Abstract: The intensive use of pesticides in agriculture poses serious risks to aquatic ecosystems and non-target organisms, yet toxicological data remain limited. This study evaluated the acute effects of three widely used pesticides—pirimiphos-methyl (10 and 60 μg/L), propamocarb hydrochloride (40 and 80 μg/L), and 2,4-D (50 and 100 μg/L)—on the liver of common carp (Cyprinus carpio Linnaeus, 1758), a sentinel species in aquaculture, but also a species equally important in risk assessment and environmental monitoring. Fish were exposed for 96 hours under controlled conditions, and histopathological, histochemical, and biochemical biomarkers were analyzed. All tested pesticides induced significant histopathological alterations, predominantly circulatory and degenerative changes, with severity increasing at higher concentrations. Propamocarb hydrochloride and 2,4-D caused more pronounced and partly irreversible hepatotoxicity compared to pirimiphos-methyl. Histochemical assessment revealed altered glycogen metabolism, while biochemical assays showed inhibition of key liver enzymes, such as ALAT and ASAT, but also ChE and LDH, indicating disrupted metabolic processes. These findings highlight the vulnerability of aquatic organisms to pesticide exposure and support the use of fish liver biomarkers as effective tools in ecotoxicology research. The study also emphasizes the need for stricter regulation and environmental monitoring of pesticide contamination in aquatic systems.

Abstract:

Background: Melatonin, an indolic neuromodulator with oncostatic and anti-inflammatory properties, is produced at extrapineal sites—most notably in the gut. Its canonical actions are mediated by high-affinity GPCRs (MT1/MT2) and by the melatonin-binding enzyme NQO2 (historically “MT3”). A growing body of work highlights a bidirectional interaction between the gut microbiota and host melatonin. Methods: We integrate two lines of work: (i) three clinical cohorts—cardiac arrhythmias (n = 111; 46–75 y), epilepsy (n = 77; 20–59 y), and stage III–IV solid cancers (25–79 y)—profiled with stool 16S rRNA sequencing, SCFA measurements, and circulating melatonin/urinary 6-sulfatoxymelatonin; and (ii) an age-spanning cognitive cohort with melatonin phenotyping, microbiome analyses, and exploratory immune/metabolite readouts, including a novel observation of melatonin binding on bacterial membranes. Results: Across all three disease cohorts we observed moderate-to-severe dysbiosis with reduced alpha-diversity and shifted beta-structure. The core dysbiosis implicated tryptophan-active taxa (Bacteroides/Clostridiales proteolysis and indolic conversions) and depletion of SCFA-forward commensals (e.g., Faecalibacterium, Blautia, Akkermansia, several Lactobacillus/Bifidobacterium spp.). Synthesized literature indicates that typical human gut commensals rarely secrete measurable melatonin in vitro; rather, their metabolites (SCFAs, lactate, tryptophan derivatives) regulate host enterochromaffin serotonin/melatonin production. In arrhythmia models, dysbiosis, bile-acid remodeling, and autonomic/inflammatory tone align with melatonin-sensitive antiarrhythmic effects. Epilepsy exhibits circadian seizure patterns and tryptophan-metabolite signatures, with modest and heterogeneous responses to add-on melatonin. Cancer cohorts show broader dysbiosis consistent with melatonin’s oncostatic actions. In the cognitive cohort, the absence of dysbiosis tracked with preserved learning across ages; exploratory immunohistochemistry suggested melatonin-binding sites on bacterial membranes in ~15–17% of samples. Conclusions: A unifying microbiota–tryptophan–melatonin axis plausibly integrates circadian, electrophysiologic, and immune–oncologic phenotypes. Practical levers include fiber-rich diets (to drive SCFAs), light hygiene, and time-aware therapy, with indication-specific use of melatonin.

Abstract: Tumor rupture is a rare complication of uterine leiomyosarcoma. We report a case of ruptured uterine leiomyosarcoma containing ectopic components, diagnosed after the onset of abdominal pain following endoscopic examination of the lower gastrointestinal tract. The patient was a 56-year-old woman who had been diagnosed with anemia at 48 years of age when she was first referred to our medical team. Contrast-enhanced magnetic resonance imaging (MRI) revealed a 48 mm x 50 mm mass in the anterior wall of the uterine body, which was diagnosed as a uterine fibroid. After 8 years of regular follow-up once or twice a year, the patient developed abdominal pain after undergoing lower gastrointestinal endoscopy, prompted by a positive fecal occult blood test. Contrast-enhanced computed tomography (CT) showed that the uterine mass had enlarged to 90 mm x 69 mm. T2-weighted contrast-enhanced MRI demonstrated moderate signal intensity and restricted diffusion, and contrast-enhanced T1-weighted MRI revealed high signal intensity suggestive of hemorrhage. The outline of the tumor and uterus was interrupted cephalad to the lesion, raising suspicion of rupture of a malignant uterine mesenchymal tumor. Therefore, total hysterectomy, bilateral salpingo-oophorectomy, and partial omentectomy were performed. Intraoperatively, tumor rupture and adhesion of the ruptured tissue to the ileum were observed, necessitating partial ileectomy. Pathological examination of the resected specimen revealed irregularly proliferating spindle cells with marked nuclear atypia, 12 mitotic figures per 10 High-power fields, coagulative necrosis, and infiltration of multinucleated giant cells. Another notable finding was the presence of ectopic osteosarcoma and chondrosarcoma components.

Abstract:

Recently, GnRHa puberty blockers have been under scrutiny, with newly identified risks of heart and brain damage and recurrent concerns about fertility, cancer risk, and bone health. This study explores the effects of GnRHa on liver morphology, function, and injury response. Peripubertal male and female Sprague-Dawley rats received daily GnRHa triptorelin (100 μg) subcutaneously. Liver oxidative stress, inflammation, and fibrosis were evaluated via malondialdehyde and 8-OHdG (oxidative damage), immunohistochemistry for CK19 (cholangiocytes) and CD45 (leukocytes), and collagen staining as well as áSMA (liver fibrogenesis) and TIMP1 (extracellular matrix breakdown) expression, respectively. Following GnRHa treatment, only male rats exhibited increased ductular reaction and oxidative stress. In contrast, GnRHa-treated female rats showed increased leukocyte infiltration. In both sexes, GnRHa-treated rats showed increased fibrosis, with significantly increased collagen deposition and áSMA expression. Interestingly, GnRHa-treated female rats exhibited increased TIMP1 expression, whereas male rats showed decreased TIMP1 expression. Overall, GnRHa puberty blocking leads to significantly increased liver injury in both sexes. Specifically, biological females are at increased risk of hepatic inflammation, while biological males are at increased risk of oxidative stress. Human clinical trials are crucial for further exploring these findings.

Abstract: This work investigates crowd dynamics in evacuation scenarios by incorporating the effects of emotional contagion. We develop a hybrid modeling framework that couples a mesoscopic kinetic approach for pedestrian motion with an agent-based model describing emotional interactions. Each individual adapts their emotional state based on the average emotion of nearby agents, which in turn affects their walking direction and speed. Numerical simulations, conducted using a Monte Carlo particle method for the kinetic motion model together with an agent-based scheme for emotional contagion, examine three representative scenarios: calm crowds without contagion, fully emotional crowds, and mixed populations. The results show that emotional contagion intensifies congestion and significantly increases evacuation times. The proposed dual-scale model provides a first step toward a comprehensive representation of panic dynamics, offering new insights into the interplay between motion and emotion, with potential applications to crisis management and safety design.

Abstract:

Metastatic relapse often reflects the survival of a small population of disseminated tumor cells (DTCs) that take up residence in distant organs and then shift into a dormant state. Rather than dividing, these cells sit quietly for long periods and rely on local niche signals to stay inactive and avoid therapy. Dormant cells are difficult to eliminate because the immune system cannot detect them, and treatments aimed at actively growing cells are ineffective. DTCs stop oncogenic signaling and start stress-response and cell-cycle arrest pathways. These pathways are often characterized by higher levels of cyclin-dependent kinase (CDK) inhibitors and greater p38 signaling than ERK signaling. LIFR–STAT3 signaling in the bone marrow supports quiescence in breast cancer cells, while inflammatory cytokines and Wnt/BMP antagonists in the lung microenvironment can trigger reactivation of cancer DTCs. Because these dormant DTCs are not cycling, standard cytotoxic agents rarely remove them. Current strategies are now testing immune-directed therapies. Recent single-cell and long-read sequencing efforts have started to reveal the transcriptional programs that mark DTCs, including stress-response and quiescence signatures that differ from the primary tumor. These insights are shaping therapies for interrupting dormancy and lowering the risk of late metastatic relapse.

Abstract: This paper focuses on algebraic-logical modeling of molecular genetic informatics systems and inherited biostructures. The focus is primarily on the development of a quantum-logical framework for modeling genetically inherited ensembles of coordinated cyclic (biorhythmic) processes characteristic of living organisms. The author develops a quantum-logical modeling approach based on the genetic alphabet of 4 unitary Hadamard matrices and cyclic power groups based on it. The possibilities and prospects of the proposed approach for the development of quantum-logical biology, genomorphic artificial intelligence, and biotechnology are discussed.

Abstract: Background/Objectives: The prevalence of gastric subepithelial lesions (SELs) is rising. Endoscopic resection (ER) technique provides a minimally-invasive alternative to manage gastric SELs. This study aims to evaluate the effectiveness and safety of ER for gastric myogenic tumors, and predictors for gastrointestinal stromal tumors (GISTs). Methods: The study was conducted between 2012 and 2024 at nine tertiary centers in Taiwan. We enrolled patients with endoscopic ultrasound (EUS) documented gastric myogenic tumors managed by endoscopic muscular dissection (EMD), endoscopic subserosal dissection (ESSD), submucosal tunneling endoscopic resection (STER) and endoscopic full-thickness resection (EFTR). Clinical manifestation, endoscopic features and outcomes were analyzed. Results: We enrolled 325 patients with 332 lesions [mean EUS size 14.5mm, 153 (46.1%) leiomyoma, 152 (45.8%) GISTs, 27 (8.1%) other histology]. ER techniques were 193 (58.1%) EMD, 46 (13.9%) ESSD, 28 (8.4%) STER, and 65 (19.6%) EFTR. Technical success, en-bloc and R0 resection rates were 97.0%, 94.3%, 88.9%, respectively. Twenty-four (9.0%) procedures were shifted to unintentional EFTR, and 21 (6.3%) patients had complications. No recurrence occurred during mean follow-up period of 921.4 days. Two (0.6%) patients died of non-procedure related reasons. Old age, fundus location, heterogeneous echotexture and exophytic growth pattern were independent risk factors for GIST (all with p < 0.05). Using the above factors, we built a prediction model with sensitivity of 77.0%, specificity of 85.6%, and AUC of 0.8771. Conclusions: ER is an efficient and safe management for gastric myogenic tumors. The malignant potential could be predicted by demographic characteristics and EUS features.

Abstract:

Allergic rhinitis (AR) is characterized by persistent epithelial remodeling, yet the upstream drivers and molecular mechanisms remain poorly defined. Analysis of nasal mucosa from AR patients revealed marked epithelial remodeling, oxidative stress, and Th2 inflammation. Transcriptome analysis of nasal mucosa revealed RhoA as one of the most upregulated genes, with expression positively correlating with disease severity. Using epithelial-specific RhoA-deficient mice (RhoA^cKO) and fasudil, a RhoA/ROCK inhibitor, we found that loss of RhoA/ROCK signaling markedly attenuated nasal Th2 inflammation, oxidative stress, and epithelial remodeling following allergen challenge. Further transcriptome analysis demonstrated that elevated RhoA activation was associated with increased epithelial cellular senescence. Both in vitro and in vivo studies confirmed that epithelial RhoA activation promotes allergen- or Th2 cytokine–induced cellular senescence, whereas genetic or pharmacologic elimination of senescent cells alleviated allergic inflammation and tissue remodeling. Pathway analysis identified PRKN (parkin) as a central node within RhoA-regulated, senescence-associated networks in AR. Functional studies showed that PRKN overexpression mitigated IL-13–induced mitochondrial dysfunction, oxidative stress, and epithelial senescence in human nasal epithelial cells. Together, these findings reveal that RhoA-driven epithelial senescence contributes to allergic inflammation and epithelial remodeling in AR and identify PRKN as a potential therapeutic target to restore epithelial homeostasis.

Abstract:

Background: Ground contact (GC) detection is essential for sprint performance analysis. Inertial measurement units (IMUs) enable field-based assessment but their reliability during sprint acceleration remains limited with heuristic and recently used machine learning algorithms. This study introduces a deep learning one-dimensional convolutional neural network (1D-CNN) to improve GC event and GC times detection in sprint acceleration. Methods: Twelve sprint-trained athletes performed 60 m sprints while bilateral shank-mounted IMUs (1125 Hz) and synchronized high-speed video (250 Hz) captured the first 15 m. Video-derived GC events served as reference labels for model training, validation and testing using resultant acceleration and angular velocity as model inputs. Results: The optimized model (18 inception blocks, window = 100, stride = 15) achieved mean Hausdorff distances ≤ 6 ms and 100% precision and recall for both validation and test datasets (Rand Index ≥ 0.977). Agreement with video references was excellent (bias < 1 ms, limits of agreement ±15 ms, r > 0.90, p < 0.001). Conclusions: The 1D-CNN surpassed heuristic and prior machine learning approaches in the sprint acceleration phase, offering robust, near-perfect GC detection. These findings highlight the promise of deep learning–based time-series models for reliable, real-world biomechanical monitoring in sprint acceleration tasks.

Abstract: Metadata extraction from the labels of natural history collections is a pivotal task for the online publication of digitized specimens. However, this is an extremely time-consuming task, given the estimated number of specimens in natural history collections (more than 2 billion specimens worldwide, of which ca. 400 million are herbarium specimens). Thus, automated data extraction from digital images of specimens and their labels is an application where state-of-the-art computer vision techniques could successfully be applied. The task of extracting information from the labels of herbarium specimens is made of three steps: text segmentation, multilingual/handwriting recognition, and data parsing. The principal bottleneck in the process is the limitation of Optical Character Recognition (OCR). This study aims to explore how to transfer the general knowledge present in multimodal Transformers into the specific sub-task of herbarium specimen label digitization. This would result in an easy-to-use, end-to-end solution, which strives to get rid of the bottleneck of classic OCR systems, while allowing for higher flexibility to adapt to different label formats. Donut-base, a pre-trained visual document understanding (VDU) transformer, was the base model selected for fine-tuning. A dataset from the University of Pisa was used as a test bed. The initial attempt achieved an 85% accuracy computed by the Tree Edit Distance (TED), demonstrating that fine-tuning is a feasible solution. Cases with low accuracies were also investigated to highlight flaws in the approach. Specimens with more than one label, especially when a mix of different handwriting and typewritten information were present, are the most difficult to deal with, and approaches aimed at targeting these weaknesses are discussed.

Abstract:

Background/Objectives: Breast cancer is the most common malignancy among women, and early detection is critical for improving outcomes. The Breast Imaging Reporting and Data System (BI-RADS) standardizes reporting, but the BI-RADS 4 category presents a major challenge, with malignancy risk ranging from 2% to 95%. Consequently, most women in this category undergo biopsies that ultimately prove unnecessary. This study evaluated whether exhaled breath analysis could distinguish malignant from benign findings in BI-RADS 4 patients. Methods: Participants referred to the McGill University Health Centre Breast Center with BI-RADS 3–5 findings provided multiple breath specimens. Breathprints were captured using an eNose powered breathalyzer , and diagnoses were confirmed by imaging and pathology. An autoencoder-based model fused the breath data with BI-RADS scores to predict malignancy. Model performance was assessed using repeated cross-validation with ensemble voting, prioritizing sensitivity to minimize false negatives. Results: The breath specimens of eighty-five participants, including sixty-eight patients with biopsy-confirmed benign lesions and seventeen patients with biopsy-confirmed breast cancer within the BI-RADS 4 cohort are analyzed. The model achieved a mean sensitivity of 88%, specificity of 75%, and a negative predictive value of 97%. Results were consistent across BI-RADS 4 subcategories, with particularly strong sensitivity in higher-risk groups. Conclusions: This proof-of-concept study shows that exhaled breath analysis can reliably differentiate malignant from benign findings in BI-RADS 4 patients. With its high negative predictive value, this approach may serve as a non-invasive rule-out tool to reduce unnecessary biopsies, lessen patient burden, and improve diagnostic decision-making. Larger, multi-center studies are warranted.

Abstract:

Background/Objectives: The vaginal microbiota (VM) represents a highly diverse microbial ecosystem shaped by the distinctive mucosal environment and immunological characteristics of the female genital tract. Recent evidence emphasizes that alterations in cervical microbial composition may contribute to high-risk gynecological conditions. In this context, the present study sought to comprehensively characterize the cervical microbiota of a well-defined cohort of Greek women. The primary aim was to evaluate the functional microbial landscape, with a focus on identifying bacterial signatures and potential microbial pathways that may influence cervical physiology, protection, and disease susceptibility. Methods: Microbial genomic DNA of 60 samples was extracted using the Magcore Bacterial automated Kit and was subjected to 16S rRNA sequencing using the Nanopore MinION™ enabling a comprehensive analysis of the microbial community. Results: More than 75% of the total microbial community of the cervical samples were represented by the species: Lactobacillus iners and Lactobacillus crispatu and Aerococcus christensenii while the species Stenotrophomonas maltophilia, S. pavanii, Acinetobacter septicus, Rhizobium rhizogenes, R. tropici, R. jaguaris, Prevotella amnii, P. disiens, Brevibacterium casei, Fannyhessea vaginae, Gemelliphila asaccharolytica, flexneri were detected in lower abundances. Conclusions: These findings highlight the predominant protective role of Lactobacillus species while emphasizing the potential contributions of low-abundance or environmentally derived bacteria whose functional implications require further investigation. Broader population studies are essential to establish microbial signatures as diagnostic markers or therapeutic targets for optimizing cervical health.

Abstract: Cleaning validation remains a cornerstone of pharmaceutical quality assurance, ensuring that manufacturing equipment is consistently cleaned to predetermined acceptance criteria that protect patient safety and product quality. The pharmaceutical industry has witnessed a significant paradigm shift from traditional compliance-based approaches toward science-based, risk-based methodologies for cleaning validation. This paper provides a comprehensive review of risk-based cleaning validation, examining the regulatory framework established by ICH Q9 and related guidelines, the evolution of acceptance criteria from arbitrary limits to health-based exposure limits, and the application of quality risk management tools such as Failure Mode and Effects Analysis. The lifecycle approach to cleaning validation, sampling methodologies, and strategies for preventing cross-contamination in multi-product facilities are discussed. This review synthesizes current literature and regulatory expectations to provide pharmaceutical professionals with practical guidance for implementing robust, scientifically justified cleaning validation programs.

Abstract:

Human breast milk evolves beyond simple nutrition to function as a complex signaling system that promotes neonatal development. This review analyzes the bioactive components, delineating how its specific constituents compensate for the physiological vulnerabilities of the neonate. Additionally, the distinct roles of colostral and mature milk are in fortifying the immature immune system and promoting gastrointestinal maturation. Focus is placed on the prevention of necrotizing enterocolitis, where milk oligo-saccharides and microbiome function to maintain mucosal integrity and symbiosis, while preventing pathogens’ adhesion. Furthermore, it is evaluated how breastfeeding duration is linked to long-term metabolic and immunological programming. Mi-croRNAs and bioactive lipids actively modulate gene expression and immune responses, thereby reducing the incidence of metabolic diseases and childhood malignancies. By integrating findings, this article underscores the irreplaceable role of breast milk in clinical dietetics and pediatric care.

Abstract: Recent decades have seen two striking epidemiological patterns: the rising prevalence of many chronic diseases and phenotypic conditions, and the earlier onset of traits once confined to old age. Here, I introduce the Accumulated Mean Annual Variation (AMAV), a new metric for integrating heterogeneous prevalence data across multiple studies, and apply it to 31 conditions. This analysis reveals consistent population-level shifts that may reflect a common, systemic process. I propose Epigenetic Degeneration (ED) — the intergenerational accumulation of epimutations — as a candidate mechanism, extending the Double Code Hypothesis of Ageing, which views ageing as the inheritance of both genetic and epigenetic information. Beyond epidemiology, the framework introduces the principle of pre-determined post-processing in neuronal biology, complementing the classic principle of labelled lines, and offers an evolutionary explanation for the persistence of traits such as homosexuality despite reduced reproductive fitness. Together, these contributions outline a unified, testable framework linking epidemiology, ageing, neuroscience, and evolution.

Abstract: Chronic, dysregulated inflammation is a recognized driver of colitis‑associated colorectal cancer (CRC). At the molecular level, the cGAS–STING pathway integrates cytosolic DNA sensing with type‑I interferon and NF‑κB responses, yet its pleiotropy complicates intervention: insufficient activity blunts antitumor immunity, whereas over‑activation fuels tissue‑damaging cytokine milieus. Motivated by the anti‑inflammatory efficacy of the marine briarane diterpenoid excavatolide B (ExcB) and recent reports of STING antagonism, we combined AlphaFold3 complex prediction with AI‑assisted docking and short explicit‑solvent MD (10 ns) to map ExcB–human STING (hSTING) interactions. Beyond the canonical Cys148/Tyr240 region (Site‑1), our pipeline identifies an entrance‑proximal pose at the CDN rim (Site‑2) and a buried pose (Site‑2′) that conditions hSTING into a CDN‑averse conformation. Competitive docking of cGAMP onto ExcB‑conditioned snapshots yields qualitatively weaker scores versus native, consistent with allosteric occlusion rather than direct steric clash. As a methodological check, we benchmarked the same docking workflow on two reported STING antagonists, SN‑011 and Astin C, reproducing their canonical CDN‑pocket contacts before applying the pipeline to ExcB. Collectively, these results support ExcB‑like, gate‑closing STING antagonists as tunable non‑activators with favorable developability, and motivate mutagenesis and competition assays around His157/Tyr167/Thr263 to dissect Site‑2 → Site‑2′ contributions.

Abstract: Background/Objectives: Polymorphous adenocarcinoma (PAC) currently termed as polymorphous adenocarcinoma (PAC) has varied clinical, and histological presentation. Moreover, the challenges in differential diagnosis of PAC, and the nuances involved in distinguishing PAC from other tumors, such as adenoid cystic carcinoma (ACC) and pleomorphic adenoma can impact the treatment plan and patient prognosis. Aim: The aim of the study was to comprehensively review polymorphous adenocarcinoma, its clinical character-istics, diagnosis, treatment approaches, and long-term outcomes. Methods: Various available databases was used like Pubmed, Embase, Scopus, Cochrane Library and Google Scholar to search for the articles published between 2013 and 2023. Results: A total of 43 articles were identified from all databases. Eventually, eight studies met the inclusion requirements and were selected for the systematic review. Conclusion: While polymorphous adenocarci-noma (PAC) predominantly affects individuals in their sixth to seventh decades of life, its clinical presentation var-ies. Histologically, PAC exhibits diverse patterns, including tubular, cribriform, and solid, influencing treatment decisions and prognostic outcomes. Surgical excision remains the primary treatment modality, often supplemented with radiation therapy in cases of incomplete resection. Significantly, our data highlights the good prognosis linked to PAC, which is demonstrated by high survival rates and comparatively low rates of metastasis. However, with long term follow ups, distant metastasis or even transformation to a high-grade adenocarcinoma has been noted. Molecular characterisation is necessary due to challenges in accurate diagnosis and differentiation from other sali-vary gland neoplasms.

Abstract: Background/Objectives: Obesity is a major risk factor for diabetes, but the underlying mechanisms remain incompletely understood. Obesity is associated with alterations in circulating lipids. This study aimed to determine whether, and to what extent, circulating lipids mediate the pro-diabetic effect of obesity. Methods: We analyzed data from 26,627 US adults. Mediation analysis was performed using the PROCESS Version 4.3 Macro for SPSS. Parallel mediation analysis included total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides as simultaneous mediators. Low-density lipoprotein (LDL) cholesterol was excluded from the parallel model due to collinearity with total cho-lesterol and was assessed separately using simple mediation analysis adjusted for con-founders. Results: After adjustment for tested confounders, parallel mediation analysis showed that increases in triglycerides and reductions in HDL cholesterol mediated 24.0% (indirect effect coefficient = 0.23; 95% CI: 0.20–0.26; p < 0.05) and 3.8% (indirect effect coef-ficient = 0.04; 95% CI: 0.01–0.06; p < 0.05) of the pro-diabetic effect of obesity, respectively. An increase in total cholesterol negatively mediated the effect by 2.3% (indirect effect coef-ficient = -0.02; 95% CI: -0.03 to -0.01; p < 0.05). Simple mediation analysis indicated that LDL cholesterol was not a significant mediator. Conclusions: Triglycerides are the most influential circulating lipid in mediating the pro-diabetic effect of obesity, accounting for 24% of the total effect. Targeting triglyceride levels may represent an underrecognized therapeutic strategy to reduce obesity-related diabetes risk.

Abstract: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Yet, its treatment has serious challenges and is unsuccessful in a considerable fraction of pa-tients. One reason may be a limited understanding of the molecular mechanisms un-derlying AF. Recent studies suggest that oxidative stress is involved in AF pathogenesis. Enhanced oxidative stress is largely determined by disrupted mitochondrial homeo-stasis, as cardiomyocytes heavily rely on mitochondrial energy production and calcium transfer between mitochondria and the sarcoplasmic reticulum. Atrial fibrillation in-volves metabolic, structural, and electrical remodeling, all of which are influenced by mitochondrial mechanisms. Mitochondrial homeostasis is controlled by mitochondrial quality control (mtQC), which is a multi-pathway mechanism to maintain integrity and functionality of mitochondria. Impaired mtQC may result in disturbed mitochon-dria-related calcium handling, decreased energy production, mitochondria-related in-flammation and fibrosis, and impaired mitophagy. Sirtuins (SIRTs) are family of 7 members of histone deacetylases, which have antioxidant properties and 3 of them are localized to mitochondria. Therefore, at least some of SIRTs may ameliorate enhanced oxidative stress related to damaged mitochondria. SIRTs have shown potential to im-prove AF outcomes in studies on AF patients and animal models. Therefore, SIRTs may have a potential to ameliorate AF through decreasing oxidative stress and restoring mitochondrial homeostasis disrupted in AF. In this narrative review we provide in-formation how mitochondrial dysfunctions, expressed as the disturbance in mtQC, contributes to AF through oxidative stress, calcium handling abnormalities, energy de-ficiency, inflammation and fibrosis, and genetic changes. In addition, we presented the protective potential of sirtuins in AF.