Search Results (1,087)

Background/Objectives: The management of dyslipidaemia in Slovakia has undergone significant changes in recent years, particularly through the relaxation of prescription restrictions for existing medications and the introduction of new innovative molecules. Achieving target levels of LDL cholesterol (LDL-C) plays a key role in preventing the onset and progression of atherosclerosis-related cardiovascular (CV) diseases. The aim of this study was to analyse how these changes have affected the effectiveness of reaching target LDL-C levels in patients at very high CV risk. Methods: This project was conducted as a retrospective analysis of anonymised LDL-C values from 2020 to 2023 using data from a collaborating nationwide laboratory. Patients included were those diagnosed with acute coronary syndrome (ACS), stroke, and, more generally, those with high and very high CV risk. Target LDL-C values were assessed based on the 2019 ESC/EAS guidelines. Results: A total of 363,020 LDL-C test records from 115,950 patients were evaluated over the four-year study period. Among patients diagnosed with ACS, 2.2–5% achieved target LDL-C levels in the respective years of observation 2020–2023. As many as 6.5–7.4% had LDL-C levels ≥ 4.9 mmol/L. For patients with stroke, only 4–6.6% reached target LDL-C levels, while 5.6–6.7% had levels ≥ 4.9 mmol/L. In the group with very high CV risk, only 1.7–3% achieved target levels, and 7.5–8.7% had extremely high LDL-C levels ≥ 4.9 mmol/L. Despite these modest improvements, over 93.4% of patients in the highest-performing subgroup failed to reach the absolute guideline target threshold in 2023. Conclusions: While the lifting of prescription constraints and the introduction of innovative treatments correlates with a doubling of absolute target attainment and a contraction of extreme hypercholesterolemia, overall control remains critically low in Slovakia. Systematic, protocol-driven combination regimens and intensive follow-up are urgently needed. Full article

Hypertension is among the most important modifiable risk factors associated with heart failure with preserved ejection fraction (HFpEF) development and progression, yet guideline-directed blood pressure (BP) targets (<130/80 mmHg) and sodium–glucose co-transporter 2 inhibitor (SGLT2i) therapies lack dedicated randomized controlled trials (RCTs) in this specific group of patients. This narrative review synthesizes 2024 ESC/ESH and 2025 JSH meta-analyses, discussing the proposed pathophysiological framework linking hypertension-associated remodeling with HFpEF. Post hoc analyses from landmark trials (EMPEROR-Preserved, DELIVER) demonstrate consistent heart failure (HF) event reductions with SGLT2i (pooled HR 0.79, 95% CI 0.67–0.93), complemented by modest systolic BP lowering (−2.3 mmHg) and biomarker insights. Soluble ST2 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) may contribute to risk stratification in HFpEF populations when interpreted in conjuction with imaging findings and clinical context; however, neither biomarker is specific for hypertension-mediated remodeling. Critical evidence gaps persist: heterogeneous BP thresholds across international guidelines, limited device therapy data (renal denervation showing −8.5 mmHg sustained reduction), and real-world implementation barriers among elderly/comorbid Europeans (adherence < 50%, polypharmacy risks). Hellenic HF Registry data highlight frailty prevalence (68% in patients > 75 years) complicating aggressive BP management. The review addresses phenotype-specific challenges through precision medicine approaches incorporating phenomapping and multi-biomarker panels (NRI 0.28 improvement). We advocate for dedicated HFpEF RCTs evaluating intensive vs. standard BP targets, SGLT2i sequencing with antihypertensives, and European real-world registries to bridge the translational gap. These strategies aim to transform guideline recommendations into optimized, patient-centered care for the rapidly expanding hypertensive HFpEF population. Full article

Accurate prediction of external short-circuit (ESC) current is important for battery safety analysis and protection design, but conventional equivalent circuit models have difficulty reproducing the strongly nonlinear current evolution under ESC conditions. This study proposes a reaction-process-corrected second-order RC model for ESC current prediction, based on ESC experiments on a 37 Ah commercial NCM pouch cell at different initial SOCs. The ESC process is described by three successive stages: bottleneck control, concentration-difference control, and separator pore closure. To represent the transport-related resistance deviation during this process, an additional correction resistance R_x and a queued-charge descriptor Q are introduced into the equivalent circuit framework. A segmented closed-loop simulation strategy is then developed to update R_x and predict the ESC current. Using the 50% SOC case as an unseen validation case, the proposed model captures the main nonlinear characteristics of ESC current, including rapid initial decay, secondary rebound, and subsequent attenuation. The proposed framework improves the physical interpretability of equivalent-circuit-based ESC simulation while retaining engineering simplicity, providing a practical approach for safety-boundary assessment and protection-oriented battery system design. Full article

Multirotor unmanned aerial vehicles (UAVs) rely on electronic speed controllers (ESCs) that decode motor commands from pulse-width modulation (PWM) signals, making the flight-controller-to-ESC command path a physical-layer attack surface for intentional electromagnetic interference (IEMI). This paper presents a mechanism-based analysis of IEMI attacks that induce motor stoppage in UAV brushless DC motor controllers. We develop a timing-error model in which a sinusoidal disturbance on the PWM line shifts the detected edge instants and drives the decoded pulse width into stop-equivalent regimes, and we show that the disturbance reaching the ESC’s thresholding node is shaped by a frequency-selective cascade of the PWM cable’s coupling response and the ESC’s input-path transfer function. We experimentally characterize this model on five commercial ESCs through conducted and radiated injection. The measured thresholds differ by more than an order of magnitude across ESCs and are reordered between frequency bands and injection modes; comparing conducted and radiated results allows us to attribute these differences primarily to the cable coupling response and reveals cases where it either hides or amplifies an ESC’s susceptibility. The susceptible frequency also shifts with PWM cable length in qualitative agreement with transmission-line resonance, confirming that observed radiated susceptibility reflects the joint design of ESC and cable rather than a single intrinsic property. The cable lengths examined here (45–125 cm) are longer than those of compact multirotors and were chosen to place resonances within our antenna’s band; we discuss the implications of this choice and identify shorter, deployment-realistic cables as a priority for future work. Full article

iPSC technology is well established in mammals but remains underdeveloped in non-mammalian species. A major barrier to generating avian iPSCs has been the lack of species-specific reprogramming factors and culture conditions capable of supporting self-renewal in avian pluripotent stem cells. Here, we report the generation of chicken iPSCs (ciPSCs) using a cocktail of seven chicken transcription factors (T7: Oct4, Sox2, Sox3, Klf4, c-Myc, Nanog, and Lin28B) combined with an optimized avian culture system. Transcriptomic and functional analyses identified Sox3, rather than Sox2, as the predominant SoxB1 factor in avian reprogramming. The resulting ciPSCs exhibited stable self-renewal for over 40 passages, expressed core pluripotency markers, differentiated into all three germ layers, and were transcriptionally similar to chicken ESCs. In chimera assays, ciPSCs contributed to somatic, extra-embryonic, and germline lineages, giving rise to gonadal PGC-like cells that did not acquire full germline competence. We further demonstrate that the T7 system generates iPSCs from quail, duck, peacock, zebra finch, and pigeon, and that duck iPSCs can form interspecies chimeras with donor cells detected in the host gonads. These findings establish a generalizable platform for avian iPSC generation with applications in developmental biology and germline preservation of endangered species. Full article

Background: Diabetic neuropathy (DN) is a common complication of diabetes mellitus that remains frequently undetected by conventional diagnostic methods. Sudomotor dysfunction, reflecting small-fiber impairment, has emerged as a potential early marker. SUDOSCAN, a rapid and non-invasive device measuring electrochemical skin conductance (ESC), has been proposed as a screening tool for early DN. The objective of this study was to systematically evaluate the diagnostic performance and clinical utility of SUDOSCAN in the early detection of DN. Methods: A systematic review was conducted in accordance with the PRISMA 2020 guidelines. Studies assessing SUDOSCAN-derived ESC in adults with diabetes were included. Data on diagnostic accuracy, correlations with established neuropathy measures, and clinical applicability were extracted. Where feasible, pooled sensitivity and specificity were estimated using a random-effects model. Results: Fifteen studies (n = 7343 participants) were included in the qualitative synthesis, with five of them contributing to the quantitative analysis. Reduced ESC values were consistently associated with DN, including early and asymptomatic cases. Pooled sensitivity and specificity for detecting DN were 0.81 (95% CI 0.73–0.87) and 0.73 (95% CI 0.57–0.85), respectively. ESC values correlated with neuropathy severity scores and autonomic dysfunction measures. However, substantial heterogeneity was observed due to variability in diagnostic criteria, ESC thresholds, and study populations. Conclusions: SUDOSCAN is a feasible, rapid, and non-invasive tool for detecting DN, particularly in the early-stage or small-fiber disease. It shows promise as a screening and adjunctive diagnostic modality, especially when combined with established clinical tools. Nevertheless, the lack of standardized thresholds limits its standalone use. Full article

Accurately quantifying the expression of individual transcript isoforms remains a formidable challenge, especially in contexts such as neurodegenerative diseases and cancers, which are characterized by high isoform diversity. The present study introduces a junction-based method, named differential splicing frequency analysis (DSFA), which enables more sensitive detection of differential splicing using RNA-seq data. Unlike the existing exon-, isoform-, and event-based methods, DSFA quantifies splice junction usage. We applied DSFA to Alzheimer’s disease (AD)-associated genes through large-scale RNA-seq data mining. The present study is the first to establish that the APP770-, APP751-, APP695-, and APP752-encoding isoforms represent major isoforms of the APP gene. Three important findings are: (1) the APP752-encoding isoform exhibits immune cell specificity; (2) the relative proportion of the APP752-encoding isoform increases during the differentiation of induced pluripotent stem cells (iPSCs) into microglia, akin to the increase in relative proportion of the APP695-encoding isoform during iPSC differentiation into neurons; and (3) the APP751-encoding isoform predominates in both cancer and immune cells. Additionally, we identified APP/58417N and App/52804N as differentially expressed splice junctions in humans and mice, respectively. Through over-expression of U1 snRNA in human embryonic stem cell (hESC)-derived neurons, we found that U1 snRNA over-expression decreases the usage of APP/58417N in neurons, similar to the effects observed in AD samples. Our research highlights that the major isoforms of a gene can differ markedly in their expression across tissue and cell types. Full article

Background: Diabetic peripheral neuropathy (DPN) is a progressive complication of type 2 diabetes mellitus (T2DM) for which no approved disease-modifying therapy exists. Palmitoylethanolamide/Baicalin (PEA/Bai; Neuridase^®) is a nutraceutical formulation with anti-neuroinflammatory and antioxidant properties; however, real-world evidence on its associations with objective neuropathy biomarkers remains limited; nutraceutical approaches to DPN remain exploratory and adjunctive in the absence of randomised controlled trial evidence of disease modification. Methods: We conducted a single-centre, retrospective, 1:1 matched-cohort study at an Internal Medicine outpatient clinic. Forty-eight T2DM patients with clinically diagnosed DPN who received PEA/Bai supplementation (Neuridase^® group) were matched to 48 untreated controls drawn from a large institutional database, using age, sex, BMI, and diabetes duration as matching variables. Acknowledged a priori limitations include baseline imbalance in neuropathy severity (VAS and ESC) and SGLT2 inhibitor use, reflecting real-world prescribing patterns (confounding by indication) and constituting potential sources of residual confounding that preclude causal inference. The primary outcome was change in VAS neuropathic pain score from baseline (T0) to 6-month follow-up (T6). Secondary outcomes were changes in electrochemical skin conductance (ESC, µS) in hands, feet, and four-limb sum measured by Sudoscan. Results: At baseline, the Neuridase^® group exhibited significantly greater neuropathic burden: higher VAS scores (median 5.5 [IQR 3.8–7.2] vs. 2.0 [0.0–5.0]; p < 0.001) and lower ESC in both hands (53.0 vs. 72.2 µS; p < 0.001) and feet (74.5 vs. 81.0 µS; p < 0.001), reflecting real-world prescribing patterns. Over 6 months, VAS decreased significantly in the Neuridase^® group (5.5→3.0; p < 0.0001; median Δ = −2.5 points, exceeding the clinically important difference), with no change in controls (2.0→2.0; p = 0.85). Differential Sudoscan trajectories were observed: the Neuridase^® group showed significant improvement in hand ESC (53.0→60.0 µS; p = 0.035) and preservation of foot ESC (p = 0.888), while controls exhibited significant deterioration across all three sudomotor indices (hand p = 0.038; foot p = 0.008; four-limb sum p = 0.004). In a complementary categorical pain trajectory analysis, VAS worsening occurred in 31.3% of controls compared with 0% of Neuridase^®-treated patients (p = 0.00022). Among patients with pathological hand ESC at baseline (<60 µS), 27.8% of Neuridase^® patients (n = 36) transitioned to non-pathological values at T6 versus 0% of controls (n = 32; p = 0.001). Conclusions: In a real-world matched cohort, PEA/Baicalin supplementation was associated with clinically meaningful pain reduction and with differential longitudinal sudomotor trajectories compared to matched untreated controls. These exploratory, hypothesis-generating findings from a retrospective non-randomised design are consistent with possible modulatory effects of PEA/Baicalin on objective sudomotor autonomic biomarkers in DPN. Confounding by indication, baseline severity imbalance, and residual confounders including SGLT2 inhibitor use preclude causal interpretation. These observations provide a rationale for adequately powered, prospective, randomised placebo-controlled trials with extended follow-up and structural neuropathy endpoints. Full article

To address the challenges of high-dimensional nonlinearity, multimodal landscapes, and stringent constraints prevalent in modern engineering design, traditional meta-heuristic algorithms often suffer from a loss of population diversity and premature convergence. Inspired by the social collaborative predation and collective information interaction behaviors of P. prominens (jumping spiders), this study proposes a novel bio-inspired meta-heuristic optimization algorithm, termed the Experience Exchange Strategy-Enhanced Philoponella Prominens Optimization (EESPPO). The proposed EESPPO integrates an Experience Exchange Strategy framework to reshape the search dynamics of the population through three progressive evolutionary stages: (1) In the Experience Scarcity (ESC) stage, the algorithm focuses on the construction and dynamic maintenance of an experience library to ensure the effective preservation of high-quality historical information; (2) In the Experience Crossover (ECR) stage, a random guidance vector generation mechanism is introduced to significantly enhance population behavioral diversity and the capability to escape local optima; (3) In the Experience Sharing (ESH) stage, an adaptive fusion update strategy is employed to achieve efficient information interaction and co-evolution among individuals. These three stages operate synergistically within the optimization cycle to establish a dynamic balance between global exploration and local exploitation, effectively overcoming the inherent defects of premature convergence in traditional meta-heuristics. Extensive empirical analysis based on the CEC2017 benchmark functions confirms that EESPPO comprehensively outperforms 12 existing advanced algorithms (including PPO, HSO, SGA, PSO, FLO, DE, HO, WOA, KEO, GWO, FDB-AGSK, and IVYPSO) in terms of convergence accuracy and robustness. Furthermore, the application of EESPPO to four challenging engineering design problems confirms its superiority. The experimental results validate the high precision and feasibility of EESPPO in solving complex constrained engineering problems. Full article

Background/Objectives: Diabetes mellitus and hypertension are major chronic conditions that markedly affect patients’ health and quality of life worldwide. With the rapid development of technology, there has been a growing interest in exploring the potential role of artificial intelligence (AI) in the management of such diseases. This study aims to assess the accuracy and reliability of artificial intelligence tools in providing information for diabetes mellitus and hypertension management. Methods: This study assessed the accuracy and reliability of the information provided by major AI tools such as ChatGPT, Gemini, POE, Claude, Consensus, and Perplexity. Twenty questions that are essential for the management of diabetes mellitus and hypertension were constructed based on the chapters of the respective guidelines and were fed to the AI tools. The outcomes were compared with evidence-based treatment guidelines, such as those from the American Diabetes Association (ADA), the American Heart Association (AHA), the European Society of Cardiology (ESC), and the National Institute for Health and Care Excellence (NICE). Answers were classified into “accurate “, “inaccurate”, and “accurate with missing information”. Three rounds of six-week intervals were conducted to assess accuracy and reliability. In addition, they were conducted to evaluate data updates by comparing answers across the rounds. Results: In round one of the evaluations, ChatGPT and Poe showed the highest accuracy, both at 65% (95% CI: 41.0–83.7), followed by Claude at 60% (95% CI: 41.0–83.7). ChatGPT had the lowest inaccuracy rate at 5% (95% CI: 1.75–33.1), while Claude demonstrated the smallest percentage of responses with missing information at only 6%. (95% CI: 12.8–54.3). In round 2, Claude markedly outperformed all other tools, achieving an accuracy rate of 95% (95% CI: 73.0–99.7) and no responses with missing information (0%). In round 3, ChatGPT came second with 70% (95% CI: 45.70–87.2) accuracy and maintained the lowest inaccuracy rate of 5% (95% CI: 0.26–26.9). Consensus had the largest inaccuracy rate at 40% (95% CI: 20.0–63.6) and the lowest accuracy rate at 40% (95% CI: 20.0–63.6). Overall, statistically significant pairwise comparisons showed that Cloud in the second round has the highest accuracy compared to Poe (p = 0.0154), Gemini (p = 0.0421), Consensus (p = 0.0035), and Perplexity (p = 0.0302). In the assessment of performance shift from round 1 to round 2, Claude achieved the greatest improvement in accuracy at 40%. In the assessment of performance shift from round 2 to round 3, Poe improved the most with an accuracy increase of 25%, while ChatGPT followed with 20%. When evaluating the unprompted and guideline-prompted questions for all AI tools using McNemar’s test, it did not reveal a statistically significant distinction in the proportion of accurate responses (p > 0.05). Conclusions: Throughout the three rounds, ChatGPT maintained the best performance, with the fewest missing data. Claude and Poe followed, showing high accuracy with relatively low inaccuracy rates. On the other hand, Perplexity and Gemini performed moderately, while Consensus had the lowest accuracy. Full article

Export supply chains (ESCs) for perishable fruits, such as mangoes and avocados, are shaped by complex supply–demand dynamics and macroeconomic conditions. However, limited forecasting of these dynamics constrains strategic planning and investment in Australia’s horticultural sector. This study assesses the longitudinal growth and future potential of mango and avocado exports. To achieve this, the study identifies influential supply–demand dynamics and applies time-series forecasting to understand the export trends. Historical export–import data were analysed for mango and avocado from 1992 to 2024, including volume, value, per capita GDP (Australia and key importing nations), real exchange rate, and real interest rate. Holt’s exponential smoothing was used to forecast export trends, supported by unit root testing in RStudio 4.2.3 and model execution in SPSS version 30. ARIMA and ARIMAX models were applied to stationary variables to improve mango export forecasts. The results show that avocado exports follow a strong upward trajectory, while mango exports remain volatile due to logistical inefficiencies and informal trade disruptions. ARIMAX modelling confirmed that production and consumption volumes significantly enhance forecast accuracy. Macroeconomic trends, rising GDP, declining real interest rates, and stable real exchange rates further reinforce Australia’s competitive position in the destination markets. The long-run trends in export volume and value suggest that both the mango and avocado sectors hold potential for further export growth, although the higher volatility observed in the avocado series indicates that expansion should be approached cautiously. To sustain this growth, maintaining a balanced relationship between production capacity and export demand, particularly for commodities exhibiting higher volatility, will be essential for ensuring stable and efficient export performance over time. Full article

Background: Intermediate-high-risk acute pulmonary embolism (APE) presents a clinical challenge, as patients are hemodynamically stable at admission yet carry a substantial risk of deterioration requiring rescue thrombolytic therapy. This study evaluated whether admission complete blood count-derived inflammatory indices, particularly the Systemic Inflammation Response Index (SIRI), are associated with subsequent thrombolytic therapy requirement. Methods: In this retrospective cohort study, 134 patients with computed tomography pulmonary angiography–confirmed intermediate-high-risk APE, classified according to 2019 ESC guidelines, were grouped based on the need for rescue thrombolytic therapy (n = 52) versus no thrombolytic therapy (n = 82). Inflammatory indices were calculated from admission blood samples, and multivariable logistic regression and ROC analyses were performed. Results: Patients requiring thrombolysis had significantly higher SIRI, SII, hs-troponin I, and systolic pulmonary artery pressure (SPAP), and lower lymphocyte counts. In multivariable analysis, SIRI (OR = 2.08, 95% CI 1.37–3.13), SPAP (OR = 1.21, 95% CI 1.06–1.37), and troponin (OR = 1.01 per 10 ng/L increment, 95% CI 1.00–1.01) were independently associated with thrombolytic therapy requirement. Conclusions: SIRI, SPAP, and hs-troponin I were independently associated with thrombolytic therapy requirement in intermediate-high-risk APE. These findings are hypothesis-generating and warrant prospective validation before clinical implementation. Full article

Endometriosis (EMs) is an estrogen-dependent inflammatory disease characterized by the presence of endometrial-like tissue outside the uterine cavity, yet its precise pathogenesis remains incompletely elucidated. TICAM1, a key adaptor protein in the Toll-like receptor (TLR) signaling pathway, is known to be involved in inflammatory responses; however, its specific role in EMs has not been defined. This study integrated evidence from clinical tissue samples of patients with ovarian endometriomas, in vitro studies, and in vivo models to explore the role of TICAM1 in EMs. TICAM1 expression was significantly upregulated in both eutopic and ectopic endometrium, with the highest levels observed in ectopic lesions, where it was primarily localized to stromal and glandular epithelial cells. Functional experiments showed that TICAM1 overexpression promoted the proliferation, migration, and invasion of human endometrial stromal cells (hESCs), while TICAM1 knockdown suppressed these activities. Concurrently, TLR3 and TLR4 were also upregulated in EMs tissues, and their activation increased TICAM1 expression. Knockdown of TICAM1 attenuated the enhanced cellular activities induced by TLR3/TLR4 activation. Mechanistically, IRF3 and IFN-β levels were elevated in both EMs tissues and TICAM1-overexpressing hESCs, while TICAM1 knockdown inhibited TLR3/TLR4-induced IRF3 phosphorylation and subsequent IFN-β production. These findings were further corroborated in a mouse model of EMs. Together, our findings suggest that TICAM1 may enhance the proliferation, migration, and invasion of hESCs by mediating TLR3/TLR4 signaling and promoting IRF3 phosphorylation and subsequent IFN-β production, thereby potentially contributing to EMs progression. Therefore, targeting TICAM1 may represent a potential therapeutic direction for ovarian endometrioma-associated EMs, while its relevance to superficial peritoneal and deep infiltrating EMs requires further investigation. Full article

Background: Chronic kidney disease (CKD) is associated with a high burden of cardiovascular remodeling and increased risk of heart failure with preserved ejection fraction (HFpEF). However, the interpretation of natriuretic peptide-based HFpEF diagnostic remains challenging in CKD populations, where structural cardiac abnormalities and elevated NT-proBNP levels frequently coexist. Methods: We conducted a cross-sectional study including ambulatory patients with CKD stages G3–G4 and NYHA II dyspnea. Clinical, metabolic, vascular, and echocardiographic assessments were performed. HFpEF was assessed using a modified HFA-PEFF-based approach derived from the ESC-recommended diagnostic algorithm. We evaluated the impact of NT-proBNP thresholds on HFpEF classification and explored the relationship between NT-proBNP, echocardiographic diastolic dysfunction, and structural cardiac abnormalities. Results: The cohort displayed a high cardiometabolic burden (74.9%), and structural cardiac abnormalities were highly prevalent. Using a modified HFA-PEFF diagnostic algorithm, HFpEF was identified in 52.9% of patients. However, when the biomarker domain was excluded, 86.7% of patients remained within the intermediate-probability range. In an exploratory analysis, a cutoff of 700 pg/mL was identified as the cohort-adapted threshold with the best diagnostic balance and identified 19.8% patients as having HFpEF. Conclusions: Patients with CKD G3–G4 exhibited substantial structural and functional cardiovascular abnormalities despite no prior diagnosis of heart failure. HFpEF classification varied according to the NT-proBNP threshold applied, while NT-proBNP demonstrated limited discriminatory performance for echocardiographic diastolic dysfunction. These findings support the need for more refined and CKD-sensitive approaches for HFpEF characterization in this population. Full article

Polycomb repressive complex 2 (PRC2) regulates the expression of pluripotency genes in embryonic stem cells (ESCs) and suppresses multiple genes associated with development, cell fate determination, and differentiation. Mouse embryonic stem cells (mESCs) derived from protein kinase C inhibition (PKCi) exhibit self-renewal and pluripotency comparable to those ESCs captured by the classical 2iL (CHIR99021, PD0325901, and leukemia inhibitory factor) system. However, the dynamic expression pattern of PRC2 in PKCi-mESCs and its role in regulating pluripotency remain unclear. This study demonstrated that the expression level of the enhancer of zeste 2 gene (Ezh2), of which protein is the catalytic subunit of PRC2 responsible for the trimethylation of lysine 27 on nucleosome histone H3 subunit (H3K27me3), is significantly higher in PKCi-mESCs than in 2iL-mESCs. EZH2 knockdown enhances the self-renewal capacity of PKCi-mESCs, as evidenced by a significant increase in the number of undifferentiated mESCs colonies. The effect of an EZH2 reduced expression is accompanied by the upregulation of specific core pluripotency gene Nanog, along with the general downregulation of differentiational genes representing the three germ layers. Conversely, EZH2 overexpression promotes a significant differentiation of PKCi-mESCs, resulting in the downregulation of pluripotency genes, including core pluripotency genes Nanog and Sox2, as well as naïve pluripotency genes Klf4, Fgf4, and Esrrb, while with a wide upregulation of three germ layer associated genes. Importantly, Cleavage Under Targets and Tagmentation (CUT&Tag) demonstrates that EZH2 directly controls H3K27me3 enrichment at the Nanog promoter near the transcription start site. Thus, EZH2, a core subunit of PRC2, exhibits the distinct regulatory functions orchestrating mESCs at a poised state between self-renewal and differentiation under PKC inhibition. EZH2 exerts histone H3 methyltransferase activity to regulate Nanog expression as one of its key targets, thereby modulating the transcriptional regulatory network that maintains pluripotency and lineage specification in mESCs. Full article