Search Results (372)

Background: Spinal Muscular Atrophy (SMA) is a neurodegenerative disease caused by reduced survival motor neuron (SMN) protein levels due to SMN1 gene mutations. The natural history of SMA has dramatically changed since innovative therapies were approved; among them, Risdiplam (an oral molecule) increases the peripheral levels of SMN by modifying the pre-mRNA slicing of the paralogous SMN2 that also codes for the protein. Methods: We performed longitudinal RNA sequencing on peripheral blood samples from 16 adult SMA patients (types II and III) before and after 12 months of Risdiplam treatment to assess transcriptomic changes. Results: During Risdiplam treatment, increased SMN2 transcript levels were observed, which was coherent with the clinical condition of the investigated SMA cohort. Upregulated mitochondria genes or pseudogenes (i.e., MT-ATP8 and MTND1P11) and downregulated autophagy-related pathways were also found. Baseline differences in gene expression between SMA type II and type III involved neurodegenerative (i.e., MS4A3, C4BPA, and NEILS3) and immune-related (B2M) genes. Conclusions: These findings support Risdiplam’s systemic impact in adult SMA subjects and reveal molecular distinctions between SMA phenotypes (types II and III), which may be of some relevance for future clinical and therapeutic strategies. Full article

Background/Objectives: Changes in the mechanical behavior of orthodontic archwires during clinical use are not fully understood, particularly when different bracket systems are employed. Self-ligating (SL) brackets have gained considerable popularity in orthodontic practice in recent years, largely due to claims of improved treatment efficiency and biomechanical performance. Nevertheless, current evidence has not consistently demonstrated statistically significant differences between conventional ligation (CL) brackets and SL systems. The aim of this study was to evaluate changes in the mechanical properties and degradation over time of nickel-titanium (NiTi) archwires after clinical use in orthodontic treatments performed with CL and SL brackets. Methods: A comparative study was conducted using archwires retrieved from orthodontic patients. Round 0.014-inch NiTi wires (GC Orthodontics America Inc., IL, USA) were analyzed. The archwires were used in 60 patients treated with either CL or SL appliances and evaluated at four time points: before clinical use (T0), and after 1 month (T1), 2 months (T2), and 3 months (T3) of intraoral service. Mechanical testing was performed according to ISO 15841:2014 + Amd. 1:2020 using a three-point bending test with a universal testing machine (Z005 Test Control II Universal Testing Machine, Zwick Roell, Kennesaw, GA, USA). The variables analyzed included the mean force delivered by the archwires at deflections of 3 mm (F3), 2 mm (F2), 1 mm (F1), and 0.5 mm (F0.5), as well as the slope of the superelastic plateau at 2 mm, 1 mm, and 0.5 mm. The static and dynamic friction coefficients, as well as the friction forces associated with the wires and the two types of brackets, were determined using a modified MTS-Bionix servo-hydraulic testing machine. The tests were conducted at 37 °C in a saline environment. Results: Both groups showed changes in the superelastic behavior of NiTi archwires. Alterations increased with longer intraoral exposure. In the SL group, significant modifications were already observed after one month of clinical use, with a reduction in the force delivered and a loss of superelastic characteristics. These changes remained relatively stable thereafter, with no statistically significant differences during the following months. In contrast, the CL group showed a progressive reduction in force delivery and superelasticity over time. This is due to the difference in friction between the wire and the CL bracket compared to the SL bracket, which results in greater force transfer for tooth movement. Conclusions: Overall, differences in the mechanical behavior of archwires between CL and SL systems were observed during the initial stages of clinical use. However, these differences diminished over time, and no significant differences were detected after three months. Considering the progressive degradation of mechanical properties, the reuse of archwires that have remained intraorally for more than three months may not be advisable. Full article

Background: The transfer of a nucleus from one oocyte to another offers patients harbouring high levels of mitochondrial DNA mutation and sufferers of frequent fertilisation failure or early embryonic arrest the potential to have healthy children. However, a small amount of mtDNA is carried over with the nucleus as the transfer takes place. Consequently, we still need to distinguish between the effects of the carryover and the transfer of a nucleus itself from a mature oocyte. Methods: To overcome this, we analysed a series of hatching stage blastocysts generated using metaphase II spindle transfer and mitochondrial supplementation. The latter approach also introduces a small amount of mtDNA into the oocyte as fertilisation takes place. For both manipulations, an autologous approach was used to overcome the effects of third-party transfer. Results: We then compared the changes in global gene expression between the two groups. We found that the nuclear transfer process affected a number of gene networks and pathways. These included metabolic, cell cycle, inflammatory and immune, and epigenetic responses. A comparison with earlier stage blastocysts did not suggest that the cause was due to developmental delay. Conclusions: Critically, these changes could affect offspring health and well-being as is the case following somatic cell nuclear transfer. Full article

Background: The NLRP3 inflammasome drives pathological inflammation in various diseases. PINK1/Parkin-associated mitophagy serves as a critical negative regulator of NLRP3 activation, yet pharmacological enhancers remain scarce. Muscone, a natural macrocyclic ketone with blood–brain barrier permeability, exhibits potent anti-inflammatory properties; however, its mechanistic role within the NLRP3-mitophagy axis remains undefined. Methods: LPS/ATP-stimulated macrophages were employed to assess stage-specific effects of muscone on NLRP3 priming (NF-κB signaling, NLRP3, and pro-IL-1β expression) and activation (ASC oligomerization, ASC–pro-caspase 1 complex formation, and IL-1β secretion). RNA sequencing and bioinformatic analysis were performed for pathway enrichment. Mitophagy was characterized by MitoSOX Red staining for mt-ROS detection, electron microscopy, Western blotting of LC3B-II in isolated mitochondria and PINK1 and Parkin in whole-cell lysates, and live-cell mitochondria–lysosome tracking. In vivo protective efficacy was assessed in an LPS-induced endotoxemia mouse model. Results: Muscone dose-dependently suppressed both the priming and activation stages of the NLRP3 inflammasome, maximally reducing IL-1β secretion by ~60% at 50 μM. Mechanistically, muscone amplified PINK1/Parkin-associated mitophagy, scavenging excessive mt-ROS and attenuating NLRP3 activation. These effects were corroborated by RNA-seq and comprehensive functional assays. In vivo, muscone (30 mg/kg) significantly improved survival (3/8 mice alive at 98 h when all LPS controls had died; 2/8 survived to the 132-h endpoint), with concomitant enhancement of mitophagy markers in peritoneal macrophages. Conclusions: Muscone functions as a PINK1/Parkin-associated mitophagy enhancer that maintains mitochondrial quality control during NLRP3-driven inflammatory responses. Its unique macrocyclic structure and blood–brain barrier permeability provide a promising scaffold for developing therapeutics against inflammatory disorders associated with NLRP3 inflammasome activation. Full article

In order to balance carbon emissions and cost reduction in China’s steel firms, this study proposes a multi-objective optimization model for carbon emission reduction based on life-cycle assessment. The baseline scenario technique was used to forecast carbon emissions at every stage of the life cycle by 2025, and the costs of reduction for four major initiatives—clean electricity procurement, recycling of scrap steel, fossil fuel consumption reduction, and clean transportation share increase—were systematically accounted. Kernel PCA and NSGA-II algorithms were used to create a multi-objective optimization model with the goal of maximizing emission reductions and reducing reduction costs. The greatest potential and economic gain, according to the results, come from using more scrap steel and using fewer fossil fuels. At 823 million CNY, the cost–benefit balanced solution reduces CO₂ by 3.0358 Mt. This approach achieved virtually maximum emissions reductions at only 10.9% of the cost of the maximum reduction scenario. This study makes two key contributions. First, it provides a systematic life-cycle cost accounting framework for major CO₂ reduction measures in the steel industry. Second, it develops a Kernel PCA-NSGA-II multi-objective optimization model that explicitly resolves the trade-off between abatement cost and emission reduction volume, offering decision support for steel enterprises under different policy and economic scenarios. Full article

The transition metal copper (Cu) is an essential trace element for humans and serves as a cofactor for numerous enzymes. Therefore, intracellular Cu homeostasis must be tightly regulated. Meanwhile, Cu is increasingly used in industrial and biomedical applications, particularly in nanoparticle (NP) form. However, studies have demonstrated that Cu(II) oxide (CuO) NPs are highly toxic. Therefore, understanding the underlying toxic effects of such compounds is of the utmost importance. In this context, transcriptomic profiling is regarded as a valuable tool. Nevertheless, comparative studies addressing organ-relevant models, such as the liver and lungs, are scarce. Furthermore, no transcriptomic studies have been conducted on human bronchial lung epithelial cells exposed to CuO NPs and Cu²⁺. In this study, we compared the cellular effects of human bronchial lung epithelial cells exposed to both CuO NPs and Cu²⁺ to the effects in human liver cells exposed to Cu²⁺ by applying RNA sequencing. Although cytotoxicity was comparable, we showed that Cu uptake was highly dependent on both the cell type and the form of Cu. The most pronounced concentration-dependent transcriptional changes were observed with CuO NP exposure in BEAS-2B cells. The only differentially expressed genes (DEGs) found by all exposures and treatments were metallothioneins (MTs). The most sensitive targets of Cu-induced toxicity were related to nuclear factor erythroid 2-related factor 2 (NRF2), nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB), and mitogen-activated protein kinase (MAPK) signaling. Furthermore, the effects observed at the transcriptome level were studied at the functional level, such as cell cycle regulation and cytokine release. Thus, we demonstrated that the two cell types differ in susceptibility, and that complementing transcriptome profiling with functional studies provides important mechanistic insights. Full article

The TOPSIS (Technique for Order Preference by Similarity to Ideal Solution) method is one of the most widely used multi-criteria decision-making (MCDM) approaches in industrial, financial, and scientific fields. However, its sequential computational cost of O(m × n), where m denotes the number of alternatives and n the number of criteria, becomes prohibitive when decision matrices have several million rows. Despite its geometric interpretability and simplicity, classical TOPSIS faces two key computational bottlenecks at scale: (i) Euclidean distance calculations O(m × n) dominating the total cost, and (ii) the O(m × log m) sorting step, both inherently sequential and memory-bound on CPUs. To overcome these limitations, we propose GPU-TOPSIS, a fully vectorized and parallel reformulation of TOPSIS based on tensor execution on graphics processing units (GPUs), whose main contributions are: (i) a formally correct reformulation of TOPSIS as a GPU tensor pipeline preserving mathematical fidelity to the original method; (ii) a two-pass fragment-processing algorithm guaranteeing exact mathematical equivalence with monolithic TOPSIS, while reducing the memory footprint from O(m × n) to O(m_t × n), where m_t < m is the size of each independently processed fragment; (iii) three independent implementations on CuPy, PyTorch, and TensorFlow, ensuring the framework’s portability and genericity. Experimental evaluations on real data from the Amazon Products 2023 dataset, using matrices of up to 200 million alternatives (via the 2-pass formulation), demonstrate speedups of up to 4.75× compared to the reference CPU implementation (NumPy), with inter-backend score differences below 5 × 10⁻⁸ and 100% ranking overlap across all tested Top-K thresholds. A perturbation sensitivity analysis of the criteria weights and cross-backend consistency tests confirms that GPU acceleration fully preserves robustness and decision reliability, making GPU-TOPSIS a practical, open, and reproducible solution for large-scale multi-criteria decision making in Big Data environments. Full article

Positive mental health (PMH) has recently become a key topic in biomedical research. Previous studies have explored the correlation between biological and psychological measures, but only a few have focused on the relationship between PMH and aging. This study aimed: (i) to explore the association between PMH and biological aging; (ii) to determine if and to what extent the observed association could be explained by shared genetic and environmental effects. A total of 401 twins (age 19–81 years, 32% male) from the Italian Twin Registry were recruited, and the twin study design was applied. A self-report psychological test battery was used to evaluate several PMH components. Blood samples were collected from participants to determine telomere length (TL) and mitochondrial DNA copy number (mtDNAcn). TL was negatively associated with attachment anxiety (r = −0.11, p = 0.037). A bivariate twin model provided heritability estimates of 0.14 (95% CI 0.001–0.43) for TL and 0.32 (0.16–0.45) for attachment anxiety, and a substantial negative genetic correlation [r_g = −0.55 (−1.00–0.00)] between them. Under the limitations of a cross-sectional study with a self-report wellbeing assessment, these results suggest that anxiety in the relationship with a partner may contribute to accelerated TL shortening, and shared genetic factors may underlie this link. Full article

Background: Prostate cancer (PCa) imposes a substantial global health burden, with robot-assisted radical prostatectomy (RARP) established as the gold standard for localized disease. While da Vinci^® Xi maintains market dominance, Toumai^® MT-1000 offers a potentially cost-competitive alternative lacking prospective validation. Objective: To evaluate perioperative safety, oncologic quality (primary endpoint: positive surgical margins), early functional recovery (continence), and surgeon learning curve between Toumai^® MT-1000 (T-RARP) and da Vinci^® Xi RARP (DV-RARP) performed in high-volume European practice. Materials and Methods: This is a prospective single-center comparative study carried out at Policlinico Gemelli, Rome (May–November 2025), enrolling 80 patients with localized or locally advanced PCa, elected for radical prostatectomy and casually allocated to receive surgery with Toumai or the da Vinci robotic platform. The primary endpoint was the comparison of positive surgical margin (PSM) rates. Secondary endpoints included the comparison of operative time (skin-to-skin), estimated blood loss, length of hospital stay, 45-day postop outcomes, specifically Clavien–Dindo complications, urinary continence recovery (0–1 pad/day), and IIEF-5 scores. Learning curve was evaluated through the cumulative summation (CUSUM) analysis of operative times and linear regression of operative times (n = 80 cases). The analyses used STATA 19 with two-sided tests at p < 0.05 significance. Results: Baseline characteristics showed balance between cohorts (p > 0.05 for most covariates). Perioperative outcomes proved equivalent: median operative time (OT) was 192.5 min (IQR 165–230) for Toumai^® versus 183.5 min (IQR 147–225) for da Vinci^® Xi (p = 0.38); estimated blood loss (EBL) was 150 mL in both groups (p = 0.87); length of hospital stay (LOS) was 2 days in both groups (p = 0.92). PSM rates were identical at 17.5% (p = 0.79). Continence recovery reached 72.5% versus 80% (p = 0.43). Complications (Clavien–Dindo ≥ II) occurred in 7.5% versus 12.5% of cases (p = 0.45). The CUSUM analysis demonstrated operative time proficiency after only four procedures; operative time regression showed no significant trend (p = 0.38). Conclusions: Toumai^® MT-1000 demonstrates similar performance to da Vinci^® Xi across different RARP quality metrics, with no detectable learning curve for surgeons previously experienced with da Vinci. These findings support a safe integration of cost-effective platforms into clinical practice, pending multicenter randomized confirmation. Full article

The development of a green hydrogen industry is a strategic priority for Russia’s energy transition, yet the dynamics of scaling up this nascent sector remain poorly understood. This study uses agent-based modeling (ABM) to simulate the co-evolution of Russia’s electricity, hydrogen, and electrolyzer sectors over 2024–2050. The model incorporates three types of heterogeneous agents (power producers, hydrogen producers, and electrolyzer manufacturers) operating under bounded rationality. Four scenarios are examined across 50 Monte Carlo runs each, varying the electrolyzer learning rate (10–25%), willingness to pay for green hydrogen (2–6 $/kg), and government support intensity. The results reveal an endogenous three-phase development pattern: Phase I (2024–2028) dominated by renewable capacity build-up reaching ~30 GW; Phase II (2029–2040) characterized by rapid electrolyzer deployment scaling to 14.5 GW; and Phase III (2041–2050) marked by stabilization at approximately 30 GW producing 1.12 Mt/year at 3.1 $/kg. Two critical thresholds are identified: renewable capacity exceeding 30–38 GW and low-cost electricity above 4–7 TWh/year. The electrolyzer learning rate emerges as the most influential parameter, while the pessimistic scenario confirms market failure without a green premium (WTP < 2 $/kg). Strategic investment losses of 2–6 billion USD are necessary catalysts for industry emergence. Russia’s 2030 production target (0.55 Mt) is found structurally infeasible under all scenarios. Full article

Rising greenhouse gas concentrations have exacerbated global warming, elevating the importance of land use and land cover (LULC) changes in achieving carbon neutrality. This is especially true in coastal areas, which face dual pressures from rapid urbanization and the need to protect carbon sinks. This study developed an SD-MCCA coupling framework to predict the dynamic changes in LULC in four SSP scenarios (SSP126, SSP245, SSP370, SSP585) in the coastal zone of Zhejiang Province from 2020 to 2100. Among them, the carbon storage was estimated by the InVEST model, and the dual-target optimization was carried out using the NSGA-II algorithm. Results indicated that construction land expanded significantly across all scenarios (50.3–110.2%), leading to a decline in carbon storage. However, outcomes were highly scenario-dependent; by 2100, carbon storage under the SSP126 pathway (1032.94 Mt) was notably higher than under the SSP585 pathway (1012.90 Mt). Coastal wetlands and forests emerged as major contributors to carbon storage, exhibiting high positive contribution scores, while construction land sites show significant negative correlations. Dual-target optimization achieved collaborative improvement: the optimized SSP126 scenario increased carbon storage by 1.16%, while economic benefits increased by 9.05%. The policy proposal emphasizes the priority of the SSP126 scenario, restricts the expansion of construction land, and enforces the ecological red line of wetlands and forests, guided by the phased Pareto optimal strategy. Full article

Background: Most individuals develop smoking habits in adolescence, highlighting the need for a smoking prevention program targeted at this age group. The use of “Implementation Intentions” (If-Then plans) about how to refuse a cigarette combined with anti-smoking messages has been shown to be effective in the UK. However, there is a scarcity of data regarding school-based smoking prevention interventions among adolescents available to countries with high tobacco consumption rates, like Greece. Objectives: To describe the cultural adaptation procedure and the evaluation protocol for the school-based “Implementation Intentions” program aimed at reducing tobacco use susceptibility among Greek adolescents aged 13–16 in school settings. Methods: The present study is part of the EU-funded FRESHAIR4Life Program. We will use a mixed-methods approach with a pre- and post-intervention design in six conveniently selected secondary schools in Heraklion, Crete, Greece, to measure the intervention’s Reach, Effectiveness, Adoption, Implementation, and Maintenance using the RE-AIM framework. The study plans to involve three Master Trainers (MTs), 20–25 school teachers (to be trained by the MTs), and approximately 480 students. Participating schools will receive the “Implementation Intentions” intervention, which is based on a goal-setting technique where individuals commit to perform a particular behavior when a specific context arises. The study will consist of five sequential phases: Phase I involves training three Master Trainers (MTs) using the International Primary Care Respiratory Group (IPCRG’s) Teach-the-Teacher (TtT) curriculum, specifically focused on the implementation of our intervention. In Phase II, workshops will be held to co-create and culturally adapt the intervention. Phase III will involve teachers trained by MTs on delivering the intervention. In Phase IV, teachers will deliver the intervention among students in their schools. Data will be collected pre- and post-intervention through surveys, session logs, fidelity observations, feedback forms, and follow-up interviews or focus groups (Phase V). Quantitative data will be analyzed descriptively and by using paired t-tests and multiple linear regression analyses, while qualitative data will undergo thematic analysis. Discussion: The study protocol’s potential benefits extend beyond educating Greek adolescents on the risks associated with smoking. Active participation will empower and motivate young people to make informed, healthy choices. We expect the results could help create more effective, context-specific interventions, support policy changes aimed at decreasing the prevalence of adolescent smoking in Crete, Greece, and potentially be used by other countries as well. Full article

Background: Diabetic foot ulcers (DFUs) are considered a prevalent complication of diabetes mellitus, frequently accompanied with compromised peripheral circulation, slower healing, as well as high risk of infection in addition to risk of amputation. Additional treatments that enhance microvascular perfusion and lessen plantar pressure may accelerate the healing process. This study was carried out to examine the impact of pulsed electromagnetic field (EMF) therapy as well as customized silicone gel insoles in terms of peripheral circulation in addition to vascular indices in patients with DFUs. Methods: A randomized, controlled clinical trial, including sixty-six adults diagnosed with type II diabetes as well as plantar DFUs (Wagner grade I–II) were divided into three groups (n = 22 each): Group A was given low-frequency electromagnetic field therapy (15–50 Hz, 2–5 mT, 30 min, three times per week for 8 weeks), Group B was given a customized silicone gel insoles produced for ulcer offloading, and Group C (control) was given conventional physiotherapy along with wound care. Peripheral microcirculation as well as tissue perfusion were the primary outcomes, and they were measured using Laser Doppler Flowmetry (LDF), Photoplethysmography (PPG), in addition to the Toe–Brachial Index (TBI). The secondary outcome included the Ankle–Brachial Pressure Index (ABPI). A blinded assessor measured the outcomes at the beginning of the study, after the intervention (week 8), and again after the follow-up (week 16). Results: EMF therapy significantly improved LDF (baseline: 45.2 ± 6.5 PU; week 8: 62.5 ± 7.2 PU), PPG (0.42 ± 0.08 mV to 0.68 ± 0.10 mV), TBI (0.64 ± 0.07 to 0.82 ± 0.08), and ABPI (0.88 ± 0.06 to 0.97 ± 0.05) compared with insoles and controls (p < 0.001, partial η² 0.25–0.37). The insole group exhibited moderate enhancements, whereas the control group demonstrated minor changes. Between-group analyses showed substantial differences in favor of EMF therapy across all measured variables (F = 13.5–19.9, p < 0.001). Improvements continued at the 8-week follow-up. Conclusions: Patients with DFUs who receive EMF therapy experience a significant improvement in their peripheral microcirculation, tissue perfusion, as well as vascular indices. This is more effective than just mechanical offloading, and custom insoles offer extra benefits by redistributing pressure. Combining EMF therapy with regular DFU care may speed up healing and lower the risk of problems. Additional research should investigate the efficacy of combined EMF as well as off-loading interventions and their long-term outcomes. Full article

Mitochondrial biogenesis requires coordinated expression from both nuclear and mitochondrial genomes. To understand the consequences of mitochondrial genome loss, we generated a mitochondrial DNA-depleted line (crm⁻) in Chlamydomonas reinhardtii via long-term ethidium bromide treatment. We then examined how mtDNA disruption affects mitochondrial ultrastructure, chloroplast function, and the mitochondrial transcription termination factor (mTERF) gene family. Our results reveal that mitochondrial dysfunction is associated with severe organelle remodeling, including mitochondrial elongation, matrix condensation, and cristae collapse. Consequently, mitochondria reduce the electron sink capacity which appears to over-reduce the chloroplast electron transport chain, correlating with causing damage to photosystem II (PSII), as indicated by higher plastoquinone PQ redox state and PSII excitation pressure and lower non-photochemical quantum yield [Y(NPQ)]. Furthermore, we identified and characterized eight nuclear-encoded mTERF genes in C. reinhardtii (CrmTERFs). Phylogenetic analysis grouped them into three clades with potential functional conservation. Collinearity analysis suggested potential evolutionary relationships between mTERF genes in Chlamydomonas and Marchantia polymorpha. Gene ontology annotation linked CrmTERFs to transcription termination and RNA biosynthesis regulation. Additionally, in silico prediction identified twelve putative miRNAs targeting seven of the eight CrmTERFs, with CrmTERF3 as the only exception, providing candidates for future experimental validation. This study provides the first comprehensive analysis of the nuclear encoded mTERF gene family in Chlamydomonas and demonstrates that mtDNA loss is correlated with mTERF genes expression, as well as mitochondrial structure and chloroplast photoprotective impairments. These findings suggest a potential role for CrmTERFs in mitochondrial retrograde signaling and organellar crosstalk, though functional validation is required to establish causality. Full article

Tissue decellularization aims to obtain bioscaffolds for regenerative applications by removing all cellular components while preserving the extracellular matrix (ECM) architecture. Although decellularization removes the majority of linear nuclear DNA (nDNA), residual amounts remain detectable. However, the fate of circular mitochondrial DNA (mtDNA) after decellularization has not yet been reported. Cell death or injury can cause the release of mtDNA, which is resistant to breakdown by exonucleases. Extracellular mtDNA acts as a damage-associated molecular pattern (DAMP) that can trigger immune responses. The aim of this study is to assess the presence of residual mtDNA in the liver, bile duct, and vascular scaffolds after decellularization and whether this causes inflammatory responses in macrophages. Decellularized tissues showed a marked reduction in total DNA content well below the threshold of 50 ng/mg tissue. However, in liver and vascular scaffolds, a relative increase in the mtDNA:nDNA ratio was detected in the remnant DNA fraction. Residual mtDNA in bioscaffolds acted as DAMPs causing macrophage activation, as shown by increased cell proliferation and cytokine production. Strategies to further reduce remnant mtDNA were tested. We found that treatment with the endonuclease enzyme HpaII was effective in degrading residual mtDNA. Importantly, mtDNA removal resulted in a significantly reduced macrophage activation. In conclusion, our study shows that mtDNA is relatively resistant to the decellularization procedure and can act as a DAMP in bioscaffolds. This underscores the importance of removing mtDNA from decellularized bioscaffolds to improve the immunocompatibility for biomedical applications. Full article