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Lung cancer remains the leading cause of cancer-related death, and, despite significant advancements in targeted therapy and immunotherapy, survival for patients with advanced non-small cell lung cancer (NSCLC) remains poor. An emerging area of interest is the role of epigenetic modifiers in both the pathogenesis and treatment of NSCLC. Herein, we review a selected group of chromatin-modifying genes implicated in NSCLC, organized by their function as writers (KMT2A, SETD2, and EZH2), erasers (the KDM2, KDM5, and KDM6 demethylase families), and readers (the SWI/SNF subunits SMARCA4 and ARID1A). Writers deposit activating or repressive marks on histones to regulate gene transcription, erasers remove these marks, and readers reposition nucleosomes and control DNA accessibility. Dysregulation of these genes has been associated with tumor proliferation, metastasis, treatment resistance, and altered response to immune checkpoint blockade in NSCLC. Research within this topic is emerging, and these genes represent promising potential therapeutic avenues as well as potential biomarkers. Finally, we review the clinical trials involving targeting these genes available in the current literature. The number of NSCLC-specific trials remains limited, with the most active development in SMARCA2 inhibitors for SMARCA4-mutated tumors and EZH2 inhibitors given in tandem with PD-1 blockade. We hope this review is hypothesis-generating for ongoing investigation into the role of epigenetic modifiers in NSCLC and their potential to expand the therapeutic armamentarium available for this disease.

The ability to selectively edit specific RNA modifications is needed to understand their roles in cellular function and disease. However, existing approaches, particularly catalytically inactive Cas (dCas)-based systems, have limited applicability owing to their reliance on eraser proteins, and their performance can vary depending on the modification type and target context. Here we introduce the RNA Modification-Blocking (RModBlock) strategy, which uses chemically modified antisense oligonucleotides (ASOs) with locked nucleic acid to precisely inhibit modifications at targeted sites. Most RNA modification writers, including those for m5C and pseudouridine, require specific structural contexts. Using representative modifications with and without eraser proteins, m5C and pseudouridine, respectively, we demonstrated that RModBlock ASOs blocked the formation of their structural context, inhibiting modified bases by up to 97% in human cells. RModBlock ASOs also inhibited m6A, despite its writer protein not requiring a strict structural context, suggesting broad applicability. Moreover, this strategy achieves comparable or superior performance when dCas13-eraser-based systems are applicable. Finally, by inhibiting cancer-relevant modifications and through in vivo delivery to the mouse liver, we highlight its therapeutic potential. This showcases the RModBlock strategy as a precise, efficient and versatile approach for manipulating RNA modifications, with broad applicability in basic and translational research.

As generative artificial intelligence (GenAI) becomes increasingly embedded in academic writing, understanding how L2 writers engage with AI-generated feedback and regulate their writing processes is critical. While prior research has focused on learners' perceptions of GenAI and writing outcomes, little is known about the processes through which learners' beliefs are enacted in GenAI-assisted writing contexts. Drawing on social cognitive theory and self-regulated learning (SRL) frameworks, this study proposes a process-oriented mediation model in which engagement with GenAI feedback links GenAI writing self-efficacy and writing SRL strategies. Survey data were collected from 564 Chinese non-English-major postgraduate students using GenAI for English academic writing. Structural equation modeling revealed that GenAI writing self-efficacy significantly predicted feedback engagement, which in turn predicted writing SRL strategies. The direct relationship between self-efficacy and SRL strategies became non-significant when engagement was included, indicating full mediation, except for the direct significant relationship between self-efficacy and cognitive strategies. The findings position feedback engagement as a central self-regulatory mechanism in GenAI-assisted writing.

RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), and adenosine-to-inosine (A-to-I) editing, constitute a dynamic epitranscriptomic network that profoundly regulates RNA metabolism and gene expression. Their dysregulation is increasingly recognized as a hallmark of cancer. This review critically synthesizes the multifaceted roles of RNA modifications to bridge the gap between descriptive epitranscriptomic mapping and functional tumor biology. We systematically evaluate how writers, readers, and erasers dictate transcript stability and translation efficiency, driving tissue-specific tumor evolution across diverse malignancies. Crucially, we explore the intersection of RNA modifications and the tumor immune microenvironment, detailing their mechanisms in orchestrating immune evasion, altering antigen presentation, and regulating immune checkpoints. Furthermore, we examine how epitranscriptomic reprogramming dictates cellular responses to chemotherapy, radiotherapy, targeted treatments, and immunotherapy. By comprehensively analyzing these mechanisms, this review aims to facilitate the translation of epitranscriptomic findings into clinical applications, laying a theoretical foundation for targeted anti-tumor strategies.

Parosmia is a qualitative olfactory disorder characterised by a distorted perception of smell, often experienced as unpleasant or offensive. Although parosmia has multiple aetiologies, post-viral parosmia has become increasingly prevalent following the COVID-19 pandemic. In the UK, post-viral parosmia affects an estimated 637&#x2009;836 individuals and has a substantial negative impact on quality of life and mood. At present, there is no licensed or standardised treatment for this condition. Gabapentin, a gamma-aminobutyric acid analogue with neuromodulatory properties, has shown potential benefits at low doses in small, non-randomised studies; however, its efficacy requires further evaluation. Use of Gabapentin in the Management of Post-Viral Parosmia: A Double-Blind, Randomised, Placebo-Controlled, Multi-Site Trial (COPANOS) is a phase III, double-blind, randomised, placebo-controlled trial comparing gabapentin with placebo in adults aged 18-65 years with post-viral parosmia persisting for &#x2265;6 months and <5 years. Participants will be randomised 1:1 to receive gabapentin, titrated to a maximum dose of 600&#x2009;mg daily or a matching placebo for 8 weeks. The primary outcome is the between-group difference in mean parosmia severity scores at the end of treatment (week 8), measured using the parosmia domain of the validated Smell-Qx questionnaire. Secondary outcomes include quality of life (Smell- Qx), olfactory function assessed using the Sniffin' Sticks test battery, safety and tolerability and objective parosmia severity measured with the Sniffin' Sticks Parosmia Test (SSParoT). The trial will recruit 90 participants across two UK sites. The results will provide robust preliminary evidence on the efficacy and safety of low-dose gabapentin for managing post-viral parosmia and will inform the feasibility and design of targeted treatment guidelines. Defining effective treatment for post-viral parosmia is essential given the significant impact on patient well-being and the absence of current evidence-based interventions. The trial protocol has been reviewed and approved by Health Research Authority (HRA) and Health and Care Research Wales (HCRW): 25/WA/0298, 21/10/2025. Results will be analysed and published as soon as possible following trial completion. Findings will be summarised on the study webpage and shared with trial participants in plain English. Trial results will also be uploaded to relevant trial registries within 12 months of trial completion. The Rosetrees Trust will be acknowledged in all publications. Publications will follow International Committee of Medical Journal Editors authorship guidelines, and professional medical writers will not be used. ISRCTN82171427, IRAS 1012783.

m1A (N1-methyladenosine) is an important epigenetic mechanism that regulates the onset and progression of many diseases, including spinal cord injury (SCI). To investigate the overall changes in m1A levels following SCI, we analyzed transcriptomic sequencing data from SCI samples and assigned m1A scores based on the levels of m1A regulatory factors. In this study, the m1A score is an inferred proxy calculated from the expression of m1A regulator genes (writers/erasers/readers). It does not directly measure RNA m1A modification levels. Our results show that the m1A score increased within the first day after SCI and then decreased, falling below baseline by day 3 and day 7. Further analysis revealed that microglia and neurons are the two cell types with the most significant changes in the m1A score. In microglia, m1A score decreased at all time points, whereas in neurons, m1A score increased at all time points. Additionally, through pseudotime analysis and function enrichment analysis, the m1A score may be associated with the phenotypic transition of microglia and neuronal energy metabolism, and this was further validated by conducting studies both in vivo and in vitro. In a word, our study unveils the characteristic changes of m1A at both the bulk and single-cell levels following SCI, and suggests potential links to neuronal function and supports the rationale for further studies exploring m1A-related regulators as therapeutic targets in SCI.

The assessment of handwriting is fundamental for identifying difficulties, which may have long-term negative consequences. However, standard evaluation typically focuses only on the final handwritten product. For this reason, Italian guidelines recommended supporting traditional evaluation with digital tools to also analyze the handwriting process. A sensorized ink pen used on paper was employed by over 700 students, ranging from first grade in Italian primary school to third grade in lower secondary school, to execute two tasks of the BVSCO-3, the gold standard for handwriting assessment. From sensorized ink pen data, handwriting indicators in the domains of Time, Force, Smoothness, Tilt, and Frequency were extracted. These indicators were then analyzed to examine their correlation with clinical scores, to model cross-sectional trends across grades, and to identify handwriting difficulties. The correlation analysis revealed significant relationships between the indicators and the clinical score, particularly for the Time domain. A cross-sectional statistical analysis showed that the indicators follow developmental trends compatible with handwriting learning curves reported in the literature: for many indicators, a performance plateau was reached in grade 3, from both motor and processing perspectives. Lastly, binary classification models successfully distinguished subjects with handwriting difficulties (based on BVSCO-3 results) from proficient writers. The sensorized ink pen allowed uncovering relevant characteristics of children's handwriting process, while guaranteeing ecological data acquisition conditions. Its use could pave the way for a prompt identification of handwriting difficulties in school settings, thus facilitating an efficient referral to clinical services.

Dietary methionine restriction has been shown to improve metabolic health and treat multiple diseases. Methionine metabolism regulates transmethylation reactions, including N6-methyladenosine (m6A) RNA methylation, by modulating the availability of S-adenosyl methionine (SAM). Both m6A RNA methylation and methionine metabolism are involved in the regulation of the circadian clock. However, it remains unclear whether dietary methionine influences circadian rhythms through the regulation of m6A RNA modification. In this study, we investigated the effects of short-term methionine deprivation on the diurnal oscillations of m6A RNA methylation in the mouse liver. We found that a methionine-deficient (MD) diet reprogrammed the cyclic expression patterns of m6A writers, erasers, and readers. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) revealed that the MD diet induced de novo diurnal m6A oscillations in genes associated with RNA processing, protein translation, protein ubiquitination, and mTORC1 signaling pathways. RNA-seq and quantitative proteomics analyses demonstrated that MD-induced changes in m6A RNA levels were linked to alterations in mRNA and protein abundance. We observed that dynamic m6A RNA methylation of the transcripts encoding two key enzymes, MAT2A and CBS, helps maintain methionine homeostasis in response to methionine starvation. These findings identify m6A RNA methylation as a key mechanism linking methionine metabolism to circadian regulation.

Methylation of histone H3 at lysine 4 (H3K4me) is a key epigenetic mark in plants, governing transcriptional regulation, development, and stress adaptation. While the enzymes that deposit and remove this mark are well studied, how H3K4me signals are interpreted by reader proteins remains less understood. This review synthesizes recent advances in the molecular recognition of H3K4me states by plant reader domains, including PHD, BAH, CW, Tudor, and chromodomain modules. Unlike prior reviews that focused on writers and erasers or on stress-specific responses, we systematically examine the reader-side mechanisms, with particular emphasis on how distinct methylation states, including trimethylated (H3K4me3), dimethylated (H3K4me2), monomethylated (H3K4me1), and unmethylated H3K4, are discriminated and translated into chromatin-based outputs. These readers function as signaling hubs, integrating environmental and hormonal cues to regulate flowering, DNA repair, and stress memory, with implications for crop performance. However, fundamental gaps remain, including the identification of H3K4me1-specific readers, the structural basis for combinatorial histone mark recognition, and the evolutionary divergence of reader pathways between monocots and dicots. Our review provides a framework for understanding H3K4me reader biology and explores its potential for application in plant breeding.

Osteosarcoma (OS) is the predominant primary malignant bone tumor in children and adolescents. Current treatments mainly include surgical resection combined with chemotherapy, but they still cannot effectively control tumor metastasis and recurrence, and may pose a risk of long-term complications. N6-methyladenosine (m6A) is the most widespread internal modification. It orchestrates various biological and disease-related events via the reversible m6A machinery comprising writers, erasers and readers. As a key epigenetic regulatory mechanism, m6A modification opens new avenues for deeper exploration of OS mechanisms and for developing new therapeutic targets and biomarkers. In this manuscript, we systematically explore the critical roles of m6A in OS cell proliferation, metastasis, metabolic reprogramming, programmed cell death, and tumor microenvironment regulation. Our aim is to provide a robust theoretical framework to underpin future basic studies and clinical applications in this field.

N6-methyladenosine (m6A), the dominant internal RNA modification in eukaryotic mRNA, plays an important regulatory role in female reproductive physiology and associated pathologies. This review systematically outlines the precise regulatory mechanisms exerted by m6A writers, erasers, and readers in core processes including germ cell development, early embryogenesis, and hormone signaling. We further elaborate on how aberrant m6A modifications contribute to the pathogenesis of various female reproductive disorders, such as gynecological cancer, polycystic ovary syndrome, and preeclampsia. In addition, we conducted a rigorous assessment of the therapeutic and diagnostic potential targeting the m6A mechanism. By synthesizing mechanistic insights from both neoplastic and non-neoplastic diseases, this review provides a comprehensive framework for understanding the epitranscriptomic governance of female reproductive health and proposes new directions for future research and clinical translation.

Epitranscriptomic regulation has emerged as a critical mechanism in cancer biology, particularly in the development of chemoresistance. RNA modifications including N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), 7-methylguanosine (m7G), pseudouridine (&#x3a8;), and A-to-I editing dynamically control mRNA stability, splicing, translation, and degradation. RNA-modifying proteins called 'writers,' 'erasers,' and 'readers' regulate post-transcriptional networks to enable tumor adaptation and chemoresistance. In platinum-resistant tumors, epitranscriptomic changes modulate DNA damage response, apoptosis, drug efflux, and detoxification pathways. Preclinical studies demonstrate that pharmacological inhibition of key regulators, such as METTL3 inhibitors (STC-15, STM2457, UZH2) or FTO inhibitors, can sensitize tumors to platinum drugs and stimulate anti-tumor immunity. However, clinical translation remains limited by off-target effects, toxicity, and highly context-specific responses. Epitranscriptomic profiling may help identify novel biomarkers and guiding precision strategies to overcome chemoresistance.

Lactate, once considered merely a metabolic byproduct, is now recognized as a cornerstone of central nervous system (CNS) homeostasis, serving as both a vital energy substrate and signaling molecule. The identification of lysine lactylation (Kla) has established this modification as a key epigenetic link between cellular metabolism and genomic regulation. This review examines the molecular mechanisms underlying protein lactylation, including enzymatic regulation by writers, erasers, and readers as well as non-enzymatic mechanisms. The multifaceted roles of Kla are explored in the context of CNS disorders, ranging from malignancies, acute injuries, and neurodegenerative diseases. The review further examines Kla's role in neuroinflammation, metabolic reprogramming, and neuroplasticity, highlighting its potential as a sensitive biomarker. Potential therapeutic strategies are also considered, including metabolic inhibitors and nanocarriers capable of crossing the blood-brain barrier (BBB) to restore metabolic and epigenetic balance.

Uterine spiral artery remodelling (SAR) is a fundamental developmental process that facilitates optimal placental perfusion and supports fetal growth. Central to SAR is the phenotypic transformation of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic state, directed by invasive trophoblast cells. To advance these findings, we sought to elucidate the epigenetic mechanisms governing trophoblast-induced reprogramming of VSMC identity, enabling plasticity required for uterine vascular adaptation. VSMC dedifferentiation was assessed by qRT-PCR, Western blotting, and immunofluorescence. Epigenetic alterations were evaluated by Western blotting. A chromatin remodelling PCR array was performed and validated by qRT-PCR and Western blotting. Chromatin remodelling factors were downregulated using antisense oligonucleotides (ASOs), and VSMC dedifferentiation was confirmed by Western blotting. E13.5 and E16.5 rat metrial glands were used for in vivo validation. An IUGR rat model was generated by administering dexamethasone from E13.5 to E20.5. In IUGR tissues, trophoblast invasion, VSMC dedifferentiation, and chromatin remodelling factor expression were validated by Western blotting. Co-culture of primary E16.5 rat trophoblast cells with VSMCs revealed a trophoblast-induced shift in the expression landscape of epigenetic regulators, resulting in upregulation of chromatin-modifying "writers" (CBP, DNMT1, DNMT3A), downregulation of "erasers" (HDAC 1,2,3), and an increase in both transcription activation marks (H3K27ac, H3K9ac) and repression marks (H3K27me3, H3K9me3). Targeted real-time PCR array profiling identified coordinated downregulation of 13 chromatin remodelling genes (ARID1B, SMARCAD1, SMARCD1, SMARCD3, BMI1, EZH2, CBX2, CBX5, CBX6, BAZ1B, ZMYND8, CHD1, MBD3,) during VSMC de-differentiation. This change in the epigenetic landscape was recapitulated in vivo within the metrial gland, the entry point of uterine spiral arteries, on E16.5. Knockdown of these factors impaired the phenotypic transition of VSMCs, establishing their mechanistic role in enabling vascular adaptation. Notably, in a model of intrauterine growth restriction (IUGR), the normal expression dynamics of chromatin remodelling factors and VSMC phenotypic markers were reversed, indicating the need for the dynamic epigenetic regulatory axis, which is essential for vascular adaptation in healthy pregnancies. These findings uncover a trophoblast-driven epigenetic axis that governs VSMC plasticity during SAR and highlight its dysregulation as a potential contributor to the pathogenesis of IUGR.

Medical school applicants engage in informal preference signaling by submitting letters of intent (which include a commitment to accept an admission offer) and letters of interest (which include no such commitment). Commitments are unenforceable and are based on an honor system. Applicants submit letters to medical schools before receiving financial aid offers, potentially disadvantaging low socioeconomic status (SES) applicants. This study describes postinterview communication patterns and analyzes associations among applicant demographics, letter submission rates, and admissions outcomes. It tests the hypothesis that low SES is negatively associated with letter of intent submission. The authors collected postinterview communications from all interviewees at the Mayo Clinic Alix School of Medicine during 3 admissions cycles (2021-2023). Authors developed and validated codebook definitions for the 2 letter types. SES was defined using the Association of American Medical Colleges education-occupation indicator. Letter submission rates were compared using mixed-effects logistic regression. Of 1,313 applicants, 1,109 submitted 1 letter or more. The sample included 257 (19.6%) low-SES and 1,056 (80.4%) non-low-SES applicants. Coders showed excellent interrater reliability (Gwet AC1 range, 0.89-0.995). Low-SES applicants submitted letters of intent with similar frequency to higher-SES applicants (33.9% [87/257] vs 33.5% [354/1,056]; odds ratio, 1.02; 95% CI, 0.76-1.37; P = .88) and submitted letters of interest at similar frequency (55.6% [143/257] vs 59.5% [628/1,056]; odds ratio, 0.86; 95% CI, 0.65-1.13; P = .27). Among 116 applicants who wrote letters of intent and were offered admission, 20 (17.2%) declined the admission offer. There was no difference in letter of intent submission based on SES, and letter of intent submission was positively associated with matriculation. Among letter of intent writers who were offered admission, 1 in 6 declined. Undergraduate medical education may wish to consider a formalized preference signaling system to promote an honest and transparent application process.

Acute kidney injury (AKI) is a clinically critical condition with a high mortality rate. Its complex pathophysiological mechanisms remain incompletely understood, and there is a lack of effective targeted therapeutic strategies. In recent years, the role of epigenetic modifications in the initiation and progression of kidney disease has been increasingly clarified. N6-methyladenosine (m6A) is one of the most important and common post-transcriptional modifications among various RNAs, including eukaryotic mRNAs, lncRNAs, and miRNAs. It is dynamically and reversibly regulated by methyltransferases ('writers'), demethylases ('erasers'), and binding proteins ('readers') to modulate processes such as RNA splicing, export, stability, translation, and degradation. This modification exerts diverse biological effects and is extensively involved in both physiological and pathological pathways. Recently, a growing body of evidence has indicated that m6A modification plays a crucial regulatory role in the development and progression of AKI. Existing studies suggest that m6A modification profoundly influences the fate of renal tubular epithelial cells (TECs) by regulating the expression of genes associated with inflammatory responses and programmed cell death, thereby modulating the severity of AKI and the subsequent renal repair process. This review systematically summarizes the latest research advances regarding m6A modification in AKI, elucidates the mechanisms by which it influences the pathogenesis of AKI through various cellular processes, and explores the potential of m6A-targeted therapies for treating AKI, thereby providing insights into the regulatory networks of m6A modification in AKI and the epigenetic regulation of transcription in this condition.

To evaluate the feasibility and reliability of an artificial intelligence-driven quality assurance system for emergency chest pain documentation in simulated cases, compared to traditional physician reviewers. We developed an automated quality assurance solution leveraging commercial Large Language Models that are customized based on College of Physicians and Surgeons of Ontario peer review standards. Seventeen simulated emergency chest pain cases of varying quality were independently reviewed by an automated auditor, six community emergency physicians, and original case writers using a 3-point evaluation scale across nine dimensions. Agreement was measured using Lin's Concordance Correlation Coefficient for overall score agreement, Root Mean Square Error for overall score accuracy, and Cohen's Kappa statistics for categorical dimension scores. Inter-rater agreement among human reviewers showed substantial variability with overall score concordances ranging from 0.28 to 0.86. The automated auditor demonstrated agreement levels within the range of human variability within the limited sample of simulated cases with the best performing model (guideline-customized Claude Sonnet 4) with a concordance value of 0.85 and root mean square error of 0.25 with respect to the average human scores on the 3-point scale. For pass/fail decisions, agreement with human reviewers ranged from 65 to 94% with Kappa scores of 0.27 to 0.85, comparable to inter-human reviewer agreement Kappa scores of -&#xa0;0.12 to 0.68. The performance of the automated auditor showed agreement within the range of variability observed among that of the small group of uncalibrated human reviewers for the simulated cases in determining documentation quality and pass/fail outcomes. Given the potential variability in human assessments, automated quality assurance may provide a more consistent evaluation of quality, with the added advantage of the mass-processing of many cases in near real-time. R&#xe9;SUM&#xe9;: OBJECTIFS: &#xc9;valuer la faisabilit&#xe9; et la fiabilit&#xe9; d&#x2019;un syst&#xe8;me d&#x2019;assurance qualit&#xe9; bas&#xe9; sur l&#x2019;intelligence artificielle pour la documentation des douleurs thoraciques en urgence dans les cas simul&#xe9;s, par rapport aux m&#xe9;decins examinateurs traditionnels. M&#xe9;THODES: Nous avons d&#xe9;velopp&#xe9; une solution automatis&#xe9;e d&#x2019;assurance de la qualit&#xe9; qui tire parti des grands mod&#xe8;les de langue commerciaux, personnalis&#xe9;s selon les normes d&#x2019;&#xe9;valuation par les pairs du Coll&#xe8;ge des m&#xe9;decins et chirurgiens de l&#x2019;Ontario. Dix-sept cas simul&#xe9;s de douleur thoracique d&#x2019;urgence de qualit&#xe9; variable ont &#xe9;t&#xe9; examin&#xe9;s ind&#xe9;pendamment par un auditeur automatis&#xe9;, six m&#xe9;decins urgentistes communautaires et des r&#xe9;dacteurs de cas originaux &#xe0; l&#x2019;aide d&#x2019;une &#xe9;chelle d&#x2019;&#xe9;valuation en trois points couvrant neuf dimensions. L&#x2019;accord a &#xe9;t&#xe9; mesur&#xe9; &#xe0; l&#x2019;aide du coefficient de corr&#xe9;lation de concordance de Lin pour l&#x2019;accord global des scores, de l&#x2019;erreur quadratique moyenne (EQM) pour la pr&#xe9;cision globale des scores et des statistiques kappa de Cohen pour les scores de dimension cat&#xe9;gorielle. R&#xe9;SULTATS: L&#x2019;accord inter-&#xe9;valuateurs parmi les &#xe9;valuateurs humains a montr&#xe9; une variabilit&#xe9; substantielle, avec des concordances de scores allant de 0,28 &#xe0; 0,86. L&#x2019;auditeur automatis&#xe9; a d&#xe9;montr&#xe9; des niveaux d&#x2019;accord dans la plage de variabilit&#xe9; humaine au sein de l&#x2019;&#xe9;chantillon limit&#xe9; de cas simul&#xe9;s, avec le mod&#xe8;le le plus performant (Claude Sonnet 4 adapt&#xe9; aux directives). avec une valeur de concordance de 0,85 et une erreur quadratique moyenne de 0,25 par rapport aux scores humains moyens sur l&#x2019;&#xe9;chelle de 3 points. Pour les d&#xe9;cisions de r&#xe9;ussite/&#xe9;chec, l&#x2019;accord avec les examinateurs humains variait de 65% &#xe0; 94% avec des scores Kappa de 0,27 &#xe0; 0,85, comparables aux scores Kappa d&#x2019;accord entre &#xe9;valuateurs humains de -0,12 &#xe0; 0,68. CONCLUSIONS: La performance de l&#x2019;auditeur automatis&#xe9; a montr&#xe9; un accord dans la plage de variabilit&#xe9; observ&#xe9;e parmi celle du petit groupe d&#x2019;examinateurs humains non calibr&#xe9;s pour les cas simul&#xe9;s afin de d&#xe9;terminer la qualit&#xe9; de la documentation et les r&#xe9;sultats de r&#xe9;ussite/&#xe9;chec. Compte tenu de la variabilit&#xe9; potentielle des &#xe9;valuations humaines, l&#x2019;assurance qualit&#xe9; automatis&#xe9;e peut fournir une &#xe9;valuation plus coh&#xe9;rente de la qualit&#xe9;, avec l&#x2019;avantage suppl&#xe9;mentaire du traitement en masse de nombreux cas en temps quasi r&#xe9;el.

Esophageal cancer is a type of malignant tumor with high incidence and mortality rates worldwide, and esophageal squamous cell carcinoma (ESCC) is the predominant pathological subtype in China. Despite continuous advancements in treatment methods, the prognosis of ESCC patients remains poor and there is an urgent need to develop new therapeutic strategies. Recent epigenetic frontiers have identified the dysregulation of lysine acetylation, a dynamic and reversible post-translational modification, as a pivotal driver of ESCC pathogenesis. This process is orchestrated by a dynamic interplay between "writers" (lysine acetyltransferases, KATs), "erasers" (lysine deacetylases, KDACs), and "readers". In this review, we systematically delineate the molecular landscape of lysine acetylation in ESCC and emphasize how these epigenetic modulators reshape the transcriptional program of tumor cells. Specifically, we highlight the oncogenic or tumor-suppressive roles of key acetylating enzymes and their non-histone substrates, which bridge the gap between epigenetic alterations and malignant phenotype. And we summarize the latest research progress and clinical application potential of KAT inhibitors (KATi), KDAC inhibitors (KDACi), and inhibitors of lysine acetylation readers in various tumor. Additionally, we discuss the challenges of drug resistance in epigenetic therapy and opportunities in targeting acetylation modification. By providing a comprehensive synthesis of the acetylation-ESCC axis, this review aims to offer theoretical guidance for the development of novel epigenetic biomarkers and targeted interventions to improve the prognosis of ESCC patients.

Ferroptosis is an iron-dependent, lipid peroxidation-driven form of programmed cell death. There is substantial evidence supporting the critical role of ferroptosis in multiple neurological diseases, including stroke, Alzheimer's disease, Parkinson's disease, epilepsy, and traumatic brain injury. Histone acylation, an important epigenetic mechanism, effectively regulates ferroptosis. To date, the regulation of ferroptosis by histone acylation in neurological diseases has rarely been summarized. Therefore, this review discusses the key mechanisms by which histone acylation regulates ferroptosis, including iron metabolism, antioxidant defense, and lipid peroxidation. Additionally, we summarize the latest advances in understanding the role of histone acylation in ferroptosis and its relation to the emerging hallmarks of neurological diseases. Furthermore, we provide the prospect of targeting key regulatory factors of histone acylation, such as writers, erasers, and readers, for potential therapeutic strategies to ameliorate neurological diseases.