Objective To evaluate an online surgical skills course integrating structured video-based self-, peer-, and tutor feedback designed to enhance individualized feedback during early surgical training. Design Prospective observational study evaluating 4 course iterations following an iterative course development phase conducted between 2020 and 2023. Setting Online surgical skills course delivered at the Department of General, Visceral, and Vascular Surgery, Universitätsklinikum Jena, Germany. Participants Seventy-three undergraduate medical students participated in 4 course iterations between February 2024 and March 2025. Sixty-seven students who submitted more than 1 video recording met inclusion criteria and were included in the analysis. Results Submission compliance varied across tasks and appeared influenced by perceived clinical relevance and exercise complexity. Higher engagement was observed for authentic tissue-based exercises compared with synthetic training tasks. Students reported high satisfaction with the course structure and strongly endorsed structured video-based feedback. Recording and reviewing performances facilitated explicit error recognition, reflective practice, and peer-supported learning. Despite reliance on low-cost materials and student-owned devices, the online format enabled close visual supervision and individualized tutor feedback within small-group sessions. Conclusions The educational value of this model lies not in digital delivery alone, but in the structured use of video analysis to support feedback-driven skill refinement. By integrating replay, annotation, and guided reflection, the approach enables precise and scalable feedback during early surgical skills training. This cost-effective model demonstrates that online instruction can maintain instructional depth while strengthening individualized feedback processes in undergraduate surgical education.

Automated analysis of hepatic vascular structures and lobules within whole-slide histological images is critical for ensuring accurate and timely morphometric evaluations and facilitating advancements in computational liver histology. Nonetheless, the intricate morphology of the tissue, variability in staining techniques, and the requirements for standard high-resolution images present substantial challenges to the precision of segmentation processes. We present a robust deep-learning pipeline using adaptive patch extraction and specialized nnU-Net architectures for segmenting vessels, bile ducts, and lobules in Glutamine Synthetase and Picro-Sirius-Red stained porcine liver sections. Our architecture incorporates a weight-boosted nnU-Net framework with an adaptive, performance-based weight adjustment mechanism to effectively manage class imbalances and improve the detection of smaller vascular structures. The model was trained on four annotated whole-slide images and validated through comprehensive testing on eight additional independent slides. Geometric and intensity-based data transformations enhanced the robustness and generalizability of the segmentation models. Evaluations conducted through five-fold cross-validation, as well as assessments utilizing independent test datasets, resulted in Dice similarity scores: 0.968 for lobules, 0.795 for central veins, 0.895 for hepatic arteries, 0.665 for portal veins, and 0.694 for bile ducts. The developed segmentation pipeline additionally supports comprehensive morphometric analyses of structural parameters, including number and size (diameter, area) of vascular structures, bile ducts, and lobules; for example, the diameter of hepatic arteries ranges between 20–90 µm. These findings underscore the practical relevance of adaptable segmentation frameworks in advancing computational histological analysis of liver tissue.

Acetaminophen (APAP) intoxication is a common cause of liver injury. Silibinin has demonstrated potent hepatoprotective properties. However, its underlying mechanisms in APAP-induced liver injury (AILI) remain unclear. Autophagy is a critical adaptive response in AILI, contributing to the clearance of damaged mitochondria and the attenuation of oxidative stress. Therefore, we focused primarily on investigating the role of autophagy in mediating the hepatoprotective effects of silibinin. The effects of silibinin were evaluated in both AML12 cells and a C57BL/6J mouse model of AILI. Both the in vitro and in vivo experiments comprised four groups: a control group, an AILI model group, a silibinin treatment group, and a silibinin plus autophagy inhibitor group using PINK1-siRNA in cell culture and 3-Methyladenine in the animal experiment. Following induction of the AILI model in mice with APAP at a dose of 300 mg/kg, the animals received the designated interventions for five consecutive days. Histopathological alterations were assessed using hematoxylin–eosin staining. Hepatocyte proliferation and apoptosis were evaluated using the CCK-8 assay and immunohistochemical staining for Ki-67 and cleaved caspase-3, respectively, as well as ELISA for Cyclin D1. Liver function was assessed by serum biochemical analysis of alanine aminotransferase, aspartate aminotransferase, total bilirubin, and albumin. Mitochondrial oxidative stress–related parameters, including superoxide dismutase and malondialdehyde, were measured using colorimetric assays. The expression of autophagy-related genes and proteins (PINK1, Parkin, AMPK, LC3 and p62) was analyzed by quantitative PCR, immunofluorescence, and Western blotting. Transmission electron microscopy was employed to examine mitochondrial ultrastructure and the formation of autolysosomes in mouse liver tissue. In AML12 cells, silibinin mitigated AILI by activating the PINK1/Parkin pathway, thereby promoting mitophagy and enhancing cell proliferation. Co-treatment with autophagy inhibitor PINK1-siRNA attenuated these protective effects of silibinin. In AILI mice, silibinin treatment markedly improved liver function, attenuated inflammatory responses, restored mitochondrial function, and enhanced hepatocyte proliferation. These improvements were associated with increased LC3-II expression and reduced p62 accumulation, indicating enhanced autophagic activity. Notably, the protective benefits of silibinin were significantly attenuated by the autophagy inhibitor 3-Methyladenine. Our findings suggest that silibinin protects against AILI by activating PINK1/Parkin-dependent mitophagy, which mitigates oxidative stress and inflammation while promoting hepatocyte regeneration.

Many liver diseases have a distinct zonation pattern. Similarly, most metabolic processes in the hepatic lobule are also spatially organized. Understanding the interplay between a zonated disease pattern and its impact on zonated metabolic liver function requires the joint quantification of both phenomena. Our study presents an image analysis workflow for the joint zonated quantification of multiple parameters from whole-slide images of conventionally stained serial sections of mouse livers. As a proof of concept, we used small stacks of six adjacent sections, differentially stained with HE, GS and four different CYP enzymes from three mice with different severities of steatosis. Portal fields and central veins were annotated and transferred to adjacent slide images via image registration. The result was visually confirmed to avoid errors in the non-rigid transformation process. This approach allowed identifying the same lobules and zones in multiple consecutive sections. Zones were obtained by arbitrarily dividing the distance between portal fields and central veins into twelve intralobular zones. Zonal distributions of various parameter combinations quantified from multiple slides were visualized in the geometry of lobules and zones and plotted as scatter diagrams. Using this workflow, we could visualize differences in the heterogeneous expression patterns of marker proteins in normal and steatotic livers. As a next step, the algorithm presented here can be applied to a scientific question such as quantifying the impact of zonated steatosis of different severity on the zonated expression pattern and the resulting metabolic function of CYP enzymes.

Rapid evaporative ionization mass spectrometry (REIMS) shows promise as a preparation-free tissue analysis tool with the prospect for real-time diagnostics. Given that hepatic steatosis is characterized by shifts in lipid species and abundance, we selected it as basis for method development, as REIMS specifically measures lipidomic profiles. However, further validation and protocol refinement are necessary to establish its clinical utility. In this study, we applied REIMS to steatotic human liver tissues, focusing on its ability to differentiate varying degrees of steatosis. We established standardized protocols for tissue handling and lipid analysis, which were essential for reliable data interpretation. Notably, our findings revealed that tissue size impacts REIMS sensitivity, with smaller samples yielding lower total ion counts and altered lipid profiles. Through principal component analysis, we identified key lipid classes, namely triacylglycerides, fatty acids, and glycerophospholipids. Despite a missing link between triacylglyceride abundance and degree of steatosis, we successfully identified condition-specific lipid patterns, with ceramides emerging as markers of advanced steatosis. Our study provides a protocol for the measurements of lipid standards showing the detailed degradation of specific lipids using iKnife-coupled REIMS. It highlights the pitfalls and limitations and provides critical recommendations for REIMS use. It also emphasizes the need for standardized biobanking and tissue preparation to ensure accurate lipid profiling, laying the groundwork for future protocol adjustments required for clinical application.

OBJECTIVE:To establish an arterial spin labeling (ASL) protocol for rat livers that improves data reliability and reproducibility for perfusion quantification. METHODS:This study used respiratory-gated, single-slice, FAIR-based ASL imaging with multiple inversion times (TI) in rat livers. Quality assurance measures included: (1) introduction of mechanical ventilation to ensure consistent respiratory cycles by controlling the respiratory rate (45 bpm), tidal volume (10 ml/kg), and inspiration: expiration ratio (I:E ratio, 1:2), (2) optimization of the trigger window for consistent trigger points, and (3) use of fit residual map and coefficient of variance as metrics to assess data quality. We compared image quality, perfusion maps, and fit residual maps between mechanically ventilated and non-ventilated animals, as well as repeated ASL measurements (session = 4 per animal) in two mechanically ventilated animals. RESULTS:Perfusion measurements over multiple sessions in mechanically ventilated rats exhibited low perfusion data variability and high reproducibility both within and between liver lobes. Image quality and perfusion maps were significantly improved in mechanically ventilated animals compared to non-ventilated animals. DISCUSSION:The implementation of mechanical ventilation and optimized quality assurance protocols enhanced the reliability and reproducibility of FAIR-based multi-TI-ASL imaging in rat livers. Our findings demonstrate these measures as a robust approach for achieving consistent liver perfusion quantification in preclinical settings.

Bone tissue, with its complex structure, often necessitates decalcification of the hard tissue for ex vivo morphological studies. The choice of a suitable decalcification method plays a crucial role in preserving desired features and ensuring compatibility with diverse imaging techniques. The search for a universal decalcification method that is suitable for a range of biophotonic analyses remains an ongoing challenge. In this study, we systematically assessed five standard bone decalcification protocols, encompassing strong mineralic acids (3% and 5% nitric acid), a commercially available formulation of hydrochloric and formic acid), as well as weak organic acids (5% trichloroacetic acid and 8% formic acid), and a chelating agent (25% ethylenediamine-tetraacetic acid) with varying decalcification durations, using mouse long bones as our experimental model. Our imaging analysis panel included classical histological staining (Hematoxylin and Eosin, H&E), immunofluorescence staining, and label-free Raman microspectroscopic imaging. We used cryosections instead of paraffin sections since paraffin interferes with tissue Raman signals. This approach is not as commonly used as it is more prone to handling artifacts, but is the preferred method for subsequent Raman analysis. Decalcification efficacy was evaluated based on various qualitative and some quantitative imaging parameters by 2–3 independent observers. Our systematic approach revealed that the chelating agent, when used for 24 h, optimally preserved bone features and, thus, would be the ideal decalcifying agent for comprehensive subsequent analysis. However, the choice of decalcifier and the ideal decalcification duration may vary depending on the type and thickness of bone, necessitating tailored adjustments to meet specific experimental requirements.

Background: Patients with angina are often suffering from comorbidities such as varying degrees of hepatic dysfunction. However, the impact of angina on the incidence of hepatic failure (HF) remains unclear. Methods: The genetic data were retrieved from genome-wide association studies. Five Mendelian randomization methods were used to investigate the causal relationship between unstable angina (UA), stable angina (SA), and HF. The result of the Inverse variance weighted (IVW) method was deemed the principal result. In addition, we performed a comprehensive sensitivity analysis to verify the robustness of the results. Results: The IVW results showed that UA (Odds ratio (OR): 2.055, 95% confidence interval (CI): 1.171–3.606, p = 0.012) was causally associated with the incidence of HF. SA (OR: 1.122, 95% CI: 0.738–1.706, p = 0.591) was not causally associated with the incidence of HF. Sensitivity analysis did not identify any bias in the results. Conclusions: UA turned out to be a risk factor for HF. SA does not have a significant causal effect on HF. Therefore, it is highly recommended that patients with chronic liver disease seek prompt medical attention and undergo regular monitoring of liver function when experiencing UA. This may help them to reduce the risk of HF.

The evaluation of teaching can be an essential driver for curriculum development. Instruments for teaching evaluation are not only used for the purpose of quality assurance but also in the context of medical education research. Therefore, they must meet the common requirements for reliability and validity. This position paper from the GMA Teaching Evaluation Committee discusses strategic and methodological aspects of evaluation in the context of undergraduate medical education and related courses; and formulates recommendations for the further development of evaluation. First, a four-step approach to the design and implementation of evaluations is presented, then methodological and practical aspects are discussed in more detail. The focus here is on target and confounding variables, survey instruments as well as aspects of implementation and data protection. Finally, possible consequences from evaluation data for the four dimensions of teaching quality (structural and procedural aspects, teachers and outcomes) are discussed.

Metabolic zonation refers to the spatial separation of metabolic functions along the sinusoidal axes of the liver. This phenomenon forms the foundation for adjusting hepatic metabolism to physiological requirements in health and disease (e.g., metabolic dysfunction-associated steatotic liver disease/MASLD). Zonated metabolic functions are influenced by zonal morphological abnormalities in the liver, such as periportal fibrosis and pericentral steatosis. We aim to analyze the interplay between microperfusion, oxygen gradient, fat metabolism and resulting zonated fat accumulation in a liver lobule. Therefore we developed a continuum biomechanical, tri-phasic, bi-scale, and multicomponent in silico model, which allows to numerically simulate coupled perfusion-function-growth interactions two-dimensionally in liver lobules. The developed homogenized model has the following specifications: (i) thermodynamically consistent, (ii) tri-phase model (tissue, fat, blood), (iii) penta-substances (glycogen, glucose, lactate, FFA, and oxygen), and (iv) bi-scale approach (lobule, cell). Our presented in silico model accounts for the mutual coupling between spatial and time-dependent liver perfusion, metabolic pathways and fat accumulation. The model thus allows the prediction of fat development in the liver lobule, depending on perfusion, oxygen and plasma concentration of free fatty acids (FFA), oxidative processes, the synthesis and the secretion of triglycerides (TGs). The use of a bi-scale approach allows in addition to focus on scale bridging processes. Thus, we will investigate how changes at the cellular scale affect perfusion at the lobular scale and vice versa. This allows to predict the zonation of fat distribution (periportal or pericentral) depending on initial conditions, as well as external and internal boundary value conditions.

There is a lack of systematic research exploring cross-species variation in liver lobular geometry and zonation patterns of critical drug-metabolizing enzymes, a knowledge gap essential for translational studies. This study investigated the critical interplay between lobular geometry and key cytochrome P450 (CYP) zonation in four species: mouse, rat, pig, and human. We developed an automated pipeline based on whole slide images (WSI) of hematoxylin-eosin-stained liver sections and immunohistochemistry. This pipeline allows accurate quantification of both lobular geometry and zonation patterns of essential CYP proteins. Our analysis of CYP zonal expression shows that all CYP enzymes (besides CYP2D6 with panlobular expression) were observed in the pericentral region in all species, but with distinct differences. Comparison of normalized gradient intensity shows a high similarity between mice and humans, followed by rats. Specifically, CYP1A2 was expressed throughout the pericentral region in mice and humans, whereas it was restricted to a narrow pericentral rim in rats and showed a panlobular pattern in pigs. Similarly, CYP3A4 is present in the pericentral region, but its extent varies considerably in rats and appears panlobular in pigs. CYP2D6 zonal expression consistently shows a panlobular pattern in all species, although the intensity varies. CYP2E1 zonal expression covered the entire pericentral region with extension into the midzone in all four species, suggesting its potential for further cross-species analysis. Analysis of lobular geometry revealed an increase in lobular size with increasing species size, whereas lobular compactness was similar. Based on our results, zonated CYP expression in mice is most similar to humans. Therefore, mice appear to be the most appropriate species for drug metabolism studies unless larger species are required for other purposes, e.g., surgical reasons. CYP selection should be based on species, with CYP2E1 and CYP2D6 being the most preferable to compare four species. CYP1A2 could be considered as an additional CYP for rodent versus human comparisons, and CYP3A4 for mouse/human comparisons. In conclusion, our image analysis pipeline together with suggestions for species and CYP selection can serve to improve future cross-species and translational drug metabolism studies.

MOTIVATION:Systems biology aims to better understand living systems through mathematical modelling of experimental and clinical data. A pervasive challenge in quantitative dynamical modelling is the integration of time series measurements, which often have high variability and low sampling resolution. Approaches are required to utilize such information while consistently handling uncertainties. RESULTS:We present BayModTS (Bayesian modelling of time series data), a new FAIR (findable, accessible, interoperable, and reusable) workflow for processing and analysing sparse and highly variable time series data. BayModTS consistently transfers uncertainties from data to model predictions, including process knowledge via parameterized models. Further, credible differences in the dynamics of different conditions can be identified by filtering noise. To demonstrate the power and versatility of BayModTS, we applied it to three hepatic datasets gathered from three different species and with different measurement techniques: (i) blood perfusion measurements by magnetic resonance imaging in rat livers after portal vein ligation, (ii) pharmacokinetic time series of different drugs in normal and steatotic mice, and (iii) CT-based volumetric assessment of human liver remnants after clinical liver resection. AVAILABILITY AND IMPLEMENTATION:The BayModTS codebase is available on GitHub at https://github.com/Systems-Theory-in-Systems-Biology/BayModTS. The repository contains a Python script for the executable BayModTS workflow and a widely applicable SBML (systems biology markup language) model for retarded transient functions. In addition, all examples from the paper are included in the repository. Data and code of the application examples are stored on DaRUS: https://doi.org/10.18419/darus-3876. The raw MRI ROI voxel data were uploaded to DaRUS: https://doi.org/10.18419/darus-3878. The steatosis metabolite data are published on FairdomHub: 10.15490/fairdomhub.1.study.1070.1.

SummaryThe SIMulation supported LIVer Assessment for donor organs (SimLivA) project aims to develop a mathematical model to accurately simulate the influence of mechanical alterations in marginal liver grafts (specifically steatotic ones) and cold ischemia on early ischemia‐reperfusion injury (IRI) during liver transplantation. Our project tackles significant research challenges, including the co‐development of computational methodologies, experimental studies, clinical processes, and technical workflows. We aim to refine a continuum‐biomechanical model for enhanced IRI prediction, collect pivotal experimental and clinical data, and assess the clinical applicability of our model. Our efforts involve augmenting and tailoring a coupled continuum‐biomechanical, multiphase, and multi‐scale partial differential equation‐ordinary differential equation (PDE‐ODE) model of the liver lobule, allowing us to numerically simulate IRI depending on the degree of steatosis and the duration of ischemia. The envisaged model will intertwine the structure, perfusion, and function of the liver, serving as a crucial aid in clinical decision‐making processes. We view this as the initial step towards an in‐silico clinical decision support tool aimed at enhancing the outcomes of liver transplantation. In this paper, we provide an overview of the SimLivA project and our preliminary findings, which include: a cellular model that delineates critical processes in the context of IRI during transplantation; and the integration of this model into a multi‐scale PDE‐ODE model using a homogenized, multi‐scale, multi‐component approach within the Theory of Porous Media (TPM) framework. The model has successfully simulated the interconnected relationship between structure, perfusion, and function—all of which are integral to IRI. Initial results show simulations at the cellular scale that describe critical processes related to IRI during transplantation. After integrating this model into a multiscale PDE‐ODE model, first simulations were performed on the spatial distribution of key functions during warm and cold ischaemia. In addition, we were able to study the effect of tissue perfusion and temperature, two critical parameters in the context of liver transplantation and IRI.

Purpose The impact of psychological factors on the incidence of hepatocellular carcinoma (HCC) in humans remains unclear. Mendelian randomization (MR) study is a novel approach aimed at unbiased detection of causal effects. Therefore, we conducted a two-sample MR to determine if there is a causal relationship between psychological distress (PD), participation in leisure/social activities of religious groups (LARG), and HCC. Methods The genetic summary data of exposures and outcome were retrieved from genome-wide association studies (GWAS). We used PD and LARG as exposures and HCC as outcome. Five MR methods were used to investigate the causal relationship between PD, LARG, and HCC. The result of inverse variance weighted (IVW) method was deemed as principal result. Besides, we performed a comprehensive sensitivity analysis to verify the robustness of the results. Results The IVW results showed that PD [odds ratio (OR) 1.006, 95% confidence interval (CI) 1.000–1.011, P = 0.033] and LARG (OR 0.994, 95% CI 0.988–1.000, P = 0.035) were causally associated with the incidence of HCC. Sensitivity analysis did not identify any bias in the results. Conclusion PD turned out to be a mild risk factor for HCC. In contrast, LARG is a protective factor for HCC. Therefore, it is highly recommended that people with PD are seeking positive leisure activities such as participation in formal religious social activities, which may help them reduce the risk of HCC. Graphical abstract

Excessive intake of fatty acids is a key factor contributing to metabolic dysfunction-associated steatotic liver disease (MASLD). However, the effects of saturated fatty acids (SFA) and unsaturated fatty acids (UFA) on the development of MASLD are uncertain. Therefore, we conducted two-sample Mendelian randomization studies and animal experiments to explore the effects of SFA, monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) on the risk of developing MASLD. The genetic summary data of exposures and outcome were retrieved from genome-wide association studies (GWASs) and used for five Mendelian randomization methods. A comprehensive sensitivity analysis was performed to verify the robustness of the results. Mice were subjected to different diets followed by assessment of severity of steatosis based on a histological score and determination of hepatic triglyceride levels to investigate the relationships between SFA, MUFA, PUFA and MASLD. The Mendelian randomization results showed that MUFA (odds ratio: 1.441, 95

This protocol presents an optimized erythrocytes-free NEVLP system using mouse livers. Ex vivo preservation of mouse livers was achieved by employing modified cannulas and techniques adapted from conventional commercial ex vivo perfusion equipment. The system was utilized to evaluate the preservation outcomes following 12 h of perfusion. C57BL/6J mice served as liver donors, and the livers were explanted by cannulating the portal vein (PV) and bile duct (BD), and subsequently flushing the organ with warm (37 °C) heparinized saline. Then, the explanted livers were transferred to the perfusion chamber and subjected to normothermic oxygenated machine perfusion (NEVLP). Inlet and outlet perfusate samples were collected at 3 h intervals for perfusate analysis. Upon completion of the perfusion, liver samples were obtained for histological analysis, with morphological integrity assessed using modified Suzuki-Score through Hematoxylin-Eosin (HE) staining. The optimization experiments yielded the following findings: (1) mice weighing over 30 g were deemed more suitable for the experiment due to the larger size of their bile duct (BD). (2) a 2 Fr (outer diameter = 0.66 mm) polyurethane cannula was better suited for cannulating the portal vein (PV) when compared to a polypropylene cannula. This was attributed to the polyurethane material's enhanced grip, resulting in reduced catheter slippage during the transfer from the body to the organ chamber. (3) for cannulation of the bile duct (BD), a 1 Fr (outer diameter = 0.33 mm) polyurethane cannula was found to be more effective compared to the polypropylene UT - 03 (outer diameter = 0.30 mm) cannula. With this optimized protocol, mouse livers were successfully preserved for a duration of 12 h without significant impact on the histological structure. Hematoxylin-Eosin (HE) staining revealed a well-preserved morphological architecture of the liver, characterized by predominantly viable hepatocytes with clearly visible nuclei and mild dilation of hepatic sinusoids.

This study explores the critical interplay between lobular geometry and the zonated distribution of cytochrome P450 (CYP) enzymes across species. We present an innovative approach to assess lobular geometry and zonation patterns using whole slide imaging (WSI). This method allows a detailed, systematic comparison of lobular structures and spatial distribution of key CYP450 enzymes and glutamine synthetase in four different species (mouse, rat, pig, and human). Our results shed light on species differences in lobular geometry and enzymatic zonation, providing critical insights for drug metabolism research. Based on our approach we could determine the minimum number of lobules required for a statistically representative analysis, an important piece of information when evaluating liver biopsies and deriving information from WSI. ### Competing Interest Statement The authors have declared no competing interest.

Ischemia-reperfusion injury is a critical liver condition during hepatic transplantation, trauma, or shock. An ischemic deprivation of antioxidants and energy characterizes liver injury in such cases. In the face of increased reactive oxygen production, hepatocytes are vulnerable to the reperfusion driving ROS generation and multiple cell-death mechanisms. In this study, we investigate the importance of hydrogen sulfide as part of the liver's antioxidant pool and the therapeutic potency of the hydrogen sulfide donors sodium sulfide (Na2S, fast releasing) and sodium thiosulfate (STS, Na2S2O3, slow releasing). The mitoprotection and toxicity of STS and Na2S were investigated on isolated mitochondria and a liver perfusion oxidative stress model by adding text-butyl hydroperoxide and hydrogen sulfide donors. The respiratory capacity of mitochondria, hepatocellular released LDH, glutathione, and lipid-peroxide levels were quantified. In addition, wild-type and cystathionine-γ-lyase knockout mice were subjected to warm selective ischemia-reperfusion injury by clamping the main inflow for 1 h followed by reperfusion of 1 or 24 h. A subset of animals was treated with STS shortly before reperfusion. Glutathione, plasma ALT, and lipid-peroxide levels were investigated alongside mitochondrial changes in structure (electron microscopy) and function (intravital microscopy). Liver tissue necrosis quantified 24 h after reperfusion indicates the net effects of the treatment on the organ. STS refuels and protects the endogenous antioxidant pool during liver ischemia-reperfusion injury. In addition, STS-mediated ROS scavenging significantly reduced lipid peroxidation and mitochondrial damage, resulting in better molecular and histopathological preservation of the liver tissue architecture. STS prevents tissue damage in liver ischemia-reperfusion injury by increasing the liver's antioxidant pool, thereby protecting mitochondrial integrity.