dopamine-functionalized lipoic acid derivative (LAD). Mimicking the mussel's adhesion mechanism, PLD expelled interfacial water via hydrophobic chains, enabling catechol and carboxyl groups to form robust bonds with wet tissue. It exhibited water-strengthened underwater adhesion (approximately from 37.06 to 50.23 kPa after 180 min water immersion) due to water-activated aggregation of hydrophobic chains. Owing to the combined effect of hydrogen bonds, π-π interaction, and hydrophobic associations, PLD displayed durable wet adhesion because it had exceptional antiswelling properties with a remarkably low swelling ratio of 2.07% after 72 h in a physiological environment. In addition, it was bioresorbable, cytocompatible, and histocompatible. The PLD adhesive may offer a promising and multifunctional alternative to conventional sutures for wound closure.

Diabetes mellitus is a chronic metabolic disorder in which persistent hyperglycemia promotes oxidative stress, inflammatory activation, and progressive liver injury. Alpha‑lipoic acid (ALA) is an endogenous and diet‑derived antioxidant with glucose‑lowering and insulin‑sensitizing actions. Still, its therapeutic efficacy is constrained by low oral bioavailability and rapid metabolism. In this context, the present study compared the hepatic pharmacodynamic effects of free ALA and ALA‑loaded chitosan nanoparticles (ALA‑CNPs) in streptozotocin (STZ)‑induced diabetic rats. Here, pharmacodynamic effects refer to the biochemical and molecular actions on hepatic tissue, including modulation of oxidative stress markers, activation of cytoprotective signaling pathways such as Nrf2/HO‑1, and inhibition of pro‑inflammatory cascades (e.g., TLR4/NF‑κB and JAK2/STAT1), which collectively contribute to hepatoprotection. Diabetes was induced by a single intraperitoneal injection of STZ (60mg/kg). Rats with fasting blood glucose ≥ 250mg/dL were randomized into six groups (n = 15/group): non‑diabetic control, non‑diabetic + ALA, non‑diabetic + ALA‑CNPs, untreated diabetic, diabetic + ALA, and diabetic + ALA‑CNPs. Treatments were administered once daily for 4weeks. STZ‑induced diabetes caused marked hyperglycemia, reduced serum insulin, dyslipidemia, increased serum alanine and aspartate aminotransferase activities, enhanced hepatic malondialdehyde, depletion of superoxide dismutase, catalase, glutathione peroxidase, and reduced glutathione, and downregulation of the Nrf2/HO‑1 pathway. These changes were accompanied by elevated hepatic tumor necrosis factor‑α, interleukin‑6, and interleukin‑1β; activation of Toll‑like receptor‑4/nuclear factor‑κB and Janus kinase‑2/signal transducer and activator of transcription‑1 signaling, and hepatocellular necrosis; vacuolation; mitochondrial swelling; and endoplasmic reticulum disorganization. Both ALA and ALA‑CNPs attenuated these metabolic, biochemical, and structural disturbances, but ALA‑CNPs produced more pronounced reductions in fasting blood glucose and improvements in lipid profile, antioxidant status, and liver histology. ALA‑CNPs also more effectively upregulated Nrf2/HO‑1 and suppressed Toll‑like receptor‑4/nuclear factor‑κB and Janus kinase‑2/signal transducer and activator of transcription‑1 activation and pro‑inflammatory cytokines. These findings indicate that nano‑encapsulation of ALA enhances its hepatoprotective pharmacological profile in diabetes‑associated liver injury by concomitantly targeting oxidative stress and inflammatory signaling cascades.

Metabolic division of labor drives synergistic production of biomass, lipid and α-tocopherol in Euglena gracilis-Chlorella pyrenoidosa co-cultures.

Aortic aneurysm and dissection (AAD) is a fatal vascular emergency with limited mechanism-based therapies. The mitochondrial AAA+ ATPase ATAD3A (ATPase family AAA domain-containing protein 3A), enriched at organelle contact sites, has been implicated in mitochondrial signaling, but its role in AAD remains unclear. AAD was induced in wild-type, ATAD3A knock-in, and vascular smooth muscle cell (VSMC)-specific knockdown (sh-ATAD3A) mice by 3-week β-aminopropionitrile monofumarate intake or 28-day AngII (angiotensin II) infusion via osmotic minipumps. Aortic dilatation, dissection incidence, rupture-related mortality, and histology were assessed. Vascular smooth muscle cells were stimulated with AngII in vitro. Mitochondrial function was evaluated using Seahorse bioenergetics, membrane potential assay, and Ca2+ imaging. ATAD3A-DLST (dihydrolipoamide S-succinyltransferase) interaction was examined by coimmunoprecipitation. Pharmacological modulation was performed with the copper chelator tetrathiomolybdate and the lipoylation inhibitor devimistat. ATAD3A expression was upregulated in human thoracic aortic dissection samples and in β-aminopropionitrile monofumarate-treated mouse aortas, with early downregulation then late upregulation in VSMCs. Systemic ATAD3A overexpression mitigated β-aminopropionitrile monofumarate-induced and AngII-induced aortic dilatation, reduced dilation incidence, and improved survival, whereas VSMC-specific knockdown accelerated vascular pathology. Mechanistically, ATAD3A overexpression reduced mitochondria-lysosome contacts, limited mitochondrial Ca2+ influx, and suppressed the FDXR (ferredoxin reductase)/FDX1 (ferredoxin 1)/LIAS (lipoic acid synthetase) lipoylation pathway, decreasing DLST lipoylation and restraining cuproptosis, thereby preserving VSMC viability and delaying AAD progression. Pharmacological inhibition of cuproptosis using tetrathiomolybdate or Devimistat attenuated disease severity in vivo. ATAD3A protects against AAD by coordinating organelle contact and metabolic signaling to restrain mitochondrial Ca2+ influx, NADPH flux, and DLST lipoylation-dependent cuproptosis in VSMCs. Targeting the ATAD3A-DLST-cuproptosis axis offers mechanistic insight and therapeutic potential for AAD.

Developing hydrogel dressings that simultaneously achieve robust wet tissue adhesion, mechanical stability, antibacterial activity, and oxidative stress regulation remains challenging. In this study, a dual-network poly (thioctic acid)/ammonium glycyrrhizinate (PTA/AG) hydrogel was developed through thermally induced ring-opening polymerization (ROP) of TA and sodium thioctate (TA-Na) to form a primary network, followed by the formation of an AG-driven secondary network during cooling. TA-Na improved the aqueous processability of TA, while the AG secondary network reinforced the stability of the PTA primary network. The resulting hydrogel exhibited a crossover strain of 454% and a wet adhesion strength of up to 16.37 kPa on porcine skin. In addition, the hydrogel showed strong antibacterial activity against S. aureus (>99%), high cytocompatibility (>95% cell viability), and effective free-radical-scavenging activity (>77% scavenging of both DPPH and ABTS radicals). Notably, the hydrogel exhibited effective intracellular antioxidant activity, reducing ROS levels to near those of the control group and increasing SOD activity by approximately 13-fold and the GSH/GSSG ratio by 97.83% relative to the H2O2 group. Overall, the PTA/AG hydrogel is a promising candidate for multifunctional wound dressing applications.